Technical and Regulatory Forum & Update

1. Technical and Regulatory Forum & Update 26th February 2010

2. Agenda • IVD Australia Update • General Government and Regulatory activities • Update on Medical Device Regulations • Amended to include IVDs • IVD Australia – TGA Working Group • Ongoing negotiations

3. IVD Australia – 9 months on! Now have 41 Members with at least 3 more to join Still 45 possible companies that could join Strong financial basis Represent over $750 million and 2000 employees Supply well over 90% of all IVDs in Australia By far best represented of all Industry associations at TICC

4. Committees/Forums TGA TGA-Industry Consultative Committee (TICC) & Medical Device Bilateral Policy and Financial Input Technical and Regulatory Consultative Forum Operational Input GHTF AQIS Standards Australia / NATA NEHTA /GS1

5. Government/TGA Issues TGA Budget “agreed” last week 2.4% ATB for Medical Devices!!! NO way of determining IVD over-recovery Meeting with Parliamentary Secretary IVD Australia TGA IVD Regulations Pathology Review Codes of Conduct Set of “essential principles” for the Sector but maybe independent Codes Possible common complaints mechanisms What about non-members??

6. Pathology Review Announced late December IVD Australia included on Consultative Committee Not yet met – perhaps late March Discussion Paper released in early January 1st Submission due 30th April (for now) Discussions held with AAPP / RCPA / AACB/ NCOPP Setting up an ad-hoc Committee to draft IVD response Draft by 15th April Review by Board

7. AQIS • IVD Australia invited to join BCC • IVD applications represent nearly 50% of all AQIS Permits • AQIS restructuring (again) so that Biosecurity is part of Biologicals Branch along with Branches • New E-permit application may speed up Permit issuance • Next Meeting – 25th March

8. GHTF SG1 IVD Subgroup • Meeting Dates: • 23rd -26th March 2010 Washington, DC • 7th -10th June 2010 Sydney, NSW • Guidance Documents • Clinical Evidence • Draft document in final stages • To be released for comment in 1st half of 2010 • STED (Summary Technical Documentation) • Comments sent to GHTF by 7 January 2010 deadline • To be reviewed at next meetings

9. TGA/Industry Regulatory & Technical Consultative Forum • Purpose • resolve regulatory issues on medical devices at an operational level • Members • TGA, MTAA, AusBiotech, Dental Industry, IVD Australia • IVD Australia has one representative • Will be increased to two when Regulations implemented for IVDs • Items discussed (example) • Labelling - Provision of Sponsor Information (Regulation 10.2) • Guidance document on ‘substantial change’ • Industry training • Annual ‘Sponsor Obligation’ day (initially for Medical Devices) • Initial Training for IVD industry will be separate.

10. Update on Medical Device Regulations (amended for IVDs) • Regulations went before Executive Council on 25th Feb • Will be tabled in parliament for 15 sitting days • Implementation date is 1st July 2010 • Amendments to current regulations will be available ASAP • http://www.comlaw.gov.au/ or access via TGA website • GMDN Codes • Collective Terms available • CT712 ABO and Rh (D)-typed reagent red cell IVDs • CT867 Drugs of abuse IVDs • CT936 Specimen receptacle IVDs • Preferred Terms being created now • At least 4000 of 12000 to date • http://www.gmdnagency.com/?id=colter • GMDN license needed to access preferred terms

11. Update on Medical Device Regulations (amended for IVDs) TGA eBS Amendments/Improvements related to Medical Devices will go forward in March New IVD functionality will be ‘switched off’ until July IVD Training environment will be created for industry training in June Pre-implementation testing may be conducted Selected Industry representatives will be invited to participate GMDN terms will be included and can be accessed through eBS Timeframe unknown

12. Training for IVD Industry Co-sponsored by TGA and IVD Australia Full Day Information Sessions Overview of Regulations plus practical examples Venues to be confirmed Brisbane – Tues 20th April Sydney – Wed 21st April Melbourne – Thurs 22nd April Half Day Hands-on (eBS) Training 12-15 people per session Questions plus eBS TGA Canberra Mid – Late June (exact dates to be confirmed)

13. TGA – IVD Australia Working Group • Technical and Regulatory Subcommittee have spent the last 12 months negotiating with TGA on the details of the new regulations • Specifically: • TGA Acceptable ISO 13485 certificates • TGA Acceptable Evidence of Conformity • Number and content of Technical File Reviews • Interpretation of Classification Rules • Business Rules for Reduced Fees • Immunohaematology Issues • Development of GMDN terms

14. Two Major Issues • TGA Acceptable ISO 13485 Certificates • TGA were originally only going to accept ISO 13485 certificates issued by European Notified Bodies • TGA Acceptable Manufacturers Evidence of Conformity Assessment for Class 3 products

