SUMMARY OF THE INDUSTRY TASK GROUP MEETING HELD AT 08:00 ON 23 JUNE 2015 IN THE CIVITAS BUILDING Present MRA/DoH Joey Gouws (JG) Estelle Taute (ET) Ndimuhulu Dowelani (ND) Shyamli Munbodh (SM) Jerry Molokwane (JM) Khamusi Mutoti (KhM) Hellen Moropyane (HM) Silverani Padayachee (SP) Momeena Omarjee (MO) Tohlang Sehloho (TS) Davis Mahlatji (DaM) Enos Motshitela (EnM) Griffith Molewa (GM) Kaizer Thembo (KT) Portia Nkambule (PN) Kefiloe Mompati (KeM) Industry Nicole Edelstein (NE) Norman Fels (NF) Sanjay Lakha (SL) Stavros Nicolaou (SN) Anita Smal (ASm) Hayley Eager (HE) Robyn Daniel (RD) Leigh Howes (LH) Avanthi Bester (AB) Anele Vutha (AV) Corinne Pillai (CP) Deepa Maharaj (DeM) Evelyn Mohanlall (EvM) 1. WELCOME AND APOLOGIES JG chaired the meeting and welcomed everybody to the meeting. She announced that the new Chairperson of Council, Prof Helen Rees will join the meeting later to address ITG and open communication channels to Council. NE expressed ITG s appreciation for the opportunity to meet and said it is a privilege and honour for ITG to meet and be addressed by the Chair of Council. Apologies were received from: Alice Sigobodhla, Santhani Chetty, Celecia Pleass, Abeda Williams, Judy Coates, Merle Scher, Trevor Phillips, Muhammad Bodhania, Vivian Frittelli, Nerine du Plessis, Ernest Schay, Miranda Viljoen, Lynette Terblanche, Tebogo Sebata, Robyn Howes, Tanya Vogt, Salma Ismail, Allison Vienings and Wayne Robinson. 2. APPROVAL OF THE MINUTES OF THE MEETING HELD ON 17 MARCH 2015 The minutes of the meeting held on 17 March 2015 were accepted as an accurate reflection of the meeting. ET proposed RD seconded 3. MATTERS ARISING AND FEEDBACK 3.1. Medicines Evaluation & Research 3.1.1. Pre-registration unit DaM reported that the revised Biostudies and Dissolution guidelines were ratified by Council and will be published on the website for implementation. - Revised Biostudies and Dissolution guidelines to be published for implementation. 3.1.2. Post-registration unit RD asked for confirmation that dossiers converted to CTD should only be submitted when next submitting Type B or C amendments in view of the deadline for conversion of all dossiers to CTD format coming closer. ET confirmed that converted dossiers should only be submitted when there is an amendment for the relevant dossier. The unit is busy evaluating amendments from January 2014, but there are still a lot from December 2013. There are still a large number of urgent amendment requests jumping the queue for priority and tender products and not enough progress is therefore made with routine submissions. Page 1 of 7
Guidelines under review: - The Post-importation testing guideline will be published for comment. - The Labelling of medicines containing sugars guideline is being finalised and will be published shortly. - Progress has been made in terms of the revision of the requirements for Section 3.2.S in the P&A guideline. Information was obtained from other regulators at the IGDRP meeting that was hosted in South Africa in May. The information has been circulated to the P&A Committee. The revision of the guideline will now be finalised and it will then be ready for comment. - The revision of the Amendments guideline will follow once the revision of the P&A guideline has been finalised. JG reported that MCC is looking at initiatives to ensure that the regulatory requirements for generic medicines are aligned with international requirements to enable faster registration timelines. One of these is the International Generic Drug Regulators Programme (IGDRP). SP provided an overview of the IGDRP. The IGDRP was formed to allow information and work sharing. Some of the regulators include those from Canada, Australia, EU, UK, Singapore, Switzerland and Chinese Taipei. EDQM and WHO participate as observers. Information is e.g. shared around the requirements for Active Substance Master Files (ASMF), bioequivalence and biowaivers. An information sharing pilot project was initiated last year. The EU Decentralised or Centralised Procedure (DCP or CP) will be used as a model to share information with authorities from Australia, Canada, Switzerland and Chinese Taipei during the scientific assessment phases of the DCP/CP. South Africa wishes to engage but a full review of the ASMF in terms of the restricted part is not done and the reports on the evaluation of the FPP are not detailed enough to share. Information can however be accessed from other IGDRP regulators. The EDQM is e.g. sharing information on ASMFs in terms of major deficiencies identified and GMP status of the API manufacturers. WHO prequalified APIs are already being accepted by MCC. The next IGDRP meeting will take place in South Korea. IGDRP launched a website where more information can be found: www.igdrp.com. - The revised Post-importation testing guideline to be published for comment. - The revised Labelling of medicines containing sugars guidelines to be finalised and published for implementation. 