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Nonclinical Safety Evaluation of Reformulated Drug Products and Products Intended for Administration by an Alternate Route

FinalCenter for Drug Evaluation and Research10/28/2015

Description

This guidance provides recommendations for the nonclinical evaluation of previously approved drug substances when a new formulation or a new route of administration for a previously approved formulation is proposed by the sponsor. This guidance is intended for sponsors and review staff in the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration (FDA) involved in the development and review of new formulations of previously approved drug substances and proposals for existing formulations to be used by a new route of administration.

Scope & Applicability

Product Classes

2
Reformulated Drug Products

Guidance provides recommendations for the nonclinical evaluation of previously approved drug substances when a new formulation is proposed

Extended Release Injected or Implanted Formulations

Toxicity study of the proposed new formulation should be carried out

Stakeholders

2
Sponsor

Entity responsible for submitting applications under section 524B

Sponsors

Assist sponsors in the nonclinical evaluation

Regulatory Context

Attributes

2
Systemic exposure

measured by systemic availability of pharmaceutical-related substances

Bioavailability

Biological property that may be altered by manufacturing changes; safety narrative should address bioavailability of the ingredients

Identified Hazards

Hazards

4
Toxicity

Assessment of toxicity required in a 351(k) BLA

Unintentional intrathecal delivery

Risks to be understood when drug is developed for epidural route

Delayed hypersensitivity

Potential for allergic reaction to be evaluated for dermal, otic, and vaginal routes.

Phototoxicity

Potential toxicity requiring risk-minimization procedures like reducing light exposure.

Related CFR Sections (1)

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See Also (8)