Those of us who have worked in pharmaceuticals or medical device are familiar with the concept and requirements of a Quality System. On August 24, 2016, the FDA issued a proposed a rule to the Good Laboratory Practices (GLPs, 21 CFR part 58), titled “Good Laboratory Practice for Nonclinical Laboratory Studies”. The concept is akin to the one dictated in the cGMPS. One primary aspect of this proposition is to implement a GLP Quality System defined as “the organizational structure, responsibilities, procedures, processes, and resources for implementing quality management in the conduct of nonclinical laboratory studies.” (Good Laboratory Practice for Nonclinical Laboratory Studies, 2016). No doubt, many organizations that conduct these studies already have a quality system or procedures that make up a quality system. These organizations will be well positioned to manage the required procedural changes from this proposed rule.
The proposed rule is a reflection of the FDA’s increased focus on data integrity. Data integrity is perhaps the largest driver of this proposed rule. We have seen the FDA take an increased regulatory concern towards issues with data integrity – through 483s and the April 2016 Data Integrity and Compliance with CGMP Draft Guidance for the Industry. There are many propositions that address data integrity in the document. One standout is the FDA formalizing the concept of “ALCOA” into the GLPs. The concept of ALCOA means that data are “accurate, legible, contemporaneous, original, and attributable”. The proposed rule does not define those terms, however, more specification may still come. ALCOA has been used for a long time in pharma, so the specific definitions should not deviate much from the industry standards.
Mandating GLP Quality System gives the FDA authority to regulate studies outside of the United States. Part of the rule deals with the issue of multisite studies, which are quite common now. Often, components of the study are managed in multiple countries. The GLP Quality System will help monitor data integrity from oversea studies by requiring the inclusion of all data generated with the study in the submission. This may include electronic audit trails from data collection, for example.
A couple of points are noteworthy from a computer systems validation perspective. In the Equipment Design section (21 CFR 58.61), the FDA proposes clarifying that computerized systems are equipment. I do not believe this will change the way organizations validate computerized systems or add new scope to validation, but it does reinforce the need for computerized system validation and qualification. Also, the FDA proposes to update provisions in Part 58 to “address electronic data capture and maintenance” (Good Laboratory Practice for Nonclinical Laboratory Studies, 2016). They state that this is an effort to keep 21 CFR Part 11 and Part 58 consistent but that they do not want to duplicate Part 11 in Part 58. Basically, they are stating what organizations understand in the industry that Part 11 applies to Part 58. They are also adding a definition of “validation”, like the one found in Part 820 and requirements to have SOPs defining computer system validation.
So, what do you think of the proposed rule? It seems a natural and perhaps obvious addition to the GLPs. We all want to find efficient ways to increase data integrity and most organizations take this seriously. Increased attention on data integrity by the FDA may have extra costs (see the proposed rule for the FDA’s information on the estimated costs of the rule), but it is a worthwhile effort. The proposed rule comment period ends November 22, 2016.