3.1.3. Biological medicines KM reported that a communication will be sent to industry regarding vaccines and that a roundtable meeting is planned to discuss the annual strain update. 3.1.4. CAMs Refer to point 4. 3.1.5. Veterinary Medicines Comments from SAAHA on the Veterinary antimastitis medicines guideline will be discussed at the next Veterinary Committee meeting. HE asked if there was any feedback in terms of the request from SAAHA that veterinary CAMs products be submitted under Act 36 and not Act 101. JG asked that the request should be submitted via the Registrar s office and recommended that the request for Section 36 exemption should include a clear motivation why the products should be regulated under Act 36. HE asked if any tentative dates have been made available for a P&A workshop for applicants with veterinary medicines. It was confirmed that no dates were finalised yet and these will be made available to SAAHA. Page 2 of 7
- SAAHA to submit a request via the Registrar s office that veterinary CAMs products are submitted under Act 36 and not Act 101. - A date for a P&A workshop for applicants with veterinary medicines should be set. 3.2. Clinical evaluation & trials 3.2.1. Clinical trials The dedicated central e-mail process will be published later in the week. The Risk-based monitoring guideline will be published for comment. The dispensing by healthcare professionals during clinical trials policy is still being discussed at Committee level. LH said that recent recommendations required the license and conditions for cold storage for shipping and warehousing of investigational products and asked if this will be required in all submissions in future. PN replied that each application is reviewed on its own merits. The Committee is working on policy documents that will cover all issues that have been identified, e.g. laboratory competence and providing accreditation certificates. LH mentioned that observational studies were previously submitted for notification and not approval. Approval letters are now being received. PN replied that the Committee reviews whatever is submitted to them, especially Phase IV studies. It is often found that some of these are not pure Phase IV studies; the comparator product might e.g. not be registered in South Africa. Acknowledgement letters and not approval letters are issued for true Phase IV studies. JG reported that it is increasingly found that a site doesn t have an emergency trolley during GCP inspections. She asked that all clinical trial sites must be reminded that they must have an emergency trolley relevant to the specific study being conducted. If these sites are not compliant, they will not be approved. The clinical trial SAE guideline is in the final stages of discussion and the aim is to table it at the next Council meeting. - Dedicated central e-mail addresses and processes to be followed to be published. - Risk-based monitoring guideline to be published for comment. - Dispensing by healthcare professionals during clinical trials policy to be finalised. - ITG to remind all investigators that they must have an emergency trolley relevant to the specific study being conducted. - Clinical trial SAE guideline to be finalised and tabled at Council. 3.2.2. Pre-registration clinical evaluation Interviews are underway to appoint three internal evaluators to improve turnaround times. ET advised that the annotated PI and PIL should be submitted in Section 1.5.5 and the clean PI and PIL in Section 1.3 when submitting responses to pre-registration clinical recommendations. 3.2.3. Post-registration clinical evaluation HM reported that a formal response is still being prepared regarding the ITG letter expressing concern regarding the strict implementation of the SR-PINs guideline and the response will be finalised and sent out soon. The Clinical Unit will do a presentation at the July SAPRAA meeting on the Regulation 9 and 10 process. Questions should be sent to the unit before the meeting to ensure that they will be addressed. The standardised text to be included for ARBs and ACE inhibitors has been updated and will be published for implementation. Page 3 of 7
