On October 14, 2015, FDA released a draft guidance entitled, General Considerations for Animal Studies for Medical Devices, Draft Guidance for Industry and Food and Drug Administration Staff“. The purpose of this document is, once final, to supercede FDAs current Guidance entitled General Considerations for Animal Studies for Cardiovascular Devices, which was issued on July 29, 2010.
The Big Picture
FDA has been ramping up their publication of guidance documents and is attempting to reinforce the rules related to submission contents and to communicate their expectations. This guidance expands the scope of a previously published guidance to all device and filing types that might utilize a preclinical study to demonstrate safety and performance. This is primarily an administrative update to align with PMA, 501(k), IDE, HDE and De Novo Requests. Very few changes from the original guidance have been made.
What is the intent of the update?
FDA is likely trying to use guidance documents to reinforce their standards for accepting data and reminding sponsor companies of the need for high quality, complete and accurate recording. To the members of the manufacturing industry this means GLP compliant studies, performed on the final device design proposed for human use, in a large controlled study with independent audits of data and final reports.
The Nuts and Bolts
So what has changed?
- Large Expansion of Scope
- Previously was just PMAs and just cardiovascular devices
- Now: all classes and classifications of devices and all application types
- Shortened by about 5 pages mainly by removing text unrelated to FDA regulation and tightening up language.
- The original document had a lot of information about non-FDA animal welfare programs (e.g. USDAs animal welfare act). In the revised version this has been replaced with excerpts from 21 CFR or edited to state that there are other laws or regulations addressing this issue
- Several longer passages have been shortened or condensed.
- Text specific to cardiovascular devices or describing cardiovascular specific concerns have been removed.
- New Research Controls have been added
- Expanded discussion and request for health screenings prior to animal enrollment, including clinical chemistry and parasitology
- Additional description of what FDA considers appropriate control of bias: financial conflict, multiple observers/operators
- Species specific environmental enrichment and socialization
So what do we think that the FDA really wants out of all of this?
We feel that they expect a well-designed study conducted on the final version of your device, preferably with a control device that examines the safety and performance and actively evaluates clinical risks youve identified in your own internal risk analyses. FDA would like fairly granular documentation in the raw data, of all study phases including the recovery and post-surgical phases to ensure confounding variables arent overwhelming your study (e.g. assure proper nutrition, maintain early and frequent health monitoring, minimize environmental stress etc.).
Pivotal safety and performance studies need to be performed at independent laboratories that are licensed by USDA, AAALAC accredited and hold active PHS animal welfare assurance statements. There appears to be an increased level of trust in such institutions as they have been inspected by 3rd parties and have SOPs and practices in place to assure proper conduct as well as trained staff and a comprehensive veterinary care program. There is also a renewed emphasis on GLP compliance. It is no longer appropriate to simply state what studies were or were not GLP compliant, FDA wants specific elements where compliance wasnt achieved. Cost is not an appropriate rationale and FDA encourages the contracting of 3rd party audits if the facility does not have a QAU.
To learn more about this guidance document and how it might impact your preclinical research program, please contact APS at 763-717-7990 or firstname.lastname@example.org