Mandating CADIFA for Drug Registration in Brazil: What You Need to Know
Navigating the API requirements for successful drug registration in Brazil can be challenging, especially when these requirements are embedded within broader drug product regulations. This was the case in Brazil, where the rules for APIs were unclear and scattered. This often meant that the pharmaceutical company, not the API supplier, was the primary point of contact with ANVISA regarding the API.
However, the landscape has changed. ANVISA has introduced dedicated regulations focusing solely on APIs, creating a centralized procedure for submitting API DMFs. A critical component of this is CADIFA.
What is CADIFA Brazil?
CADIFA (Carta de Adequação do Dossiê de Insumo Farmacêutico Ativo) is a letter of suitability that confirms the compliance of DIFA (Dossier of Active Pharmaceutical Ingredient) as per Resolution RDC 359/2020. This requirement, effective since August 2020, became mandatory in August 2023.
All pharmaceutical companies (both domestic and international) wishing to register their drug products in Brazil must now obtain a CADIFA from ANVISA. It is important to note that only the DMF (Drug Master File) holder can officially request a CADIFA.
The Role of CADIFA in the Brazil Regulatory Drug Approval Process
Confirming API Quality
CADIFA serves as a confirmation that the API’s quality is suitably controlled. While manufacturers must ensure the API adheres to Good Manufacturing Practice (GMP) requirements, the CADIFA application assessment does not verify GMP compliance services on its own. This is why both a CADIFA and a GMP certificate are necessary for the brazil drug registration and approval process.
Key Point: A CADIFA does not replace a Certificate of Analysis.
Suggested Submission Order by ANVISA:
ANVISA suggests the following order of submission to streamline the medicinal product registration in Brazil:
- CADIFA Application: Submitted with the DIFA reference number.
- ANVISA API GMP Certificate Application: This application must include the ANVISA API GMP certificate application number.
- New Product Marketing Authorization/Post-Approval Variation Application.
CADIFA Application Assessment Timelines
The assessment timelines for CADIFA applications are based on the new product marketing authorization services or post-approval change application deadlines. The clock starts from the date the marketing authorization/post-approval change application is submitted.
Ordinary Category:
- Marketing Authorization: 365 days
- Post-Approval Variation: 180 days
Priority Category:
- Marketing Authorization: 120 days
- Post-Approval Variation: 60 days
For new drugs treating rare diseases, the CADIFA assessment timelines are:
- First Manifestation: 60 days
- Analysis of Deficiency Letter Response (if required): 45 days
How to Communicate with ANVISA: The Solicita System
The Solicita system is ANVISA’s web-based portal for exchanging regulatory information between the agency and the DIFA holder. DIFA holders must register on this system to manage their applications.
Initial CADIFA Application Types:
- Associated CADIFA Application: Submitted with a marketing authorization or post-approval change application for a drug product.
- Expression of Interest: For DIFA holders who intend to have a CADIFA via a stand-alone procedure.
- Standalone CADIFA Application: Submitted when demanded by ANVISA after the approval of an Expression of Interest or by a public invitation from ANVISA’s DICOL/board of directors.
To learn more about CADIFA and ensure a successful drug registration in Brazil, get in touch with our regulatory affairs consulting team.