Results of animal studies are frequently used by both plaintiffs and defendants in medical device litigation. Each side uses studies to support certain themes or to refute the strength or validity of the opposing side’s studies. Because animal studies can provide key evidence of the safety and efficacy of the devices at issue, adherence to regulatory and industry standards and recommendations can be beneficial.
On October 14, 2015, the FDA issued a draft guidance document titled “General Considerations for Animal Studies for Medical Devices: Draft Guidance for Industry and Food and Drug Administration Staff.” If the guidance document becomes final, it will supersede the July 29, 2010, guidance titled “Guidance for Industry and FDA Staff: General Considerations for Animal Studies for Cardiovascular Devices.”
In the draft guidance, the FDA expands the scope beyond prior guidance documents and makes a couple of “strong” recommendations to the device industry about animal testing. Because the FDA must think simple “recommendations” might be ignored, twice in the draft guidance the FDA “strongly recommends” certain actions. First, the FDA “strongly recommends” that members of industry “work with a pathology expert such as a veterinarian boarded by the American College of Veterinary Pathology to develop the study protocol.” Later, the FDA “strongly recommends” that submitting parties “conduct definitive animal studies on the market ready device except as required to scale, if needed, to implant in the animal model.”
This second “strong recommendation” is part of a theme repeated in the draft document. In the draft document, the FDA emphasizes that submitting parties should use the “market ready device” (mentioned twice) or the “final clinical design” (used twice in the same paragraph) or the “final design” (used in bold type in Appendix B: Sample Decision Tree for Medical Device Animal Studies question 2). So, not only has the Agency made it a “strong recommendation,” it has also emphasized the strength of the recommendation by repeating it in the document and placing it in boldfaced print.
This is not exactly a new recommendation, but in the existing guidance on cardiovascular devices, the Agency used that concept only once – in Appendix B: Sample Decision Tree for Animal Studies in the Cardiovascular System using the phrase “final design iteration.”
This draft guidance also reflects a broadening of the applicability of the FDA’s recommendations for animal studies involving medical devices. As the title for the July 29, 2010 guidance suggests, it is limited to animal studies involving “devices intended for use in the human cardiovascular system.”
The new draft guidance document is not limited to cardiovascular devices. Rather, FDA intends the new guidance to apply to all “medical devices intended for use in humans, as defined in section 201(h) of the Federal Food, Drug and Cosmetics Act (FD&C Act).” The new guidance will “apply to animal studies submitted in support of an IDE application, premarket approval (PMA) application, premarket notification (510(k)), humanitarian device exemption (HDE) application, or a request for de novo classification.” Thus, this new guidance will apply to far more devices than the existing guidance.
Because the new draft guidance applies to more categories of devices, the draft guidance has deleted language from the existing guidance which applied only to cardiovascular devices. Additionally, the draft guidance contains numerous format and stylistic changes including moving certain statements from one section to another or one paragraph to another.
But the new draft guidance also makes a number of substantive changes as well. For instance, in the “Overview” section, FDA expressly states that for animal studies being submitted to Agency to support the safety of a device, Good Laboratory Practice (GLP) 21 C.F.R. Part 58 applies.
In the existing guidance for cardiovascular devices, FDA merely stated that submitting parties “should follow Good Laboratory Practice (GLP) for all animal studies involving cardiovascular devices that are to be submitted to the Agency.” In FDA parlance, “should” means that “something is suggested or recommended, but not required.”
The new draft guidance repeatedly emphasizes that compliance with GLP and Part 58 is required. In the new “Study Assurances” section, the FDA states bluntly that “[a]nimal studies that are intended to support the safety of a medical device must comply with the GLP requirements detailed in 21 CFR Part 58.” Unlike the existing guidance which does not use the word “must” at all, the draft guidance uses the word 19 times. In fact, the draft guidance then uses the word “must” three more times in the first paragraph of the “Study Assurances” section alone. In short, the FDA makes a clear shift to requiring compliance with specific subsections of Part 58.
Another new theme throughout the draft guidance is that the FDA repeatedly encourages industry participants to use the Pre-Submission Program before undertaking the animal studies. See the FDA guidance issued on February 18, 2014 titled “Requests for Feedback on Medical Device Submissions: The Pre-Submission Program and Meetings with Food and Drug Administration Staff.” The existing guidance document mentioned the former Pre-IDE program only once and that was only if the submitting party “would like FDA feedback on your proposed animal study strategy.”
For instance, in Appendix B, the Sample Decision Tree for Medical Device Animal Studies, the Agency has added a new question. The new question asks whether “the risk analysis suggest than an animal study is necessary to assess potential safety problems.” If yes, then the party can move to the next question. If not, then the party should “consider submitting a Pre-Submission and request FDA feedback.”
Interested parties have 90 days from the publication of the draft guidance in the Federal Register to submit comments or suggestions concerning the draft.