White Paper. WHO assessment of vaccines regulatory system: Proposal for establishment of maturity level concept

Transcription

1 1. Working group members A working group had been set up including the following country regulatory experts: Australia: Chris Rolls, Therapeutic Goods Administration (TGA) Cuba: Celeste Sánchez, Centro para el Control Estatal de la Calidad de los Medicamentos (CECMED) Egypt: Faten Fathalla and or Heba Wali, Egyptian National Regulatory Authority (ENRA) France: Pierre Henry Bertoye, Agence Française de Sécurité Sanitaire de Produits de Santé (AFSSAPS) India: Surinder Singh, Central Drug Standard Control Organization (CDSCO) Indonesia: Lucky Slamet, National Agency of Food and Drug Control (NAFDC) Thailand: Teeranart Jivapaisarnpong, Department of Medical Sciences, Ministry of Public Health (MoPH) United States of America: Norman Baylor, Center for Biologics Evaluation and Research, US Food and Drug Administration (USFDA) Senegal: Youssou Ndao, Health Manager of Public Market Central Department, Ministry of Finance and Economy Switzerland: Franz Reigel, Independent WHO regions PAHO/AMR: Jose Peña SEAR: Stephane Guichard 2. Background Since 1996, the World Health Organization (WHO) has documented several experiences of vaccine quality issues with EPI vaccines that were starting to jeopardize the impressive achievement of the National Immunization Programmes and raised issues of the competent oversight of the quality, safety and efficacy of vaccines at country level. For this purpose a WHO programme had been launched to 13April 2010 Page 1 of 8

2 strengthen National Regulatory Authorities (NRA) 1 in the area of vaccines. This programme recommended assisting member countries through the implementation of a five steps capacity building programme such as: a. Development of a benchmarking system b. Conducting assessment of NRAs against the benchmark c. Developing institutional development plan (IDP) d. Providing Technical input including training through a Global Training Network (GTN) e. And conducting monitoring and evaluation through routine follow up and re-assessment of NRAs The process as it was initially developed had to meet several challenges such as the development of an assessment tool that would include performance continuously revised to meet the most up to date regulatory 's competencies and skills, be versatile enough to allow flexibility in its use, and simple enough to be cost effective. The benchmarking system including the assessment tool was revised through consultation of experts in 1999, 2001, 2002, 2004 and Before 2002, there was no link between NRA assessments and vaccine prequalification, all assessments were targeting any countries whether they had prequalified or not any prequalified products. In 2002, WHO decided to implement two major decisions, first of all WHO decided to link the NRA assessment to the WHO vaccines prequalification procedure by requiring as mandatory the NRA assessment in all the countries with manufacturers wishing to apply for vaccine prequalification. The rationale behind this decision was to ensure that countries with prequalified products had a functional NRA exercising adequate regulatory oversight of these prequalified products. At the time the decision was made, this was not always the case. This decision helped to refine the NRA assessment tool and to increase efforts to ensure consistency between NRA 1 NRAs, may also be named as Medicines Regulatory Authority (MRA), National Control Authority (NCA), and Drug Regulatory Authority (DRA). 13April 2010 Page 2 of 8

3 assessments in different countries, aimed at building capacity and improving NRA oversight. The assessments are complemented through training activities and technical support provided to address the identified gaps which are reflected in the institutional development plan of each NRA. The vaccines prequalification assessment that focuses on the products and manufacturers provides useful "real life" feed back on the actual quality and extent of regulatory oversight exercised by the responsible NRA. The second decision implemented in 2004 was to introduce the concept of "" in order to meet the PQ needs for improved and continuous performance of NRA in countries candidate for PQ vaccines. The concept of " " was expanded and used for all regulatory functions as minimum requirements to be met in order to assess the NRA as "functional" for prequalification purposes. 3. Problem statement/ challenges faced Between 1997 and 2009, WHO has been able to assess 101 countries, and has conducted more than 370 follow up visits that helped to document better the issues and constraints of the NRA such as: a. Indicators do not reflect always the degree of performance of the functions, as the process may exist and be appropriately documented but insufficiently implemented. b. Functions include a mix of several types of such as: system development, process development, or and outcome. c. Indicators do not differentiate between two NRAs that have strong QMS and poor performance, and high performance and poor QMS, d. Indicators do not reflect the level of experience and skills that some NRAs have to overcome vaccine quality issues e. Indicators do not always address long term sustainability of performance f. Some NRAs declared as functional still show gaps in performance that are reflected in PQ submissions by manufacturers from the relevant country. 13April 2010 Page 3 of 8

