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Benefit-Risk Considerations for Product Quality (B-RCPQ)

Assessments Guidance for Industry dated May 2022)

  1. General Comments

  • Comments and suggestions regarding this draft document should be submitted by July 2022.

  • Guidance describes the benefit-risk principles applied by FDA when conducting product quality-related assessments of the (CMC) information submitted for FDA assessment as part of original new drug applications (NDAs), original (BLAs), or supplements to such applications, in addition to other information (e.g., inspectional findings) available to FDA during its assessment.

  • 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.

  • 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 identified is safe and effective.

  • Applicants must submit data and supporting information to demonstrate that they can ensure and preserve a drug product’s identity, strength, quality, and purity.

  • Small molecule drug product examines the method of synthesis and isolation of the drug substance to ensure purity and control over levels of any impurities and degradation products including mutagenic impurities; the stringency of validation and suitability of the analytical procedures; and the processing and related process controls to ensure that they are designed and controlled to ensure consistent product quality, including, product sterility if applicable.

  • A typical sources of product quality-related uncertainty may include gaps in current knowledge, such as projecting shelf-life performance due to a limited stability data provided.


  • The Interrelationship Among Therapeutic Context, Potential Benefits, and Product Quality-Related Risk Considerations

  • The determination of a drug’s overall clinical benefit(s) is outside the scope of the product quality assessment.

  • During the product quality assessment, assessors may use the interdisciplinary team’s understanding of the therapeutic context and the assessment of benefit.

  • The (B-RCPQ) should be in alignment with Benefit-Risk Assessment for New Drug and Biological Products Guideline dated (September 2021)

  1. Assessment of Risks Posed by a Product Quality should consider:

  • Risk-based considerations related to therapeutic context.

  • Extent of impact on safety and/or effectiveness.

  • Totality of product quality information.

  • Inspectional findings.

  • ICH guidance for industry Q8(R2) Pharmaceutical Development (2009).

  • ICH guidance for industry Q10 Pharmaceutical Quality System (2009).

  • Other considerations that could affect the product quality assessment.

  • Possible mitigation strategies.

  • Control of Nitrosamine Impurities in Human Drugs Guidance (February 2021).


  • Quality Determination

  • Unresolved Quality Issues

  • ANDAs

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