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Benefit-Risk Considerations for Product Quality Assessments

Before approving an application, FDA must determine whether the drug product is both safe and effective for use under the conditions prescribed, according to the product labeling and the instructions it contains.

Section 505(b) and (d) of the FD&C Act identify the key components required for approval of a new drug under an NDA.

Among them are product quality related requirements to demonstrate the applicant has developed a drug product and drug substance, manufacturing process, and control strategy that will consistently result in a drug product of acceptable quality to ensure it is both safe and effective for use.

Specifically, section 505(b)(1)(C) and (D) of the FD&C Act requires a new drug applicant to submit a full statement of the composition of such drug as well as a full description of the methods used in, and the facilities and controls used for, the manufacture, processing, and packaging of such drug; this information informs the Agency’s assessment of whether the applicant can ensure the identity, strength, quality, and purity of the drug substance and drug product.

Likewise, BLAs have similar considerations with respect to product quality-related requirements. Under section 351(a)(2)(C) of the PHS Act,10 FDA will approve a BLA based demonstration that the biological product is safe, pure, and potent and that the facility in which the biological product is manufactured, processed, packed, or held meets standards designed to ensure the biological product continues to be safe, pure, and potent.

Applicants must submit data and supporting information to demonstrate that they can ensure and preserve a drug product’s identity, strength, quality, and purity for NDAs or a biological product’s safety, purity, and potency for BLAs.

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.

A drug product approved in an ANDA relies on FDA’s finding that the RLD identified in the ANDA is safe and effective, and therefore, relies on FDA’s determination that the RLD provides benefits that outweigh its known and potential risks. This reliance is premised on the generic drug product having the same active ingredient(s), conditions of use, route of administration, dosage form, strength, and (with certain permissible differences) labeling as the RLD, as well as demonstrating that the generic drug product is bioequivalent to the RLD.

This guidance also discusses how unresolved product quality issues may be addressed in the context of regulatory decision-making.


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