Description
The intent of this guidance is to clarify for drug sponsors and other stakeholders how considerations about a drug’s benefits, risks, and risk management options factor into certain premarket and postmarket regulatory decisions that the Food and Drug Administration (FDA or Agency) makes about new drug applications (NDAs) submitted under section 505(c) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) as well as biologics license applications (BLAs) submitted under section 351(a) of the Public Health Service Act (PHS Act). This guidance first articulates important considerations that factor into the Center for Drug Evaluation and Research’s (CDER) and the Center for Biologics Evaluation and Research’s (CBER) benefit-risk assessments, including how patient experience data can be used to inform the benefit-risk assessment. It then discusses how sponsors can inform FDA’s benefit-risk assessment through the design and conduct of a development program, as well as how they may as well as how they may present benefit and risk information in the marketing application.
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
4Subject of the benefit-risk assessment guidance
Requires analytical comparability per ICH Q5E
drugs that are scheduled under the Controlled Substances Act
A higher degree of uncertainty is common in drug development programs for rare diseases.
Stakeholders
2Entity responsible for submitting applications under section 524B
Convened to provide advice on withdrawal issues
Regulatory Context
Regulatory Activities
6New Drug Application
Critical timepoint for discussions on benefit and risk considerations
Biologics License Application
Sixth authorization of the Prescription Drug User Fee Act
Table 1 provides considerations for premarket benefit-risk assessment of NDAs, BLAs, and Efficacy Supplements.
Pathway for drugs and biologics for serious conditions; Regulatory pathway supported by surrogate or intermediate endpoints; Regulatory pathway based on surrogate or intermediate endpoints; Pathway for products based on surrogate or intermediate clinical endpoints
Document Types
9Data intended to provide information about patients' experiences with a disease
Periodic Benefit-Risk Evaluation Report; Periodic Benefit-Risk Evaluation Report used for safety reporting.; Periodic Benefit-Risk Evaluation Report used for benefit-risk assessment
A graphical or tabular summary of results for benefits and risks.
Captures the value patients place on important attributes of a medical product
Specific labeling requirement for safety
Inclusion of PRO data in the prescribing information
CBER integrated the Benefit-Risk Framework into its clinical review template.
FDA-approved patient labeling
The primary section of drug labeling where SLCs are implemented
Attributes
3Standard required for drug effectiveness approval
Status of PRO instruments for regulatory decision-making.
Condition where patients lack treatment options
Technical Details
Testing Methods
4Tools used to measure neurologic function and daily life functioning
Studies designed to elicit patient values and tradeoffs; studies used to define the context of benefit-risk tradeoffs
Section 8.6 trial assessments
Examples of COAs including work productivity
Processes
2Changes to this process may affect the identity and NDI status of an ingredient.; Changes to this process may create an NDI; you should describe the manufacturing process and provide detailed information; includes fermentation as an intrinsic part of identity
Purposeful activity to incorporate benefit-risk assessment throughout the lifecycle
Clinical Concepts
3Reporting adverse events when engaging with patients.; changes may be related to benefits, tolerability, and/or unintended effects
Information relevant to safety of animals with IGAs
Anticipated risks that must be outweighed by benefits
Identified Hazards
Hazards
2Risks incorporated into benefit-risk assessments for controlled substances
Information suggesting a new potentially causal association or a new aspect of a known association between an intervention and an event.
Standards & References
Specifications
1Efficacy endpoints in Phase 3 trials
ICH References (2)
Periodic Benefit-Risk Evaluation Report (PBRER) standard for marketed products; Periodic Benefit-Risk Evaluation Report guidance; The primary guidance document for Periodic Benefit-Risk Evaluation Reports.; Periodic Benefit-Risk Evaluation Report (PBRER) guidance
The Common Technical Document (CTD)—Efficacy.
Related CFR Sections (6)
- 21CFR600.80§ 600.80 Postmarketing reporting of adverse experiences.
(a) Definitions. The following definitions of terms apply to this section:Read full regulation →
- 21CFR314.80§ 314.80 Postmarketing reporting of adverse drug experiences.
(a) Definitions. The following definitions of terms apply to this section:Read full regulation →
- 21CFR314.50§ 314.50 Content and format of an NDA.
NDAs and supplements to approved NDAs are required to be submitted in the form and contain the information, as appropriate for the particular submission, required under this section. Three copies of the NDA are required: An archival copy, a review copy, and a field copy. An NDA for a new chemical enRead full regulation →
- 21CFR201.56§ 201.56 Requirements on content and format of labeling for human prescription drug and biological products.
(a) General requirements. Prescription drug labeling described in § 201.100(d) must meet the following general requirements:Read full regulation →
- 21CFR201.57§ 201.57 Specific requirements on content and format of labeling for human prescription drug and biological products described in § 201.56(b)(1) .
The requirements in this section apply only to prescription drug products described in § 201.56(b)(1) and must be implemented according to the schedule specified in § 201.56(c) , except for the requirement in paragraph (c)(18) of this section to reprint any FDA-approved patient labeling at the end oRead full regulation →
- 21CFR600.3§ 600.3 Definitions.
As used in this subchapter:Read full regulation →
Related MFDS Guidelines
Korean regulatory guidelines covering similar topics
See Also (8)
- Development and Licensure of Vaccines to Prevent COVID-19: Guidance for Industry (Status: Final)
- Postmarketing Adverse Experience Reporting for Human Drug and Licensed Biological Products: Clarification of What to Report (Status: Final)
- How to Complete the Vaccine Adverse Event Reporting System Form (VAERS-1): Guidance for Industry (Status: Final)
- Postmarketing Safety Reporting for Human Drug and Biological Products Including Vaccines: Draft Guidance for Industry (Status: Draft)
- Evaluating the Risks of Drug Exposure in Human Pregnancies (Status: Final)
- Biological Product Deviation Reporting for Licensed Manufacturers of Biological Products Other than Blood and Blood Components (Status: Final)
- Postmarketing Adverse Event Reporting for Nonprescription Human Drug Products Marketed Without an Approved Application (Status: Final)
- Safety Reporting Requirements for INDs (Investigational New Drug Applications) and BA/BE (Bioavailability/Bioequivalence) Studies: Guidance for Industry and Investigators (Status: Final)