1. FEEDBACK FROM SAPRAA WORKSHOP WITH PPB DR DORCAS PETA 18 NOVEMBER 2011

2. QUESTIONS RECEIVED CTD GMP Inspections Analysis of Samples Product Retention and Fees Harmonisation Medical Devices Cosmetics and Complimentary Medicines Other Questions

3. CTD Questions Summary Product Characteristics (SPC): Here we normally refer to the attached SPC. However, our agent was told by a PPB representative that we cannot only refer to the SPC, but need to provide a summary of the SPC within the cover pages of Module 1. Response: Attach full SPC

4. CTD Questions cont. Our agent was told that we could not only refer to the relevant overviews and summaries in the Body of Data of Module 2, but that we had to provide actual summaries of the QOS, Non-Clinical Overview and Summaries, as well as Clinical Overview and Summaries, within the Module 2 cover pages. Response: Module 1 and 2 are required in word format and have to be specific information for the sections within the form. The reason is for the evaluators to make comments during evaluation and create a report. Do not cross reference.

5. CTD Questions cont. Should dossiers be completely converted from the old to the new format when updating dossiers? Response: If the registration is in the old format and is concluded, can remain in that format until such time PPB makes a decision. Industry has until December 2011 to conclude all pending issues in the old format, other wise the dossier will have to re-submitted in the new CTD format. For products with different strengths, is it possible to combine modules 3, 4 and 5? Response: No. All the information to be included in each strength.

6. CTD Questions cont. Which documents should be submitted in electronic format? The complete dossier (Modules 1 - 5) and in which format? Word or pdf? Response: 1 original hard copy and 1 electronic hard copy in PDF and Modules 1 and 2 in MS-Word, other sections in PDF

7. CTD Questions cont. The application form – please advise the amount of detail you want on it. Is it acceptable to put refer to? Response: No. Specific information for Modules 1 and 2 to be included in the form The numbering system in the application is different to the CTD – would you accept if we sent a dossier with the CTD numbering? Response: Yes

8. CTD Questions cont. Will it be acceptable to submit a Product Summary File as per WHO requirement for a WHO prequalified product. (vaccine) Response: Yes, but applicant to use PPB form Some vaccines were established many years ago where there are no non-clinical data and in some cases no characterization details / information available as it wasn’t done, can we request exemption for those parts. Response: No. Applicant to generate the data, including post surveillance data.

9. CTD Questions cont. The query read thus: I have to respond to a resolution for a product submitted in Kenya and our agent in Kenya has suggested that we resubmit the entire dossier when we respond, although only sections 18 and 19 will be updated (These sections are the Bioavailability and Clinical sections in Parts XII and XIII old format of application forms). Response: Submit full dossier mark the sections which have been changed. NB: The deadline to submit queries from old dossier is December 2011, after December applicants will be required to submit full dossier in the new format

10. GMP Inspections cont. If the manufacturing site is FDA or PIC approved why is it necessary for the PPB to also perform an inspection? Response: Want to maintain ability to conduct inspections. They will not perform paper evaluation Why doesn’t the East African Region share inspection reports between the different Health Authorities? Response: It is being looked into. There is lack of goodwill from other HA to share the reports

11. GMP Inspections cont. What is the frequency of site re-inspections after first approval? Response: 3 years According to our agent, once the Inspection form, SMF and payment have been submitted to the PPB the onus is on the manufacturer to ensure that an inspection is carried out at the site. Response: The applicant to follow up with PPB

12. GMP Inspections cont. The increase in costs from $500 every 5 years to $300 every year we can live with, but the additional costs like GMP inspection fees of $4000 per site is just excessive. I also hear that these GMP fees will also need to be paid every 3-4 years for the PPB GMP certificate to be renewed. Response: The fees are gazette into law. Yes, applicants to pay re-inspection fees.

13. GMP Inspections cont. Are they actually going to inspect all the sites, and if so how are they going to accomplish this with limited personnel and in what timeframe. Could they not accept GMP certificates from well established health authorities or PIC countries. Is the EAC not now a PIC observer? If this is to be introduced by 2012, how will they ever be able to issue PPB GMP certificates for all manufactures in time? Response: PPB has enough staff complement to carry out inspections. 15 inspectors for foreign inspections and 5 inspectors for local inspections.

14. GMP Inspections cont. Can they please extend the deadline for applying for GMP certificates, which is required when you apply for retention of the product. Response: No registration until GMP inspection is conducted. Applicant can appeal not to have product pulled out of the market

15. GMP Inspections cont. If the product is a WHO pre-qualified product will PPB still want to do a GMP audit at the site of manufacturer already audited and approved by WHO? Response: Yes, according to the board, all sites are to be inspected. NB: SA is to be inspected in January 2012, only if inspection fees are paid

16. GMP Inspections cont. Some companies share a common manufacturing facility, e.g. one manufacturing site supplies product to four applicants. Must each applicant pay the US$4000 GMP inspection fee? Will it be acceptable for the applicants to share the US$4000 (e.g. each applicant pays only US$1000, or only one of the four applicants pays the US$4000 in full)? Response: Yes, companies can share costs

17. Analysis of Samples Pre-registration analysis of the product: Is product analysis only valid upon first registration of product in Kenya? Response: No. There is periodic analysis. Kenya has 3 laboratories approved by PPB. Regarding testing of vaccines, the labs will determine if they are able to test or not. If not, the applicant can use an independent lab which is WHO pre-qualified.

