FDA Guidance for the Industry

July 2015
Pharmaceutical Quality/CMC

Analytical Procedures and Methods Validation for Drugs and Biologics

This guidance supersedes the draft of the same name that published on February 19, 2014 (79 FR 17 9467) and replaces the 2000 draft guidance for industry on Analytical Procedures and Methods Validation and the 1987 Guidelines for Submitting Samples and Analytical Data for Methods Validation.

It provides recommendations on how you, the applicant, can submit analytical procedures and methods validation data to support the documentation of the identity, strength, quality, purity, and potency of drug substances and drug products. It will help you assemble information and present data to support your analytical methodologies. The recommendations apply to drug substances and drug products covered in new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologics license applications (BLAs), and supplements to these applications. The principles in this guidance also apply to drug substances and drug products covered in Type II drug master files (DMFs).

This guidance complements the International Conference on Harmonisation (ICH) guidance Q2(R1) Validation of Analytical Procedures: Text and Methodology (Q2(R1)) for developing and validating analytical methods.

This guidance does not address investigational new drug application (IND) methods validation, but sponsors preparing INDs should consider the recommendations in this guidance.

For INDs, sufficient information is required at each phase of an investigation to ensure proper identity, quality, purity, strength, and/or potency. The amount of information on analytical procedures and methods suitability will vary with the phase of the investigation.

For general guidance on analytical procedures and methods validation information to be submitted for phase one studies, sponsors should refer to the FDA guidance for industry on Content and Format of Investigational New Drug Applications (INDs) for Phase 1 Studies of Drugs, Including Well-Characterized, Therapeutic, Biotechnology-Derived Products.

General considerations for analytical procedures and methods validation before conduct of phase two and three studies are discussed in the FDA guidances for industry on INDs for Phase 2 and 3 Studies of Drugs, Including Specified Therapeutic Biotechnology-Derived Products (February 1999) and IND Meetings for Human Drugs and Biologics, Chemistry, Manufacturing, and Controls Information.

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Download “Analytical Procedures and Methods Validation for Drugs and Biologics” ucm386366.pdf – Downloaded 345 times – 134 KB

Books for Method Validations

FDA Reviewer Guidance’ Validation of Chromatographic Methods

November 1994

The purpose of this technical review guide is to present the issues to consider when evaluating chromatographic test methods from a regulatory perspective. The document discusses the points to note and weaknesses of chromatography so that CDER reviewers can ensure that the method’s performance claims are properly evaluated, and that sufficient information is available for the field chemist to assess the method. Analytical terms, as defined by the International Conference of Harmonization (ICH), 1993, have been incorporated in this guide.

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Download “FDA Guidance for Chromatographic Methods” UCM134409.pdf – Downloaded 324 times – 703 KB

U.S. Department of Health and Human Services Food and Drug Administration Center for Veterinary Medicine JULY 1999



(October 21, 2010, this guidance document was revised to update contact information, correct broken internet links and minor formatting changes)

This document is complementary to the parent document which presents a discussion of the characteristics that should be considered during the validation of analytical procedures. Its purpose is to provide some guidance and recommendations on how to consider the various validation characteristics for each analytical procedure included as part of a registration application for approval of veterinary medicinal products submitted to the European Union, Japan, and the United States. In some cases (for example, demonstration of specificity), the overall capabilities of a number of analytical procedures in combination may be investigated in order to ensure the quality of the drug substance or drug product. In addition, the document provides an indication of the data which should be presented in a registration application.

All relevant data collected during validation and formulae used for calculating validation characteristics should be submitted and discussed as appropriate.

Approaches other than those set forth in this guideline may be applicable and acceptable. It is the responsibility of the applicant to choose the validation procedure and protocol most suitable for their product. However it is important to remember that the main objective of validation of an analytical procedure is to demonstrate that the procedure is suitable for its intended purpose. Due to their complex nature, analytical procedures for biological and biotechnological products in some cases may be approached differently than in this document.

Well-characterized reference materials, with documented purity, should be used throughout the validation study. The degree of purity necessary depends on the intended use. In accordance with the parent document, and for the sake of clarity, this document considers the various validation characteristics in distinct sections. The arrangement of these sections reflects the process by which an analytical procedure may be developed and evaluated.

In practice, it is usually possible to design the experimental work such that the appropriate validation characteristics can be considered simultaneously to provide a sound, overall knowledge of the capabilities of the analytical procedure, for instance: specificity, linearity, range, accuracy and precision.

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Download “VICH GL2 FDA Guidance” ucm052379.pdf – Downloaded 291 times – 218 KB

Last Updated: 2016-02-26

Analytical Method Validations
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