REPORT ON DRUG REGULATORY SYSTEM ASSESSMENT OF MONGOLIA

Transcription

1 REPORT ON DRUG REGULATORY SYSTEM ASSESSMENT OF MONGOLIA ULAANBAATAR 2011

2 Abbreviations... 3 Acknowledgement... 4 Executive Summary General information on the assessment Purpose of this assessment report Objectives Place and date of the assessment Method Members of the assessment General information on the country Findings Legislation Regulatory functions Funding Infrastructure Human resource management Quality management system Impartiality, transparency and accountability Information management systems and Communication activities Medicines registration (marketing authorization) Licensing of activities of pharmaceutical establishments Registration of Pharmacy personal Import and export control Market surveillance Control of Drug Promotion and Advertising

3 3.9 Pharmacovigilance Control of Clinical Trials Regulatory inspection and enforcement activities Quality Control Laboratory Control of Narcotics, Psychotropic Substances and Precursors International Cooperation and Harmonization Conclusions and Recommendations Annex 1 Assessment tool Annex 2 List of organizations visited and list of persons met Annex 3 References: Annex 4. Quantitative indicators for regulatory purposes Annex 5 Organogram of Drug Regulatory organizations of Mongolia Annex 6 Action plan

4 Abbreviations ADB ADR API BP CT DOH GASI GCP GDP GLP GMP GXP HMO HSUM ICH IEC IRB KFDA MA MAH MCA MEC MOH MNS NDCL NGO NMRA NPSP NRA OTC PI PPC QMS SPC WHO Asian Development Bank Adverse drug reaction Active pharmaceutical ingredient British Pharmacopoeia Clinical trial Department of Health General Agency for Specialized Inspection Good clinical practices Good distribution practices Good laboratory practices Good manufacturing practices Good practices Health Minister s Order Health Sciences University of Mongolia International Conference for Harmonization Independent ethics committee Institutional review board Korean Food Drug Administration Market authorization Market authorization holder Millennium Challenge Account Medical Ethics Committee Ministry of Health Mongolian National Standard National drug control laboratory Nongovernmental organization National Medicine Regulatory Authority Narcotics, psychotropic substances and precursor chemicals National Regulatory Authority Over the counter Product information Pharmacy Professional Committee Quality management system Summary of product characteristics World Health Organization 3

5 Acknowledgement This Drug regulatory assessment of Mongolia was assigned by the Ministry of Health and completed with the financial and technical support from the World Health Organization We would like to acknowledge with gratitude the contribution of all people who participated representing the following institutions and associations: Division of Pharmaceuticals and Medical Devices, Ministry of Health of Mongolia, Division of Drug regulation, Health DepartmentImplementing Agency of the Government Mongolia, and Human Drug Council of Mongolia, Ministry of Health of Mongolia Health and Education Monitoring Office, Professional Inspection AgencyRegulatory Agency of the Government of Mongolia, Central Laboratory, Professional Inspection AgencyRegulatory Agency of the Government of Mongolia, Drug Reference Laboratory, Quality Control Laboratory of Pharmacy School, Health Sciences University of Mongolia, The Regulatory Agency for Fair Competition and Consumer Protection and Criminal Police Department of Mongolia. 4

6 Executive Summary This assessment was commissioned by the Ministry of Health of Mongolia, Health Sector Development Project 4 by Asian Development Bank and Word Health Organization. It aims to assess the legal basis, structure, procedures and implementation of drug regulation in Mongolia including registration, inspections and enforcement, licensing, clinical trial, market, import and export control, drug advertisement and promotion controls, pharmacovigilance, and control of narcotics and psychotropic substances. The assessment was conducted using the WHO Data Collection Tool for the Review of Drug Regulatory Systems. The drug regulatory activities gained many successes and benefits during recent years. Drug regulatory legislation is mainly based on The National Drug Policy, the Law on Drug and Medical Devices, and on the Law on Health. The government and international organizations support specific actions towards the implementation of the National Drug Policy, and its strategies were undertaken. Some regulatory activities, such as registration and import authorization are relatively stable, and the online system Licemed for drug registration, licensing and special permissions is established. Most of the drug regulatory activities are organized according to the legal and regulatory papers based on WHO guidelines. The Drug Regulation Division of DOH is established as a National Medicines Regulatory Authority (NMRA) and has started its operations. One of the notable steps is that the first edition of a Mongolian Pharmacopeia has been published. However, there is still a gap for further improvement. Drug regulatory functions are undertaken by different organizations such as the Division of Drug Regulation of Department of Health, Government Implementing Agency for Health and Education Division of State General Agency for Specialized Inspection. Although it was explained that DOH is mainly responsible for internal regulations, and GASI conducts external inspection actions, there is still a lack of efficient cooperation and exchange of information between these organizations. The legal provisions for some of the regulations are missing: market surveillance and pharmacovigilance programmes need to be defined; drug promotion and advertising elements should be clarified according to international standards; drug promotion activities organized by medical representatives and distributors should be controlled. As the Drug Regulatory Division of Department of Health was only recently established, its human resources should be strengthened, and more staff needs to be recruited. The staff training needs should be assessed, and training should be 5

7 conducted according to the needs defined with cooperation of national and international training organizations. Moreover, DOH should improve its transparency by having an internal policy on potential conflicts of interest for staff members; a model format for a declaration of conflicts of interest for staff and experts; and mechanisms to recognize conflicting interests and manage them appropriately. Also, DOH should be more open to the public and improve its information distribution and publicity. Drug and other health products advertisement activities to the public have started to be controlled and assessed to some extent; an advertisement permission procedure has been introduced, and was reviewed by the Pharmacology Sub Committee of Human Drug Counsel. However, there is a room for further improvement on drug promotion and capacity should be built at DOH, State Inspectorate Agency, and The Unfair Competition and Consumer Rights Protection Regulatory Agency The issues of clinical trials and other biomedical research activities are mainly managed by the Medical Ethics Committee. However, there is a lack of cooperation between the Medical Ethics Committee and Drug and Medical Devices Division of MOH, Drug Regulatory Division of DOH, and GASI; information sharing mechanisms; limited participation of the drug organizations; and lack of drug related guidelines. There are 3 state laboratories to perform quality control testing of pharmaceutical products. Currently, the Drug and Bio Preparation Unit in the Central Laboratory of GASI is the main laboratory, and conducts quality control testing of the pharmaceutical products in the country. The other two laboratories, at the Health Science University and at the Public Health Institute, are performing tests within the limited area for the contracted organizations. Currently those laboratories cannot carry out proper quality control of pharmaceutical products. The capacity of those laboratories needs to be improved in terms of human resources, equipment and maintenance. The implementation and enforcement of legal and regulatory papers is very weak, and action needs to be taken. 6

8 1. General information on the assessment. 1.1 Purpose of this assessment report This report aims to give an overview of the legal basis, structures, processes and implementation of medicines regulation in Mongolia. It is anticipated that it will help policy makers, funders and other interested stakeholders to better understand the situation and to design appropriate actions to strengthen regulatory systems in Mongolia. 1.2 Objectives The objectives of this report are: to highlight the main strengths and weaknesses of medicines regulation in Mongolia; to put the findings into the context of the global regulatory situation and of internationally recommended standards for effective medicines regulation; to provide a baseline and perspective for future assessment strategies. 1.3 Place and date of the assessment The assessments summarized in this report were conducted during visits to NMRAs Mongolia in November to December Method This assessment conducted according to Drug Regulatory Assessment Tool developed by WHO. Written terms of reference and an agenda for the visits were agreed beforehand with the regulatory authority being assessed. The duration of the visits varied depending on the complexity of the regulatory functions, most visits took approximately two to three working days. Data were collected by interviewing personnel, reviewing documents (manuals, records, reports, and files), analyzing data and/or observing activities. Findings were recorded on a comprehensive drug regulatory assessment tool sheet. The draft report was submitted to the regulatory authority after the visit together with a draft plan of action, and comments were invited. This summary report was produced mainly on the basis of the reports provided to the NMRAs assessed. The completed data collection tools were consulted to verify and complete the findings where necessary. 7

9 1.5 Members of the assessment This assessment commissioned by MOH Mongolia and conducted with financial support of WHO. The assessments were conducted by teams composed of external consultants Dr. Purevsuren Sodnomtseren Ph.D, lecturer of School of Pharmacy, HSUM and Ms. Munkhdelger Byambaa MBA, Em Association. It was supervised and consulted by Dr. Munkhdelger Chimedtseren, Head of Pharmaceuticals and Medical Devices Division, Ministry of Health. 2. General information on the country The territory of Mongolia is located in the central part of Asia between of attitude and of longitude, neighbouring with Russian Federation along 3543 km in the north and with Peoples Republic of China km in the south. At 1.564,116 km 2 (603,909 mi²), Mongolia is the world's 19thlargest country in the world. The total population of Mongolia in 2010 was with an annual population growth rate of 1.70% i. The annual GDP growth rate is 1.25 %. Some economic indicators are shown in table 1. Table 1. Economic indicators in 2010 Indicators 2010 Annual change of GDP, % 6.1 GDP per capita, thousands MNT 3,001, GDP per capita, USD 2, Inflation rate, annual average % 10.1 General government revenue, bn. MNT 3, Exchange rates, annual average, MNT/USD Exchange rates, annual average, MNT/EUR Exports, mln.usd Imports, mln.usd Source: Mongolian Statistical yearbook. National Statistical Office of Mongolia, 2010 Table 2. Health indicators in 2010 Indicators 2010 Life expectancy at birth for men (Years) Life expectancy at birth for women (Years) Infant mortality rate, between birth and age 1 (/1.000 live births) 19.4 Under 5 mortality rate, (/1.000 live births) 24.6 Maternal mortality ratio, ( live births) 45.5 Neonatal mortality rate (/1.000 live births) 11.6 Agestandardized mortality rate by cardiovascular diseases ( population) Agestandardized mortality rate by cancer ( population) Mortality rate for tuberculosis (/ population) 3.3 Source: Health Indicators. Department of Health, Government Implementing Agency,

10 3. Findings 3.1. Legislation The National Drug Policy of Mongolia (NDPM) was approved in December, 2002 by the State Great Khural of Mongolia. The NDPM is an integrated part of the Comprehensive Policy on the Mongolian National Security. The NDPM shall be directed to provide health organizations, veterinary hospitals and people with highly effective, qualified, registered drugs and medical equipments continually, sufficiently and equally, and to introduce and promote appropriate use of drugs. The NDPM consists of the areas covering the legislation, drug selection, manufacturing, distributing, drug financing, drug quality assurance and rational use of drugs. The Law on Drug and Medical Device of Mongolia has been revised totally three times, after the 1 st approval in Since then, several modifications have been completed. Law on Drug and Medical Device enacted by Parliament and Health Minister s Order N 278 provide for the establishment of a NMRA. NMRA performs its regulation activity in the frame of Law on Drug and Medical Device, Law on State Inspection, Law on Government Service, and Law on Government Agency. Regulations provide details of how regulatory functions are to be carried out. Based on the legislation, guidelines are needed to interpret the legislation and to advise on how to comply with a regulation. The legal framework should allow effective implementation and provide adequate powers to the NMRA. Legislation covers all products for which medicinal claims are made, as well as related manufacture and trade activities, in the public and private sectors. 3.2 Regulatory functions Regulatory activities are organized and performed at a central level of the country. Drug regulatory functions are undertaken by different organizations which make coordination difficult and create inefficiencies. Organizations involved in drug regulation are: Pharmaceutical and Medical Devices Division, MOH Division of Drug Regulation, the Department of Health, Government Implementing Agency Health and Education Division, General Agency for Specialized Inspection (GASI) 9

11 Pharmaceutical and Medical Devices Division, MOH is responsible for the policy development on medicines and medical devices, drug registration, import authorization, pharmacovigilance and and drug assurance are under the Government Implementation AgencyDepartment of Health. The General Agency for Specialized Inspection (GASI) is responsible for pharmaceutical inspection, border inspection, and operations of the drug control laboratory. Decentralization and cooperation between authorities is insufficient. According to Health Minister s Order 278/2011, Division of Drug Regulation, Department of Health implements the following activities: Marketing authorization of drug and biologically active products; Post marketing surveillance; License of manufacturers, importers and distributors; Drug information, advertising; Drug assurance; GMP assessment; Development of standards and pharmacopeia monographs, monitoring on the implementation; Monitoring, analysis and assessment of drug prescription and usage; Import and export authorization; Price regulation of drugs in EDL; Pharmacovigilance; Professional inspection At the time of visit the activity of license of manufacturers, importers and distributors are not performed by Division of Drug Regulation. Division of Medical Care was responsible for this activity. Because the Division of Drug Regulation has been just reformed, some activities were not performed by the time of visit. The activities of Post marketing surveillance, GMP assessment, and Professional inspection were not performed. The NMRA has not established an Institutional Development Plan and action plan. 10

12 3.2.1 Funding The NMRA depends on government funding and with all fees paid directly to the Ministry of Finance and not receives donor funding. Fees commonly charge for initial marketing authorization, renewal and retention and drug assurance Infrastructure According to Health Minister s order 278/2011, 20 officers should work at the Division of Drug Regulation, Department of Health. At the time of visit, there were 8 officers at Division of Drug regulation, because the Division has been just organized. Key personal for drug regulation are Vice Chairmen for Medicine and Head of Division of Drug Regulation, and there is no scientific person. The work space, work environment, equipment and support services are inadequate. 2 drug inspectors work at the Health and Education Division of the General Agency of Specialized Inspection, Regulatory Agency of the Government Human resource management An organization Chart for the NMRA staff is established and updated. The duties, functions and responsibilities of the key personnel are established in the job descriptions. The NRA has established the necessary competencies (education, training, skill and experience) needed for the key personnel to perform the assigned work. The selection of staff is performed by Government Service Counsel according to Law on Government Service. The NMRA has not human resource development plan. An initial and periodic staff appraisal system is not established and there is no induction program for newly recruited staff. The NMRA has no scientific advisor, and not involved in a global network with relevant scientific associations and professional societies. Although the NMRA takes advantage of external experts for registration and drug assurance and involves them in its regulatory processes, there is no written policy for the recruitment and the designation of external experts and members of experts committees calling for candidates, defining the review by a selective jury, appointments and publishing of the final decision, and to cross off. A contract between the NMRA and each external expert defining roles and responsibilities was established and signed by both parties Quality management system NMRA not implements a comprehensive QMS. 11

13 3.2.5 Impartiality, transparency and accountability NMRA had a website ( at the time of visit, but it was not functioning correctly and it was not possible to get all information related to drug regulation activity from this website. Transparency of NMRA need be improved. There are no internal policy on potential conflicts of interest for staff members and no model format for a declaration of conflicts of interest for staff. There is no written policy for the recruitment and the designation of external experts and members of experts committees calling for candidates, defining the review by a selective jury/panel, appointments and publishing of the final decision but also to cross off. Conflicting interests need to be recognized and managed appropriately. To provide credible regulatory services, NMRA must have specific measures in place to avoid conflict of interest in decisionmaking, to ensure confidentiality, to make their rules and decisions, transparent and to consult with stakeholders. Although there is documented Code of conduct for members of Human Drug Counsel, but no code for staff members involved in drug regulatory and experts. Consultation with stakeholders takes place in Mongolia, although it tended to be limited to specific issues (e.g. regulations) or groups (e.g. professional associations). Current information was not always publicly available. Although the NMRA organizes meetings with the key stakeholders and open days for the public, the industry, consumers and patients representatives are not involved as observers in technical committee meetings. The agendas of the technical committees are not published in advance and the minutes of the meetings are not publicly available. A competent contact person or a public relations unit is not established and known by the interested parties. An annual report with the allocated budget mentioning the origin of fund is not published on a periodic basis and is not publicly available. The legislation not provides requirements for monitoring and accountability of the NMRA by stakeholders. The regulatory processes are not reviewed in order to identify problems, gaps and inconsistency within the regulatory authority Information management systems and Communication activities Though the NMRA has its own website ( but it has not established an integrated network of all computers related to regulatory functions. The NMRA does not employ its own IT staff. The NMRA has not established a communications strategy to maintain confidence in the regulations and a crisis plan for coping with major incidents and information. 12

