Applying Pharmaceutical QbD concepts to Medical Device Stability Studies

Transcription

1 Applying Pharmaceutical QbD concepts to Medical Device Stability Studies Laure L. Larkin M.Sci., CPP Manager Package Qualification Management

2 MEDICAL DEVICE RELEASE CRITERIA Medical device regulations relating to stability, both in the US and ous, are concerned with design review. The short list for Design Review: Quality Systems Requirements ISO Requirements ISO 9000 Requirements 2

3 US MEDICAL DEVICE REGULATIONS FDA - QSR 21 CFR Subpart K--Labeling and Packaging Control Sec Device labeling. Each manufacturer shall establish and maintain procedures to control labeling activities. (a) Label integrity. Labels shall be printed and applied so as to remain legible and affixed during the customary conditions of processing, storage, handling, distribution, and where appropriate use. Sec Device packaging. Each manufacturer shall ensure that device packaging and shipping containers are designed and constructed to protect the device from alteration or damage during the customary conditions of processing, storage, handling, and distribution. 3

4 ous MEDICAL DEVICE REGULATIONS ISO 13485:2003(E) Preservation of product The organization shall establish documented procedures or documented work instructions for preserving the conformity of product during internal processing and delivery to the intended destination. This preservation shall include identification, handling, packaging, storage and protection. Preservation shall also apply to the constituent parts of a product. 4

5 US & ous CONSENSUS STANDARDS ISO :2006(E) 6.4 Stability testing Stability testing shall demonstrate that the sterile barrier system maintains integrity over time Stability testing shall be performed using real-time aging Stability testing, using accelerated aging protocols, shall be regarded as sufficient evidence for claimed expiry dates until data from real-time aging studies are available. 5

6 US & ous CONSENSUS STANDARDS ISO :2006(E) 6.4 Stability testing continued Real-time and accelerated aging tests should begin simultaneously When expiry dates are based upon product performance, stability testing for expiry dating should be conducted along with package stability testing. 6

7 When Do We Start Evaluating a Device for Stability Testing? Testing strategies should be identified while the project is still in the concept stage. Waiting can be catastrophic to timelines. All sterile parts! Non-sterile items? For example batteries and oils experience performance degradation over time What about raw materials, manufacturing materials, components? (ex. HDPE granules, sterile gloves, temperature indicating labels) 7

8 How Do We Decide What To Do For Device Stability Testing? Strategic Testing Early Risk Assessments Stability Families QbD Concepts Forced Degradation Studies Understand The Product Understand The Risks 8

9 Quality by Design (QbD) The foundation of Quality by Design is to establish process understanding and link it to product reproducibility. How do we apply this to Medical Devices? 9

10 How Does QbD Fit into the Stability Validation? Plant Operations 10

11 DEFINE What are the unknowns? Chemical Degradation Physical Degradation Microbial Degradation Therapeutic Degradation Toxicological Degradation We must understand the risks! What is the desired design space? 11

12 DESIGN What is the product quality profile? What are the Critical Material & Quality Attributes (CMA s & CQA s)? How do we prevent? Chemical Degradation Physical Degradation Microbial Degradation Therapeutic Degradation Toxicological Degradation 12

13 Forced Degradation / Stress Testing Borrow tool from Pharmaceuticals to apply to Devices Forced decomposition using extreme conditions Temperature heat freeze/thaw Chemical ph high oxygen tension hydrogen peroxide oxidation ozone oxidation Sterilization Methods Humidity 13

14 CONTROL Is a well controlled or understood production process required? What are the Critical Process Parameters (CPP s)? Equipment Requirements Process Requirements Environmental Requirements 14

15 IDENTIFY Determine what to control (worst cases) in the protocol? Product related Process/equipment related Environmental related Package related Distribution/storage related 15

16 A design window large enough to fly a Pterodactyl through! Checklists Up front testing Forced Degradation Studies Lots of well characterized: Materials Processes Packages Defendable sampling and testing plan during stability protocol NLT 95% Confidence & 95% Probability 16

17 CMA/CPP/CQA in medical devices Risk Tables Tiered risk assessment approach Raw Materials Equipment/Processes Distribution/Storage Patient Impact 17

18 Known Unknowns? 18

19 How to Identify Unknowns Develop a checklist based on FDA CDRH device guidance 19

20 Use Information From Other Sources The article includes a nice set of references! 20

21 Understanding Risk! Which activity has a higher risk? Conducting full scale stability testing Expensive Resource intensive Possible late stage failures Missed launch dates Approving a Stability Adoption Cheap Fast Failure is not an option Launch date is a slam dunk! HC SVNT DRACONES 21

22 Risk vs. Gambling Deciding to limit stability testing when Data on sample/testing cost is available Data on environmental sensitivities is limited Data on production processes is limited Data on test methods is limited Data on interactions is limited Data on materials is limited Scientist/Engineer Opinion = Bet the farm on Red 7 L. Larkin 09/25/12 DJ10105 Rev A 22

23 Resisting the pressure to gamble High cost of samples and testing Long duration Complexity of the testing Lack of onsite testing facilities and expertise C-Suite psychology Overconfidence is a powerful source of illusions, primarily determined by the quality and coherence of the story that you can construct, not by its validity. If people can construct a simple and coherent story, they will feel confident regardless of how well grounded it is in reality. McKinsey Quarterly

24 It is imperative that we understand our products If it is not our companies knowledge (IP) it will eventually be some ones: Patients Doctors Competitors Regulating Agencies News Agencies Lawyers 24

25 Final Message? It is our responsibility to make sure we don t misunderstand our medical device stability risk! 25

26 THANK YOU FOR YOUR ATTENTION Thanks to my team! Matt Zagorski Lynne Fulton L. Larkin 03/04/14 DJ13174 Rev A