FDA frequently issues guidance documents in the form of Questions and Answers.  The August 28, 2013 draft is still lingering on the FDA website pending comments.  But with the FDA’s Refuse to File Checklist, some companies may be in for a shock if preclinical studies are submitted without a statement of compliance to Good Laboratory Practices.  For many years, device studies have been informally allowed to skim GLP regulations but future studies may be in peril if the sponsors don’t appreciate the risks involved in failure to demonstrate GLP compliance.

The Good Laboratory Practice for Nonclinical Laboratory Studies Regulations, 21 CFR part 58 are NOT a suggestion!  According to the GLP preamble, safety studies must follow GLPs, but “functionality studies” are excluded.  This has been the source of confusion since for many device manufacturers, testing an animal-version of a medical device constitutes a “functional” model.  Unfortunately this draft guidance does nothing to clarify this definition. To understand the meaning of this exemption the device test sponsor must understand that the GLP regulations grew out of the pharmaceutical industry where a “safety” study in animals was quite different from one that evaluated the “function” of a drug. When device manufacturers evaluate a medical device for biocompatibility, bone in-growth or potential wear; particularly when histopathology is an outcome measure, FDA typically views these studies as first and foremost: safety.  For all the trouble to develop this guidance, it might have been nice if FDA had made this clear.

If it is too late and your study is complete and you must submit the data to FDA with a submission, it is important to recognize that the FDA will allow a well-written deviation discussion.  It is important to understand that if a study is a pilot trial, failed to include sufficient specimen and there are no “controls”—even literature, then FDA may still reject the data from the study as inadequate for its purpose.  As the saying goes, “you can’t make a silk purse out of a sow’s ear”—pun intended.  If you believe the study was scientifically sound but the laboratory does not employ a Quality Assurance Unit (QAU), there may be ways to demonstrate how well the study was managed and that the data has integrity.  We employ an itemized checklist and demonstrate section by section how the study quality was maintained.  Post-study data auditing can be useful to demonstrate the data should be considered valid, as well as including the laboratory’s AAALAC and/or USDA inspection results with your report.  The most critical issue may be simplest: can you account that all test specimen and all test articles resulted in reported data?  If animal data is missing, if animals died during the study without an autopsy or vet examination of the cause, don’t expect FDA to jump right into believing the data have integrity.  This is risky business and no medical device study sponsor should go into a preclinical study with the idea the study can be conducted as “GLP-like”.  You don’t want to bet your submission, and maybe your company, on the prospect that FDA will accept your position.

Paladin Medical can assist you in developing a scientifically sound preclinical protocol that will result in data that will support your submission.  We can help you to qualify the laboratory and instruct you on methods to augment GLP-compliance deficiencies if certain sub-contractors are not currently compliant.  Despite the FDA’s Question and Answers guidance, it is still more cost and time effective to do the best study the first time with the best laboratory for your device.  Go to www.paladinmedical.com for additional information.