14 3.3 Medicines registration (marketing authorization) Authorization of medicines for sale in a country, based on a scientific assessment of their safety, efficacy and quality, could be considered as the core regulatory function. Legal basis and regulations Law on Drug and Medical Devices requires marketing authorization (registration) for all pharmaceutical products on the market however exceptions for registration exist. Law on Drug and Medical Devices and Registration regulation enables the NMRA to issue a marketing authorization for a pharmaceutical product, to suspend it for a period of time and to withdraw it. Registration regulation approved by Health Minister s order N38, 2007 requires the applicants to demonstrate the quality, safety and efficacy of the pharmaceutical product that is subject of the application. At the time of this assessment draft on new registration regulation is on the discussion. Law on Drug and Medical Devices has a provision which exempts some products (such as orphan drug, donations and other products) from registration. Provisions for renewal of marketing authorizations were in place, usually after 5 years. But there isn t a legal requirement for handling periodic reviews to MAs. Legal provisions do not require the notification to the NMRA of any variations to the initial MA which may affect the quality, safety and efficacy of the products. The legal provisions do not envisage the case of demonstrated bioequivalence of multisource generic products with innovator. 18 provision of Law on Drug and Medical Devices specifies the information to be provided with the products (packaging, labelling, leaflet, Summary of characteristics, etc). There is no legal provision regarding the MA holder and manufacturer s liability for defective products. Guidelines The aim of the visits was not to verify compliance with WHO guidance systematically, but rather to assess the adequacy of national guidelines and to identify gaps. Any of the following guidelines were developed: Guidelines on the content of Product Information Leaflets, Summary of Product Characteristics (SPC), packaging and labelling. Guidelines on the applicable requirements on various process validation Guidelines on the applicable requirements on analytical method 13

15 validation. Guidelines on the applicable requirements on stability testing of pharmaceutical products (API, finished products). Guidelines on the applicable requirements to the demonstrate bioequivalence/bioavailability. Guidelines for applicants or their representatives on the content of the application, the format and the procedures to follow in order to submit an application for a MA. Guidelines for marketing authorization holders defining the types and scopes of variations, the format and the documentation required as well as specifications of the variations that are subjected to prior approval. Guideline on drug donation. Guidance on risk management programs, premarketing risk assessment and development of pharmacovigilance plans Application requirement and format are on Organization and structure Marketing authorization activities are organized and performed at a central level of the country. Division of Medicine Regulation, Government Implementing Agency Department of Health, is responsible for marketing authorization. There should be 4 officers for registration and they are responsible for: Registration of medicine; Registration information; Registration of biologically active products; Registration of vaccine Decision for registration is developed by Human Drug Council on the basis of expert conclusion. Assessment procedures The product information, Summary of Product Characteristics (SPC), packaging and labeling are indicated on LICEMED. Timeframes for assessment of applications is 3 months. Fasttrack mechanism is not existed for products registered. 14

16 Documented procedure is only implemented for decisionmaking and to issue the marketing authorization in a standardized format. In other case the documentation is not implemented. Department of Health has not advisory committees and uses 38 pharmaceutical and clinical experts for assessment procedures. Provisions for confidentiality and declaration of interest were lacking. The manufacturer's or license holder's representatives are registration experts and are involved in assessment work. Different criteria are used for the evaluation of MA applications of imported, local, traditional medicines and raw materials. Each pharmaceutical product receives a unique identification number that appears on the labeling, packaging and product information. Although Division of Medicines Regulation uses regulatory decisions, reports or information from other NMRAs or international bodies for decision making, external information for decision making on the applications submitted are not readily available. Assessment procedure doesn t cover costbenefit and benefitrisk analysis assessment. The risk management program and pharmacovigilance plan, internal tracking system is not used in registration procedure. Human and other resources The job descriptions for the staff are defined. By the assessment time only 2 officers work at Division of Medicine Regulation and officers for registration of biologically active products and vaccine don t work. There is no internal planning of human resource utilization. NMRA has an archive for documents, but no storage space for under the registration files and equipment for MAs functions. There is no networked computerized system designed for medicines registration in place. Records and availability of information There is no list of all the product applications received, approved, suspended or withdrawn and of the applications refused. The NMRA retains a master file of each registered product including the application, approved drug information, assessment report, etc. Master files of refused products are given to applicants. A list of all the registered approved products is established, updated, published and made publicly available (LICEMED). 15

17 A summary of the assessment report as a basis for decisionmaking is not published officially and positive decision is publicly available. The decision is put on LICEMED, and Journal of Drug Information. The list of all the licenses withdrawn, suspended or refused is not published Licensing of activities of pharmaceutical establishments NMRA is responsible for licensing of drug suppliers and manufacturers. Licensing of pharmacies is not performed at center level of the country. Legal basis and regulations Mongolia has a system in place to license pharmaceutical establishments. The legislation requires a company which manufactures and imports a pharmaceutical product or an active pharmaceutical ingredient to hold a license. Law on Licensing, Law on Health, Law on Drug and Medical Devices requires pharmacies and retail outlets or prospective pharmacies and retail outlets of pharmaceutical products to hold a license. The legislation enables the NMRA issue a license for a manufacturer of pharmaceutical products, an importer, an exporter and a distributor, pharmacies to suspend it for a period of time and to withdraw it. There are no legal exemptions to licensing requirements with defined criteria. Drug manufacturers, drug suppliers and pharmacies should comply with MNS. Although legal requires that all drug manufacturers should follow, there are no drug manufacturers with GMP certification because no authority is responsible for GMP certification. Guidelines Only one guideline for GMP is developed and published for drug manufacturers. Guidance based on the WHO model and its supplementary guidance provides information on compliance with GMP requirements. Other guidelines needed for drug manufacturers, drug suppliers and pharmacies are not available. Organization and structure Licensing activities for drug manufacturers and importers, distributers are organized and performed at a central level of the country and Government Implementing Agency Department of Health is responsible for it. Although according to Health Minister s Order N278, license function should be performed by Division of Drug Regulation under the Vice chairman for Drug affairs, by the time of this assessment 16

18 this function was performed by Division of Medical Care under the Vice chairman for Medical affairs. Activities to other agencies, authorities follow the Mongolian Laws, standards and procedures. Licensing activity for pharmacies are organized and performed by Health Departments of provinces at local level and there is no central organization responsible for pharmacies. Decentralization of licensing, involving regional authorities was not organized efficiently. Lack of coordination between departments and with enforcement agencies was highlighted. Licensing assessment procedures According to License Law the decision on license should be issued within 21 working days since receiving the application. An internal tracking system is not established to follow the targeted time. The same criteria are used for licensing regardless of the affiliation. Documented procedure is implemented for decisionmaking and to issue the license in a standardized format. In other case the documentation is not implemented. A written license, signed by a person with the adequate delegation, is sent to the applicant, including conditions or restrictions. Documented quality control is not performed. Human and other resources The job descriptions for the staff are defined. By the assessment time staff for licensing of manufacturers and importers, distributors is not belonged to the Division of Drug Regulation, DOH. 1 officer for drug affairs works at Health Department of Ulaanbaatar and human resource is not enough for license function. There is no internal planning of human resource utilization. NMRA and Health Department of Ulaanbaatar have not enough storage space for licensing files and equipment for licensing functions. There is no networked computerized system designed for license. Records and availability of information There is a list of all licensed manufacturers, importers, distributors and pharmacies. The NMRA retains a master file of each licensed manufacturers, importers and distributors, including company, name and contact details, key personnel, address, equipment, list of drugs manufactured, imported and supplied, and etc. A list of all the pharmacies is publicly available ( Journal of Drug Information). 17

19 The list of all the licenses withdrawn, suspended or refused for manufacturers and distributors is not published and is not publicly available Registration of Pharmacy personal Legal basis and regulations 25 th provision of Law on Health and Health Minister s Order 280, 2011 require a pharmacist and pharmaceutical technician should be registered by a Regulatory Authority. According to Health Minister s Order 135/2006, pharmacists and pharmaceutical technicians perform their duties in accordance with a code of ethics of the pharmaceutical profession. There are legal requirements defining the necessary criteria that must be met regarding the pharmaceutical qualification and the experience for a pharmacist and pharmaceutical technicians. Pharmaceutical Professional Committee Pharmaceutical Professional Committee was organized in 2008 by Health Minister s Order 252/2008. The composition of the PPC is clearly defined. The mission, responsibilities and powers of the PPC are clearly defined and include in particular: The issuance of standards of practice and conduct, The setting of standards of education and training for pharmacists and pharmaceutical technicians. Medical Ethics Committee Medical Ethic Committee was established by Health Minister s order 135, The composition of the EC and the mission, responsibilities and the powers of MEC are clearly defined on this order. Guidelines and Registration procedures There is no guideline on the content, the format of the applications and the procedure to follow for the registration of pharmacists and pharmaceutical technician. Documented procedures are implemented for assessing the applications for registration and for issuing the licenses and renewal: as a pharmacist and pharmaceutical technician. This procedure considers in particular a continual professional education. Organization and structure, human and other resources 18

20 Registration of medical personal is organized and performed at a central level of the country and Government Implementing Agency Department of Health is responsible for it. A mechanism of exchange of information was not established and implemented in order for the decentralized organization to receive requests and directives from the central authority and to report to it. 1 officer for the registration of medical person works at Division of Medical Professional Development, DOH and human resource is not enough for license function. There is no internal planning of human resource utilization. Records and outputs and availability of information Health net program was developed in 2009 by the funding from WHO and a list of all registered pharmacists and technicians was available on this program. But it didn t work since The NMRA retains a file of each registered pharmacist and pharmaceutical technician containing at least the following types of information: name, place of exercise, diploma or qualification and contact details Import and export control The legal provisions require the importer to hold an importing authorization before organizing the importation activities. Before each importation, importers should hold an import certification and the origin, name, formulation, dose, amount, manufacturer s name of the product, border name and importation period are indicated on the import certification. The import license activities are organized and performed at a central level of the country by the NMRA. This function was performed by Ministry of Health and according to Health Minister s Order N 343 this function has been just transferred to NMRA by the assessment time. A system to grant marketing authorization for pharmaceutical products is not in itself a sufficient mechanism to control the quality of products circulating in the country. Control of imported products is weak. Mechanism of exchange of information is weak. There was no efficient system to verify the marketing authorization status and exemptions for imported products. Cooperation of NMRA with police and customs is weak. No guidelines for importers and exporters on the format and content of the application and the procedure to follow for these authorizations Market surveillance Because market surveillance is not developed in Mongolia, there is no market surveillance strategy, program, and quality monitoring program. NMRA lacks a written procedure to organize an effective recall. 19

21 3.8 Control of Drug Promotion and Advertising In 2010 the Law on Drug and Medical Devices was amended by new article No 13 on drug information and advertisement together with its enforcement points. Also the Law on Advertisement has articles on regulation of information distribution related to health and other health products. Those legal provisions are contributed to the combating with the false information on drug and other health products and proper use of the drugs. According to the Law on Drug and Medical Devices amendment, the conditions and criteria for the advertisement of the pharmaceutical products to the general public is defined, the advertisement activities for drug and other products have been started to be controlled and assessed in some extent and capacity has been building up at DOH, GASI and The Unfair Competition and Consumer Rights Protection Regulatory Agency According to the WHO definition "promotion" refers to all informational and persuasive activities by manufacturers and distributors, the effect of which is to induce the prescription, supply, purchase and/or use of medicinal drugs. Moreover article No 26.3 of the Law on Drug and Medical Devices stated that the drug information should be factual and substantial and independent from manufacturer and distributor. Then drug promotion conducted by the medical and sales representatives is considered as new drug information for the healthcare staff and credit hour certificate is awarded for the attended healthcare staff. Up to date, there are about 60 medical representatives and 10 sales representative offices are conducting promotional activities to improve the drug sales and prescription writing. So it could be said this regulation of credit hour certificate award is against the above mentioned Law article. Also there is another article No of the law on Drug and Medical Devices stated that drug wholesaler or distributor should prohibit the supply, offer or promise to persons qualified to prescribe, to supply and to dispense the pharmaceutical products any gift, pecuniary advantage or benefit of any kind unless strict conditions are met. Also there is no existing legal provision in relation to free distribution of drugs for the purpose of promotion, control of promotion activities organized during scientific meetings and symposiums and criteria for the professional knowledge level of person who is conducting drug promotion. DOH has started to collect the application materials for advertisement permission. The applications and submitted relevant materials for the drug advertising permission are reviewed by the Pharmacology sub Committee of Human Drug Council, MOH. The amendment of the Law on Drug and Medical Devices stated the permission issues for not only drug advertisement but also for biologically active products and supplements. As a result of enforcement activities, 13 non authorized biologically 20

22 active product promotions on TV and Radio were stopped by The Unfair Competition and Consumer Rights Protection Regulatory Agency However, there are some gaps in this area including non existence of legal provision for some important elements, lack of clearly defined guidelines to keep the process effective, transparent and open to the public, poor enforcement environment and lack of human resource and other supports. DOH activities in providing permission and authorization for the drug advertisement is lacking of transparent manner. It does not maintain the updated database of the authorization materials, sufficient information sharing and publication through its website and other communication channels and control of the drug promotion content for the healthcare staff. Therefore community involvement in controlling drug promotion is really missing. There is no officially authorised independent reference and information source about drug and materials in Mongolian is not sufficient. Another challenging issue is lack of human resource and logistic supports. The Pharmacology Sub Committee, which is responsible for review and assessment of the submitted materials for drug advertising authorization, consists of only nonvacant members and any external experts are not invited. 3.9 Pharmacovigilance Legal basis The issue of pharmacovigilance have been introduced to the country officially in 2003 when the relevant articles No 6 and 25 were included in the Law on Drug and Medical Devices. In accordance to the Law articles Health Minister Order 183 on registry of adverse drug reaction (ADR) was approved in 2006 and it was revised and newly approved as Order No378 in A number of important elements of pharmacovigilance is described in those legal and regulatory papers such as reporting and reviewing of ADR. For instance healthcare staff and citizens are required to inform the ADR through the website while hospitals and pharmaceutical organizations have to inform and register ADR. Pharmaceutical supplying organizations should have box and form to fill in to collect ADR information. Hospitals and Pharmaceutical organization has to submit the ADR registration report in order to extend its permission certificate of conducting pharmaceutical activities. Medicine therapeutic committees of tertiary and secondary hospitals will be responsible for both of registration and assessment, and primary healthcare facilities and private hospitals are required to register ADR. The Medicine therapeutic committee of hospitals are in charge of conducting assessment on the information of ADR. Every quarter, those 21

23 committees of hospitals required to submit the assessment report to Drug Regulatory Division, DOH. The reporting guideline along with its form is defined in the Health Minister Order No378. However, there are some gaps in the regulatory papers which make the insufficient legal provision for pharmacovigilance system. For instance, unclear regulation between pharmaceutical organization and DOH in terms of timeline of reporting, manufacturer and marketer cooperation has not defined and non existence about the assignment of special officer for the vigilance purpose. The issues of actions following the assessment are not clearly specified. The requirements for reporting safety issues related to specific categories of products including vaccines, biologicals, and biological products are not described. Adverse drug event is explained in the Law but other terms including adverse drug reaction and serious drug reaction are not defined in the legal papers. Guidelines Detailed guidelines and requirements on enabling adequate education and experience level of the focal person, reporting timeline (periodicity and delay) and means of reporting of safety issues are missing. Organizational structure In terms of organization, vigilance activities are organized and performed at DOH. Focal person designated in charge of pharmacovigilance in 2011.Pharmacology Sub Committee members are involved in the review of the information transmitted through the vigilance network. Internal procedures External information sources and reference materials for decision making on ADR and safety monitoring are not readily available and there is language barrier for the responsible people. External experts are not invited in the assessment process.doh does not have any defined pharmacovigilance plan and maintain the procedure to register and assess day to day ADR reports. The timeline for the assessment and decision making on ADR is not defined and internal tracking system to follow the targeted time frame is not working. Up to date, any quality control measures including peer review on ADR were not conducted and any recommendation on ADR was not issued from the involved parties. Also manufacturers, importers, exporters and distributors are not involved in the vigilance activities and they are not inspected. 22

24 Human and other resources Human resource is not sufficient, supply of relevant equipments is not enough and education and experience of the focal people need to be improved. Records and outputs In 2011, there are 33 information on ADR was reported and 21 of them were assessed by the Pharmacology Sub Committee. Human Drug Council did not discuss those information and assessment reports and there is no existing follow up action. It shows the poor reporting, assessment and output on ADR. In 2011, 1 case of ADR came from patient. Website does not work. It shows the lack of citizens and medical professionals involvement. DOH does not organize basic campaigns on a regular basis to promote adhesion to vigilance. Availability of information The information on ADR in Mongolian is not available to the public and medical professionals except one article published at the journal Drug Information from DOH Control of Clinical Trials Legal basis and guidelines The legal environment on clinical trial was enabled within the following articles of the health related legal papers. They are article No 21 of the Law on Drug and Medical Devices, article No26.1 of Law on Health and Health Minister Order No 223 approved in In 1999, the Medical Ethics Committee was established in order to oversee the ethical codes implementation within the medical research conducted in the country. The Committee has to develop general ethical guideline for the medical research ethical subcommittees, conduct review and assessment of the clinical trial request materials, make changes and notification in the initial protocol of clinical trials and evaluate the completed trial. However, the Committee does not have power to stop or change the clinical trial if there is ethical conflict occurrence and its action is limited only within the submission of the report to the related administration authority. Numbers of important elements of the clinical trial were approved by the Health Minister Order 223. They are definition of adverse drug reaction, serious adverse reaction, formats of reporting those reactions, reporting of the adverse reactions within 10 days and defined criteria, accredited hospitals and laboratories for conducting the man involved researches, the ethical duty of sponsors in provision of 23