18. Analysis of Samples cont. Please clarify exactly which tests the Laboratory is to carry out on the Drug Product. Will the Laboratory carry out all the tests listed on the CoA of the Drug Product or are there only certain compulsory tests that need to be performed? Response: In some cases, some tests fail therefore they would like to perform all the tests. They test according to USP or BP monograph or in-house method, whichever is filed.

19. Analysis of Samples cont The need to have all products tested at a local Kenyan lab with new retention fees. Again this is a huge additional cost and logistical nightmare for all applicants. We have actually had cases where the labs have returned tests that have failed, as they were in most likelihood not performed correctly. When moved to another lab they were fine. In many cases API standard, reagents and columns may need to be provided and this just escalates costs even further. If they do insist on this, would they want the samples to be tested every year? Response: No

20. Analysis of Samples cont Will the labs be able to cope with all the new tests that need to be done? Response: Analysis in not performed for product retention.

21. Analysis of Samples cont Why are we required to submit samples when applying for retention of a product. Why are they refusing to accept samples labeled with S.A label for these applications. Due to minimum order quantities manufacturers are refusing to just pack three samples for retention applications. Response: To ensure that product is the same as in the market. Label has to comply with the PPB requirements (e.g. mfg + exp. date required on pack and this is not a requirement in SA)

22. Analysis of Samples cont Is there a reason why they don't want to accept samples with 24 month shelf-life, when applying for 36 month shelf-life. Because of minimum order quantities can we be allowed to submit registration samples with 36 month shelf-life marketed in other countries (i.e. won’t comply to PPB label requirements). Response: We can submit samples with 24 months shelf-life with the corresponding stability data up to 36 months. Label has to comply with the PPB requirements

23. Analysis of Samples cont Samples & Pre-registration Laboratory analysis of the product sample – Our products (vaccines) must be kept under cold chain conditions i.e. -20 °C and between 2 °C – 8 °C; must we submit the samples under cold chain conditions and does PPB have the fridges to keep the samples at recommended storage conditions? Response: Yes

24. Analysis of Samples cont 5g of active material for lab analysis is too much especially for speciality products which are expensive. Can the requirement be re-phrased to request enough to do 10 runs? Response: Dr Humphrey Mwavali to take this up with PPB Can the applicant request exemption on the number of samples required for fridge items e.g. speciality products? Response: Yes, but must get an exemption letter from the NQL in Kenya. The applicant may send the methods of analysis to the lab prior to the application for the lab to make the decision. If the lab grants the exemption, then the applicant must submit 3 samples for evaluation with the dossier application.

25. Retention fees Is the document on retention fees an official guideline? Response: The retention fees are gazetted. SAPRAA to obtain a copy from PPB and to distribute to members.

26. Retention fees cont. The new guideline for retention fee payment and site inspection - is there a timeline when we need to complete this task? Response: Effective date is 1 August 2011. Approved registrations prior to August 2011 are valid for 5 years and no retention fee payments during the period. Products registered after August 2011, registration is valid for 1 year and are subjected to annual retention fees payment and site re-inspections if they do not have a Kenya GMP Certificate which is valid for 3 years).

27. Retention fees cont. The 5 year registration renewal fee (US$500) has apparently been replace with a US$300 annual retention fee. Please confirm if this is true. Response: Yes If the US$300 annual retention fee is applicable, then does this mean that a renewal dossier is no longer required? Response: Yes Is it true that all the products registered with the PPB must be tested annually by a Kenya laboratory? If this is true, what are the requirements and how should one go about to get your products tested? Response: No testing is to be performed annually. One sample is requested for the retention application annually.

28. Harmonisation What progress has been made on the EAC harmonisation initiative as far as medicines registrations is concerned? Response: Progress is very slow. They share other information like counterfeiting, benchmarking and product tracking.

29. Medical Devices Please provide an update on the status of medical device registration in Kenya, timeframes etc. Response: Draft guideline out for comments by January 2012. Previously medical devices were regulated by Kenya Bureau of Standards.

30. Cosmetics and Complimentary Medicines What are the guidelines for Cosmetics and Complementary medicines (herbals, Vitamins, etc) Response: Guideline for complementary medicines only What is the review and approval process for these types of products? Response: 3 months to approve Is there a guideline or standard currently in place for limits for ingredients in cosmetic products. Response: No, currently cosmetics are regulated by Kenya Bureau of Standards

31. Other Questions Can we have more than one agent in the country provided they selling different products e.g. one sells OTC and the other Pharma products. Response: No, only one Technical Representative (RA agent) but can have more than one distributor Does the PPB have variation guidelines as currently there is nothing on the website. Response: No. PPB is working on the guideline and will be posted on the website before the end of the year for comment.

32. Other Questions cont. Why are we required to pay for each notification covered by one cover letter (i.e. if there are five notifications then you pay 5 x USD 200 = 1000), this was according to our agent. Response: Currently, this is correct. Applicants to pay per change per product but the guidelines are being reviewed.

33. Other Questions cont. It is required to provide a Batch Manufacturing Record (BMR) of a real batch manufactured within at most six months before the submission of the application. In some cases the manufacturer do not want to provide this document and state that it is available for viewing by the National Regulatory Authority (NRA) at the manufacturing site. Response: This is acceptable

34. Other Questions cont. Is there an updated pharmacovigilance guideline? Response: Yes, on website.