Proposta de guia para validação de métodos bioanalíticos por ensaios de ligação de ligantes para análise de biossimilares

Abstract

With the increase of biosimilar drugs on the market, it is essential that there be a more consistent regulatory framework in the different regions of the globe so that the efficacy of therapeutics and patient safety are preserved. To prove pharmacokinetic (PK) similarity, biosimilar drugs need to be proven through bioavailability tests that are similar to biological drugs. To perform these tests is necessary validate the bioanalytical method to be used. Because biologicals are macromolecules, the method normally employed uses the ligand binding technique, unlike synthetic molecules that normally employ liquid chromatography coupled to mass spectrometry. Most regulatory agencies in the world have developed guidelines to guide industries how validation needs to be done in both types of technique. Brazilian Health Regulatory Agency (ANVISA) does not have specific guideline for ligand binding assay (LBA), making companies have doubts on how to present validation of methods to be used in biosimilars studies. In order to assist companies in trials to be presented for bioanalytical method validation, which employs LBA, in relative bioavailability studies to be presented in the submission of the registry this work had as objective to elaborate a guide of bioanalytical methods validation by LBA to support the demonstration of PK biosimilarity among biological medicines in Brazil based on the guidelines of the main regulatory agencies in the world, as well as to describe the validation tests of bioanalytical methods in Brazilian legislation and the assays of LBA described in guidelines of main regulatory agencies. Thus, a descriptive analytical bibliographic study was carried out with the collection of qualitative data from published bioanalytical method validation guidelines by LBA of the main regulatory agencies of the world and the International Council of Harmonization (ICH). This study presents a description with the requirements for validation of bioanalytical methods by LBA of ANVISA and the main regulatory agencies and ICH, for reference standards, specificity, selectivity, residual effect, matrix selection, minimum required dilution, calibration curve, quality control, precision, accuracy, dilution linearity, parallelism, stability and reagents. In addition, a guide was made with the assays to be presented by companies in order to support the validation of the bioanalytical methods of pharmacokinetic similarity studies for biological drugs with the suggestion that the same becomes in future an ANVISA resolution for bioanalytical methods validation that employ LBA.