25 healthcare services, ethical issues of the medical research sponsored by foreigners and the duties of researcher and sponsors in getting informed consent. However, some of the issues are missing in those regulatory papers. For instance, criteria and requirement of the licensing of manufacturers and importers of investigational drugs, requiring the products for investigation to comply with the applicable GMP are not clear and guideline to control the import and export of the trial drugs are not defined. The criteria for the selecting the principal investigator, his/her roles and responsibilities and other team members are not well defined. The definition is limited within the sentence that is man involved research should be guided by the highly experienced personnel under the well developed study design. The issues of clinical trial and other biomedical research activities are mainly organised and managed by the Medical Ethics Committee and drug divisions of MOH and DOH have very much limited participation which is submission of the information about clinical trials are reported to the Human Drug Council. There is lack of mechanism to enable good cooperation between the ethical committees and Drug Divisions of MOH and DOH. Ethical oversight Ethical oversight of clinical trials is managed by the Medical Ethics Committee on Medical Research within the Biomedical Research Ethics Code based on the Declaration of Helsinki. The main activities of the Committee, its composition with chair, deputy, secretary and other members, requirement for the members, auditing process and reviewing of the clinical trial protocol and its amendment approved without informed consent are defined and regulated by the Health Minister order No 223. Also the issue of conflict of interest was specified in detailed manner including the main policy on conflict of interest, contract format and declaration formats. It was not able to evaluate the documentation of above mentioned activities. Organizational structure About the organizational structure, there are 5 Ethical Sub Committees at Medical Institute, Health Science University and other research organizations and they follow the guidelines and rules developed by the Medical Ethics Committee. The Medical Ethics Committee conducts assessment of the sponsored trials and researches while studies for postgraduate degrees are reviewed by the Medical Ethics Subcommittee at Health Science University. There is weak mechanism to exchange information among these committees and there is no existing joint database of the biomedical researches. 24

26 Assessment procedures Assessment procedures are defined at the same paper Health Minister Order No223. The Medical Ethics Committee conducts assessment of the research materials, external experts are invited and its regulation is approved. The similar criteria are used for the researches except some additional criteria were approved for the researches sponsored by the foreign organization. The Ethical Committee does not ask inspectorate to control the quality certificates GMP, GCP and GLP of the manufacturers, healthcare organizations and laboratories. Drug and Medical Devices Division, MOH does not control the Committee activities and lack of cooperation. Information availability The list of the approved trials and assessment report are not published for the general public and it was difficult to see what kinds of studies are going where and conducted by whom. In 2011, the Committee received 6 applications of new research, 1 amendment application and issued approvals for 4 applications. The review of the clinical trial section is based on legal and regulatory papers due to the busy schedule of the Secretary of the Committee Regulatory inspection and enforcement activities Legal basis Regulatory inspection and enforcement activities are defined in the Law on State Inspection and Monitoring and Law on Drug and Medical devices. The Law on State Inspection and Monitoring defined details of inspection activities with purpose of relevant law enforcement, including how to define the timeline, assignment of inspection officer, his/her responsibilities and rights, check compliance with the applicable regulations and assigning related fines to the organizations. In according to the article No of the Law on Public Service, it is not permitted to conduct inspection at the foreign manufacturing premises of the company which applied for the permission to include its drug into the Drug Registration List. In the other hand, the capacity of the national personnel should be improved in order to conduct the inspection at the foreign premises. Guidelines Environmentally conscious disposal of expired/unusable substances reagents and finished products is regulated by the joint order No249/201 of Health Minister and Nature, Environment and Tourism Minister. 25

27 There is not any guidance on the compliance and enforcement strategy taken by the NRA defining the pyramid of sanctions applicable and conducting pre and postlicensing inspections. Organizational structure The organizational structure is complex and several independent organizations are involved. GASI is responsible for external inspection and monitoring while Drug Regulatory Division of DOH is in charge of internal monitoring. The Inspection Offices at aimag and city level and Border Inspection Units are working under the GASI. Those offices and units use and follow all the guidelines and rules approved by the central organization. About the internal monitoring, some of the activities of DOH are transferred to Health Departments at aimag and city level. But still there is need to improve the information exchange and cooperation. Quality Management system In according to the article No of the Law on Government Inspection and Monitoring, GASI has been implementing a quality management system ISO 31000:10 which is risk based standard to improve the inspection process. Top management provided political and financial support for introduction of the system and focal person was assigned and trained. It has 85 check lists which contains 29 indicators and criteria and brochure on proper usage of these checklists was published and distributed to the personnel. The baseline evaluation was conducted and result was introduced to the staff. Except the above mentioned quality improvement system, once a year, the monitoring division conducts internal auditing for every division of the Agency. Report of audit and follow up actions are introduced to the staff and discussed among them. Internal planning and procedures In 2011, GASI developed inspection and monitoring checklist based on the national standards for manufacturer, importing company and pharmacy and the checklist was expanded by some of the indicators and criteria of GMP, GDP and GCP. Documented procedures are implemented for the followings; the planning of inspection activities showing in particular the duration and frequency of the inspections, internal planning for inspection activities is established and updated to cover all regulated activities, the preparation and the development of adequate materials for an inspection, the inspections and in particular on assessing the critical steps of the processes and validation and for inspections based on specific requirements for specific classes of products and facilities (generics, sterilization, innovator products). They have a standard format for reporting inspection gaps or deficiencies such as an inspection 26

28 report. The same criteria and indicators are used for national, international, public and private organizations. Human and other resources There are 35 inspectors in charge of drug and bio preparation inspection in GASI. However human and other resources are really lacking. In rural and border offices do not have complete numbers of inspection officers and education and experience level of all the officers capacity need to be improved. The training needs should be defined and follow up actions should be done including different training at national and international level. The enrolment criteria criteria is limited within the exam for public servant, education level and number of years having working experience and those are not enough to select the well prepared personnel as inspection officer. Therefore, these criteria need to be expanded in direction of more professional side. There is lack of adequate equipments, office supply and work space especially for the rural and border offices. The drugs for the inspection activities are collected and placed in the offices because storage is not available. Transportation and communication service is very poor, especially border officers are not provided by the transportation to conduct the inspection. Records and output. The database of the inspected organizations is established and all the relevant materials are stored as soft files including inspection assignment, inspection report, explanation of the inspection to the inspected organization, final decision etc. The file of inspection and monitoring activities are collected and stored for every organization and it is reviewed when the organization apply for further permissions such as extension of the licenses etc. In 2011, as result of the inspection activities, 11 importing companies were temporarily closed while 5 other companies were completely closed down. Also 3 issues of organization and company staff were transferred to the relevant judge. There is need of improving network and programme supply. Availability of information Inspection and monitoring information are placed on the website in order to disseminate to the general public. The list of the designated inspectors is available to the companies subjected to inspection for one year and summary results (notices of compliance penalties, prosecutions engaged) of the conducted inspections were published on the website. The whole list of the inspected organizations was not published and was not available to the public. 27

29 3.12 Quality Control Laboratory Legal basis Currently, there are 3 state laboratories to perform quality control testing of pharmaceutical products. The first laboratory of testing pharmaceutical products was established in 1965.In 2002, according to the Parliament Resolution No58 five different laboratories were joined under the name of United Central Laboratory of the GASI. Now United Central Laboratory s Drug and Bio preparation unit is the main laboratory and conducts quality control testing of the pharmaceutical products in the country. The other two laboratories, one is at Health Science University and another is drug reference laboratory of MOH at Public Health Institute, are performing tests within the limited area for the contracted organizations. Therefore, the assessment was mainly based on the activities of the United Central Laboratory. It has received an accreditation and a right to conduct the quality control testing and issue the official result from the State Standardization and Meteorology Agency. The Laboratory is regarded as external quality control laboratory and inspection experts are assigned by the Chair Order of the Laboratory. These three laboratories do not have a mechanism to share and exchange the information with each other and maintains independent activities by themselves. Guidelines There are number of guidelines in relation to conducting quality control testing for the pharmaceutical products. In according to the article No of the Law on Drug and Medical Devices on safety and quality surveillance for the drugs and biologically active products is enabled testing at pre and post marketing periods. Collection, packaging and submission of samples are regulated by the Government Resolution No 39 (2004/04/11) on collection of samples and GASI Chair Order No 35 on sample storage duration, sample size and sample receiving. The Central Quality Control Laboratory issued list of the standards and reference materials which should be used in drug quality control testing. Complaining and appealing against the decisions of the Laboratory is regulated by the appeal guideline approved by the State Standard and Meteorology Agency. Organizational structure Drug and Bio preparation unit of the United Central Control Laboratory has several sub units including Chemical, Microbiological, Biological, and Traditional medicine technical sub units. Chemical sub unit conducts test for drugs and bio preparations. Microbiological sub unit do the Sterility test, Microbiological contamination and 28

30 Potency of antibiotics. Biological sub unit carries out Progenies test, Toxicity test and LAL test. Traditional medicine sub unit tests Macro and microscope examination, photochemical test and Microbiological test. The Unit does not have a full capacity of conducting relevant tests for different vaccines. Quality management system The United Central Control Laboratory has been implementing ISO/IEC/17025:2007 standard based quality management system. The guideline for the quality system management and implementation was published and distributed to the staff and quality manager was trained. 13 objectives are defined and have been implemented in order to completely implement the quality system. The monitoring reports are presented and discussed among the staff and managers. Also annual internal auditing has been done continuously and follow up actions are defined and implemented. However, the quality guideline of the laboratory is very general and serves all the units of the laboratory. There is only one quality manager is working for the whole laboratory. Every unit does not have the sub guideline included its own special issues and Drug and Bio preparation unit does not have independent quality manager. The Chair of the unit is in charge of the quality management system. The United Central Control Laboratory attended the programme on Evaluation Scheme of Nutrition Products Testing by FEFAS and other programme organized by APLAC. Within framework of these programmes, the capacity of the United Central Laboratory was evaluated (excluding drug and biological products testing). The drug and biologically active products testing unit was not attended these kinds of compared testing international programmes due to its lack of adequate equipments and well trained experts. The United Central Laboratory follows all the quality control guidelines and rules but still there is need of updating and revising them in accordance to the international standards. The lab does not have a lab equipment calibration and validation program as part of the quality systems. Quality control procedures Although there are several documented procedures implemented for preparation and storage of standards, samples, performing the testing, and dealing with non complaint products, it has not reach to the standards properly in reality. The inadequate space of storage room of this laboratory does not keep the retention samples. Laboratory administration applies the strategies, programs and procedures for introduction and validation of new or improved testing. The experts used to record the test performance and reporting result on their own notebook. Now standard formatting worksheet has 29

31 been implemented in those procedures. Also Drug and Bio preparation unit implemented the documentation procedures for meeting with clients when open day to the public as a report only. There is no other channel of reporting and distribution of information. Human and other resources Currently United Central Laboratory s Drug and Bio preparation unit has 15 experts which are not sufficient. The workload has been increasing and number of tests for drug sample has been growing because of establishment of Drug Division of DOH and its active requirement of sample testing. Also the numbers of experienced experts are few and it takes 36 months to train the newly recruited expert internally. The Laboratory chair defines by his order the experts and their task assignments and it may influence the transparency of the organization. There are not any mechanisms to manage any conflicts of interests and confidentiality mechanism just started to implement. Therefore, human resource capacity needs to be improved not only for the analysts but also for the technical personnel. Infrastructure and equipment Work space and storage are not sufficient and supply of transportation and communication is not enough. There are not adequate equipment and instruments for testing activities. Procedure for cleaning, calibration and maintenance activities of the equipments are not very good and not in timely manner. The most of the equipments manufacturer instruction is missing and not translated into Mongolian. Therefore documentation procedures are not implemented for the correct use of the equipment according to the manufacturer instruction. The log book of the equipment is fulfilled by wrong way so it does not capture the right information. The laboratory has a new HPLC that is not being used for 2 years and just have been inviting external expert from abroad. Clearly, there is need to update the current equipments, improve the equipment proper usage, strengthen equipments maintenance and training of the engineers on appropriate maintenance of the equipments. Reference and standards/ materials and reagents The first national pharmacopeia was published and it supports quality control testing activities in some extent. There is need to improve the tendering process to supply the reference materials and maintain regular supply system for reference standards/materials. There is need to strengthen documented procedures are implemented for sourcing, preparation storage and use of reagents of assured quality. 30

32 Safety programme The list of hazardous substances is approved by the Government and it has not updated recently. The responsible staff is not designated for the management of a safety programme and it may interrupt the continuity of the safety programme. Sub contracting, records and outputs The United Central Laboratory does not transfer some of its responsibilities and make subcontracts with other laboratories. Although the data base of all the products tested is maintained, it needs to be improved and modern equipments to write and issue laboratory papers. Analysts write all the information and reports by hand on the paper and then they insert them to the software programme by hand. Therefore, they need to have updated equipments and software programme to eliminate the double writings. The United Central Laboratory issues certificates of analysis under its own name Control of Narcotics, Psychotropic Substances and Precursors Legal Basis Mongolia is signatory member of the International conventions on Narcotic Drugs (in1990), Psychotropic Substances and Drugs (in 1999) and Narcotics Psychotropic Substance Control (in 2001) which are approved by UN in 1961, 1971 and 1981 respectively. In Mongolia, Law on Narcotics Psychotropic Substance Control was approved in 2002 and was amended in The purpose of the amendment was to improve the control and regulation of narcotic drugs including definition of special prescription for those drugs, requirements for importing organizations and pharmacies in handling narcotic drugs and changes in assignment of fines according to the social changes. Also the National Committee with its own budget and office was established in order to strengthen control of illegal usage of narcotic and psychotropic drugs. The responsibility of the Committee is to prevent from the crime related with those drugs, reduce illegal usage and supply of those drugs and substances, improve the legal environment and develop international cooperation in this area. Moreover, in 2011, the guideline for pain management using those drugs was published with support from MCA. However, there are gaps in terms of cooperation, human resource and multiple parties involvement. There is poor cooperation and information exchange between the organizations working to control the circulation of those drugs and substances and joint information database is absent. The surveillance study was not conducted to see the appropriate use of narcotic drugs and psychotropic substances. There is nonexistence of legal provision to assign focal person at every organization handling with 31

33 the drugs and substances. It could be exemplified by the recent case of narcotic drugs were sold by hospital nurses. Civil society and healthcare staff involvement in control of those drugs and substances is very poor due to lack of relevant information and references and insufficient promotion actions to raise the awareness. Moreover there is need of building capacity in terms of human resource, funding and logistics. Lack of personnel who have the adequate knowledge and experience in the field is described by few of the officers who almost have not attended the relevant trainings at national and international level International Cooperation and Harmonization Parliament Resolution No 68 on Approval of Drug Policy in 2002 promotes the international cooperation and harmonization of the pharmaceutical sector in its article 5.2. However, there is no policy paper which defined the main principles and direction of international cooperation in accordance to the Parliament Resolution. MOH has signed on the cooperation agreement with the central drug regulatory organization of Germany, Poland, Turkey and Korea. The cooperation agreements aimed to improve drug safety, licensing and assuring through information sharing and capacity building. In July 2011, Drug Division of DOH signed cooperation agreement with KFDA of Korea in order to intensify the implementation of the Drug Policy. The cooperation proposal on drug safety issues were delivered to the relevant organization of China. However, there is no existing official cooperation with Russian Drug Regulation Organization at central level and drugs imported from Russia compose the most of the drugs in the market. MOH recognizes and uses regulatory decisions, reports inspection, evaluation, (vigilance), guidance, certification schemes and formats recommended by WHO. For instance, in according to WHO guideline, the requirements of GMP, CCP, BCPP certificates were included in the regulatory documents. Up to date, the certification schemes are not provided in the country and the preparation work is in the process. Health and Education Division and United Central Laboratory do not participate in peer reviewed or joint activities due to their affiliation under the GASI. Also they have very poor participation in proficiency testing schemes, regional collaborative studies or the WHO External Quality Assurance Assessment Scheme due to insufficient capacity of the laboratory, lack of adequate human resource and other logistic factors. 32

