Pre-Clinical Testing for Devices and Diagnostics

Transcription

1 Pre-Clinical Testing for Devices and Diagnostics Larry O. Blankenship Evergreen Research, Inc. April,

2 Many Levels, Many Approaches The requirements differ dramatically by class and category and specific application Start by finding out: Is it a medical device/diagnostic? What are the risks? What s the classification/approval path? THEN Appropriate preclinical testing can be selected April,

3 Is it a medical device? What is the intended use? What is the impact on the user/patient? What are the claims? April,

4 Is it a Medical Device/Diagnostic? "an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is: recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them, 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 which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its primary intended purposes. From: US Federal Food Drug & Cosmetic (FD&C), Section 201(h) April,

5 Is it a medical device? What is the intended use? What is the impact on the user/patient? What are the claims? Examples: Bathroom scale versus ICU scale Laptop PC Apps for smart phones classifies most everything April,

6 What s the clinical involvement? Does it touch the patient? Where? For how long? In what way? Is it used with multiple patients? Is it used to apply therapy? Is it used to make patient care decisions? April,

7 What are the risks? What happens if it doesn t work correctly? What happens if it isn t used correctly? What happens if it s built from the wrong materials? April,

8 Regs related to Pre-Clinical Testing QSR: 21CFR820 the Quality System Regulation Design Controls GMPs: Good Manufacturing Practices GLPs: Good Laboratory Practices GCPs: Good Clinical Practices ISO 13485: European QSRs/Design Controls/GMPs ISO 14971: Risk Management (FTA, FMEA, etc.) ISO 17025: European GLPs ISO 14155: European GCPs April,

9 What s the classification/approval path? (determines amount & type of testing via Design Controls) Class 1 (exempt): GMPs only, no design controls Registration/listing only, no filing Class 1 (non-exempt): Full QSR, incl. design controls Registration/listing, typically no filing Class 2 (no clinical): Full QSR, incl. design controls 510(k) filing with pre-clinical testing Class 2 (with clinical): Full QSR, incl. design controls 510(k) with pre-clinical and clinical results Class 3: Full QSR (with clinical), incl. design controls PMA with pre-clinical and clinical test results April,

10 Design Controls and V&V Requirements Document(s) Hazard/Risk Assessment(s) (ISO 14971) Trace Matrix Trace Matrix Does it meet spec? Drawings, Specs, Mfg. Instructions, Device Master Record Prototypes Products Does it work? (i.e., is it Safe and Effective? ) April, Diagram from: FDA Design Control Guidance For Medical Device Manufacturers

11 Verification: Pre-Clinical Testing Guided by the Design Input Testing the Design Output (in final product form) Examples: Function: Does the IV pump deliver 0.1 to 999 ml/hr? Safety: Does detect air in the line, stop & alarm? What about testing during development not on final products, but prototypes? Important to the Design Process, but not Verification April,

12 Biocompatibility & Sterility Examples of special testing requirements for representative finished products/components only Biocompatibility (ISO 10993, FDA G95) Must be tested on processed materials (final parts/products) Sterility Depends on type (ISO and FDA guidelines for each) Terminal sterilization or resterilizable? Steam (aka Autoclave) Ethylene Oxide Radiation (gamma or e-beam) Chemical (glutaraldehyde, hydrogen peroxide, etc.) The sterilization PROCESS must be verified / validated April,

13 April,

14 Validation: Pre-Clinical Guided by the Functional/User Requirements Testing the Product (in final product form) Examples: User training & interface testing (with clinicians) Can be in a laboratory or simulated use environment Includes GUI testing (Graphic User Interface, touch screen) In vitro validation (i.e., lab testing safety/effectiveness) Example: Diagnostic tests on extracted tissue/serum samples In vitro tissue testing (e.g., laser tissue cutting) In vivo testing (e.g., animal lab testing) Note: Must be GLP to be acceptable for FDA submittal April,

15 Documenting the Results The Design History File (DHF) A key requirement of Design Controls A repository of documentation for the design process Contains all design input, output, hazard & risk assessments (incl. FTAs and FMEAs), design reviews, test protocols, test reports, analyses of test reports, conclusions, actions and closure of action items. Key DHF sections (e.g., pre-clinical protocols/reports) will be part of regulatory approval submittals (e.g., 510(k), IDE, PMA) April,

16 How do I know what s needed? Check FDA Guidelines and recognized standards Examples: Heart valves: ISO FDA guideline Ultrasonic imaging: Multiple guidelines & standards A guideline may allow an abbreviated 510(k) Ask the FDA or an EU Notified Body Call DICE (Division of Industry & Consumer Education) Request a pre-submittal review Notified bodies for medical devices (examples): BSI (British Standards Institute) DEKRA (The Netherlands) TUV (Germany) NSAI (National Standards Authority of Ireland) April,

17 PLAN AHEAD!! The Most Important Step The information is available from many sources Expert consultants are available to help guide you Qualified test labs and agencies abound Failing plan to is truly planning to fail! The unacceptable situation: After years of work and millions of dollars, to be told by the FDA you need to do or re-do a test that will now delay you by months or years that could have been done in advance. April,

18 Fear not Seem daunting? Not if you plan ahead. Success, not the devil is in the details. Thank You! If I can help, let me know! Larry O. Blankenship lblankenship@evergreenresearch.com April,