This guidance describes the benefit-risk principles applied by FDA when conducting product quality-related assessments of chemistry, manufacturing, and controls (CMC) information submitted for FDA assessment as part of original new drug applications (NDAs) under section 505 of the Federal Food, Drug, and Cosmetic Act (FD&C Act), original biologics license applications (BLAs) under section 351 of the Public Health Service Act (PHS Act), or supplements to such applications, in addition to other information (e.g., inspectional findings) available to FDA during its assessment.
This guidance discusses how FDA assesses risks, sources of uncertainty, and possible mitigation strategies for a product quality-related issue and how those considerations inform FDA’s understanding of the potential effect on a product. The product quality assessment determines whether an applicant’s product development studies, manufacturing process, and control strategy will consistently result in a finished product of acceptable quality when manufactured at the facilities named in the application. When a regulatory decision regarding the approval of an NDA or BLA is made, FDA considers the overall benefit(s) and risk(s) identified for the product, including any residual risk related to unresolved product quality issues. This guidance also discusses how unresolved product quality issues may be addressed in the context of regulatory decision-making.
This guidance is not intended to address the review by other disciplines or sections of a marketing application (e.g., clinical, nonclinical, biostatistics, pharmacology).
Sections II and III of this guidance focus on product quality assessment in the context of FDA’s review of an NDA or BLA. Although not specifically addressed in sections II and III, product quality assessments are also done for abbreviated new drug applications (ANDAs). However, the product quality assessment of an ANDA can be different to the extent that the ANDA relies on FDA’s finding that the reference listed drug (RLD) identified is safe and effective. As with NDAs and BLAs, an ANDA will not be approved if the applicant’s product development studies, manufacturing process, and control strategy will not consistently result in a finished product of acceptable quality when manufactured at the facilities named in the application. Section IV of this guidance, which discusses how unresolved product quality issues may be handled in the context of regulatory decision-making, specifically addresses how FDA may handle such issues as part of its review of an ANDA.
The contents of this document do not have the force and effect of law and are not meant to bind the public in any way, unless specifically incorporated into a contract. This document is intended only to provide clarity to the public regarding existing requirements under the law. FDA guidance documents, including this guidance, should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidance means that something is suggested or recommended, but not required.
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