15. Conformity Assessment

16. Conformity Assessment • Conformity Assessment – assessment, possibly independent, of conformity to defined requirements • In this presentation we are referring to conformance with Australian MD Regulations (as modified for IVDs) • Manufacturers Evidence: • “Manufacturers Evidence of Conformity Assessment” • E.g, TGA Conformity Assessment Certificate • ISO 13485 certificate: • Is not evidence of Conformity with the Regulations • It is evidence of Conformity with the ISO 13485 Standard

17. Conformity Assessment Procedures • Obligations on the manufacturer of IVDs • A set of requirements that the manufacturer must apply to an IVD. • Requirements for class 2, 3 and 4 IVDs include assessment of the Quality Management System (QMS) by the TGA • For class 3 and 4 IVDs: • TGA must review the technical documentation • TGA issues a Conformity Assessment Certificate BUT • Regulations make provision for the TGA to accept evidence that the assessment has been carried out by a body with the competence and authority to do so • for overseas manufacturers only • E.g., European IVDD Notified Bodies are considered competent • IVDD NB issues a Conformity Assessment Certificate

18. Conformity Assessment Routes • Procedures applicable to IVDs • Part 1 Full Quality Assurance Procedures • Includes processes for design and production • Part 1.6 Examination of Design – only for Class 4 • Equivalent to EU IVDD Annex IV • Part 2 Type Examination Procedures • Equivalent to EU IVDD Annex V • Part 4 Production Quality Assurance procedures • Excludes processes for design • Equivalent to EU IVDD Annex VII • Part 6 Self-Declaration • Equivalent to EU IVDD Annex III

19. Conformity Assessment Procedures • Requirements relate to: • Use of a Quality Management System for manufacturing medical devices • Demonstrating compliance of medical devices to Essential Principles • Manufacturer’s Declaration of Conformity • To Australian Requirements • Notify the TGA of changes to QMS (including scope) • Post market monitoring of devices • Keeping records

20. Evidence of conformity Assessment • Quality Management System (QMS) • ISO 13485 certification • With design – meets QMS requirements of Part 1 (Annex IV) • Without design – meets QMS requirements of Part 4 (Annex VII) • QMS & Essential Principles (Product Requirements) • TGA Conformity Assessment Certificate, or • EU IVDD Conformity Assessment Certificate • Canadian Product License + CMDCAS ISO 13485 • Require ISO 13485 compliance (or equivalent) • Include IVD Performance Requirements

21. TGA AcceptableISO 13485 certificates

22. ISO 13485 Certificates issued by: Certification arm of an IVDD Notified Body To find current NBs look under the IVDD on: http://ec.europa.eu/enterprise/newapproach/nando/index.cfm?fuseaction=directive.main Canadian CMDCAS accredited Registrar Look for the CMDCAS logo on the certificate Certification Body accredited by an IAF member IAF member must be a signatory to the Multilateral Recognition Arrangement (MLA) To find current signatories: http://www.iaf.nu/ Note: Ensure scope of certificate is appropriate All Product families covered All aspects covered, eg design, production etc TGA Acceptable ISO 13485 certificates

23. TGA AcceptableEvidence of Conformity Assessment

24. Minimum TGA Acceptable Manufacturers Evidence of Conformity by Class • Class 1 (self-declared) • Declaration of Conformity (DoC) to the Regulations • Class 2 • ISO 13485 Certificate and a DoC (to be held by manufacturer) • Class 4 • TGA Conformity Assessment Certificate (as agreed)

25. Class 3 Acceptable Evidence • TGA Conformity Assessment Certificate, or • 98/79/EC IVDD Certificate, or • Canadian Class 3 license + CMDCAS ISO 13485 Certificate AND • Declaration of Conformity (DoC) • submitted to TGA at time of Application OR • ISO 13485 Certificate AND DoC (submitted to TGA) AND Technical File Review

26. IVDD 98/79/EC Certificate • Scope is: • Conformity Assessment Route • E.g., Annex IV Full Quality Assurance Procedures • Products listed on the certificate • Only these products are covered

27. Canadian Class 3 License • Scope • Covers only one product as listed on the license • Note: Assays may not be the same class in Canada • A class 2 license cannot be used for an Australian Class 3 product

28. Inclusion on the ARTG(using TGA eBS program) • Two step process • Three step process for Class 4 products and Australian Manufacturers • Step 0: Apply for TGA Conformity Assessment • Only mandatory for Class 4 products and Australian manufacturers • Step 1: Submit Manufacturers Evidence of Conformity • Step 2: Apply for Inclusion of group of products on the ARTG

29. Proposed TGA Acceptable Evidence for Class 3

30. Technical File Reviews (Application Audits)

31. Mandatory Technical File Review (TFR) IVDs that will have mandatory technical file review (as defined in regulations) (Sponsor pays for mandatory review): IVDs for home use IVDs for PoC use IVDs for sexually transmitted infections Assays for genotyping and viral load testing for Hepatitis/Retrovirus Non-assay specific controls used for Class 4 IVDs National screening program assays Assays reimbursed on PBS (government rebate) Assays that do not have acceptable manufacturers evidence of conformity assessment Mandatory TFR is unrelated to Class