34 4. Conclusions and Recommendations Conclusions The Review of Drug Regulatory System of Mongolia was completed and the followings are concluded: The legal basis of Drug Regulatory is established and the government supports and undertakes definite actions towards the implementation of the National Drug Policy and its strategies, Some regulatory activities, such registration, and import authorization is relatively stabled. Establishment of the online system Licemed for drug registration, licensing and special permissions Funding and support from donor organizations are increased in recent years. Some WHO standards and guidelines are used in Drug regulatory activity Establishment of NMRA is emerged Mongolian first Pharmacopeia is published However, the following deficiencies occur in the Drug regulatory systems: NMRA has little power and autonomy, and oversaw a limited range of regulatory functions with little accountability or managerial commitment. Most of the regulatory organizations suffer from staff shortages. There is lack of training and specialization in national and international level. Assessors and inspectors were not at the level of current scientific and technical expertise needed for their regulatory tasks. Regulatory requirements and processes were not in line with recommended WHO standards. Guidelines, SOP, reference, information and statistics are inadequate. Medicines regulation was not carried out to the full extent required to ensure the quality, efficacy and safety of medicines in Mongolia. Pharmacovigilance and post marketing surveillance is not performed. Quality Management System is not established in DOH. Documented procedure is not implemented in Drug regulatory system 33

35 Drug regulatory functions are undertaken by different organizations which make coordination difficult and create inefficiencies. Impartiality, transparency and accountability are insufficient. There are no internal policy on potential conflicts of interest for staff members and no model format for a declaration of conflicts of interest for staff. There is no documented Code of conduct for staff members involved in drug regulatory and experts. Information management systems and Communication activities of Regulatory system are insufficient. International Cooperation and Harmonization are weak Licensing of drug manufacturers and importers, distributors is performed and issued by Medical Care Division, DOH 34

36 RECOMMENDATIONS Improve law implementation, and develop policy, plan and regulation needed for regulatory activity Provide the power and autonomy of Regulatory Authority and increase funding, human and other resources. Strength Drug Regulatory Functions. Establish Medicine Regulatory Agency, and organize and perform drug regulatory activities at central level. Licensing of drug manufacturers and importers, distributors should be performed and issued by Drug Regulatory Division, DOH. Improve information management systems and Communication activities of Regulatory system. Establish the mechanism of information and practice exchange and implement. Establish Quality Management System in DOH and implement WHO guidelines and ISO standards. Ensure that the local drug organizations comply with WHO GXP guidelines. Improve the quality, efficacy and safety of medicines. Establish a post marketing surveillance and pharmacovigilance activities. Improve impartiality, transparency and accountability of Drug Regulatory organizations and stakeholders. Develop a policy paper to expand the international relationship. Enrol as a member of the international organizations working in the drug and biologically active products. Develop guidelines, SOP, references needed for drug regulatory activity. Implement a documented procedure in Drug regulatory system. Strength human resource development, provide the training and specialization of regulatory staff in national and international level. Improve the Information management system and Communication activities of Regulatory system. Prepare assessors and inspectors with current scientific and technical expertise needed for their regulatory tasks. 35

37 Annex 1 Assessment tool MODULE 1 GENERAL INFORMATION: 1.1 Information on the country Country: Mongolia Name and address(es) of Institution(s) assessed: MOH, HSUM, NGOEm association Assessment focal point: Ulaanbaatar Address of focal point: Ch.Munkhldelger, Head of Pharmaceutical and Medical Devices Division, MOH Tel of focal point: Government building VIII Olympic street Sukhbaatar district Fax of focal point: of focal point: munkhdelger@moh.mn 1.2 Information on the assessment Date of the assessment: Purpose of the assessment: To give an overview of the legal basis, structures, processes and implementation of medicines regulation in Mongolia Scope of the assessment: To cover all organizations involved in drug regulatory Assessment performed by: Purevsuren S Munkhdelger B Address of assessors: School of Pharmacy Health Sciences University of Mongolia Ulaanbaatar, Mongolia PO48, Box186 Tel of assessors: , Fax of assessors: of assessors: puujmar88@yahoo.com sanalaa@gmail.com MODULE 2 NATIONAL REGULATORY SYSTEM COMMENTS: 2.1 Structure The Ministry of Health has delegated or assigned to one or more authorities (institutions/agencies/autonomous bodies) its responsibilities regarding the regulation of pharmaceutical products The responsibilities/functions/organization of each of these authorities is clearly defined, in particular as regards the scope of the regulation (regulatory functions) they have under their control All the regulatory areas (regulatory functions) are under the supervision of at least one of these authorities in charge of it The activities of the various authorities involved are coordinated by an administrative mechanism. 2.2 Legal basis for the establishment of the regulatory system The legal basis of the regulatory system applied to the pharmaceutical sector is clear and comprehensive. 36 Health Minister s Order N278, 2011 By Law on Drug and Medical Devices, State Inspection Law The main steps to be followed for the implementation of the NRA established

38 legislation are defined and followed The legislation enables the appropriate institutions to issue regulations The development of regulations involves the Regulatory Authorities in charge of their implementation and enforcement The development of regulations involves the various sectors of the civil society (such as NGOs, consumers and patients, representatives of health professionals and industry,) Adequate regulations have been enacted and published The legislation is made known to the people who are to be governed by it and the ways of communication used are adequate. MODULE 3 NATIONAL REGULATORY AUTHORITY (NRA) 3.1 Legal basis The legislation provides for the establishment of a NRA and clearly defines, its mission, Terms of Reference, powers, functions and responsibilities If more than one institution is involved, legislation provides for coordination/linkage among these institutions and the respective empowerment is defined The legal provisions specify that the NRA has the power to/or the delegation to decide whether a specific product falls within the definition of a medicinal product, a medical device, or any another category of products The legal provisions specify that the NRA has the power to/or the delegation for appointing special officers/inspectors and provides them with adequate powers to carry out inspection of pharmaceutical products and practices The legal provisions specify that the NRA has the delegation, the enforcement powers and responsibilities to deal with noncompliant products The legal provisions specify that the NRA has the power to/or the delegation to issue a written notice of violations to companies and recommend their prosecution The legal provisions enable the NRA to issue and publish appropriate guidance or notes for applicants The legal provisions enable the NRA to set up technical/scientific advisory committees for regulatory purposes. 37 Registration regulation Assurance regulation Regulation on registration and report of side effects Regulation of Pharmacopeia Council Em association COMMENTS: Law on Drug and Medical Devices, State Inspection Law, Government Service Law, Government Agency Law, Health Minister s Orders Internal inspection ± No scientific advisory committees

39 There Technical committees are The legal provisions define the terms of reference for each advisory committee in particular their role in the decision making process, and circumstances under which the advice of the experts/advisory committees must be obtained by the NRA The legal provisions enable the NRA to collect fees for regulatory 38 Licensing Committee, Assurance committee Registration and assurance fee service provided 3.2 Corporate Governance There is a governing /administrative body for strategic development. Human drug Council The functions of the Governing Board/Council are defined, documented and implemented particularly in advising on strategy and orientation of the NRA There are bodies within the DRA to manage and organize routine functions The roles and responsibilities of such bodies are defined and documented particularly for implementation of routine decisions, strategic objectives and reporting thereof Communication channels among such bodies are established There is a scientific body to advise the NRA on scientific matters and future orientations. 3.3 Institutional Development The NRA has established an Institutional Development Plan which is implemented and updated The Vision and the Mission Statement for the NRA is established The objectives of the NRA have been set in particular target time frames for the various functions Action plans are established and implemented to achieve the objectives set Indicators are established to monitor/assess progress towards the objectives. 3.4 Organization and structure Regulatory activities are organized and performed at a central level of the country Decentralized activities to other agencies/authorities follow the standards, guidelines and procedures as agreed/decided with the central authority In case of decentralization, a mechanism of exchange of information is established and implemented in order for the decentralized organization to receive requests and/or directives from the central authority and to report to it The mechanisms in place allow exchange and harmonization of best practices, appropriate cooperation and collaboration among the decentralized organizations. 3.5 Quality Management System The NRA has implemented a Quality Management System for all the regulatory processes.

40 3.5.2 The NRA s top management is committed to the development and implementation of the Quality Management System in particular by providing financial and organizational support The Quality Management System is based on recognized standards as reference (e.g. WHO, PIC/S, ISO, other) A quality policy and related quality objectives are defined and documented A qualified person is designated as responsible for the development and implementation of the Quality Management System The NRA has identified its processes for each regulatory function, determined their interactions and methods needed to control these processes The documentation needed to establish, implement and maintain the QMS is defined (Quality manual, records, SOPs, etc) The documentation required by the QMS is controlled following a documented procedure A documented procedure is established by the NRA to plan, and to assess if the QMS is effectively implemented and conforms to planned arrangements Internal audits of the complete QMS are done at least once every 12 months. Records of the results are maintained The corrective and preventive actions taken as a result of audits or from other non conformities are implemented and documented. Their efficacy is checked and documented The top management of the NRA reviews on a regular basis, at least once every 12 months, the QMS to evaluate its efficiency as well as its effectiveness. Records of the review are maintained. 3.6 Funding The sources of funding of the NRA to perform its regulatory functions are defined The scale of fees for regulatory services provided are established and published, including any preferences applied to local products or industry Provisions concerning fee reductions or exemptions to ensure the availability of vital or lifesaving drugs for a limited market are provided Funding is partly provided by development partners or donors such as WHO, The World Bank, etc The NRA has the authority and the procedures in place to collect fees and internally utilize the generated funds The NRA is obliged to periodically publicize its budget. 39 ± Registration regulation, Assurance regulation, Health Minister s Orders, Order of Chairman of Department of Health Salary from Ministry of Finance Registration fee, assurance fee Tuberculosis medicines HIV/AIDS medicines, diabetic medicines, cancer medicines are free of charge ADB Not use the fee internally. Fees for regulatory activities are paid to state budget

41 3.7 Management of human resource An organization Chart/organogram for the NRA staff is established and updated The NRA s key technical and scientific personnel have been identified based on their authorities and responsibilities. ± Vice Chairmen for Medicine, Head of Department of Drug Regulation, The duties, functions and responsibilities of the key personnel are established in the respective job descriptions The NRA has established the necessary competencies (education, training, skill and experience) for the key personnel to perform the assigned work The NRA is able to select and recruit its own staff following documented procedures based on its own written criteria (experience, minimum educational background, advanced training, etc.) An initial and periodic staff appraisal system is established to review performance and competencies, identify academic and training needs; and agree on performance targets There is an induction program for newly recruited staff A training plan is established for all staff in order to satisfy/fulfil the needs identified. Training activities are performed and recorded by the NRA A documented mechanism is in place to evaluate the impact and to demonstrate the effectiveness of the training activities Budgetary provisions are made for staff training. 3.8 Committees and external expertise The NRA takes advantage of external experts and involves them in its regulatory processes A model contract between the NRA and each external expert defining roles and responsibilities is established and signed by both parties The NRA has set up advisory committees of experts involved in the regulatory processes of the NRA There is a written policy/procedure for the recruitment and the designation of external experts and members of experts committees calling for candidates, defining the review by a selective jury/panel, appointments and publishing of the final decision but also to cross off Documented procedures are implemented for the management of the advisory committees (designation of chair and composition, secretariat responsibilities, quorum, declaration of interests, agenda, minutes and operational procedures) There is a general policy on potential conflicts of interest for external ± experts and members of advisory committees There is a general policy on confidentiality and a code of conduct for 40 No scientific key person Government Service Counsel is responsible for selection of state staff Registration regulation ± Annex 5 of Health Minister s Order 402, 2011 Declaration of interest for members Human Drug Council and Sub Committees

42 external experts and members of advisory committees The NRA is involved in a global network with relevant scientific associations and professional societies There is a documented mechanism to manage potential conflicts of interest of internal and external experts and members of committee by collecting declarations of interests, including ensuring updates of these declarations, for all regulatory functions The agenda of the technical/advisory committee is elaborated prior to the meeting and the minutes of the discussions are recorded. 3.9 Transparency and confidentiality The legislation stipulates the requirements on confidentiality and transparency There is a documented policy on public disclosure of information with exemptions/exceptions Information on legislation, regulations, procedures and guidelines are publicly available and are kept up to date on websites or other mechanisms used to ensure the proper availability of information An annual report with the allocated budget mentioning the origin of funds, is published on a periodic basis and is publicly available The decisionmaking processes as well as decision criteria are publicly available The information on decisions is publicly available, including the negative decisions in specific cases (i.e. when legislation permits) in a timely manner The Information on outputs of regulatory functions performed is publicly available and kept up to date (web sites or other mechanisms). 41 State Employment Law State Employment Law Journal of Drug information Journal of Drug information Journal of Drug information Journal of Drug information By media The information on sanctions, recalls and public health warnings are published and are publicly available A guideline on complaints and appeals against regulatory decisions is available An appeal mechanism against the NRA s decisions is available and implemented The NRA consults or involves specific sectors of the civil society (such as NGOs representing health professionals, the industry, consumers and patients) during the development of guidelines A documented procedure is implemented to consult, collect and to deal with the comments received during the development of guidances The declarations on interests of internal and external experts as well as members of technical/advisory committee are publicly available The industry, consumers and patients representatives are involved as observers in technical/advisory committee meetings The agendas of the technical/advisory committees are published in advance and the minutes of the meetings are publicly available A competent contact person or a public relations unit is established and known by the interested parties The NRA regularly organizes meetings with the key stakeholders Meeting with the

43 and open days for the public. key stakeholders is not regularly The NRA is represented at meetings organized by the stakeholders (industry associations, professional associations of practitioner, patients associations, ) Independence and impartiality There is a documented Code of conduct /activities/ for staff members involved in drug regulatory functions There is an internal policy on potential conflicts of interest for staff members/personnel There is a documented policy/procedure to avoid the accumulation of responsibilities for registration, procurement or reimbursement agreements with the same authority/individuals There is a model format for a declaration of conflicts of interest Infrastructure The work space and work environment are adequate The equipments provided for performing the regulatory functions are adequate Support services provided (for example in terms of transport and communication) are adequate Monitoring and accountability The legislation provides requirements for monitoring and accountability of the NRA by stakeholders The regulatory processes are regularly and systematically reviewed in order to identify problems, gaps and inconsistency within the regulatory authority Periodic reports on regulatory processes performed are submitted to the institution/organization in charge of the overseeing and reviewing of the NRA functions 3.13 Information management systems The NRA uses computerized systems for automation of repetitive functions and for reporting activities The NRA uses computerized systems for data management and for enhancing data import/export capacity The NRA uses computerized systems for accessing technical/scientific information The NRA has established an integrated network of all computers related to regulatory functions The NRA has its own website or has made an arrangement to use others The NRA employs its own IT staff or has assured access to IT services Documented procedures are in place to gather data and use the software applications as well as query tools Communication activities The NRA has established a communications strategy to maintain confidence in the regulations and to provide timely, necessary and helpful information This strategy considers the different target audience (patient, public, industry, healthcare professionals) and the available means of 42 Open days for the public

44 communication (media, website, stakeholders meeting, conference) The NRA has prepared a crisis plan for coping with major incidents and information that could potentially alarm the public Success of this communications strategy is measured by adequate means. MODULE 4 MARKETING AUTHORIZATION (MA) 4.1 Legal basis The legal provision requires one to hold a Marketing Authorization (MA) before putting a pharmaceutical product on the market The legislation enables the NRA to issue a marketing authorization for a pharmaceutical product, to suspend it for a period of time and to withdraw it There are legal provisions requiring the applicants to demonstrate the quality, safety and efficacy of the pharmaceutical product that is subject of the application There are legal provisions regarding the information to be provided with the products (packaging, labelling, leaflet, Summary of characteristics, etc ) There is a legal requirement regarding the limited duration of the validity of the MA and for handling periodic reviews to MAs. COMMENTS: 7.22 provision of Law on Drug and medical Devices Health Minister s order N38, 2007 Health Minister s order N38, provision of Law on Drug and Medical Devices Registration for 5 years The legal provisions require the notification to the NRA of any variations to the initial MA which may affect the quality, safety and efficacy of the products. Specific kinds of variations can be subject to authorization by the NRA The legal provisions envisage the case of demonstrated bioequivalence of multisource/generic products with innovator The legal provisions envisage the case of provisional or conditional MA exempting applicants from meeting specific requirements based on the established criteria (orphan drug, public health interest, presumed positive benefit/risk balance) There is an exemption for pharmaceutical product donations following the established criteria The legal provisions specify the MA holder/manufacturer s liability for defective products. 4.2 Guidelines There are guidelines on the applicable requirements on quality, safety and efficacy There are guidelines on the content of Product Information Leaflets, Summary of Product Characteristics (SPC), packaging and labelling There are guidelines on the applicable requirements on various process validations (manufacturing, IT, etc ) There are guidelines on the applicable requirements on analytical method validation There are guidelines on the applicable requirements on stability 43 No legal requirement for handling periodic reviews to MAs Registration regulation 22.7 provision of Law on Drug and Medical Devices 22.7 provision of Law on Drug and Medical Devices No guideline. Applicable requirements on