HM asked applicants to comply with the following: - Applicants should not submit double sided copies when submitting clinical responses. - The approved PI and PIL must be included in Sections 1.3.1.1 and 1.3.2 respectively when submitting amendments. - All changes to the approved text should be indicated by underlining for additions, strike through for deletions and broken underlining for re-wording in the annotated PI submitted in Section 1.5.5. - A copy of the latest innovator PI must be included in applications for generic medicines. Applicants sometimes include a foreign SPC for the innovator, but a copy of the local innovator PI must always be included. - The three copies of amendment submissions must be submitted as three separate copies/volumes and not all bound into one volume. NE queried the status of the backlog in terms of evaluation of safety updates. HM replied that they have nearly completed all 2011 submissions and are busy with submissions up to May 2012. The unit is trying to allocate newer and older submissions for the same product to the same evaluator. In this regard it is important to state in new submissions that previous submissions are still pending and to include clear cross-references to the previous submissions. - Response will be sent to ITG regarding the concerns expressed in terms of the implementation of the SR-PINs guideline. 3.2.4. Pharmacovigilance PN reported that the Post-marketing ADR guideline will be published for comment this week. DHCPLs it was confirmed that DHCPLs should be distributed via surface mail, and distribution via e-mail can be added. The guideline on Risk Management Plans (RMPs) is still under discussion by the PV committee. JG informed the meeting that a lot of work is being done in the PV unit including initiatives to sensitise reporting and to include vigilance for medical devices and CAMs. The unit is also working more closely with the WHO and is investigating implementation of the WHO VigiFlow programme which already makes provision for herbal medicines and CAMs. SL asked for clarification regarding the requirements for annual summary reports as some applicants are asked to submit reports and others are told not to submit. PN replied that the revised Post-marketing ADR guideline will address the requirements. - Post-marketing ADR guideline to be published for comment. 3.2.5. Section 21 SM reported that the Section 21 guideline was tabled at Council and that it was referred back for further input and to align requirements with those of other stringent regulatory authorities. The guideline will cover all unregistered allopathic medicines and CAMs. The revised guideline will be tabled again at the next Council meeting. JG asked that the GMP status of the manufacturing facility should be included in the application for Section 21 approval for unregistered products. The emergency after hours phone number is 072 134 4546. The treating physician must phone and verbal authorisation will be followed-up with written authorisation the next day. When emergency authorisation for named patients is required over a weekend, the documentation must be submitted in writing and telephonic approval will be given. - Section 21 guideline to be finalised and published for comment. Page 4 of 7
3.3. Inspectorate & Law Enforcement 3.3.1. Inspectorate unit Comments were received from most wholesalers on the Guideline for Wholesalers to Export Medicines. Not many comments were received from applicants. The guideline will be finalised and tabled at Council. A workshop will be arranged on the requirements as there appears to be confusion between commercial ownership (when the wholesaler buys and owns the product) and regulatory ownership. Applicants must know when their products are exported. The GWP guideline is on hold until the matters around exporting of medicines have been sorted out. Applicants are reminded that a hard copy of SMFs must be submitted, together with an electronic copy on CD-ROM. The guideline on how Inspection Reports should be responded to was discussed at Council and will be published. Requirements will be similar to those of the TGA and MHRA to ensure responses are prepared and submitted in a standardised manner. A workshop will be arranged with CAMs manufacturers regarding GMP standards in August 2015. Expectations from the regulator and industry challenges will be discussed with the view to develop a clear roadmap on how and by when the CAMs manufacturers will need to comply with GMP standards. Applicants must submit full motivations with valid reasons for requests for once-off approvals in the case of shortages of medicines. Each application is evaluated on its own merits. Inspections are planned in Serbia and Turkey in July. Inspection trips are planned to India, Mexico and Brazil in the rest of the year. EnM and JG explained that international inspections are planned based on applications received. New sites and sites that previously had a negative GMP status are prioritised. Trips are usually planned for a month to specific countries or regions. Once approval is received for a trip, the plan to the various sites to be