32. Mandatory Technical File Review (TFR) IVDs that will have mandatory technical file review (as defined in regulations) (Sponsor pays for mandatory review): IVDs for home use IVDs for PoC use IVDs for sexually transmitted infections Assays for genotyping and viral load testing for Hepatitis/Retrovirus Non-assay specific controls used for Class 4 IVDs National screening program assays Assays reimbursed on PBS (government rebate) Assays that do not have acceptable manufacturers evidence of conformity assessment Mandatory TFR is unrelated to Class

33. Mandatory Technical File Review (TFR) • A Product or Group of Products will require a Technical File Review by TGA if adequate evidence of Conformity Assessment is not provided • A Single Audit Fee will apply per Application for Inclusion • $5290 + 2.4%!!! • No limit to the number of TFRs per inclusion • Case-by-case basis • Sponsor will need to provide details of assays in application so TGA can choose products for TFR • Sponsor may supply details by providing Instructions for Use • Criteria for selection (not exclusive): • Different Technologies, e.g., Immuno v NAT

34. Mandatory Technical File ReviewOutstanding Issue Addition of a new product to an existing ARTG Inclusion No requirement to notify TGA for Medical Devices In early 2009, IVD Australia agreed to submit a Variation to the Inclusion for assays requiring mandatory TFR e.g., HIV-1 viral load assays Prior to addition of final mandatory TFR category IVD Australia is negotiating to ensure that new assays covered by an existing inclusion do not require a variation to the ARTG entry

35. Technical Files/Design Dossiers • Summary Technical Document (STED) • Requirements aligned with GHTF guidance document • http://www.ghtf.org/sg1/sg1-proposed.html • Presentation by TGA on requirements • http://www.tga.gov.au/ivd/prescurrent.htm

37. Technical Files/Design Dossiers Key Points: There will be a standard format for the STED Non-mandatory initially BUT Technical File must be cross-referenced or well-indexed to the specific STED Headings Specific contents of STED: Technical File – Design/Manuf and Valid/Verif will not be required Design Dossier – is an expanded STED Essential Principle checklist to be submitted also Raw/Line data – TGA wants ‘Line data’

38. Business Rulesreduced regulatory fees for in vitrodiagnostic medical devices (IVDs) • Relate to reduction in assessment fees • No reductions in application fees • Assessment types • Conformity assessment, Design Dossier, Application audits (technical file review), surveillance audits • Basis for abridged fees • Relies on submission of acceptable supporting evidence that reduces the degree of review and assessment by the TGA • E.g., Audit reports from recent TGA GMP audit, European Notified Body audit or Canadian Registrar audit, Design Dossier review by overseas regulator, acceptable local data to reduce performance testing • Similarity in Technical Files/Design Dossiers between applications • Needs to allow for concordant assessment

39. Business Rulesreduced regulatory fees for in vitrodiagnostic medical devices (IVDs)cont. Recent amendments to the Business Rules An additional Rule has been included to cover a single assessment fee per application for inclusion even if multiple Technical File Reviews are done Amended to include acceptance of Canadian Regulatory approval to support applications 3-Tier fee structure for Design Review of Class 4 products already sold on the Australian market Further amendment Allowance for submission of FDA PMA summary report and approval letter for the purposes of a Class 3 TFR Reduced fee - $3010 – equivalent to Medical Device Level 1 Application Audit

40. TGA Tender Tender for Entities to Perform Technical Reviews on behalf of TGA Tender covers assessment of Technical Information for all classes of IVDs. Desk top review and performance evaluation are open at this time including HIV/HepC evaluation even though a contract exists EOIs for both physical review and document review of products were received in late 2009 A select Tender has now been sent out to EOI responders and some groups who were not informed of EOI. Industry concerned over potential confidentiality issues and bias of assessing organisations. TGA indicated they will have tight confidentiality agreements. Tender closes End of Feb 2010

41. Immunohaematology • TGA presentation on Immunohaematology • Dec 2009 • http://www.tga.gov.au/ivd/prescurrent.htm

42. Immunohaematology Summary of Presentation and Discussions: Only ABO, Rh, Duffy, Kidd will be Class 4. All others - Class 3 6 x Level 2 Collective Terms only Maximum 4 x Class 4 groups Maximum 5 x Class 3 groups Potentially 1 x class 2 group (controls) TGA to confirm that non-assay specific IH controls will be Class 2 Class 4 Design Dossiers: 1 x $12 000 (full fee) plus up to 3 @ reduced fee of $5 330 as long as similar technology IH groups – to be entered on to ARTG as L2 Collective Term TGA want each Unique Product Identifier (UPI) under the grouping.

43. Industry Wins • ISO 13485 certificates • acceptance of the majority of certificates • Acceptance of Health Canada as a Competent Body • Canadian certification and product licenses • Single Application Assessment (TFR) fee • Regardless of number of TFRs per application for inclusion • Acceptance of FDA PMA documentation and approval letter for Class 3 TFR

44. Next Steps • Training • Technical Files • Guidance Documents

45. Questions/Comments??