45 testing of pharmaceutical products (API, finished products) There are guidelines on the applicable requirements to the demonstrate bioequivalence/bioavailability There are guidelines for applicants or their representatives on the content of the application, the format and the procedures to follow in order to submit an application for a MA There are guidelines for marketing authorization holders defining the types and scopes of variations, the format and the documentation required as well as specifications of the variations that are subjected to prior approval. No guideline Application format is on There is a guideline on drug donation. Health Minister s Order 105/ There is guidance on risk management programs, premarketing risk assessment and development of pharmacovigilance plans 4.3 Organization and structure Marketing authorization activities are organized and performed at a central level of the country. 4.4 Assessment procedures A documented procedure is implemented on a voluntary basis to allow applicants to meet with the DRA before the submission of an application Documented procedures/tools are implemented for the assessment of the different parts of the application and for the assessment of specific requirements of specific classes of products (e.g. multisource/generics, products containing new active substances, new strengths, hightech or particularly innovative products etc.) A documented procedure is implemented to exchange information between the applicant and the DRA if needed Documented procedures are implemented to periodically review the MAs granted Documented procedures are implemented for assessing the applications for variation of MAs There is a model format for the assessment/evaluation report The same criteria are used for the evaluation of MA applications Deferent criteria for regardless of the source (e.g. domestic, foreign, public/private sector) of the products concerned. imported, local, traditional medicines and raw materials The product information, Summary of Product Characteristics (SPC), packaging and labelling is approved by the NRA as part of the MA The risk management program and pharmacovigilance plan are approved by the NRA as part of the MA A documented procedure is implemented to follow the commitments of the MAH and in particular the Risk Management Program (see also Module 11 on pharmacovigilance) External information (information sources and reference materials) for decision making on the applications submitted are readily available. 44 Special regulation for biologically active products LICEMED

46 Documented procedures are implemented to control the quality of the assessment process in place such as peerreview There are enough personnel (internal and external) with the adequate expertise (education, experience and training) for the assessment of the different parts of the application for all types of 45 ± Expert conclusion, result of laboratory analysis Pharmaceutical and clinical experts External experts are involved in the assessment of the applications for MAs An advisory committee of experts is involved in the review of MAs applications A documented procedure is implemented for decisionmaking. Protocol The decision making procedure takes into account a cost/benefit analysis A documented procedure is implemented to issue the marketing authorization in a standardized format The NRA recognizes and/or uses regulatory decisions, reports or information from other NRAs or international bodies for decision making The procedure takes into account the integration of the different parts of the dossier into an overall benefit/risk analysis assessment Documented procedures are implemented to ensure the involvement and communication between the assessors and the QC laboratory for product compliance and the regulatory inspectorate for compliance to applicable good practices There are time limit(s) for the assessment of the applications. Within 3 months An internal tracking system is established to follow the targeted time frames (statutory or not) There is a documented fasttrack mechanism for specific products of Registration particular public health interest. timeframe of products registered in EU, USA and Australia is short. But there is no Fasttrack mechanisms The steps/requirements for waived MA assessment are documented There is a model format for the decision on a marketing authorization application (approval, rejection, withdrawal) A written marketing authorization, signed by a person with the adequate delegation, is sent to the applicant, accompanied by the approved product information, including conditions or restrictions of this approval Each pharmaceutical product receives a unique identification number that appears on the labelling/packaging and product information. 4.5 Human and other resources The job descriptions for the following staff are defined: head of registration (supervisor), head of registration unit by products and assessors with their areas of assessment (bioequivalence, chemist, medical officer, microbiologist, statistics, Toxicology, PD/PK, etc ). 18 provision of Law on Drug and Medical Devices There should be 4 staffs for registration, but only 2 staffs work at Department of Medicine regulation, DOH

47 authorized pharmaceutical products There is internal planning of human resource utilisation for performing any upcoming and periodical reviews of the applications The manufacturer's or licence holder's representatives are never involved in assessment work at any level/stage, including expert committees There are lines of authority reflecting the independence of decisionmaking in the MAs system from manufacturers, supply systems or government There is an adequate office, working environment and storage space for MAs files There is an adequate equipment for MAs functions. 4.6 Records and outputs There is an uptodate list/data base of all the product applications received, approved, suspended or withdrawn and of the applications refused The NRA retains a master file of each product licensed or applications refused as well as of all the variations and renewals with the supporting documentation including the application, approved drug information, assessment report, risk/benefit assessment, etc. All exemptions are documented in this file. 4.7 Availability of information A list of all the approved products is established, updated, published and made publicly available A summary of the assessment report as a basis for decisionmaking is published and is publicly available (positive or negative decision) The list/database of all the licenses withdrawn, suspended or refused is published and is publicly available. MODULE 5 LICENSING OF MANUFACTURERS 5.1 Legal basis The legislation requires a company which manufactures or intends to manufacture a pharmaceutical product or an active pharmaceutical ingredient to hold a licence The legislation enables the NRA to issue a licence for a manufacturer of pharmaceutical products or active pharmaceutical ingredient, to suspend it for a period of time and to withdraw it The legal provisions require the manufacturers to comply with the applicable good manufacturing practices. Compliance with applicable GMP is a condition for keeping its license The legal provisions require notification of the NRA of significant changes/variations to the initial licensing conditions There are specific legal provisions concerning repacking/relabeling of pharmaceutical products and quality control activities performed by manufacturers There are legal provisions requiring at least one qualified responsible person for each manufacturing premises. 46 The manufacturer's or license holder's representatives are involved Only approved Only licensed product LICEMED, published every year LICEMED, Journal Drug information COMMENTS: Licensing Law, Law on Health Licensing Law, Law on Health Law on Drug and Medical Devices, MNS Basic requirement of Drug manufacturers MNS Basic requirement of Drug

48 manufacturers There are legal exemptions to licensing requirements with defined criteria. 5.2 Guidelines A guidance provides detailed information on compliance with GMP requirements. This guidance is mainly based on the WHO model and its supplementary guidance There are guidelines for manufacturers on the content of the application, the format and the procedure to follow in order to submit an application for a manufacturing license There are guidelines for waiving license requirements/procedures/steps There are guidelines for applicants on the definition of types and scopes of variations and the documentation required There are guidelines on the content of the Site Master File There are guidelines on the appointment and qualification of the Qualified Responsible Person. 5.3 Organization and structure Licensing activities are organized and performed at a central level of the country Decentralized activities to other agencies/authorities follow the standards, guideline and procedures as agreed/decided with the central authority In case of decentralization, a mechanism of exchange of information ± Mechanism of is established and implemented in order for the decentralized exchange of organization to receive requests and/or directives from the central authority and to report to it. information is not so good The mechanisms in place allow exchange and harmonization of best practices, appropriate cooperation and collaboration among the decentralized organizations. 5.4 Licensing assessment procedures Documented procedures are implemented for meetings with applicants before an application is officially lodged Documented procedures/ checklists are implemented to assess the applications for licensing A documented procedure is implemented for waiving certain requirements or steps A documented procedure is implemented for assessing the applications for variation of licenses Documented quality control measures are in place such as peerreview A documented procedure is implemented for decisionmaking Documented procedure is implemented to issue the licence in a standardized format The NRA recognizes and/or uses regulatory decisions, reports or information from other NRAs or international bodies for decisionmaking Documented procedures are implemented to ensure the involvement and communication between the administrative staff in charge of the assessment of the application for licensing and the regulatory inspectorate for compliance to applicable good practices The same criteria are used for licensing regardless of the affiliation (e.g. domestic, foreign, public, private sector, NGO) of the 47

49 manufacturer concerned There are defined timelines for the assessment of applications. Within 21 working days An internal tracking system is established to follow the targeted time frames (statutory or not) A written license, signed by a person with the adequate delegation, is sent to the applicant, including conditions or restrictions attached to the licence (validity and renewal). 5.5 Human and other resources There is enough personnel (internal and external) with adequate expertise (education, experience and training) for the assessment of the applications and for issuing of licences There is adequate office and storage space (documents, ) There is adequate equipment for licensing activities. 5.6 Records and outputs There is a list/data base of all licensed manufacturers The NRA retains a site master file of each premise licensed, including the approved changes with the supporting documentation. The file contains at least the following information: company name, key personnel, premises address/map of the facilities and contact details, equipment, list of drugs and dosage forms approved for manufacture. All exemptions are documented in this file. 48 Staff for licensing is not belonged to the department of Drug Regulation 5.7 Availability of information The list/data base of all the licensed manufacturers is published The list/data base of all the licenses withdrawn, suspended or refused for manufacturers is published and is publicly available. MODULE 6 LICENSING OF IMPORTERS, EXPORTERS, WHOLESALERS COMMENTS: AND DISTRIBUTORS 6.1 Legal basis The legislation requires that a company which imports or intends to import any pharmaceutical product or active pharmaceutical ingredient to hold a licence. Licensing Law, Law on Health The legislation requires that a company which exports or intends to export any pharmaceutical product or active pharmaceutical ingredient to hold a licence The legislation requires that a company which acts as a wholesaler or distributor of pharmaceutical products or active pharmaceutical ingredient or intends to do so to hold a licence The legislation enables the NRA to issue a licence for an importer, an exporter and a wholesaler/distributor, to suspend it for a period of time and to withdraw it The legal provisions require importers, exporters, wholesalers and distributors to comply with the applicable good storage and good distribution practices for licensing The legal provisions require the notification to the NRA of significant changes/variations to the initial license There is a legal provision for at least one qualified responsible person for each importer, exporter wholesaler or distributor There are legal exemptions to licensing requirements with defined criteria. 6.2 Guidelines Licensing Law, Law on Health Licensing Law, Law on Health Licensing Law, Law on Health Licensing regulation MNS Basic requirement of Drug suppliers

50 6.2.1 There is a guidance that provides detailed information on compliance with Good Distribution Practice requirements. This guidance is in line with the relevant WHO Guidance There are guidelines for importers, exporters, wholesalers and distributors on the content of the application, the format and the procedure to follow in order to submit an application for licensing There are guidelines on waiving license requirements/procedures/steps There are guidelines for applicants that define the types and scopes of variations and the documentation required There are guidelines for the content of the Site Master File There are guidelines for the appointment and qualification of the Qualified Responsible Person. 6.3 Organization and structure Licensing activities are organized and performed at a central level of the country Decentralized activities to other agencies/authorities follow the standards, guidelines and procedures as agreed/decided with the central authority In case of decentralization, a mechanism of exchange of information ± Mechanism of is established and implemented in order for the decentralized exchange of organization to receive requests and/or directives from the central authority and to report to it. information is not so good The mechanisms in place allow exchange and harmonization of best practices, appropriate cooperation and collaboration among the decentralized organizations. 6.4 Licensing assessment procedures Documented procedures for meetings with applicants and other interested parties A documented procedure/standard checklist to assess the applications for licensing of importers, exporters, wholesalers and distributors A documented procedure is implemented to issue the licence in a standardized format A documented procedure is implemented for waiving certain requirements or steps A documented procedure is implemented for assessing the applications for variation of licenses Documented quality control measures are in place such as peerreview Documented procedures are implemented for decisionmaking and for the issuance of the licence Documented procedures are implemented to ensure the involvement and communication between the administrative staff and the regulatory inspectorate for compliance with applicable good practices The same criteria are used for licensing regardless of the affiliation (e.g. domestic, NGO, foreign, public, private sector) of the applicant concerned There are timelines for the assessment of the applications. Within 21 working days 49

51 An internal tracking system is established to follow the targeted timeframes (statutory or not) A written license, signed by a person with the adequate delegation, is sent to the applicant, including conditions or restrictions attached to the licence (validity and renewal). 6.5 Human and other resources There is enough personnel (internal and external) with adequate expertise (education, experience and training) for the assessment of the applications for and issuing of licences There is adequate office and storage space and the equipment for licensing There is adequate equipment for licensing activities. 6.6 Records and outputs There is a list/data base of all licensed importers, exporters, wholesalers and distributors The NRA retains a site master file of each premise licensed, including the approved changes with the supporting documentation. This file contains at least the following types of information: company, name and contact details, key personnel, premises address, equipment, list of drugs supplied (if adequate). All exemptions are documented in this file. 6.7 Availability of information The list/data base of all the licensed importers, exporters, wholesalers and distributors is published and is publicly available The list/data base of all the licenses withdrawn, suspended or refused for importers, exporters, wholesalers and distributors is published and is publicly available. MODULE 7 LICENSING PHARMACIES AND RETAIL OUTLETS COMMENTS: 7.1 Legal basis The legislation requires that pharmacies and retail outlets or prospective pharmacies and retail outlets of pharmaceutical products to hold a licence. Law on Licensing, Law on Health There is a legal provision for licensing internet pharmacy or retailers. No internet The legislation enables the NRA to issue a licence for a pharmacy, a retail outlet or an internet pharmacy, to suspend it for a period of time and to withdraw it The legal provisions require the retailers, sellers or dispensers to comply with the applicable Good Dispensing Practices or Good Pharmacy Practices The legal provisions require the notification of the NRA of significant changes/variations to the initial license There is a legal provision for at least one qualified responsible person for each pharmacy and retail outlet There are legal exemptions to licensing requirements with defined criteria. 7.2 Guidelines There are guidelines for pharmacies and retail outlets on the content of the application, the format and the procedure to follow when applying for a licence There are guidelines on waiving license requirements/ procedures/ steps. 50 pharmacy MNS Basic requirement of pharmacy MNS Basic requirement of pharmacy

52 7.2.3 There are guidelines for applicants on the definition of the types and scopes of variations and the documentation required There are guidelines for pharmacies and retail outlets on the Good Dispensing Practices or Good Pharmacy Practices There are guidelines on the appointment and qualification of the responsible person. 7.3 Organization and structure Licensing activities are organized and performed at a central level of At local level the country Decentralized activities to other agencies/authorities follow the standards, guideline and procedures as agreed/decided with the central authority In case of decentralization, a mechanism of exchange of information is established and implemented in order for the decentralized organization to receive requests and/or directives from the central authority and to report to it The mechanisms in place allow exchange and harmonization of best practices, appropriate cooperation and collaboration among the decentralized organizations. 7.4 Licensing assessment procedures A documented procedure is implemented for meetings with applicants and other interested parties Documented procedures/ standard checklists are implemented to assess applications for licensing Documented procedures are implemented for waiving certain ± On meeting requirements or steps. protocol Documented procedures are implemented for assessing the applications for the variation of licences Documented quality control measures are in place such as peerreview Documented procedures are implemented for decisionmaking and for the issuance of the licences A documented procedure is implemented to issue the licence in a standardized format The same criteria are used for licensing regardless of the affiliation (e.g. public, private sector, NGO) of the applicant concerned There are defined timelines for the assessment of applications. Within 21 working days An internal tracking system is established to follow the targeted time frames (statutory or not) A written license, signed by a person with the adequate delegation, is sent to the applicant, including conditions or restrictions attached to the licences (validity and renewal). 7.5 Human and other resources There is enough personnel (internal and external) with adequate expertise (education, experience and training) for the assessment of the applications and for issuing of licences staff for drug affairs works at Health Department of Ulaanbaatar There is adequate office and the storage space There is adequate equipment for licensing activities. 7.6 Records and outputs There is a list/data base of all licensed pharmacies and retail outlets. Journal of Drug

