US FDA has issued a draft guidance on the Bioanalytical Method Validation. The rules provide assistance to sponsors of investigational new drug applications (INDs), new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologic license applications (BLAs), and supplements. The guidance is for developing bioanalytical method validation information used in human clinical pharmacology, bioavailability (BA), and bioequivalence (BE) studies that require pharmacokinetic (PK) or biomarker concentration evaluation.

It also applies to bioanalytical methods used for non-clinical pharmacology/ toxicology studies. For studies related to the veterinary drug approval process (Investigational New Animal Drug Applications (INADs), New Animal Drug Applications (NADAs), and Abbreviated New Animal Drug Applications (ANADAs)), this guidance may apply to blood and urine BA, BE, and PK studies.

The information generally applies to bioanalytical procedures, such as gas chromatography (GC); high-pressure liquid chromatography (LC); combined GC and LC mass spectrometric (MS) procedures. This covers applications using  LC-MS, LC-MS-MS, GC-MS, and GC-MS-MS. It includes ligand binding assays (LBAs), immunological and microbiological procedures that are performed for the quantitative determination of drugs, metabolites and therapeutic proteins in biological matrices, such as blood, serum, plasma, urine, tissue, and skin.

This guidance provides general recommendations for bioanalytical method validation. The recommendations can be modified depending on the specific type of analytical method used. Originally issued in 2001, this guidance has been revised to reflect advances in science and technology related to validating bioanalytical methods. It is now reissued in draft to enable public review and comment before it is finalized, said the regulatory authority.

Validating bioanalytical methods includes performing all of the procedures that demonstrate that a particular method used for quantitative measurement of analytes in a given biological matrix like for instance the blood, plasma, serum, or urine is reliable and reproducible for the intended use.

Fundamental parameters for the validation include accuracy, precision, selectivity, sensitivity, reproducibility, stability and validation which involves documenting, through the use of specific laboratory investigations. There is need to ensure that the  performance characteristics of a method are suitable and reliable for the intended analytical applications. The acceptability of analytical data corresponds directly to the criteria used to validate the method. For pivotal studies that require regulatory action for approval or labelling, such as BE or PK studies, the bioanalytical methods should be fully validated. For exploratory methods used for the sponsor’s internal decision making, less validation may be sufficient, said the regulatory authority.

The Indian CRO and pharma industry have appreciated the guidance which will help during submission of INADs, NDAs and ANDA submission apart from carrying out the BA/BE studies.