Boas práticas de fabricação na indústria farmoquímica: revisão da legislação vigente e proposta de metodologia de inspeção

Abstract

With the approval of the new regulatory framework for good manufacturing practices (GMP) in accordance with international standards and the publication of the Resolution of the Collegiate Board RDC 301 in 2019, audits of suppliers of Active Pharmaceutical Ingredient (API) became mandatory for the pharmaceutical industry. The API GMP program has existed in Brazil since 2005 is currently governed by RDC 654 (2022), harmonized and recognized by international agencies. However, conducting the audits is at the discretion of the responsible auditor who, through a risk assessment, defines what must be verified in the inspections. The general objective of the present work is to identify the quality criteria that are being applied by some of the most prestigious agencies and forums in the international market and to propose a methodology for onsite audit activities in non-sterile solid API manufacturers obtained through the organic synthesis of materials considering the legislation and guides that guide GMPs in regulated markets. For the strategy of elaborating the proposed methodology, a review of the GMP legislation of Brazilian National Health Surveillance Agency (ANVISA) and also of the North American (FDA) and European regulatory agency (EMA) was carried out, in addition to the international guide of GMP for the production of API of the International Conference on Harmonization (ICH) ICH-Q7 and the Pharmaceutical Inspection Convention and Scheme (PIC/S). Data available in the annual report of inspections in national pharmochemicals by ANVISA were also used. Once the main points were identified, the specific guides were reviewed to define the critical parameters to be evaluated and an inspection schedule and a checklist was proposed. It was observed that GMP practices in API production are well-established in the national and international markets. There is an effort between agencies and forums to harmonize quality criteria. This will contribute to ensuring that the practices carried out in the manufacture of APIs are in accordance with international quality criteria, in addition to facilitating market access and harmonization between regulatory agencies, and protecting consumer safety. An opportunity was identified to propose a methodology that guides GMP inspections in pharmochemicals in a way that establishes a logical flow that helps to clearly demonstrate the quality practices carried out by the audited company, considering the guide as a basis of ICH Q7 and RDC 654/2022, including items such as periodic product review, process and cleaning validations, equipment and systems qualifications, in addition to other aspects related to the company's quality system and infrastructure.