Regulatory Open Forum

 View Only

  • 1.  Requirements for Absorbable Implants

    Posted 07-Apr-2016 09:31

    Hey everybody, I work for a medical device manufacturer and we are developing a new line of implants made out of a polymer that degrades hydrolytically.  Besides the standard biocompatibility and extractable tests, what type of degradation tests are required for release to market in the US and EU?  We are using the same material as one of our competitors and they are marketing a specific degradation time frame and even bone replacement of the implant.  However, we aren't currently planning on doing any laboratory/material analysis to prove that they are the same, so I'm thinking we don't really have much to stand on.  We also have previous analysis from the material supplier, but that is all on the base unsterile material.  Our molding and sterilization processes will affect the material to some degree, so how much can we leverage that data?  This is a new project for me, so any guidance or suggestions would be greatly appreciated.  Thanks!

    ------------------------------
    Paul Vagts
    Sarasota FL
    United States
    ------------------------------


  • 2.  RE: Requirements for Absorbable Implants

    Posted 08-Apr-2016 08:07

    Hi Paul

    Just a quick comment that it is best if after you do this competitive analysis (including literature review) and your own technical assessment of the product, you strongly consider doing a pre-submission to the FDA to discuss this and other pressing questions.

    For materials that degrade or polymerize in-situ, the biocompatibilty is anything but standard in FDA's eyes. In fact FDA statements on recognition of these ISO standards strongly recommend you contact them before doing biocomp so you don't waste time and money.

    Yes, the product you put into biocompatibilty testing should be representative of the final product and sterile if final will be sterile; representative means similar formulation and raw material source, manufacturing/processing steps, and sterilization method (e.g., gamma versus ETO) for example.

    Happy to take additional questions offline if you desire, but whatever path you choose wish you good luck on the project.

    Best regards,

    Ginger Cantor,  RAC
    Centaur Consulting LLC
    centaurconsultingllc@gmail.com

    I




    Original Message


  • 3.  RE: Requirements for Absorbable Implants

    Posted 08-Apr-2016 10:51

    I know of no premarket tests that are required by FDA. 

    FDA requires companies to follow design controls, including design verification and validation.  The requirements for verification and validation of a specific medical device are established by the product development team, based on the design specifications they have developed, the risk analysis they have conducted, and their technical knowledgeable applicable to the product (including clinical knowledge related to its intended use), rather than by regulatory agencies.

    Often a given internal team won't have all the technical expertise needed, but they will have ready access to the appropriate technical expertise externally (e.g., biocompatibility expertise).  Under both the QSR and ISO 13485, the provision of adequate resources is the responsibility of executive management.

    The product development team must then be able to present a compelling case to FDA as to why their verification and validation data are adequate to support the safety and effectiveness of the product for its intended use.

    ------------------------------
    Julie Omohundro, ex-RAC (US, EU), still an MBA
    Principal Consultant
    Class Three, LLC
    Durham, North Carolina, USA
    919-544-3366 (T)
    434-964-1614 (C)
    julie@class3devices.com

    Original Message


  • 4.  RE: Requirements for Absorbable Implants

    Posted 10-Apr-2016 21:09

    Paul, Sorry for the brief and nonspecific reply, but … plan on the whole 9 yards. It sounds like there are no short cuts here.

    Art

     




    Original Message


  • 5.  RE: Requirements for Absorbable Implants

    Posted 11-Apr-2016 13:19
    Edited by Kevin Randall 11-Apr-2016 13:22

    Paul,

    Remember the standard rule of thumb, especially with regards to the U.S. FDA:  Any performance claim made by the manufacturer must be substantiated by actual data.  This applies not only to dynamic performance claims such as degradation time and bone replacement, but also to comparative equivalence claims between the subject device and predicate.  Consequently, if a firm foregoes corresponding laboratory/material analysis aimed at a) objectively comparing the subject and predicate, and b) substantiating performance claims, then the firm would likely run into a series of costly regulatory roadblocks.

     

    To give you an idea of the kind of "ante" required to get into the game for this particular kind of device, here is an overview of some of the data I was required to have when achieving regulatory clearance/approvals and supporting dynamic performance claims on previous resorbable bone void filler projects:

     

    • Material Characterization Studies (Density, Porosity, Pore Interconnectivity, Elemental Analysis, Phase Purity, etc.)
    • Bench Performance Testing (Mechanical, Dissolution, etc.)
    • In Vivo Performance Testing in Animal Models (histo and CT studies to assess things like resorption, new bone formation, bone volume, graft volume, scaffold degradation, phagocytic activity, biomechanics, and others)
    • Shelf Life;
    • Package Integrity;
    • Transport and Storage Validation;
    • Biocompatibility Testing (Full formal "Biological Evaluation" plus cytotoxicity, sensitization, Intracutaneous Reactivity, Systemic toxicity, Genotoxicity, and Carcinogenicity and Reproductive Toxicity
    • Sterilization Validation

     

    This list is not exhaustive.  Moreover, some products will require additional types of studies, while others may require less.  But one thing is for certain (to echo Art's comment):  Resorbable bone void fillers are not good candidates for a plan that excludes laboratory/material analysis.  And to echo Ginger's comment: A pre-submission (U.S.) may be of value for your U.S. marketing plan.

     

    Finally, remember also that the fundamental intent of an FDA 510(k) is different than a European design dossier / CE Mark.  Specifically, a 510(k) is aimed at showing substantial equivalence between the subject device and predicate device.  In contrast, a European CE mark is based on demonstrating conformity with essential requirements for safety and effectiveness.  Therefore a European technical file / design dossier will be structured differently, and will have some different contents (but also many overlaps) when compared to a 510(k).

     

    Hope this helps,

    ------------------------------
    Kevin Randall RAC (U.S., Canada, Europe)
    Principal Consultant
    ComplianceAcuity, Inc.
    Golden CO
    United States

    Original Message