53 7.6.2 The NRA retains a site master file of each premise licensed, including the approved changes with the supporting documentation. This file contains at least the following types of information: name, key personnel, premises address, list of drugs approved for dispensing/sale (if adequate). All the exemptions are documented in this file. 7.7 Availability of information The list/data base of all the licensed pharmacies and retail outlets is published and is publicly available The list/data base of all the licenses for pharmacies and retail outlets withdrawn, suspended or refused is published and is publicly available. MODULE 8 REGISTRATION OF PHARMACY PERSONNEL 8.1 Legal basis There is a legal requirement for a person not to practise as a pharmacist unless his/her name has been registered by a Regulatory Authority There is a legal requirement for a person not to practise as a pharmaceutical technician unless his/her name has been registered by a Regulatory Authority There are legal requirements for the pharmacists and the pharmaceutical technicians to perform their duties in accordance with a code of ethics of the pharmaceutical profession There are legal requirements defining the necessary criteria that must be met regarding the pharmaceutical qualification and the experience for a pharmacist There are legal requirements defining the necessary criteria that must be met regarding the pharmaceutical qualification and experience for a pharmaceutical technician. information Journal of Drug information Journal of Drug information COMMENTS: 25 article of Law on Health, Health Minister s Order N280, article of Law on Health, Health Minister s Order N280, 2011 Health Minister s Order N135, Pharmaceutical Practice Committee There is a legal provision for the establishment of a Pharmaceutical Health Minister s Practice Committee (PPC). Order 360/ The composition of the PPC is clearly defined. Health Minister s The mission, responsibilities and the powers of DC are clearly defined and include in particular: the issuance of a reprimand or a warning, the recommendation to suspend or to remove a registered pharmacist or a registered technician from the respective register. 52 Order 360/ The mission, responsibilities and powers of the PPC are clearly defined and include in particular: the issuance of standards of practice and conduct, the setting of standards of education and training for pharmacists and pharmaceutical technicians. 8.3 Disciplinary Committee There is a legal provision for the establishment of a Disciplinary Health Minister s Committee (DC). order 135, The composition of the DC is clearly defined. Health Minister s order 135, 2006 Health Minister s order 135, 2006

54 8.4 Guidelines There is a guideline on the content, the format of the applications and the procedure to follow for the registration: as a pharmacist as a pharmaceutical technician. 8.5 Organization and structure Registration activities are organized and performed at a central level of the country Decentralized activities to other agencies/authorities follow the standards, guideline and procedures as agreed/decided with the central authority In case of decentralization, a mechanism of exchange of information is established and implemented in order for the decentralized organization to receive requests and/or directives from the central authority and to report to it The mechanisms in place allow exchange and harmonization of best practices, appropriate cooperation and collaboration among the decentralized organizations. 8.6 Registration procedures Documented procedures are implemented for assessing the applications for registration and for issuing the licenses and renewal: as a pharmacist as a pharmaceutical technician This procedure considers in particular a continual professional education 8.7 Human and other resources There is enough personnel (internal and external) with adequate expertise (education, experience and training) for the assessment of the applications for registration of pharmacy personnel There is adequate office and the storage space The equipment is adequate and well maintained for regulatory activities. 8.8 Records and outputs A list/data base of all registered pharmacists and technicians is established and kept uptodate. ± Healthnet, but not works since The NRA retains a file of each registered pharmacist and pharmaceutical technician containing at least the following types of information: name, place of exercise, diploma or qualification and contact details. 8.9 Availability of information The list/data base of all the registered pharmacists and technicians is published and is publicly available. MODULE 9 POST MARKETING SURVEILLANCE AND CONTROLS 9.1 Import and export controls The legal provisions require the importer to hold a marketing authorisation or to have its pharmaceutical products registered before organising the importation activities The legal provisions require the importers/exporters to hold an authorization for each importing and exporting act of a pharmaceutical product. 53 COMMENTS: 7.22 article of Law on Drug and Medical Devices 7.22 article of Law on Drug and Medical Devices Health Minister s order N344, The legal provisions require the importers and exporters to register 15 article of Law on

55 information on the origin and the destination of the products imported and exported. Drug and Medical Devices There are guidelines for importers and exporters on the format and content of the application and the procedure to follow for these authorizations The activities are organized and performed at a central level of the country by the NRA Decentralized activities to other agencies/authorities follow the standards, guideline and procedures as agreed/decided with the central authority In case of decentralization, a mechanism of exchange of information ± Mechanism of is established and implemented in order for the decentralized exchange of organization to receive requests and/or directives from the central authority and to report to it. information is not so good The mechanisms in place allow exchange and harmonization of best practices, appropriate cooperation and collaboration among the decentralized organizations Documented procedures are implemented in the NRA to assess the application for import and export certificates/authorizations Documented procedures are implemented to issue import and export certificates/authorizations, in standardized formats There are records or a data base kept by the RA on imported and exported products There is a collaboration/agreement with the Customs or other enforcement agencies on the control of import and export. 9.2 Market Controls There are legal provisions to deal with noncompliant products. Law on Drug and Medical Devices, Law on State Inspection, There is a legal provision for sampling and testing samples of Law on pharmaceutical products on the market. standardization and Documented procedures are implemented to sample the products sold or supplied on the market and to send them for testing to the drug control quality laboratory The criteria for sample collection are based on risk assessment There are provisions and criteria for compensation for the samples collected The activities are organized and performed at a central level of the country Decentralized activities to other agencies/authorities follow the standards, guidelines and procedures as agreed/decided with the central authority In case of decentralization, a mechanism of exchange of information is established and implemented in order for the decentralized organization to receive requests and/or directives from the central authority and to report to it The mechanisms in place allow exchange and harmonization of best practices, appropriate cooperation and collaboration among the decentralized organizations Documented procedures/programs are implemented for collecting information, detecting and combating noncompliant products A market surveillance strategy based on inspection activities, control 54 conformity

56 activities and other information is established and implemented under the format of surveillance program for example A surveillance program (quality control plans and sampling strategy) is established to cover various dosage forms of different drug/medicinal products and is based on the potential health risks identified or expected for the patients The strategy and the surveillance program are periodically reviewed and its effectiveness is assessed The RA keeps the records or information/data base on the samples collected of noncompliant products A collaborative agreement with the Customs and other enforcement agencies is established for market control activities, in particular for sharing information and exchanging best practices A documented procedure is implemented for communication/collaboration and cooperation with the relevant authorities/jurisdiction in the investigations and the prosecution of breaches of regulation. 9.3 Noncompliant products and recall procedures The legislation enables the RA to instruct for the recall of pharmaceutical products (e.g. due to defects, inappropriate labelling or packaging or contamination ) The legislation enables the RA to suspend or stop the manufacture, import, export, distribution, sale or use of pharmaceutical products There is a legal requirement for records to be maintained within the distribution chain to ensure batch traceability and facilitate an effective recall system There is a legal provision concerning the disposal of defective/noncompliant products There is a legal requirement for manufacturers/importers to notify the NRA before initiating a recall and upon request to inform on the progress There is a legal requirement for manufacturers/importers to notify the NRA about product complaints regarding quality There are guidelines for manufacturers, importers, exporters and distributors on how to organise a recall and to organise the disposal of defective/noncompliant products Documented procedures are implemented in the NRA to assess the notification of recalls and product complaints Documented procedures are implemented in the NRA to ensure the removal of defective products, organize an effective recall and disposal of defective/noncompliant products There are defined criteria to determine the appropriate means and the level of communication of a recall with a feedback mechanism The effectiveness of the recall system is regularly validated There is guidance on the mechanism to ensure that appropriate actions (including destruction when necessary) have been taken The NRA approves the closure of a recall and certifies the disposal of defective/noncompliant products The NRA keeps the records or an information/data base on recalled and disposed defective/noncompliant products. MODULE 10 CONTROL OF DRUG PROMOTION AND ADVERTISING 55 Law on standardization and conformity

57 Legal basis There are legal provisions for the control of promotion of pharmaceutical products to avoid communication of false or misleading information The legal provisions allow, under certain conditions and criteria, the promotion of the pharmaceutical products to the general public The legal provisions allow under certain conditions and criteria the promotion of pharmaceutical products to those persons qualified to prescribe, supply or dispense these products The legislation enables the NRA to grant the authorization of marketing products, to suspend and to withdraw it or to stop any promotional campaign and to cease the distribution of promotional documents The legal provisions prohibit the distribution of free samples of pharmaceutical products to the general public for promotional purposes The legal provisions allow under certain conditions the distribution of free samples of pharmaceutical products to those persons qualified to prescribe, supply or dispense these products The legal provisions require the medical or sales representatives to have adequate scientific knowledge and training. Article No 26.7 of the Law on Drug and Medical Devices and articles No 13, 24.1 and 24.6 of the Law on Advertisement. Law on Drug and Medical Devices (article No26.2 and 26.3) and the Law on Advertisement (article No6.2, 13.1, 13.3 and 13.4) article No 6.2 and 24.6 of the Law on Advertisement The legal provisions require to use the approved product information (e.g. SPC) as reference materials to monitor promotion and advertising activities and materials The same legal provisions are applicable to the promotion of pharmaceutical products on internet. The legal provisions prohibit the supply, offer or promise to persons qualified to prescribe, to supply and to dispense the pharmaceutical products any gift, pecuniary advantage or benefit of any kind unless strict conditions are met Guidelines There are guidelines on the content, the format of the application and the procedure to follow for receiving the approval of promotional and advertising material There are guidelines on the control of advertisements and promotion during symposiums and other scientific meetings There are guidelines on the control of the operations of Medical and Sales Representatives 10.3 Organization and structure Promotion and advertisement authorization activities are organized DOH 56 Article 27.3 of the Law on Drug and Medical Supply The article No of the law on Drug and Medical Device

58 and performed at a central level of the country Internal procedures Documented procedures are implemented in the NRA to assess and to approve promotional and advertising materials Documented procedures are implemented in the NRA to review any complaints received regarding medicine promotion and advertising activities External experts are involved in the assessment of the applications for promotion and advertising authorization An advisory committee of experts is involved in the review of the applications for promotion and any matters related to the control of drug promotion The NRA has developed a proactive monitoring program to check advertisement and promotions in scientific journals or literature for healthcare practitioners Civil Society groups, professional associations and NGOs are involved in detecting unethical promotion and advertising activities The Inspectorate staff is involved in the detection of unethical or unauthorized promotional and advertising materials The NRA staff responsible for issuing MAs of pharmaceutical products is involved in the assessment of the applications for the promotion of pharmaceutical products and any investigations on promotional activities Human and other resources There is enough personnel (internal or external) with the adequate expertise for the assessment of the applications, for issuing the approvals and for implementing the surveillance program There is adequate office and storage space The equipment is adequate and well maintained for regulatory activities Records and outputs The application and other submitted materials for the drug advertising permission are reviewed by the Pharmacology sub Committee. GASI and The Unfair Competition Regulatory Authority The RA keeps the records or information / data base on approved and refused promotional material and advertisements with the supporting documentation Availability of information The list of authorized promotional materials and advertising campaigns is published and is publicly available. 57 ± DOH keep the records of approved and refused applications. But the information was not included in any of the databases of the organization. not updated from

59 The list of unauthorized and unethical promotional materials and advertising campaigns is published and is publicly available MODULE 11 PHARMACOVIGILANCE 11.1 Legal basis` There are legal provisions on post marketing safety monitoring of pharmaceutical products The legal provisions require the NRA to implement a vigilance system in order to collect the information useful in the surveillance of medicines, to evaluate such information and to take the appropriate decisions There are legal provision for all stakeholders to report adverse reactions/event or any safety issues to the NRA under defined conditions There are legal provisions for MA holders that require the registration, data collection and maintenance, assessment and monitoring of adverse reactions/event and to report to the NRA on these activities April content of information not adequate. COMMENTS Article 6.1, Law of Drug and Medical device and part 26 MOH order 378/2010 ± MOH order 378/ The legal provisions require the manufacturers, distributors, importers, exporters to report the adverse reactions/events to the MAH and NRA under specific conditions The legal provisions requires the healthcare professionals to report any adverse events/reactions to MA holders or to the RA or another delegated authority There are specific requirements for reporting safety issues related to specific categories of products (e.g. vaccines, biologicals, biological products, etc) There are specific requirements for Marketing authorization holders, manufacturers, importers, exporters, distributors, wholesalers to designate a qualified person in charge of post Marketing Authorization safety monitoring There are legal provisions to define the terminology used such as adverse event, adverse reaction, serious adverse event, etc The legal provisions specify the delay and/or the periodicity for reporting of adverse events There are specific requirements for health care institutions (clinics, hospitals, etc..) to designate a focal person for post marketing safety monitoring Guidelines There are guidelines on post MA safety monitoring regarding the registration, the reporting and the format to be used (initial report, periodic reporting) There are guidelines on classification of safety events The guidance on safety reporting provides for a scientific 58 Article 2.12 of MOH order 378 /2010 Part 2 of MOH order 378/2010, report to DOH ± Adverse reaction, serious adverse event not defined Article 2.11 MOH order 378 /2010 Medicine therapeutic committee of tertiary and secondary hospitals designated Article 2.3 of MOH order 378 /2010

60 evaluation of the risk/benefit balance of medicines There are guidelines defining the adequate scientific knowledge and training of qualified persons and focal persons in charge of vigilance There are guidelines on the criteria to determine the reporting timelines and means of reporting of safety events (serious, expected, etc ) Organization and structure Vigilance activities are organized and performed at a central level of the country Decentralized activities to other agencies/authorities follow the standards, guideline and procedures as agreed/decided with the central authority In case of decentralization, a mechanism of exchange of information is established and implemented in order for the decentralized organization to receive requests and/or directives from the central authority and to report to it The mechanisms in place allow exchange and harmonization of best practices, appropriate cooperation and collaboration among the decentralized organizations Internal procedures External information (information sources and reference materials) for decision making on ADR and safety monitoring are readily available Documented procedures are implemented in the NRA to register and to assess day to day ADR reports A documented procedure is implemented to follow implementation of pharmacovigilance plan (see also module 4 on MA) Documented procedures are implemented in the NRA to analyse the safety trends for signal detection A wellestablished system is in place for prioritization of drug safety signals according to the public health impact and to demonstrate that high risk issues are investigated immediately or in the first instance External experts are involved in the assessment of the information on safety transmitted through the vigilance network An advisory committee of experts is involved in the review of the information on safety transmitted through the vigilance network and any other matters related to the safety of pharmaceutical products There are defined timelines for the assessment and decision making on ADR An internal tracking system is established to follow the targeted time frames (statutory or not) Documented procedures are implemented for decisionmaking and for defining the recommended actions to be taken by the NRA, by the MAH, by the manufacturer or any other stakeholders There are documented quality control measures in place such as peerreview The NRA organizes on a regular basis campaigns to promote adhesion to vigilance 59 DOH ± Pharmacology sub committee ± MOH and DOH organized ADR training in 3 provinces

61 Consumers and patients are involved in the safety monitoring ± program The NRA has developed a proactive monitoring program to check compliance of the MAH to applicable regulatory requirements and best practices MAH, manufacturers, importers, exporters, distributors are periodically inspected by inspectorate on pharmacovigilance practices Human and other resources There is enough personnel (internal or external) with adequate expertise (education, experience and training) for safety monitoring activities There is adequate office and storage space. ± The equipment is adequate and well maintained for regulatory ± activities Records and outputs The information collected on safety is used for making or amending regulatory decisions on initial MA (adding information on SPC, restricting the use of drug, review of PIL, recall or withdrawal of products, etc.) The NRA keeps the information/data base on safety events reported and on the actions taken. The terminology used is the one promoted by the WHO (WHOART) Query tools on the data collected enables the NRA to assess and interpret safety signals( calculation of incidence rate, assessing of causality) ± 11.7 Availability of information Information on ADR and safety monitoring measures taken are communicated to the public, including the safety notice. MODULE 12 CLINICAL TRIALS Legal basis There is a legal provision for the authorization, suspension and withdrawal of clinical trials by the NRA or by another delegated authority for pharmaceutical products. COMMENTS MOH order 223/2007 annex There is a legal provision requesting the establishment of IRB/IEC. Article 26,1 law on Health, Medical Ethical Committee There is a legal provision requesting an ethics opinion of an MOH order IRB/IEC. 223/ The legal provisions require the notification and approval of the NRA of significant changes/variations to the initial clinical trial protocols The legal provisions require the investigational/research centres to comply with Good Clinical Practices and Good Laboratory Practices There are legal provisions on licensing of manufacturers and importers of investigational products. 60 annex 1guidline 2 MOH order 223/2007 Annex 1 ± Accredited hospitals laboratory and

