Part15PublicHearingFDARegulationofCombinationProductsNov

1、Part 15 Public Hearing FDA Regulation of Combination ProductsNovember 25, 2002Rockville, MDMichael Gross, Ph.D., RACVice-President Worldwide ComplianceAventis BehringKing of Prussia, PAmichael.grossPERSONAL EXPERIENCEInhalation device 510(k)Passive transdermal patches ANDAMedicated tooth paste INDIo

2、ntophoretic drug delivery systems RFD, IND, 510(k)NDAPrefillable syringes DMFPens, liquid- and liquid-dry RFD, 510(k), MAF Autoinjector RFD, 510(k)Nasal delivery syringe BMF Diluent syringes RFD, 510(k)Flush syringes 510(k)Disposable syringes, needles 510(k)Surgical kits NDA, 510(k)Surgical scrubs N

3、DAInfusion Pumps 510(k)Jet and powder injectors 510(k)Inhalation delivery systems 510(k)-NDADOWNSTREAM ISSUESUser Fees PDUFA, MDUFMA Quality Systems: 21CFR 210, 211, 820Manufacturing/Design Changes: 21CFR 314.70, 601.12, 807.81 814.39Adverse Events/Experiences: 21CFR 314.80, 600.8, 803Toxicology/Bio

4、compatibility: 21CFR 312.23, ISO-10993-Orphan Drug/Humanitarian Device: 21CFR316, 814.100Applications: 21CFR 312, 314, 600, 807.81 812, 8141. What guiding principles should be used when revising the existing Inter-center Agreements?Guidance level documents, subject to comment periodConsistent format

5、, clear language and content; examplesDistinguish between combination products (Combination Products Office) and products of unclear designation (Product Jurisdiction Office)For a combination product do not say, “its a drug” or “its a device”, or “its regulated as a ” ;these statements pertain to a

6、product of unclear designation.Address only jurisdiction and application of investigational exemptions and pre-market regulatory authorities; address “downstream issues” in separate guidance(s)Describe and diagram designation and dispute resolution processesReaffirm that reviews are consultative and

7、 not collaborativeVirtual Combination Products are created only when brand names are specified and labeling is mutually conforming2. What factors should be considered in determining primary mode of action?Primary Jurisdiction established according to primary mode of actionIn special cases where the

8、effects are synergistic or mechanism is unclear also consider :RiskToxic or adverse mode of action Intended use Center capability to assess safety and effectivenessMust have foundation in FD&CA, fit drug or device definitionsDescribe/diagram determination/dispute resolution processes in Inter-center

9、 Agreement rewrites3. Is one pre-market review (notification) mechanism more suitable than another?Is it appropriate to regulate combination products under 510(k)?Can there be “substantial equivalence” for a combination product?Should a consistent level of regulatory approval be applied to all compo

10、nents i.e., 510(k) is not pre-market approval? Consider a new (unique) application (CPAA) for combination products? This would require legislation. 4. What criteria should be used in determining if single or multiple applications are necessary? Should the need to use a mixed regulatory approach infl

11、uence this?5., 6. What principles should be followed in determining the quality system and adverse event reporting requirements for a combination product?Each Guidance should include descriptions/diagrams of determination/dispute resolution processes.Guidance should be predictable and consistent on

12、application formatting (e.g., single application, imbedded pull-out, linked or stand-alone). For quality systems, design control may be useful for managing combination products; perhaps design reviews throughout development and post-marketing should be required for all combination products, as it wi

13、ll help to identify and manage interactions between the components. For adverse events:Reports should be sent to both Centers indicating the report is for a combination productFDA must sort out duplicate reporting 7. Other comments?Virtual Combination Products are created only when brand names are specified and labeling is mutually conformingCertain combination product examples cited in the CDER-CDRH Inter-center Agreement (which are not composed of finished medical devices) should be recon