On May 10, 2022, FDA published draft guidance entitled, “Benefit-Risk Considerations for Product Quality Assessments”, which describes the benefit-risk principles applied by FDA when conducting product quality-related assessments of chemistry, manufacturing, and controls (CMC) information submitted for FDA’s review as part of original new drug applications (NDAs), original biologics license applications (BLAs), or supplements to such applications.

In the draft guidance, FDA reiterates its risk-based regulatory approach and applies it in the product quality assessment context. Specifically, the draft guidance states that FDA continues to identify potential risks to product quality associated with the formulation, manufacturing process, and packaging components when conducting a product quality assessment as well as the proposed control strategy for mitigating those risks.

Guidance describes evaluation principles

The draft guidance states that FDA will continue to routinely apply the following principles when evaluating product quality issues:

  • Risk-based considerations related to therapeutic context – FDA’s assessment considers relevant characteristics of the target population and whether certain product quality attributes are intended to address specific unmet needs.
  • Extent of the impact on safety and/or effectiveness – FDA maintains that drug products should be designed to meet the needs of the intended patient population and consistently deliver the intended product performance
  • Totality of the product quality information – FDA considers the totality of information available and relevant to the product during its review, which includes, but is not limited to, the effectiveness of the pharmaceutical quality system, clinical experience during pivotal trials, scientific literature, and/or FDA’s knowledge of a given issue or class of drugs.
  • Inspection findings – FDA uses a risk-based approach to determine whether a preapproval or prelicensure inspection is needed using information provided in the application and information FDA may have regarding the facilities named in the application
  • Other considerations that could affect the product quality assessment, such as the need for additional testing. – FDA acknowledges there may be additional considerations regarding unique aspects of a drug’s development or advancements in pharmaceutical science that require additional/new information to understand the potential risks.
  • Possible mitigation strategies. – FDA considers the applicant’s ability to mitigate or reduce any risks associated with product quality issues. Note that FDA cautions that potential mitigation strategies must not introduce new product quality issues or exacerbate any previously identified issues.

Unresolved quality issues also addressed

FDA also addresses unresolved quality issues in the draft guidance. Generally, unresolved quality issues mean that FDA will not approve the application. However, there are some exceptions in which the risk posed by the unresolved issue may be outweighed by the benefit of the product or the ability to bring it market quickly, such as a product that addresses an unmet medical need. In those cases, FDA may allow some information to be submitted after approval.

Overall, this draft guidance provides more guidance and insight into FDA’s approach resolving product quality issues and how applicants can proactively address those issues.