62 These is a legal provision requiring the products for investigation to comply with the applicable GMP There are legal provisions on specific labelling and packaging requirements for the investigational products There are legal provisions requiring authority for the importation and exportation of investigational products There are legal provisions requiring during the conduct of a clinical trial, the notification, data collection, assessment and monitoring of adverse drug reactions/events and to report to the NRA under specific conditions There are legal provisions defining the terminology used, for clinical trial purpose, such as adverse event, adverse reaction, serious adverse event, unexpected, etc Legal provisions specify the delay and/or the periodicity for reporting of adverse events during the clinical trial There are exemptions to clinical trial requirements following defined criteria 12.2 Guidelines There are guidelines for sponsors or sponsors representatives on the content of the application, the format and the procedure to follow in order to submit an application for conducting clinical trials There are guidelines for applicants on the types and scopes of variations/amendments and on the documentation required There are guidelines on conditions (e.g. validity, amendment of the protocol, etc) attached to the clinical trial approvals issued There is a guideline on monitoring of adverse reactions (give details) and on periodical reporting of their results to the NRA There is a guideline on the criteria for selecting the Principal Investigator and his roles and responsibilities There are guidelines for licensing manufacturers and importers of investigational products There are guidelines on compliance with the GMP requirements for the manufacturers of investigational products A guidance for investigation centres/clinical trial sites provides detailed information on compliance with GCP and GLP requirements. This guidance is in line with the WHO format There are guidelines on the control of importation and exportation of investigational products 12.3 Ethical oversight The ethical oversight established is based on the Declaration of Helsinki. 61 MOH order 223/2007 Annex 8 MOH order 223/2007 Annex 8 6.1, 6,2 MOH order 223/2007 Annex 8 6.1, 6,2 MOH order 223/2007 Annex1, guideline 2,3,6 MOH order 223/2007 Annex 8 4.1, 4,2 MOH order 223/2007 Annex 8 4.1, 4,2 MOH order 223/2007 Annex 8 6.1, 6,2 ± MOH order 223/2007 Annex 1 MOH order 223/2007

63 There is a requirement on the composition, functions and mode of operation of the IRB/IEC Documented procedures are implemented to review the trial in particular the clinical trial protocols and amendments, documented informed consent and recruitment procedure There is a requirement on the establishment of an IRB/IEC supervising authority. MOH order 223/2007 annex 8 part 2 ± MOH order 223/2007 annex 8 part 4. Documentation not reviewed MOH order 223/2007 annex 8 part The funding for IRB/IEC is based on the fees for the services _ provided There is an approval and supervisory system for IRB/IEC A procedure details the review and the methodology used for the MOH order supervision of the IRB/IEC 223/2007 annex 8 part 10 audit procedure A general policy on potential conflicts of interest for members of IRB/IEC is established and implemented A general policy on confidentiality and a code of conduct for members of IRB/IEC is established and implemented There is a documented mechanism to manage potential conflicts of interest of members of IRB/IEC by collecting declarations of interests, including ensuring updates of these declarations Organizational structure The activities are organized and performed at a central level of the country Decentralized activities to other agencies/authorities follow the standards guideline and procedures as agreed/decided with the central authority In case of decentralization, a mechanism of exchange of information is established and implemented in order for the decentralized organization to receive requests and/or directives from the central authority and to report to it The mechanisms in place allow exchange and harmonization of best practices appropriate cooperation and collaboration among the decentralized organizations. 62 MOH order 223/2007 annex 8 part 2.2 MOH order 223/2007 annex 8 part 2.2 ± MOH order 223/2007 annex 8 part 2.2 Documentation not reviewed MOH Ethical Committee 5 Ethical Sub Committees. They follow the guidelines and rules developed by the Ethical Committee

64 12.5 Assessment procedures Documented procedures are implemented for the assessment of NA CT applications Documented procedures are implemented for assessing the application for amendments of CT protocols NA The Investigator s Brochure, Informed Consent procedure, investigation plan, data collection tools are assessed and approved as part of the approval for the clinical trial External experts are involved in the assessment of CT applications MOH order 223/2007 annex 8 part An advisory committee of experts is involved in the review of CT application and any other matters related to the research investigations on human being MOH order 223/2007 annex 8 part Documented procedures are implemented for decisionmaking on CT The assessment report on the CT is fulfilled following a standardized format Documented procedures are implemented to ensure the involvement and communication between the assessors and the regulatory inspectorate for compliance to applicable good practices (GMP, GCP and GLP) NA NA The NRA has developed a proactive monitoring program to check compliance with applicable regulatory requirements, applicable good practices and as per the authorization delivered IRB/IEC, investigators and sponsors are periodically inspected by the inspectorate of the DRA The same criteria are used for the evaluation of CT applications Additional ethical regardless of the origin of the request (e.g. domestic, foreign, criteria of the public/private sector). medical research sponsored by foreigners There are timelines for the assessment of CT applications. NA An internal tracking system is established to follow the targeted NA time frames (statutory or not) There is a fasttrack mechanism for the assessment of CT NA applications for specific products of particular public health value A documented procedure is implemented to issue CT related NA authorization in a standardized format A written authorization, signed by a person with the adequate NA delegation, is sent to the sponsor, including conditions or restrictions attached to this authorization Human and other resources There is enough personnel with adequate internal and external NA expertise (education, experience and training) for the assessment of CT applications Manufacturer's or sponsor's representatives are never involved in NA the assessment of CT (at any level/stage including expert 63

65 committees) There are lines of authority reflecting the independence of NA decisionmaking in the CT approval system from sponsors, investigators or government There is adequate office and storage space. NA The equipment is adequate and well maintained for regulatory activities Adequate support services are provided in terms of communication, equipment and infrastructure Records and outputs There is a list/data base of all the approved and rejected CT applications The NRA retains a file of each CT approved and rejected, including the amendments approved or rejected and the supporting documentation which includes the summary assessment reports. All the exemptions to clinical trials requirements are documented Availability of information A list of CT approved and CT applications rejected, including the summary assessment reports is published and is publicly available. MODULE 13 REGULATORY INSPECTIONS AND ENFORCEMENT ACTIVITIES There is a legal provision to inspect premises where regulated activities are performed in order to check compliance with the applicable regulation good practices and standards There is a legal provision specifying the periodicity for regulatory inspections There is a legal provision allowing the inspection of foreign sites of manufacturers There is a legal provision designating the inspectors and their powers The inspectors have adequate powers and authority to carry on their missions There are exemptions to the inspection requirements with defined criteria The legislation provides for adequate and proportional sanctions, penalties and prosecution upon conviction based on violation of the applicable legislation. NA NA NA NA Articles , Law on State inspection and monitoring Articles 51.3, 51.2 Law on State inspection and monitoring Article 10 Law on State inspection and monitoring Articles 10.9, Law on State inspection and monitoring Risk assessment criteria Articles 16 Law on State inspection and monitoring and article 29 law on Drug and Medical 64

66 13.2 Guidelines There is a guidance on the compliance and enforcement strategy taken by the NRA defining the pyramid of sanctions applicable This enforcement strategy is based on voluntary decisions regulatory measures (warning letter, cancellation of licence or MA). devices There is a deadline for GMP, GCP, GLP and GDP compliance for all domestic facilities (in case of recently adopted legal provisions) There are guidelines for conducting pre and post licensing inspections There are guidelines for the environmentallyconscious disposal of expired/unusable substances reagents and finished products Organization and structure Inspection activities are organized and performed at a central level of the country Decentralized activities to other agencies/authorities follow the standards, guideline and procedures as agreed/decided with the central authority In case of decentralization, a mechanism of exchange of information is established and implemented in order for the decentralized organization to receive requests and/or directives from the central authority and to report to it The mechanisms in place allow exchange and harmonization of best practices appropriate cooperation and collaboration among the decentralized organizations 13.4 Quality management system A quality management system is implemented for the inspectorate 65 GMP 2011 the joint order No249/201 of Health Minister and Nature, Environment Minister GASI, Drug regulatory division of DOH The Inspection Offices at aimag and city district level The management of the inspectorate is committed to the development and implementation of the Quality Management System, in particular providing financial and organizational support The quality management system is based on recognized ISO 31000:10 standards as reference(who PIC/S, ISO, other) The quality policy and related quality objectives of the Inspectorate are defined and documented A qualified person is designated as responsible within the inspectorate for the development and implementation of the quality management system The documentation needed to establish, implement and maintain the QMS is defined(quality manual, records, SOPs) The documentation required by the QMS is controlled following a

67 documented procedure A documented procedure is established by the Inspection to plan, and to assess if the QMS is effectively implemented and conforms to planned arrangements The Inspectorate performs internal audit of its QMS at least once every 12 months. Records of the results are maintained The corrective and preventive actions taken as a result of audits or from any other non conformity are implemented and documented. Their effectiveness is checked and documented The top management of the inspection reviews on a regular basis, at least once every 12 months the QMS to evaluate its efficiency as well as its effectiveness Records of the review are maintained 13.5 Internal planning and procedures The inspectorate establishes compliance monitoring programs Checklist based on activities that are supervised (GMP, GDP, GCP, Pharmacy, Retail outlets, etc ) Documented procedures/tools are implemented for the planning of inspection activities showing in particular the duration and frequency of the inspections The internal planning for inspection activities is established and updated to cover all regulated activities Documented procedures/tools are implemented for the preparation and the development of adequate materials for an inspection (checklist, reference materials, plans, etc ) Documented procedures/tools are implemented to perform the inspections and in particular on assessing the critical steps of the processes and validation Documented procedures/tools are implemented to check compliance with the GMP, GDP, GCP, GLP, Good vigilance practices and good dispensing practices Documented procedures are implemented for inspections based on specific requirements for specific classes of products and facilities (generics, sterilisation, innovator products) There is a standard format for reporting inspection gaps or deficiencies such as an inspection report The observations of non compliance are classified/categorized according to the risk (critical, major and minor) Documented quality control measures are in place such as peerreview External experts are involved in the inspection processes A committee of internal experts within the DRA is involved in the inspection, evaluation of the inspection reports and in decisionmaking Documented procedures are implemented for decisionmaking Documented procedures are implemented for followups on deficiencies/violations to enforce compliance (including timeframes) and to issue notices on the violations Documented procedures are implemented on investigation activities, any seizure or prosecution. 66

68 Documented procedures are implemented to ensure the adequate involvement and communication between the inspectors, QC laboratory staff and licensing or registration staff The same criteria are used for the inspection of domestic, foreign, public and private facilities There are time limits for the publication of Inspection reports An internal tracking system is established to follow the targeted time frames (statutory or not) A documented procedure is implemented to issue Good Practices related certificates in a standardized format 13.6 Human and other resources Job descriptions are established for the following staff: head of the inspectorate (supervisor) head of the inspection unit by products, inspection team leader and inspector There is enough personnel (internal and external) with adequate ± expertise (education experience and training) for the inspection of all, pharmaceutical products and regulated activities such as manufacturers of active pharmaceutical ingredients, manufacturers of finished pharmaceutical products, pharmaceutical quality control laboratories importers and exporters, wholesalers and distributors, Institutions for conducting clinical and nonclinical trials, Pharmacies and retail outlets MA Holders The minimum qualification, experience and training for ± performing all kinds of inspections is defined The inspectors have the knowledge of the local judiciary procedures if they are supposed to initiate actions in the courts of justice There is a documented process on qualification and review to confirm the competencies required for being inspectors A documented procedure is implemented for the designation of inspectors The inspectors are trained on the specific areas (GMP, GDP, GCP, and GLP).following a training program. The training activities are recorded and such records are kept uptodate Manufacturer's or license holder's representatives are never used to conduct inspections The list of inspectors that are qualified with their specific areas of competencies is available and is kept uptodate There is adequate office and storage space for the inspectorate s ± activities The equipment is adequate and well maintained for regulatory ± activities Adequate support services are provided in terms of transport and communication 13.7 Records and outputs There is a list/data base of all inspected facilities The NRA retains a file of each inspection including the information on the mission, the inspection report, the comments of the 67

69 company inspected and the final decision taken with supporting documentation Each exemption is documented in this file The information collected on the company is used for making or amending regulatory decisions on initial licenses or MA (Recall or withdrawal of products, etc) Availability of information The list and identity of the designated inspectors is available to the companies subjected to inspection The list/data base of all the inspected facilities is published and is publicly available A summary of the inspection reports are published and are publicly available, following applicable local confidentiality requirements The information regarding the enforcement activities such as notices of compliance penalties, prosecutions engaged are published and are publicly available MODULE 14 QUALITY CONTROL LABORATORY 14.1 Legal basis There is a legal provision for the establishment of a Regulatory Quality Control Laboratory (RQCL) The RQCL is part of the NRA. COMMENTS Parliament Resolution No58Goverment resolution 162/ There is a legal provision on the designation of analysts and their powers The legislation empowers a RQCL to perform quality control testing of the pharmaceutical products and to issue official results 14.2 Guidelines 14.2 There is a defined policy for testing in the premarketing and postmarketing period There are guidelines on collection, packaging and submission of samples There are guidelines on the references or standards applied by the RQCL There are guidelines on how to complain and appeal against the decisions of the RQCL. 68 Chair Order of the Laboratory Article 13,2 Law on standardization and conformity Article 6.2.1Law on drug and medical devices Government Resolution No 39 (2004/04/11) on collection of samples and State Inspectorate Agency Chair Order No 35 Quality manual book Standardization and Meteorology

70 14.3 Organization and structure Testing activities are organized and performed at a central level of the country Decentralized activities to other agencies/authorities follow the standards, guidelines and procedures as agreed/decided with the central authority In case of decentralization, a mechanism of exchange of information is established and implemented in order for the decentralized organization to receive requests and/or directives from the central authority and to report to it. NA NA agency accreditation procedure The mechanisms in place allow exchange and harmonization of best practices appropriate cooperation and collaboration among the decentralized organizations Quality management system A quality management system is implemented for the RQCL. NA The management of the RCQL is committed to the development and implementation of the Quality Management System, in particular providing financial and organizational support The quality management system is based on recognized standards as reference (WHO PIC/S, ISO, other) The quality policy and related quality objectives of the RQCL are defined and documented A qualified person is designated as responsible within the RCQL for the development and implementation of the quality management system The documentation needed to establish, implement and maintain the QMS is defined(quality Manual, records, SOPs The documentation required by the QMS is controlled following a documented procedure A documented procedure is established by the RQCL to plan and to assess if the QMS is effectively implemented, and conforms to planned arrangements The RQCL performs internal audit of its QMS at least once every 12 months Records of the results are maintained The corrective and preventive actions taken as a result of audits or from any other non conformity are implemented and documented. Their efficacy is checked and documented The RQCL is regularly audited by an external organization(e.g. certification, accreditation) and the results are available. MNS ISO/IEC 17025:2007 Quality policy and 13 objectives were defined ± ± ± Standardization and Meteorology agency 69

71 accreditation The RQCL participates in a proficiency testing scheme and in external quality assurance programs Top management of the RQCL reviews on a regular basis, at least once every 12 months the QMS to evaluate its efficiency as well as its effectiveness. Records of the review are maintained 14.5 Quality control procedures Documented procedures are implemented for meetings with clients and other interested parties Documented procedures are implemented for preparation and storage of standards, samples, etc Documented procedures are implemented for performing the testing There is appropriate planning of testing and maintenance activities Documented procedures are implemented for handling and storage of incoming and retention samples Documented procedures are implemented for testing specific ranges of products There are specific documented procedures to deal with noncompliant products There are strategies, programs and procedures for the introduction and validation of new/improved tests Documented procedures are implemented for the evaluation of test results and decisionmaking Documented procedures are implemented for handling outofspecification results including a retesting policy There is a standard format for recording and reporting results of analysis (work sheet and CoA) Documented procedures are implemented for followups of non compliant products to enforce compliance (including timeframes The same criteria are used for testing all products from domestic, foreign, public and private facilities A documented procedure is implemented to issue certificates in a standardized format Human resources Job descriptions are established for the following staff: head of RQCL (supervisor Analysts, storekeeper and reference material coordinator ± Administration analysis meeting ± ± ± NA ± Work sheet ± 70

72 There is enough personnel (internal and external) with adequate expertise (education experience and training) for the testing of Active pharmaceutical ingredients Pharmaceutical products, Biological, Traditional/Herbal medicines There are mechanisms to manage any conflicts of interest, including ensuring updates of declarations of conflicts of interest There are mechanisms to ensure that confidentiality requirements are met, for example by the observance of a code of conduct by the analysts 14.7 Infrastructure and equipment There is adequate working space, work environment and storage space for laboratory activities Equipment and instruments for testing activities are adequate and well maintained Documented procedures are implemented for the correct use of the equipment according to the manufacturer[s instruction There are operation manuals and logs books for the equipment (registers of operations/use/maintenance/calibration) ± ± ± Plans for cleaning, calibration and maintenance activities are established and implemented There are qualification protocols and reports for the equipment. ± There are adequate support services provided in terms of transport and communication Reference standards/materials and reagents There is a system to establish and qualify the national reference standards/materials There is a regular supply system for reference standards/materials Documented procedures are implemented for the appropriate handling and use of reference standards/materials Documented procedures are implemented for sourcing, preparation storage and use of reagents of assured quality Safety programme ± ± ± A list of hazardous substances is available and updated ± The responsible staff is designated for the management of a safety programme 71

73 A documented procedure are implemented for the storage, handling and disposal of hazardous substances Subcontracting A list of all the categories of testing activities the NDCL subcontacts to another laboratory or organization is established A formal agreement/contract defines the roles and responsibilities of each stakeholder in particular as regards conflict of interest and confidentiality A documented procedure is implemented to ensure that the requirements that apply to the NDCL are also applied in the same way to the subcontracting organization Records and outputs ± NA NA NA There is a list/data base of all the products tested Testing records/reports are maintained and are readily available at the RQCL The RQCL issues certificates of analysis under its own name or in the name of the NRA. ± Issued its own name MODULE 15 CONTROL OF NARCOTICS, PSYCHOTROPIC SUBSTANCES AND PRECURSORS The country is a signatory to the International Conventions on the control of Narcotics, Psychotropic Substance and their Precursors There are legal requirements for manufacturing, importing, exporting, storage, distribution, and consumption of Narcotics, Psychotropic Substances and their Precursors. The parts 4 to 8 of the Law on Narcotics Psychotropic Substance Control There are legal requirements for reporting, reconciliation and disposal of Narcotics, Psychotropic Substances and their Precursors There are guidelines on the formats for permits, for advice of receipt and for submission of returns of the controlled substances These activities are organized and performed at a central level of the country Decentralized activities to other agencies/authorities follow the standards, guidelines and procedures as agreed/decided with the central authority 72 The part 8, 9 of the Law on Narcotics Psychotropic Substance Control. Part 4 of the order regulates advice of the receipts and part 7 stated submission of returns forma MOH and DOH Department of health in the UB and provinces.

