1. Medsafe – GMP update / release for supply / communicating quality issues Derek Fitzgerald Manager, Compliance Management 11 July 2013 RACI Pharmaceutical Science Group (NSW)

2. Medsafe and GMP Medsafe – an introduction GMP update Release for supply – New Zealand Communicating quality issues 2

3. Medsafe The New Zealand Medicines and Medical Devices Safety Authority Relevant legislation – Medicines Act 1981, Medicines Regulations 1984 Comprises several ‘Branches’ Compliance Management Product Regulation Clinical Risk Management 3

4. CMB – area of operation GMP audit and licensing / certification Medicines and medical devices complaints & recalls Investigations and prosecutions Medicines testing programme Medical devices listing database (WAND) Advertising complaints and issues Advice on legislation and policy Legislative compliance Border control 4

5. CMB Teams Product Safety (Wellington) (8 staff) Post-market complaints, recalls & market actions GMP Medicines testing programme Medical devices – WAND Advertising issues Supply of unapproved products Investigations & Enforcement Team (Auckland) (5 staff) Investigations and prosecutions Border control and importation 5

6. Some post-market statistics For the full financial year: Jul 2012 – Jun 2013 Medicines incidents handled / closed: 478, of which 29 were recalls Medical devices incidents handled / closed: 1,067, of which 284 were recalls or market actions GMP audits conducted: 49 Packages inspected at the border:  11,500 6

7. The New Zealand GMP Scene Currently around 50 ‘active’ sites Wide range of manufacturing operations 8 API – including clinical trials, biologicals 10 complementary medicines 8 blood service or similar 5 gas sites 2 overseas 4 testing laboratories 10 packing sites 7

8. GMP operations Medsafe performs around 50 audits annually with 3 auditors (recent increase) Audit frequency is determined through risk assessment performed at each audit Various mechanisms used to ensure resolution of GMP issues is achieved Ongoing interaction and follow up is common Growing requirement for advice on post- market issues 8

9. GMP developments Now a PIC/s member ANZTPA B2B – B4 Information sharing Joint training Joint audits Future alignment of processes Closer relationship with TGA Application to EU in respect of API third country exemption status 9

10. ANZTPA Intention of both Governments to proceed with the establishment of a joint agency Key points – Joint Agency, new / updated legislation (especially for New Zealand) Work is underway on planning the establishment process Currently NZ and Australia are closely aligned with respect to Good Manufacturing Practice 10

11. Trans-Tasman GMP relationship Over 2 decades of cooperation Close GMP alignment Strong relationship build up to ANZTPA #1 Being a competent and credible small GMP regulator requires close relationships and cooperation with others Looking forward to a continuing and growing relationship 11

12. Release for supply in NZ - overview Legislative requirements Licensing of ‘sponsors’ Issues noted GMP / contractual arrangements Process 12

13. Legislative requirements Sale of a medicine Requirement to be licensed Section 42 – specifications and testing Sections 20 and 24 – product approval Recall and other market actions (regulation 50) 13

14. Licensing of sponsors Licence to Sell Medicines by Wholesale Audits carried out by Ministry of Health Monitoring of compliance through interactions during quality investigations / recalls 14

15. Issues noted Stock imported and distributed when not for the NZ market Failure to meet current approved specifications Off-shore actions creating liability in NZ Failure to understand responsibility Need to fully understand products, GMP / technical issues and legal issues 15

16. Contractual arrangements Distribution chain can be complex Need to ensure technical arrangements are met and responsibility clear Flexible – several models of operation accepted 16

17. Process summary A licensed NZ entity responsible for market release NZ approved product details are held Stock is received into quarantine C of A is received and compared with approved details Batch is identified and labelling is examined Release can be made 17

18. Communicating quality issues Responding to the regulator Responding to a market issue Dealing with issues successfully Response is important and determines the level of confidence a regulator can have in a manufacturer / sponsor 18

19. Responding to quality issues - when the regulator has questions Ensuring a clear line of communication between manufacturing site / NZ sponsor / Medsafe The NZ sponsor is legally responsible Rapid response is required – even if full answers may take time Risk assessment based on product knowledge – important Effective action in the distribution chain 19

20. Responding to market quality issues How is a quality complaint received? Who is involved in making early decisions? Ensure rapid risk assessment Systems should be integrated – production, marketing, distribution, clinical, QA How will decisions be made? 20

21. Regulatory expectations Medsafe has the expertise to understand your explanation We are looking for you to demonstrate competence in handling issues We look at what you send and assess it Important to be consistent Be honest Ensure all questions are answered 21

22. A good technical response There should be a clear description of the problem Describe the investigation so far Ensure clinical assessment is provided, if appropriate Distribution details are important Identify the possible manufacturing issues Be clear about testing performed / planned Provide rationale for possible explanations and for ruling out possibilities 22

23. Thank you Contact details: Medsafe website: www.medsafe.govt.nzwww.medsafe.govt.nz Email contacts for specific questions GMP: askmedsafe@moh.govt.nzaskmedsafe@moh.govt.nz Product Safety Team: recalls@moh.govt.nzrecalls@moh.govt.nz 23