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Guidance Snapshot

Benefit-Risk Assessment for 

New Drug and Biologic Products

Final Guidance for Industry

What Is Covered in This Guidance?

This final guidance provides an overview of 

the important considerations that factor into 

FDA’s benefit-risk assessment conducted 

during the regulatory review of new drug 

applications and biologics license applications and throughout 

the drug lifecycle. It also provides considerations about how 

sponsors can inform FDA’s benefit-risk assessment, through 

the design and conduct of the development program, as well 

as through the presentation of benefit and risk information in a 

drug product marketing application. 

Why Is This Guidance Important?

At the FDA, the benefit-risk assessment 

is used to make an informed judgment 

as to whether the benefits (with their 

uncertainties) of the drug outweigh the risks 

(with their uncertainties and approaches to managing risks) 

under the conditions of use described in the approved product 

labeling. The benefit-risk assessment for a new drug can be 

straightforward in cases when a drug’s benefit is established 

as clinically meaningful and the drug’s safety profile is wellcharacterized with no serious risks identified. The benefit-risk 

assessment becomes more challenging in cases where there 

is greater uncertainty surrounding benefit or known or potential 

serious safety risks are identified, e.g., risks that are lifethreatening or associated with significant morbidity. 

Benefit-Risk 

Assessment Is 

Case-Specific 

and Considers:

 THE EVIDENCE 

submitted in the 

premarket application and/

or generated in the postmarket 

setting that informs FDA’s understanding of 

the benefits and risks of the drug

 THE THERAPEUTIC CONTEXT in which 

the drug will be used, including the nature 

and severity of the condition the drug is 

intended to prevent, treat, cure, mitigate, or 

diagnose, and how well patients’ needs are 

being met by current available treatments

 THE UNCERTAINTIES about the drug’s 

benefits and risks. Although uncertainty can 

be reduced through careful study design and 

conduct, some uncertainty in the body of 

evidence available at the time of regulatory 

decision-making is inevitable, e.g., the 

frequency of rare serious adverse events or 

whether the drug’s effectiveness persists in 

long-term use.

 THE REGULATORY OPTIONS to reduce 

uncertainties and manage risks.

learn more about the benefit-risk assessment for human drug and biological products, 

read the guidance.
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Specific Topics the Guidance Covers

Benefit-Risk Planning:

Benefit-risk planning by the sponsor, beginning early in development, can add value by helping to ensure 

that the clinical trial data and other supporting information collected are best suited to support the benefit-risk 

assessment. Benefit-risk planning is most valuable in cases where a challenging benefit-risk assessment 

can be reasonably anticipated. The goal of benefit-risk planning would be to direct drug development toward 

reducing important uncertainties and to increase the likelihood of establishing a favorable benefit-risk 

assessment of the submitted NDA or BLA.

Additional benefit-risk analyses to help inform the overall benefit-risk assessment may add value in some 

circumstances, such as decisions involving significant or unexpected uncertainties regarding the drug’s 

benefits and risks. Consultation with FDA and careful planning early in drug development can increase the 

potential value of the benefit-risk analysis.

Interactions Between FDA & Sponsors:

FDA can provide insight and regulatory perspective that can inform 

a sponsor’s benefit-risk planning appropriate to the issues 

identified at a particular stage of development. Thoughtful 

planning can also enhance the assessment of risk needed 

to support informed benefit-risk assessment. In particular, 

the discussions at an End of Phase 2 meeting can be 

particularly important when preclinical, early clinical, or 

other data identify a potential safety issue that would 

require greater certainty about the drug’s benefits 

and/or risks to support approval.

Patient Experience Data:

Patients are experts in the experience of their 

disease or condition, and they are the ultimate 

stakeholders in the outcomes of medical 

treatment. Therefore, patient experience data, 

including patient preference information, can 

inform nearly every aspect of FDA’s benefit-risk 

assessment throughout the drug lifecycle.

Presenting Benefit Risk Information:

The effective communication by sponsors of the drug’s 

benefits, risks, and uncertainties is important to informing 

the benefit-risk assessment that supports regulatory 

decision-making.

To learn more about the benefit-risk assessment for human drug and biological products, 

read the guidance.
www.fda.gov 3

Background About the Guidance

Under the Federal Food, Drug, and Cosmetic Act (FD&C 

Act), for a drug to be approved for marketing in the United 

States, FDA must determine that the drug is effective 

and safe for use under the conditions prescribed, 

recommended, or suggested in the product’s labeling. FDA 

interprets “safe” under the FD&C Act to mean the benefits 

of the drug outweigh its risks. The guidance provides 

considerations about the benefit-risk assessments that 

support FDA’s regulatory decisions for new drug applications 

and biologic license applications.

Drug Development Timeline

The Guidance may be relevant to stakeholders throughout the drug development lifecycle

BASIC 

RESEARCH

PROTOTYPE 

DESIGN OR 

DISCOVERY

PRECLINICAL 

DEVELOPMENT

CLINICAL 

DEVELOPMENT

PHASE 1 PHASE 2 PHASE 3

FDA 

FILING & 

APPROVAL

POSTMARKET OR 

POSTAPPROVAL 

STUDIES

Guidance Recap Podcast

Speaker: Jim Smith, MD, Director of CDER’s Office of New Drug Policy

Click here to listen

Click here to 

read transcript

To learn more about the benefit-risk assessment for human drug and biological products, 

read the guidance.

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