In order to ensure higher quality in the medicines consumed in Brazil, on August 3, 2020, the National Health Surveillance Agency (ANVISA) published three resolutions that updated the regulation on active pharmaceutical ingredients (IFAs).
The new regulatory framework revokes, as of March 1, 2021, RDC No. 57/2009, which provides for active pharmaceutical ingredients and related documents. Therefore, as of this date, there will no longer be an IFA registration submission, but the Adequacy Letter of Active Pharmaceutical Dossier, which is an administrative simplification of the registration.
The first published rule, RDC nº 359/2020, instituted the Active Pharmaceutical Input Dossier (DIFA) and the Adequacy Letter of Active Pharmaceutical Input Dossier (CADIFA) for IFAs used in the manufacture of new, innovative, generic and similar drugs.
The active pharmaceutical ingredient (IFA) is the substance that gives the medicine its pharmaceutical characteristic, that is, what makes a certain medicine work, the DIFA was established by the standard as a set of administrative and quality documents of a certain active pharmaceutical ingredient, while CADIFA is the administrative instrument that certifies the adequacy of DIFA.
It should be noted that it does not apply to atypical inputs and those used in the formulation of a pharmaceutical product notified or framed as a biological product, herbal medicine or traditional herbal medicine, specific medicine or dynamized medicine, nor to IFA in association with synthetic or semi-synthetic product IFA. new, innovative, generic or similar medicine.
The second published rule, RDC nº 361/2020, provides for submission of the Active Pharmaceutical Input Dossier both in the registration and in the post-registration of medicines, respectively, determining that the grant of registration of the drug is subject to the certification of Good Manufacturing Practices of valid IFA and CADIFA.
The third resolution, RDC nº 362/2020, establishes the criteria for the Certificate of Good Manufacturing Practices (CBPF) for international establishments that manufacture IFAs obtained by plant extraction, chemical synthesis, classic fermentation or semi-synthesis and institutes the program of inspection for international establishments of active pharmaceutical ingredients.
In general, certification will depend on verifying compliance with the requirements recommended by the IFA Good Manufacturing Practice standards, using one of the following measures:
- evaluation of documents for companies inspected by a health authority recognized by Anvisa as equivalent in relation to the measures and controls applied to prove GMP of IFA;
- evaluation of documents and conducting risk analysis that justifies the issuance of the certificate; or
- evaluation of an inspection report issued by the Agency as a result of conducting an on-site inspection, motivated by conducting a risk analysis or by the absence of an inspection report.
It is important to note that according to RDC nº 362/2020, Anvisa may carry out a routine health inspection or investigation of complaints or possible irregularities in any manufacturer of active pharmaceutical ingredients used in medicines in Brazil, regardless of the certification process. The certification does not exempt the company from receiving the Agency’s on-site inspection, even during the validity of the GMP certificate.
The new regulatory framework for IFAs comes to guide and harmonize the increase in the levels of manufacturing, also bringing equality to domestic and foreign manufacturers. The new resolutions, by providing for the direct sending of documentation by the DIFA holder to Anvisa, alter the dynamics currently established, that of intermediation of the holder of the drug registration in Brazil. It will be the first time that a foreign company, without CNPJ, will be able to petition Anvisa’s systems for purposes of documentary approval.
Coauthors: Sueli de Freitas Verissimo Vieira and Raíssa Pinati do Nascimento
