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Generic Development of Topical Dermatologic Products: Formulation Development, Process Development, and Testing of Topical Dermatologic Products

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An Erratum to this article was published on 03 September 2015

Abstract

This review presents considerations which can be employed during the development of a semi-solid topical generic product. This includes a discussion on the implementation of quality by design concepts during development to ensure the generic drug product has similar desired quality attributes to the reference-listed drug (RLD) and ensure batch to batch consistency through commercial production. This encompasses the concept of reverse-engineering to copy the RLD as a strategy during product development to ensure qualitative (Q1) and quantitative (Q2) formulation similarity, as well as similarity in formulation microstructure (Q3). The concept of utilizing in vitro skin permeation studies as a tool to justify formulation differences between the test generic product and the RLD to ensure a successful pharmacodynamic or clinical endpoint bioequivalence study is discussed. The review concludes with a discussion on drug product evaluation and quality tests as well as in vivo bioequivalence studies.

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Abbreviations

Q1:

Same components as the reference-listed drug

Q2:

Same components in same concentration as the reference-listed drug

Q3:

Same components in same concentration with the same arrangement of matter (microstructure) as the reference-listed drug

IIG:

Inactive Ingredient Guide

RLD:

Reference-listed drug

QbD:

Quality by design

MDD:

Maximum daily dose

SAR:

Structure–activity relationship

NLT:

No less than

NMT:

No more than

API:

Active pharmaceutical ingredient

ICH:

International Conference on Harmonization

Q3A:

Guidance for industry Q3A impurities in new drug substance

Q3B:

Guidance for industry Q3B impurities in new drug product

Q3C:

Guidance for industry Q3C impurities: residual solvents

Q1A:

ICH topic Q1A stability testing of new drug substances and products

IT:

Identification threshold

QT:

Qualification threshold

ANDA:

Abbreviated new drug application

FDA:

Food and Drug Administration

USP:

U.S. Pharmacopeia

CFR:

Code of Federal Regulations

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Authors and Affiliations

  1. Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 7500 Standish Place, Rockville, Maryland, 20855, USA

    Rong-Kun Chang, Andre Raw, Robert Lionberger & Lawrence Yu

Authors
  1. Rong-Kun Chang
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  2. Andre Raw
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  3. Robert Lionberger
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  4. Lawrence Yu
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Corresponding author

Correspondence to Andre Raw.

Additional information

The opinions expressed in this review by the authors do not necessarily reflect the views or policies of the Food and Drug Administration (FDA).

An erratum to this article is available at http://dx.doi.org/10.1208/s12248-015-9823-8.

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Chang, RK., Raw, A., Lionberger, R. et al. Generic Development of Topical Dermatologic Products: Formulation Development, Process Development, and Testing of Topical Dermatologic Products. AAPS J 15, 41–52 (2013). https://doi.org/10.1208/s12248-012-9411-0

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  • DOI: https://doi.org/10.1208/s12248-012-9411-0

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