By Allyson B. Mullen –
On August 28, 2013, FDA’s Center for Devices and Radiological Health issued a draft guidance, “The Applicability of Good Laboratory Practice in Premarket Device Submissions: Questions & Answers.” This new, short guidance restates the requirements of the Good Laboratory Practices (“GLP”), set forth in 21 C.F.R. Part 58, and provides some additional clarification.
By regulation, GLPs must be followed when “conducting nonclinical laboratory studies that support or are intended to support applications for research or marketing permits for products regulated by the Food and Drug Administration, including food and color additives, animal food additives, human and animal drugs, medical devices for human use, biological products, and electronic products.” 21 C.F.R. Part 58. The guidance clarifies that nonclinical laboratory studies are in vivo and in vitro experiments which prospectively evaluate a test article under laboratory conditions to determine safety. Draft Guidance at 4. In addition, for purposes of the draft guidance, a test article is a medical device for human use. Id. However, the draft guidance acknowledges that in vitro diagnostic device studies typically do not require compliance with GLPs because they generally use human subjects or specimens derived from human subjects; thus, the testing samples are outside the scope of GLPs. Id. at 7.
In addition, the draft guidance requires companies submitting medical device marketing and research applications, including, without limitation, 510(k)s, PMAs, and IDEs, to indicate whether the applicable studies being submitted have complied with GLPs. Id. at 5. In addition, applicants are now required to include a statement within their submissions indicating that the nonclinical laboratory studies in the submission comply with GLPs. Id. at 5-6. This requirement applies to all studies regardless of whether they were conducted in the United States or abroad. Id. at 7. To some, it may appear as though this statement is a new requirement for medical device submissions. For example, 21 C.F.R. § 807.87 does not require applicants to address GLP compliance as part of necessary information in a premarket notification. However, FDA has been requiring such a statement as part of its “Refuse to Accept Policy for 510(k)s” issued at the end of 2012. FDA, Guidance for Industry and FDA Staff, Refuse to Accept Policy for 510(k)s, 39 (December 2012). (This indicates how a seemingly innocuous checklist can effectuate changes in practice.)
The draft guidance goes on to explain that if the studies have not complied with GLPs, the applicant should indicate such non-compliance and include an explanation. Draft Guidance at 6. The draft guidance also suggests information to provide when a study has not complied with GLPs, including, for example, a detailed list of deviations from the regulations, an explanation of how the sponsor limited study bias, and an explanation of how the sponsor ensured the validity and integrity of the data. Id. at 6.
Lastly, FDA concludes the draft guidance with questions regarding testing facilities. The draft guidance indicates that companies performing nonclinical laboratory testing to support device safety are required to allow FDA to inspect the applicable facilities. Id. at 7. Further, if a testing establishment does not permit FDA to conduct such an inspection, FDA will not consider study data generated by such facility in support of a device application. Id. Therefore, applicants should be advised to choose their testing facilities wisely and ensure that such companies are able and willing to endure an FDA inspection. Overall, this document will mean more companies will need to pay more attention to GLPs than has been the case.