Benefit-Risk Assessment for Product Quality Evaluation

Before approving an application, the 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. The applicant must demonstrate that 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 determining whether a drug or biological product meets the standard for approval, the agency conducts an overall benefit-risk assessment (see also FDA’s Benefit-Risk Framework). The draft guidance therefore describes the FDA principles when conducting product quality-related assessments of chemistry, manufacturing, and controls (CMC) information in addition to other available information (e.g., inspectional findings).

Principles for FDA´s 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 to:

  • Gain a greater understanding of the patient population and disease for which the product will be used
  • Identify whether the drug addresses an unmet medical need
  • Identify potential sources of product quality risk that could result in a risk to the patient

Although each application will contain unique information on CMC strategies, FDA routinely applies the following principles when evaluating quality issues during its assessment:

  • Risk-based considerations related to therapeutic context
  • Extent of impact on safety and / or effectiveness
  • Totality of product quality information
  • Inspectional findings
  • Other considerations that could affect the product quality assessment (e.g., a novel combination of a drug or biological product with another medical product, such as a medical device, or the introduction of a novel technology in the manufacturing process or analytical procedures)
  • Possible mitigation strategies

Product Quality Determination

At the end of the assessment, the product quality assessment team provides its recommendation to approve or not approve a marketing application. The agency will usually not approve the application when unresolved quality issues remain. However, in rare circumstances, an application may meet the standard for approval despite the presence of certain unresolved quality issues. Examples could include cases where it is not feasible for the product quality issue to be resolved before approval and it can be addressed post-approval without an unacceptable level of risk (e.g., providing post-approval confirmatory photostability data to address a change in film-coat composition that affects shading of film-coat color).

More information is provided in FDA´s draft Guidance for Industry Benefit-Risk Considerations for Product Quality Assessments.

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