A new draft guidance document released by the US Food and Drug Administration (FDA) explains that good laboratory practice (GLP) regulations under 21 CFR 58 generally-but not always-apply to medical device premarket and research applications.
Just as good clinical practices (GCPs) are intended to govern the proper conduct of clinical trials to ensure the collection of adequate data and good manufacturing practices (GMPs) are intended to ensure the adequate production of materials and products, GLPs are intended to ensure the proper collection of pre-clinical data.
Under 21 CFR 58, GLPs cover a wide swath of activities and records that are in many ways analogous to both GCPs and GMPs. Those areas include:
- organization of staff functions and personnel
- facilities, including general provisions, provisions for the care of animals, and the control of operation areas
- the design and maintenance of equipment
- the operation of testing facilities, including standard operating procedures and the use of reagents and solutions
- the use of test and control articles
- the protocol of studies conducted in the laboratory
- maintenance of records and reports
- criteria that would render a facility disqualified from conducting testing
While the GLP regulations have been on the books since the late 1970s, FDA explains in its new draft guidance that it still regularly encounters questions with respect to one area: medical devices.
Devices Under the GLP
Under 21 CRF 58.1 ("Scope"), GLPs specifically cover "medical devices for human use," including test articles, control articles and in vivo/in vitro experiments. And per 21 CFR 58.3(e)(14-22), this definition includes applications for all of the following:
- a Premarket Approval Application (PMA) under Section 515 of the Federal Food, Drug and Cosmetic Act (FD&C Act)
- a Product Development Protocol (PDP) under Section 515
- an Investigational Device Exemption (IDE) application under Section 812 of the FD&C Act
- data and information regarding a medical device submitted as part of the procedures for classifying such devices, described in part 860
- data and information regarding a medical device submitted as part of the procedures for establishing, amending, or repealing a performance standard for such devices, described in part 861
- data and information regarding an electronic product submitted as part of the procedures for obtaining an exemption from notification of a radiation safety defect or failure of compliance with a radiation safety performance standard, described in subpart D of part 1003
- data and information regarding an electronic product submitted as part of the procedures for establishing, amending, or repealing a standard for such product, described in section 358 of the Public Health Service Act
- data and information regarding an electronic product submitted as part of the procedures for obtaining a variance from any electronic product performance standard as described in 1010.4
- data and information regarding an electronic product submitted as part of the procedures for granting, amending, or extending an exemption from any electronic product performance standard, as described in 1010.5
As FDA notes, these device regulations only apply when testing is conducted in support of a research or marketing application for a regulated product, and do not apply to studies utilizing human subjects (which fall under GCP regulations) or functionality studies. Early safety studies, however, would fall under GLP regulations.
"The GLP regulations only apply to nonclinical laboratory studies that support research or marketing applications," FDA explains in the guidance. "Per 21 CFR 58.3(d), 'nonclinical laboratory study' does not include 'basic exploratory studies carried out to determine whether a test article has any potential utility . . . .'"
"Therefore, basic exploratory studies carried out to determine whether a device has any potential utility, or to determine physical or chemical characteristics of a device, are not subject to the GLP regulations (21 CFR 58.3(d))," FDA added.
FDA also explains in the draft guidance that it does not read the GLP regulation as distinguishing between PMA, humanitarian device exemption (HDE), or premarket notifications (510k), meaning that any research involving a regulated product that meets the GLPs scope would need to adhere to its requirements as well.
Assuming non-conforming data from a GLP-deficient study is used in a research or marketing submission, FDA said the submission "should contain a statement explaining the reasons why the study was not in compliance with GLP regulations and describe in detail all deviations from the regulations." That statement will help FDA to determine if the data can be used and whether the validity of the data can be assured.
The rest of the draft guidance, which includes a total of 13 questions and corresponding answers, is available on FDA's website. Comments are due to the agency by 26 November 2013.
The Applicability of Good Laboratory Practice in Premarket Device Submissions: Questions and Answers - Draft Guidance for Industry and Food and Drug Administration Staff
21 CFR 58