For a long time, an API manufacturer communicated with ANVISA only through the Pharmaceutical company, the marketing authorization holder. (MAH). However, this is no longer the case. On August 3rd, 2020, new API regulation came into force in Brazil.  

The new set of rules includes three distinct guidelines for APIs in Brazil, known as the Resolutions of the Collegiate Board (RDCs). RDC 359/2020, RDC 361/2020, and RDC 362/2020 represent a complete overhaul of Brazil’s API Regulatory environment.

• RDC 359 pertains to the API manufacturer and specifies the technical requirements for ANVISA approval of the API. It also explains how this API's lifecycle will be handled.
• RDC 361 applies to the drug product's manufacturer, the MAH, and describes the process for the MAH to link its dossier to a CADIFA, either through a new submission or a variation procedure. It also defines how to handle variation procedures for APIs in case there will be no link to a CADIFA or if a CADIFA was already issued for the API and linked to that dossier.
• RDC 362 specifies how ANVISA will authorize good manufacturing practice certificates to these API manufacturers, also known as DIFA holders.

A CADIFA is a letter from ANVISA, meaning that DIFA (Active Pharmaceutical Ingredient dossier or the DMF) is approved. All the quality attributes of an API are specified in a document called Drug Master File (DMF). The DMF, along with  other administrative documents, is what we refer to as DIFA. ANVISA can issue a CADIFA after evaluating a DIFA and determining that it meets the standards outlined in RDC 359.

So, if the API manufacturer owns a CADIFA, it will begin communicating directly with ANVISA about the API.

The CADIFA includes basic API information, such as the CADIFA number, API name, name and address of the DMF holder, manufacturing sites where API and its intermediates are manufactured, storage conditions, packaging description, API specifications, retest or expiry date, and declaration of access.

A CADIFA is similar to a CEP in Europe but with the added flexibility of not being tied to a specific monograph, i.e., ANVISA allows for the use of any of their recognized pharmacopoeias (RDC 511/2021) or even in-house specifications.

Starting from August 2023, any domestic or foreign company wanting to register its drug products in Brazil must first obtain a CADIFA.

It is necessary to be fully aware of the new regulations in Brazil. To know more about the functioning of the ANVISA and the distinct Regulatory processes in Brazil, contact Freyr for expert Regulatory solutions today!