inspected within the region is finalised. SL asked if a letter can be issued by the Inspectorate for type C amendments, once they have finalised their part of the evaluation. EnM replied that it is being considered but they have a challenge in terms of capacity. Four administrative assistants are being recruited to provide assistance. Fast tracking of certain processes is also being investigated to speed up issuing of amended registration certificates. JM and JG informed the meeting that API manufacturers will be inspected in future and API manufacturers in South Africa will be licensed. A guideline on API GMP requirements will be implemented. - Workshop to be arranged regarding the Guideline for Wholesalers to Export Medicines, and guideline to be finalised and tabled at Council. - The guideline on how to respond to inspection reports will be published. - Workshop on GMP standards to be arranged with CAMs manufacturers. 3.3.2. Licensing unit RD reported that ITG is working on various options for a central repository for PIs. Once a proposal is ready, an appointment will be made to discuss the proposal and way forward. - ITG to share proposal regarding the central PI repository with the N&S Committee once finalised. 3.3.3. Law Enforcement Autogenous vaccines and compounding of veterinary products are still being discussed. 3.4. Operations & Administration Retention fees are being complicated by applicants who are paying retention fees as per the new fees that were published for comment. ET asked that applicants should please pay the fees as per the reminder letter that was sent out. Where incorrect fees were paid, arrangements must be made to refund the entire amount, and a new payment made for the correct amount. Applicants should also please pay attention to submit proof of payment with a cover letter with AFJ as the working code. Page 5 of 7
NE queried the status of the new proposed fees. JG replied that only 1 comment had been received that indicated acceptance of the fees. The Minister of Health will be requested to publish the new fees for implementation in July 2015. Routine post-screening submissions submitted January to March 2012 are currently being allocated for evaluation. The fast-track submissions and submissions for priority diseases are taken out of the routine queue and allocated for review depending on availability of the relevant expert evaluators. NB: Industry is again requested not to follow-up on products submitted (postscreening) after January to March 2012, unless these were approved for fasttrack evaluation. Screening outcome letters are being sent for products up to July 2014. If screening outcomes have not been received for products submitted prior to July 2014, applicants can follow up on these with Santhani Chetty. ET reported that a new MCC website is being developed. The development is being done in stages. In the first phase the current content will be transferred. The content will be searchable and there will be an option to download or e-mail documents. The website will be more secure and user friendly. The target is to launch this stage by end July 2015. In the next stage an interactive part will be developed for Module 1.2.1 and will eventually link to the EDMS and ectd. Going live with ectd is delayed due to the lack of IT infrastructure and is not dependent on registration of all the products in the pilot project. The guidelines, validation criteria, specifications and DTD will be revised taking all the learnings in the pilot project into account. A workshop will be arranged with Industry. SL asked if there was any feedback to the letter sent by ITG to request that submission of modules 4 and 5 be allowed in electronic format and that the requirements be clarified in the guidelines as an interim measure due to the delay in the rollout of the ectd. ET replied that guidelines cannot be amended for interim measures. Requests can be submitted to Ops & Admin and will be reviewed case by case. Applicants must take responsibility and know what they are submitting. The size of a submission can be reduced significantly if care is taken to remove all the raw data. Paper copies are still required for evaluators until ectd is rolled out. The electronic copy, if agreed to, will be kept as the file copy with the proviso that paper copies have to be submitted on request. 