Regulatory Focus™ > News Articles > FDA Updates Bioanalytical Method Validation Guidance to Include Biomarkers, Diagnostics

FDA Updates Bioanalytical Method Validation Guidance to Include Biomarkers, Diagnostics

Posted 12 September 2013 | By Alexander Gaffney, RAC

A new draft guidance document released by the US Food and Drug Administration (FDA) aims to assist sponsors of investigational new drug applications (INDs), biologic license applications (BLAs) and new drug applications (NDAs) with developing bioanalytical method validation information required to support most applications.

Background and Basics

The draft guidance, Bioanalytical Method Validation, was originally released in May 2001. In the ensuing 12 years, FDA said it has held a number of workshops and other events that have informed the development of numerous changes to the document. But the main changes, FDA said, simply have to do with scientific advancements that have taken place over the course over the last decade.

"The revised draft guidance contains a number of new sections, including sections on endogenous compounds, incurred sample reanalysis, biomarker assays, use of diagnostic kits and new technologies, system suitability, and examples of report formats for tabular data listings," FDA wrote in its Federal Register notice on the guidance. "In addition, FDA has updated sections where needed, such as the sections on chromatography and ligand-binding assays."

At issue is how drugs, metabolites and biomarkers undergo quantitative evaluations, and whether the analytical methods used by industry to study their products can ultimately be trusted by FDA regulators. In order to ensure the use of validated analytical tests, the guidance established six "fundamental parameters" for validation:

  • accuracy
  • precision
  • selectivity
  • sensitivity
  • reproducibility
  • stability

The studies in question should be well-known to anyone within industry: Pharmacokinetic (PK), pharmacology, bioavailability (BA), bioequivalence (BE) and biomarker concentration studies.

The extensive and largely technical document covers a wide range of potential occurrences, including the situations in which full (re)validation would be needed, or simply partial or cross validations. To paraphrase, full validation will be required only for novel bioanalytical methods, analyses of new drug entities or for revisions to existing analytical methods that add metabolite quantifications. Most other changes will require only a partial validation of the modification.

FDA adds that any laboratory conducting this testing should have written standard operating procedures (SOPs) in place to "cover all aspects of analysis from the time the sample is collected and reaches the laboratory until the results of the analysis are reported [to FDA]."

Comments on the guidance are due in 90 days after official publication (scheduled for 13 September 2013).

Bioanalytical Method Validation

Federal Register

[Editor's note: While I ordinarily try to provide more in-depth analysis, the highly technical nature of this particular guidance does not lend itself well to summarizing.]

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