4 All these issues were discussed during the NRA ' meeting organized in December 2007, and the experts' discussions recommended to continue to improve the assessment tool, to harmonize it with the WHO medicines tool and other initiatives, as well as to assess the feasibility of using the EMA experience in using "maturity levels" to benchmark European regulatory agencies. The BEMA exercise (Benchmarking of Medicines Agency) was found interesting and recommendations were made to WHO to use this experience to study the feasibility of its introduction into the WHO NRA assessment programme. The current assessment tool is aimed at assessing the NRA status (functional or not functional), and is composed of 7 components (national regulatory system and 6 functions), 53 and 183 sub-. It was initially recommended to identify at which level the maturity concept should be implemented (status, functions, or sub-). The may be applied through one of the following 3 options: 1 st option : Applying the concept to the final outcome of assessment only : "Functional" or "non Functional": Status of NRA as "functional or not functional" At the end of each NRA assessment, the WHO team present the findings and the status of all regulatory functions assessed. The findings are translated into a report with a detailed assessment tool listing all functions,, and sub-. Each function is then assessed as "implemented" or "not implemented" while all are scored as "met", "not met" or "partially met" with a respective assigned score of 1, 0 or 0.5. This process will remain and the same type of findings will be issued with NRAs assessed as "functional" or "not functional. 13April 2010 Page 4 of 8

5 Implementation of the Maturity level Once the NRA is assessed as "functional" or "not functional", the WHO team of experts will further meet and will assign a certain level of "Maturity" to the NRA that has been declared as "functional" or "not functional". As matter of fact, the WHO team will then use the "Maturity Level Matrix"(in preparation). The maturity level Im p le m e nta tio n of th e m a tu rity le ve l to W H O N R A a sse ssm e nt Steps for assessing the m aturity level As sessm ent c onducted S y s t e m M A A PM S /A E FI Lot release Lab.access In s p e c t io n s C lin i c a l tr ia l s Assessment com pleted N R A declared Functional or not functional A ss e ssm e n t o f m a turity le ve l Functional N o t functional Applies m aturity Level 3,4 or 5 Applies m aturity Level 1 or 2 table will be used by applying the areas listed in the proposed table against the information collected during the assessment. When the NRA is assessed as "functional", assessors will use the level 3, 4 or 5 as reference to assign a maturity level, and when the NRA is assessed as "not functional", assessors will use the level 1 or 2 for assigning the maturity level. The areas should refer to (main and or sub-) included in the assessment tool as it is proposed or subsets of these as described in the table below: 13April 2010 Page 5 of 8

6 Status of NRA Maturity level Critical Non Functional 5 100% met 100% met Functional 4 100% met 90% met Functional 3 100% met 90-70% Non functional % met 70%-50% Non functional 1 Less 50% Less 50% Limitations and or constraints: The discussions within the working group concluded that it was an interesting concept however it needs further refinement to clarify better the minimum level and better definition of the different level for the NRA to meet. It was also suggested that working out such system should provide an added value to the NRAs, with incentive to continuously improve to move from one level to the next, otherwise they may remain in the same level for years. The internal discussions within the WHO secretariat when the experts outcome was presented, was that this concept if applied to the functionality might introduce a dual standard of the definition of functionality. It was then recommended to better improve the existing and not to introduce the to assign different level of functionality. 2 nd option : Apply the to the regulatory functions only : The current NRA assessment tool includes 7 components such as: National regulatory system Marketing authorization and licensing activities Post marketing surveillance including AEFI surveillance NRA lot release Laboratory access Regulatory inspections Oversight of clinical trials 13April 2010 Page 6 of 8

7 The 2nd option is to apply the concept of maturity level in the same way to the regulatory functions as follows: Components National regulatory system 2. Marketing authorization and licensing activities 3. Post marketing surveillance including AEFI surveillance 4. NRA lot release 5. Laboratory access 6. Regulatory inspections 7. Oversight of clinical trials Function is not met, less than 50% met, and less 50% non met Function is not met, as only 50%-70% met, and only 50%- 70% non met. All met (100%) and 70%-90% of non met All met (100%) and 90% of non met. All met (100%) and all non met (100%) Limitations and or constraints: This proposal was not fully discussed and therefore was it was recommended to test it and before discussing it further. The advantage of the 2 nd option is that the functional/non functional definition remains the same as before, however the performance of the regulatory functions to be met will be subject to more scrutiny with this system. WHO PQ could on this basis assign a minimum level of performance to be met (3 or 4 or even 5) before considering the functions to be met. The need for higher performance is adjusted by the number of that needs to be met and number of non that need to be met. 13April 2010 Page 7 of 8

8 3rd option: Applying the maturity level to the only: This option is similar to the previous one and will be applied to all listed in the assessment tool, the scoring will be the same (1 to 5), and WHO PQ will have to decide which level is considered as meeting PQ requirements. Limitations and or constraints: Complexity of the tool and its implementation would increase significantly as it includes more than 54 that would need to be scored between 1 to 5, then further work and definition should be developed to meet the WHO PQ. 4. Recommendations for the implementation of the into the WHO NRA assessment programme Conduct testing with NRAs already assessed and others to be assessed (April- September 2010) in order to explore the feasibility of applying the concept at the level of regulatory functions and. Revise the white paper using the feedback from the field testing (September - December 2010) Submit for endorsement to the next NRA expert's consultation (early 2011). Wide implementation for all NRA assessment planned after the NRA 's experts consultation. 13April 2010 Page 8 of 8