Stability and Shelf Life of Combination Products. John McMichael FDA/CDRH

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1 Stability and Shelf Life of Combination Products John McMichael FDA/CDRH

2 Combination Products Regulations under 21 CFR 4.4(b) provides that combination product manufacturers may meet the requirements of both the drug CGMPs and device QS regulation by designing and implementing a CGMP operating system that demonstrates compliance. 2

3 Device Terminology FDA Guidance Shelf Life for Medical Device Shelf life is the term or period during which a commodity remains suitable for the intended use. An expiration date is the termination of shelf life, after which a percentage of the commodity, e.g., medical devices, may no longer function as intended. 3

4 Drug Product Terminology The United States Pharmacopoeia (USP) Stability: "the extent to which a product retains, within specified limits, and throughout its period of storage and use (i.e., its shelf life), the same properties and characteristics that it possessed at the time of manufacture. 4

5 Relevant Regulations Drug Product 21 CFR , Stability testing 21 CFR , Expiration dating Device Quality Systems 21 CFR (a) (h) 5

6 Stability Testing (a) There shall be a written testing program designed to assess the stability characteristics of drug products. The results of such stability testing shall be used in determining appropriate storage conditions and expiration dates. The written program shall be followed and shall include: (1) Sample size and test intervals based on statistical criteria for each attribute examined to assure valid estimates of stability; (2) Storage conditions for samples retained for testing; (3) Reliable, meaningful, and specific test methods; (4) Testing of the drug product in the same container-closure system as that in which the drug product is marketed; (5) Testing of drug products for reconstitution at the time of dispensing (as directed in the labeling) as well as after they are reconstituted. 6

7 Stability Testing (b) An adequate number of batches of each drug product shall be tested to determine an appropriate expiration date and a record of such data shall be maintained. Accelerated studies, combined with basic stability information on the components, drug products, and container-closure system, may be used to support tentative expiration dates provided full shelf life studies are not available and are being conducted. Where data from accelerated studies are used to project a tentative expiration date that is beyond a date supported by actual shelf life studies, there must be stability studies conducted, including drug product testing at appropriate intervals, until the tentative expiration date is verified or the appropriate expiration date determined. 7

8 Recommended Testing Combined Stability Device Essential Performance Requirements Drug Product Specifications Preconditioning Real Time vs Accelerated Aging Component vs Final Finished In-Use Time Implicit vs Explicit Testing 8

9 Use Life vs Shelf Life Other Considerations Reusable devices Establishing shelf life does not include life-cycle testing Exhaustive preconditioning Worst case use scenario/environments Label and performance requirements should be indicative of both (e.g. reusable devices) 9

10 References FDA Guidance Q1A(R2) Stability Testing of New Drug Substances and Products Shelf Life of Medical Devices cgmp Requirements for Combination Products ectd Technical Conformance Guidance Device Specific Guidance (Pen Injector, Infusion Pump, Nasal Spray, etc.) USP <1191>, Stability Considerations in Dispensing Practice <1150>, Pharmaceutical Stability 10

11 Thank You! Contacting the General Hospital Devices Branch (ODE/DAGRID/GHDB) Contacting the Office of Combination Products (OCP) (Tel) 11

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