4. ADDRESS BY CHAIR OF MCC, PROF HELEN REES JG welcomed and introduced the Chair of MCC, Prof Helen Rees (HR). HR said the Minister of Health asked her to chair Council and to steer the course towards SAHPRA. The new MCC was appointed and had their first meetings. Some Council members stayed on and there are some new members bringing new expertise to Council. There is a lot of energy in MCC and recognition that things can be done better. Issues such as the backlog and other matters holding industry back will be addressed. HR acknowledged that there is a need for better communication and wants to create forums for communication and set up a communications group for the secretariat. Working groups are being set up to look at how things can be done differently and to address new issues, e.g. CAMs, medical devices. The intention is to find novel and innovative ways of addressing all the issues, including the backlog, while maintaining the mandate of the MCC. SN welcomed HR back and cautioned that the expectation in terms of the transition from MCC to SAHPRA must be calibrated realistically especially in terms of human resources and asked how industry can become involved. He mentioned that the public health enhancement fund social compact could perhaps be used to bolster funds for human resources. He commended Council for their willingness to engage transparently and openly and pleaded for collaborative engagement with Council going forward. NF said industry is seeking clarity in terms of the regulatory dilemma regarding CAMs. He asked when the Regulations of 2013 will be rescinded and new Regulations published incorporating e.g. the Health Canada monographs. Page 6 of 7
HR responded that one of the biggest hindrances is human resource capacity. Consultants were hired in the past and some progress was made but things slipped back again. It is important to build sustainable capacity. International donors are willing to assist. A short course in regulatory sciences training is already being set up in collaboration with the University of the North West. The Institute for Regulatory Science is seriously being looked at. International funding has been obtained and the intention is to build up regional capacity keeping an eye on harmonisation. The availability of funds from industry is noted and a motivation will be taken back to the DG and Minister of Health to make use of the funds. Sustainable funding must be obtained to appoint more staff. Consultants is not the way to go, SAHPRA must become self-sustaining. JG added that 52 posts have been advertised since November and interviews and recruitment are ongoing for administrative and technical staff. JG said the CAMs Regulations are being discussed. The definition will be changed taking industry proposals into account. Labelling requirements for CAMs were tweaked end 2014. They have listened to stakeholders and spoken to other regulators that are regulating CAMs. A team was sent to Health Canada to look at their framework and how they evaluate CAMs. TGA and MHRA processes were also evaluated. The TGA said they will also be changing their requirements to be more in line with those of Health Canada and the MHRA. The information brought back from Health Canada and the MHRA was workshopped by the Complementary Medicines Committee (CMC) and secretariat in November. The guidelines are being redrafted taking the information obtained from other regulators into account. Frequent meetings are being held and the plan is to table the first guideline documents at the August Council meeting and then publish them for comment. NF welcomed the feedback and said industry want to work together and be part of the solution. NE said a Specialist Committee was formed in ITG to deal with CAMs related matters and asked what industry could do to assist going forward. JG said the CMC and CAMs unit have put in a huge effort to move forward since the new MCC was appointed. The revised guidelines will be published and industry will then be invited to a workshop. NE asked if the list of queries and points requiring clarification that have been identified by industry should be submitted in the interim. JG and KT asked that the queries be submitted as soon as possible. The CMC and CAMs unit could then try to address the issues before the revised guidelines are finalised. JG informed the meeting that the Medical Devices Regulations will be published soon for a one month comment period. HR concluded that MCC members are committed to push forward and prepare for the transition to SAHPRA while keeping up with the day to day activities of Council. A new committee has been established that will meet after the ITG meeting to tackle the backlog issue and put a timeframe, vision and strategy in place to deal with the backlog. 5. MEETING DATES FOR THE REST OF 2015 The meeting dates for the rest of 2015 are 18 August & 10 November. 6. CLOSURE JG closed the meeting and asked that the burning issues that were not addressed should be sent to her via e-mail. HR committed to try and join future meetings. NE thanked JG for the meeting and HR for attending on behalf of ITG. The meeting closed at 10:10. Page 7 of 7