Molecular Diagnostics: The Shift to Complexity. Molecular Diagnostics Regulation: Where do we go from here? David W Feigal, Jr.

Transcription

1 Molecular Diagnostics: The Shift to Complexity Molecular Diagnostics Regulation: Where do we go from here? David W Feigal, Jr., MD MPH April 17, 2015

2 Oversight of In Vitro Diagnostics States Center for Devices and Radiological Health Medical Devices Health Professionals IRB s Health Facilities Clinical Laboratories Improvement Amendments (CLIA) Program

3 Is this an FDA regulated Device?

4 Is this an FDA regulated drug?

5 FDA Authority FDA Definition of a Device Instrument, apparatus, implement, machine, contrivance, implant, in Vitro reagent, or other similar or related article, including any component, part, or accessory, which is - intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or intended to affect the structure or any function of the body of man or other animals, and

6 CLIA Authorities Laboratory or clinical laboratory defined: As used in this section, the term laboratory or clinical laboratory means a facility for the biological, microbiological, serological, chemical, immuno-hematological, hematological, biophysical, cytological, pathological, or other examination of materials derived from the human body for the purpose of providing information for the diagnosis, prevention, or treatment of any disease or impairment of, or the assessment of the health of, human beings.

7 FDA and CLIA It isn t either / or In clinical medicine it is always both

8 Medical Device Approval Process

9 Historical Overview of Devices No FDA Authority No Pre-market Authority but could take action for devices on the market Some products reviewed as drugs : NDA-devices (sutures, implants ) Risk stratified requirements Premarket approval for some devices

10 Device Regulatory Path Class I Pre Amendment Marketed Devices Class II New Products: Risk-based Regulation Grandfathered No further review to stay on the market 1976 Class III Classified into risk groups by FDA and Advisory Committees

11 Device Regulation Class I & II Exempt Class I & II Non Exempt Class III Not Regulate d Regulator y Discretion LDTs Registe r & List MDR Informed Consent IDE (Sig Risk) (k) PMA ??? no no? Usually no

12 Investigational Use IDE* May be required for medical device clinical trials, usually for Class III products If the study presents non-significant risk then an FDA IDE application is not needed Whether IDE or not must follow Good Clinical Practices Protocol & record keeping Qualified investigators IRB approval Informed consent * Very similar requirements to an IND for Drugs or Biologics

13 Medical Device Quality Systems (QSR) Why approach medical devices differently than drugs and biologics? Do the CLIA standards replace QS?

14 CDRH and Standards Development Standards Recognition Process Candidate standards reviewed by multidisciplinary team; FR Notice published when standards are recognized Examples: ASTM F04.93: ISO/TC150/SC3/ISO FDIS 9713: Neurosurgical Implants - Self-Closing Intracranial Aneurysm Clips ANSI/AAMI/ISO TC 194, :1995: Biological Evaluation of Medical Devices - Part 6: Tests for Local Effects After Implantation (Reaffirmation, Revision or Withdrawl) IEC TC 62/SC 62A/: 62A/XXX/NP: New Work Item: Medical Device Software - Software Life Cycle Processes ASTM F04.21: Revision of F (2000) Standard Specification Wrought 18 Chromium-14 Nickel-2.5 Molybdenum Stainless Steel Surgical Fixation Wire (UNS S31673)(Main Committee Ballot F040101, Item#24)

15 How FDA has Dealt with New Technology 1902 Biologics Existing vaccine and toxin manufactures had to be licensed and inspected annually Nothing grandfathered Half of the companies shut down

16 How FDA has Dealt with New Technology 1906 Pure Food and Drugs Act Labels not misbranded, products not adulterated Nothing grandfathered Burden on FDA to prove violations

17 How FDA has Dealt with New Technology 1938 Food Drug & Cosmetic Act New Drug Applications Existing drugs grandfathered 1962 Kefauver Amendments New Drug Applications Pre-1938 Drugs grandfathered Tens of thousands drugs removed from the market through the DESI Review Process

18 Is this an FDA regulated drug?

19 How FDA has Dealt with New Technology 1969 Bactodisk Supreme Court Decision Finding: Diagnostics are Drugs FDA Responds by not requiring NDAs but with labeling standards 1976 Device Amendments Pre-1976 devices grandfathered Devices classified Call for PMAs for class III removes many products from the market

20 How FDA has Dealt with New Technology Voluntary Efforts that Failed: Meat packing inspectors Advertising standards Animal Research standards Clinical Research Standards Mamography Quality Postmarketing Study Comittments

21 IVD and Disease Linked Cycles CDC NIH IVD Manufacturers Research Labs Clinical Labs CDC WHO Public Health Networks FDA CLIA

22 Are LDT s all Potti Trained?

23 Diagnostics: Need to be Fit for Use Regulatory Requirements: (the consumer protections) Need to be Fit for Purpose

24 Personal Recommendations Risk Diagnostic Regulation Integrate CLIA standards with Quality Systems Standards based lab processes (CLIA) General purpose lab equipment (FDA) Good Clinical Practices / Recalls add to CLIA oversight Class III diagnostics Always regulated by FDA LDT or not Class II Diagnostics Novel: FDA regulated to set standards. Once standards set: 510(k) exempt Analytes standards needed