On August 24, 2016, the US Food and Drug Administration (FDA) issued a Proposed Rule1 on Good Laboratory Practice for Nonclinical Laboratory Studies (Proposed Rule), which broadens the application and authority of Good Laboratory Practice (GLP) regulations. The Proposed Rule imposes heightened quality requirements for laboratory studies, including safety and toxicity studies, that are intended to support both product applications and other regulatory submissions that are not directly related to product approval. The Proposed Rule also modifies provisions for the care and handling of animals under the so-called Animal Rule and expands requirements to encompass tobacco products. Interested parties have until November 22, 2016, to submit comments, suggestions and feedback.
The Proposed Rule requires the use of a complete quality system approach (GLP Quality System) for nonclinical laboratory studies when such studies support or are intended to support marketing applications or other submissions to FDA.2 FDA proposes to mandate use of a GLP Quality System that is consistent with International Organization for Standardization (ISO) standard ISO 9001:1994, "Quality
Systems—Model for Quality Assurance in Design, Development, Production, Installation and Servicing"; "FDA's Quality System Regulation (QSR)" in 21 CFR Part 820; and wherever possible, Organisation for Economic Co-operation and Development guidance documents for GLP.
Collectively, these standards require tighter controls and procedures for the laboratory Quality Assurance Unit (QAU) and documentation and monitoring of equipment, data and personnel. Among other requirements, FDA proposes to amend provisions related to facility management to specify that the QAU must submit written periodic status reports on GLP Quality System performance for each study to specifically designated management personnel with "executive responsibility" for the facility's operations. The Proposed Rule also imposes new requirements for communication among personnel, internal quality audits, and the creation and documentation of Standard Operating Procedures (SOPs). Notably, FDA proposes to exercise enforcement discretion with respect to the review and evaluation of QAU records by stating that such records will not be subject to routine inspections, but they will be inspected for litigation or during inspections "for cause" under an inspection warrant.
The Proposed Rule also expands the application of Part 58 to efficacy studies conducted on animals under the Animal Rule pathway. Under this pathway, the FDA may grant marketing approval through the use of animal studies to establish the safety and effectiveness of human drugs or biological products when human efficacy studies are unethical or field trials are infeasible (e.g., deliberate exposure of healthy human volunteers to potentially lethal or permanently disabling toxic chemicals). The Proposed Rule differentiates between the types of Animal Rule-specific studies that must adhere to Part
58, noting that the data quality and integrity requirements are not necessarily appropriate for all types of Animal Rule-specific studies (e.g., studies using challenge agents that require high-containment facilities). The proposed "covered Animal Rule studies" include the adequate and well-controlled efficacy studies that serve as substantial evidence of effectiveness necessary for approval or licensure of human drugs or biological products; pharmacokinetic or pharmacodynamics studies in animals used to select a dose and regimen in humans; and natural history studies to support qualification of new animal models under FDA's Animal Model Qualification Program, the model-defining natural history studies. FDA seeks comment on whether current or proposed requirements pose a unique or disproportionate obstacle or burden on the conduct of certain animal studies specific to product development under the Animal Rule.
In recognition of FDA's authority to regulate tobacco products under the Family Smoking Prevention and Tobacco Control Act of 2009, the Proposed Rule addresses requirements for laboratory studies involving tobacco products. FDA proposes to apply the new GLP requirements to studies designed to "provide evidence regarding the relative toxicities of new or modified risk tobacco products," as specified in sections 905, 910 and 911 of the Federal Food, Drug, and Cosmetic Act (FDCA). The Proposed Rule states that the labeling of a tobacco product may not be used to characterize such a product if it is used as a control or reference article in a nonclinical laboratory study, because labeling of currently marketed tobacco products does not provide the information required for full product characterization, e.g., chemical and microbiological composition or design parameters. FDA plans to issue regulations under section 910(g) of the FDCA, providing conditions under which tobacco products intended for investigational use may be exempted from general tobacco product requirements under the FDCA.
The chart below describes these and other revisions to key provisions of the rule in greater detail. The chart compares selected provisions of Part 58 in its current form with the Proposed Rule and describes potential implications of the changes, in the event any or all of the Proposed Rule's sections are implemented in its final iteration.3
1 81 Fed. Reg. 58,342 (Aug. 24, 2016).
2 According to FDA, other submissions include nutrient content and health claim petitions for food, authorizations to market edible animal products, product development protocols for medical devices and data supporting changes to medical device performance standards. See 81 Fed. Reg. 58,367–58,368 (Aug. 24, 2016).
3 Note, the chart does not contain every proposed modification. It excludes certain items, deemed minor or described elsewhere in this document.
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