74 In case of decentralization, a mechanism of exchange of information is established and implemented in order for the decentralized organization to receive requests and/or directives from the central authority and to report to it The mechanisms in place allow exchange and harmonization of best practices, appropriate cooperation and collaboration among the decentralized organizations There is a specific requirement for institutions to designate a focal person for the control of Narcotics, Psychotropic Substances and their Precursors in each facility using or utilizing these substances Documented procedures are implemented to evaluate the returns for quantification and detection of abuse or diversion There is enough personnel (internal and external) with adequate expertise (education, experience and training) for control of narcotics, psychotropic substances and their Precursors The civil society and healthcare professional are involved in the activities for the control of Narcotics, Psychotropic Substances and their Precursors There are defined reporting timelines and means of submitting returns on these substances There is information/data base on consignments received and returns submitted for these substances. ± Article 9.1 of the Law on Narcotics Psychotropic Substance Revolving Control ± MOH, GASI, State Police Office and State Custom Office each have their own information database on movement of those drugs and substances Any abuse or diversions and actions taken are registered and documented by DRA. 73 ± GASI and State Police Office register and document any abuse or diversions and actions taken. MOH does not collect and receive above mentioned information.

75 Information sources and reference materials on the control of Narcotics, Psychotropic Substance and their Precursors are readily available MODULE 16 INTERNATIONAL COOPERATION AND HARMONISATION There is an internal policy to facilitate international cooperation and harmonization There are agreements signed between the DRA and RA of other countries or agencies for cooperation and harmonization The NRA participates or follows the development of International and/or Regional standards The NRA participates or follows any harmonization initiative or forum The NRA participates in working groups within the harmonization initiative or forum for regulators The NRA recognizes and/or uses regulatory decisions, reports (inspection, evaluation, and vigilance), guidance or information from other NRAs or international bodies The NRA recognizes and uses the WHO recommended certification schemes and formats The NRA issues CPP certificates following a documented procedure The Inspectorate participates in peerreviewed or joint activities (e.g. PIC/S) The RQCL participates in proficiency testing schemes, regional collaborative studies or the WHO External Quality Assurance Assessment Scheme (EQAAS) The NRA participates in the WHO Drug Safety Monitoring Programme The NRA participates in INCB s international monitoring 74 Parliament Resolution No 68 on Approval of Drug Policy in 2002,article 5.2 ± Germany, Korea, Turkey, Poland ± MOH do use the international and regional standards However, MOH do not participate in the development process of the international and regional standards MOH ± MOH recognizes and uses regulatory decisions, reports inspection, evaluation, (vigilance), guidance which were approved by WHO. WHO guideline, the requirements of GMP, CCP, BCPP certificates were included in the regulatory document. Uppsala Monitoring centre

76 operations on control of Narcotics, Psychotropic Substances and their Precursors The NRA participates in coordinating activities/measures in case of identification of noncompliant products at a regional/international level Documented procedures are implemented to ensure satisfactory cooperation, collaboration and exchange of information with other RA for the various regulatory functions (MA, Inspection Vigilance). 75

77 Annex 2 List of organizations visited and list of persons met Meeting with the Ministry of Health (MOH) Munkhdelger Ch, Head of Division of Pharmaceuticals and Medical Devices Amarjargal Ch, Division of Pharmaceuticals and Medical Devices, Officer in Charge of policy coordination for quality and safety of medical devices Chuluunzezeg D, Division of Pharmaceuticals and Medical Devices, Officer in Charge of policy coordination for the proper usage of pharmaceuticals. Tuya B, Division of Foreign relationship, Officer in Charge of policy coordination for bilateral relations and cooperation in the health sector Burmaajav B Strategic Policy and Planning Department of Officer in Charge of science and technology policy planning. Meeting with Department of Health Government Implementing Agency Uranchineg M, Deputy Director, in charge of drug regulation Uranchineg D, Officer in charge of standardization Zuzaan Z, Officer in charge of ADR Munkhtuul T, Officer in charge of drug information and advertisement Bolortuya Ts, Officer in charge of Drug registration Tsetsensanaa G, Officer in charge of Import authorization Munkhtsetseg B, Officer in charge of Licensing Dondogmaa, Officer in charge of registration of medical personal Meeting with State Professional inspection Agency Altantuya D, Senior Inspector of drug and bio preparation. Tumendemberel D, Officer of risk assessment. Meeting of Central Quality Control Laboratory Mr Amar B, Head of QC central joint laboratory 76

78 Mrs.Ulziidulam D, Senior Analyst, QC laboratory Mrs. Munkhtuya. B Quality manager Meeting with Drug Reference Laboratory Zorig T, Head of drug reference laboratory Meeting with QC laboratory of Pharmacy School, Health Sciences University of Mongolia Surenmandakh G, Quality manager and analyst Meeting with the Authority for Fair Competition and Consumer Protection of Mongolia Munguntseteg T, Department of consumer protection, inspector in charge of advertisement Meeting with Criminal Police Department of Mongolia Ulziibayar G, Officer in charge of narcotics psychotropic substance control 77

79 Annex 3 References: 1. Laws and policy papers Law on Health (July 7, 1998) Law on Medicines and Medical Devices (May 27, 2010) Law on Advertisement (May 30, 2002) Law on State Inspection Law (Jan 03,2003 amended in June 10, 2010) Law on Narcotics Psychotropic Substance Revolving Control (Oct 28, 2002 and amended in May 26, 2011). Law on Consumer protection (Dec 26, 2003) Law on State Employment (June 28, 2002) Law on Government Agency ( April 15, 2004) Law on Licensing (Feb 01, 2001) Law on standardization and conformity (May 15, 2003) Law on Public Service (June 28,2002 amended in March 28, 2009) National Drug Policy (Oct 11, 2002) Government resolution Some implementation issue of the Law on Narcotics Psychotropic Substance Revolving Control Government resolution No 196 ( 2003) HMO 306/2003 HMO 378 /2010 HMO 223/2007 HMO 278/2011 HMO 252/2008 HMO 360/2011 HMO 344/2011 HMO 280/2011 HMO 402/2011 HMO 38/2007 The joint order No249/201 of Health Minister and Nature, Environment and Tourism Minister. MNS Basic requirement of Drug suppliers MNS Basic requirement of Drug manufacturers MNS Basic requirement of pharmacy 2. Web sites

80 3. Books and journals WHO Data Collection Tool for the Review of Drug Regulatory Systems, WHO Practical Guidance for Conducting a Review. WHO Handbook Medical ethics MOH Mongolia WHO Edited by B.Burmaajav, Kh.Damdinjav 2011 Drug information Bulletin number 1(56) 2011 published by DOH Mongolia Drug information Bulletin number 2(57) 2011 published by DOH Mongolia Drug information Bulletin number 3(58) 2011 published by DOH Mongolia 79

81 Annex 4. Quantitative indicators for regulatory purposes Module 3 Regulatory Authority QI 3.1 Total number of the NRA's employees at the end of a reference year 9 QI 3.2 Number of the NRA's scientific staff performing regulatory functions 0 QI 3.3 Number of the NRA's support staff 0 QI 3.4 Number of the NRA's staff IT specialist 0 QI 3.5 Number of the NRA's staff involved in QMS 0 QI 3.6 Number of the NRA's staff recruited in the reference year 2 QI 3.7 Number of the NRA's staff's cancellation in the reference year 0 Module 4 Marketing authorization QI 4.1 Number of scientific staff involved in the registration process 0 QI 4.2 Number of products with a valid Marketing Authorization 2476 QI 4.3 Total number of applications received in the reference year 936 QI 4.4 Number of applications received for a new drug in the reference year 237 /registered/ QI 4.5 Number of applications received for a generic product in the reference year 35 /registered/ QI 4.6 Number of applications received for variations in the reference year 261 QI 4.7 Number of applications received for renewal in the reference year 64 QI 4.8 Number of decisions taken (positive, refusals, suspension) in the reference year 272 QI 4.9 Number of applications pending as backlog 3 QI 4.10 Average number of days for decisionmaking on a new drug 90 QI 4.11 Average number of days for decisionmaking on a generic product 90 QI 4.12 Average number of days for decisionmaking on variations 30 QI 4.13 Average number of days for decisionmaking on renewals 30 Module 5 Licensing of manufacturer QI 5.1 Number of scientific staff involved in establishment licensing 0 QI 5.2 Number of manufacturing plants licensed 30 QI 5.3 Number of manufacturing plants of API licensed 0 QI 5.4 Number of applications received for a new premise in the reference year 1 QI 5.5 Number of modifications of an initial license received in the reference year 1 QI 5.6 Number of decisions taken (positive negative, suspension or withdrawn) in the 5 reference year QI 5.7 Number of applications pending as backlog 1 QI 5.8 Average number of days to issue a decision 21 Module 6 Licensing of importers, exporters, wholesalers and distributors QI 6.1 Number of scientific staff involved in establishment licensing 0 QI 6.2 Number of licensed wholesalers, importers and exporters Drug 147 Medical Device 139 /geminated/ QI 6.3 Number of licensed wholesalers, importers and exporters of API 30 QI 6.4 Number of applications received for a new premise in the reference year 45 QI 6.5 Number of modifications of an initial license received in the reference year 5 QI 6.6 Number of decisions taken (positive, negative, suspension or withdrawn) in the 39 reference year QI 6.7 Number of applications pending as backlog 8 QI 6.8 Average number of days to issue a decision 21 Module 7 Licensing of pharmacies and retail outlets /In Ulaanbaatar/ QI 7.1 Number of scientific staff involved in establishment licensing 0 80

82 QI 7.2 Number of licensed pharmacies and dispensing/selling outlets 530 QI 7.3 Number of applications received for a new premise in the reference year 23 QI 7.4 Number of modifications of an initial license received in the reference year 16 QI 7.5 Number of decisions taken (positive, negative, suspension or closed) in the 42 reference year QI 7.6 Number of applications pending as backlog 0 QI 7.7 Average number of days to issue a decision 21 working days Module 8 Registration of pharmacy personnel QI 8.1 Number of administrative staff involved in registration of pharmacy personnel 1 QI 8.2 Number of pharmacist and pharmaceutical technicians registered 2987 QI 8.3 Number of application received in the reference year 1428 QI 8.4 Number of decisions taken (positive, negative, suspension or radiation) in the 728 reference year QI 8.5 Average number of days to issue a decision 30 Module 9 Market surveillance Import and export Control since Dec QI 9.1 Number of application received (import and export) 2664 QI 9.2 Number of authorizations for importation granted in the reference year and/or 2656 number of product authorized for importation QI 9.3 Number of certificates for export issued in the reference year 2 QI 9.4 Average number of days to issue these administrative document 5 Market Control QI 9.5 Number of products monitored 0 QI 9.6 Number of products detected as noncompliant or of poor quality in the reference year 0 Noncompliant Products / Recall Procedures QI 9.7 Number of complaints on pharmaceutical products received in the reference 0 year QI 9.8 Number of products/batches recalled in the reference year 0 Module 10 Control of drug promotion QI 10.1 Number of staff involved in the control of drug promotion 5 QI 10.2 Number of drugs advertisement applications received in the reference year 53 QI 10.3 Number of promotion and advertisement document monitored 53 QI 10.4 Number of decisions taken (approbations, refusals, suspensions) on drug 53 advertisement in the reference year QI 10.5 Average number of days for decisionmaking on drug promotion 14 QI 10.6 Number of drug advertisements found to be in violation of the regulation and withdrawn in the reference year 13 Module 11 Pharmacovigilance QI 11.1 Number of NRA's professionals involved in the assessment and management of ADR/ADE QI 11.2 Number of contact points (moral or physical person having sent an ADR/ADE) 0 QI 11.3 QI 11.4 Number of ADR/ADE reported by MAH. Manufacturers, importers or distributors and assessed in the reference year Number of ADR/ADE reported by health professional/contact point and assessed in the reference year QI 11.5 Number of ADR/ADE reported by patients and assessed in the reference year

83 QI 11.6 Number of periodic report received and assessed in the reference year 21 QI 11.7 Number of decisions taken (no action taken, product recall, Dear doctor letters, notices for users, etc )in the reference year QI 11.8 Number of ADR/ADE reported pending as backlog NA QI 11.9 Average number of days for decisionmaking on pharmacovigilance issues NA Module 12 Clinical trial QI 12.1 Number of staff involved in the control of Clinical trial 3 QI 12.2 Number of clinical trials applications received in the reference year 5 QI 12.3 Number of applications for amendments of clinical trials received in the 1 reference year QI 12.4 Number of decisions taken (approvals, refusals, suspensions) on clinical trials 6 applications in the reference year QI 12.5 Average number of days for decisionmaking for NRA 0 QI 12.6 Average number of days for decisionmaking for IRB/IEC 45 QI 12.7 Number of staff involved in the inspection of clinical trials 3 QI 12.8 Number of clinical trials inspected in the reference year QI 12.8 Average number of days spent onsite per inspection 3 Module 13 Regulatory Inspection and enforcement activities QI 13.1 QI 13.2 QI 13.3 QI 13.4 QI13.5 Total number of inspectors for the pharmaceutical products sector Total numbers of inspections carried out in the reference year Number of manufacturing inspectors Number of manufacturing facilities inspected including foreign manufacturers in the reference year Number of manufacturing facilities inspected for preapproval inspection for marketing authorization QI 13.6 Number of manufacturing facilities of API inspected in the reference year 0 QI 13.7 Average number of days spent onsite per manufacturing inspection 3 QI I 13.8 Number of importers, exporters, wholesalers and distributors inspectors 31 QI 13.9 Number of wholesale/import/export facilities inspected in the reference year 77 QI Number of wholesale/import/export facilities of API inspected in the reference year QI Average number of days spent onsite per wholesale/import/export inspection 3 days if have a branch 5 days QI Number of inspectors for retail facilities 31 QI Number of retail facilities inspected in the reference year 770 QI Average number of days spent onsite per retail facility inspection 12 QI 3.15 Number of facilities inspected on pharmacovigilance in the reference year 26 QI Average number of days spent onsite per facilities inspected on 1 pharmacovigilance

84 QI 3.17 QI 3.18 QI Number of administrative measures (notice of non compliance or warning letters) issued in each of the last three years Number of license withdrawn or suspended in each of the last three years for noncompliance issues Number of criminal prosecution submitted to court and/or penal sanctions requested in each of the last three years QI Number of legal sanctions applied by the judiciary in each of the last three years Module 14 Quality Control 1 14 withdrawn 30suspend ed In criminal persecution requested NA QI 14.1 QI 14.2 QI 14.3 QI 14.4 QI 14.5 QI QI 14.6 QI 14.7 Number of pharmaceutical products tested in the framework of an application for a MA in the reference year Number of active pharmaceutical ingredients tested in the framework of an application for a MA in the reference year Number of pharmaceutical products tested for import control in the reference year Number of pharmaceutical products tested for market control in the reference year Number of pharmaceutical products tested/certificate issued in the reference year Number of pharmaceutical products tested and failed to be compliant 253 Number of pharmaceutical products recalled based on the results issued by DCL in the reference year Number of MA suspended or withdrawn based on the results issued by DCL in the reference year QI 14.8 Number of scientific staff in the Quality Control laboratory ,5 million tugrug medical devices and drugs have been recalled QI 14.9 Surface of the Quality Control laboratory 240 sq.m QI Number of analysis not performed because of lack of adequate equipment 20 83

85 Annex 5 Organogram of Drug Regulatory organizations of Mongolia 84