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Pharmaceutical Technology QUALITY AND REGULATORY SOURCEBOOK EBOOK MARCH 2022 15 that includes, among other changes, the publication of statements of non-compliance with GMPs. Ways to minimize risks associated with method validation For drugs, biologics, and medical devices, there is a considerable amount of data compiled during devel- opment. While reviews for completeness and accuracy capture most errors and omissions, no system is per- fect. Therefore, it's important to implement strategies to address potential observations and minimize any impact on product approval. The following activities represent best practices for minimizing risks: • Pre-submission gap assessments: Review of all development data, specifications, methods, and method validations should be reviewed for potential deficiencies prior to submission of investigational new drug application, investi- gational device exemption, clinical trial autho- rization, premarket notification (i.e., 510(k), PMA), and new drug application submissions. While it may not be possible to address all de- ficiencies, with such an assessment, a detailed remediation plan can be developed to mini- mize risks to product approval. • Pre-submission meetings with regulatory agencies: Method development and validation strategies along with validation data can be sub- mitted to get agreement that the data to be pre- sented will be sufficient. This may not be neces- sary for all combination products, but it is a step that should be considered. • Post-submission review and gap assessment: Once the final dossier is submitted, regulatory agencies will provide written questions. This is so that a gap assessment can identify areas of deficiency and allow time to address them prior to being questioned. Having answers prepared and deficiencies addressed allow sponsors to perform necessary studies to en- able responding to regulatory deficiencies within expected timeframes. • Pre-inspection audits: Pre-inspection readiness audits are performed to assess both manufactur- ing and laboratory controls. Laboratory controls will include data integrity audits to identify areas that could impact data related to the product and method validation. Conclusion: understand the guidance and mitigate the risk FDA, EMA, and other regulatory bodies have pro- vided extensive guidance and guidelines that relate to combination products. It is vital for sponsors to fully understand the guidance documents as they relate to their products because improper method validation can result in a wide array of deficien- cies and can incur significant delays in getting important products to patients. Given the critical- ity, a strategy to ensure proper method validation should be employed throughout the product devel- opment lifecycle. Communication with regulatory authorities regarding methods and product speci- fications should happen early on and throughout the development of a combination product. In this way, mitigating the risk surrounding validation of methods will help to ensure a robust marketing ap- plication and go far to reduce the risk in attaining marketing approval. References 1. CFR Title 21 (Government Printing Office, Washington, DC), ecfr.gov/current/title-21, accessed Feb. 23, 2022. 2. EMA, EMA/CHMP/QWP/BWP/259165/2019, Guideline on Quality Documentation for Medicinal Products When Used with a Medical Device (July 2, 2021). PT