Advamed Calls CDRH ‘Inconsistent with ISO’ in New Guidance

By: Jim Dickinson

AdvaMed says that a CDRH draft guidance on using international standard ISO-10993 on biological evaluation of medical devices is inconsistent with agency acceptance of the principles in ISO-10993-1:2009. For example, Advamed says the draft guidance puts a strong emphasis on biological test selection, with minimal guidance on the earlier standard’s three-step process for biological evaluation.

According to AdvaMed, the draft guidance implies that FDA favors biological testing rather than using the principles established in ISO 10993-1:2009 to prompt necessary testing using a risk-based approach for evaluating biological safety of medical devices. “Ignoring such a fundamental change to a key international standard is a major oversight that needs to be addressed,” Advamed's statement says.

Comments from the 510(k) Coalition, a lobby group of medical device companies, say that in addressing biological evaluation of new medical devices, FDA must balance the need for appropriate biological evaluation to identify real life risks with the need for timely patient access to new medical devices. “An inappropriate standard has the real potential of slowing medical innovation, limiting patient access to better devices, and consuming valuable agency and industry resources,” AdvaMed says.

The coalition urges that FDA implement least burdensome principles, ensure that the draft guidance is not prematurely implemented, provide a logical implementation timeframe, ensure a reasonable probability of actual exposure before testing is required, ensure that one is not obligated to test materials already approved by FDA or routinely used in medical devices, revise the definition of “material” to make it consistent with general usage of the term, ensure that the agency maintains the 510(k) regulatory pathway, address risk/benefit questions, and link the document into the modifications requirements and guidances, among other things.

In separate comments on the draft, three experts from the ISO Technical Committee 194 that writes the ISO 10993 series of standards caution that the specific approach taken in the document “does not adequately capture the letter or the intent of the current versions of ISO 10993-1 and ISO 14971. Rather, the draft guidance continues and in some ways extends the earlier approaches … where there is undue emphasis on adherence to a predetermined list of tests to be carried out, and insufficient attention to rigorous expert evaluation of biological risks and focus on the significant risks identified in a risk management-based evaluation.”

In its comments to the docket, the Medical Device Manufacturers Association (MDMA) voices support for the comments from the 510(k) Coalition and reiterates several of its key concepts.

Merck recommends that FDA strengthen the draft guidance by including specific recommendations for scenarios where chronic in vivo testing may be considered to clarify the likely length of testing as it relates to device contact duration.

Roche says the guidance appears to focus mainly on requirements for additional in vivo studies beyond those proposed by ISO 10993-1 and it might be better to focus on studies that may be eliminated from the testing program consistent with industry efforts to reduce animal use.

Johnson & Johnson says it generally agrees with the draft guidance and believes some areas of it would benefit from more complete harmonization with ISO 10993-1 and the entire ISO 10993 series of standards. It also voices support for the comments from AdvaMed and the 510(k) Coalition.

Finally, People for the Ethical Treatment of Animals says the draft guidance fails to incorporate support for use of non-animal methods and other refinements in many of its recommendations. It says,“We urge FDA to strengthen its stance on use of non-animal methods and other humane practices in the final guidance document so as to reduce confusion in industry regarding FDA’s acceptance of procedures that replace the use of animals in procedures, lessen the pain and suffering they endure, or reduce the number of animals required.”