ANVISA has just published the new version of the Cadifa Manual, but what were the main changes? Was there any flexibilization? Check out the text below:
The new updates are:
1. Inclusion of an analysis period following the deadlines provided by Law No. 6.360/1976 (§ 2, art. 17-A), counted from the registration or post-registration protocol of the drug and which may be extended up to one third of the original term (§ 5, art. 17-A):
a) Ordinary category: 365 (three hundred and sixty-five) days for registration and 180 (one hundred and eighty) days for post-registration of medication; and
b) Priority category: 120 (one hundred and twenty) days for registration and 60 (sixty) days for post-registration of medication.
This is a very important point, as it makes it clear that the analysis of APID (the Active Pharmaceutical Input Dossier) must be parallel to that of the drug, to avoid delays with the registration. On the other hand, it makes it clear that ANVISA has no intention of analyzing APIDs that are unrelated to registration dossiers.
2. In the company's register, they included a clarification, explaining that the APID holder must be the administrative headquarters of the API (Active Pharmaceutical Input) manufacturer, or holding of the group to which it belongs.
A note was also included, suggesting companies which are not domiciled in Brazil to be represented by a branch or another authorized company in Brazil, in order to ease the communication and understanding of the legislation.
Note: This note demonstrates the concern that foreign companies are not prepared to deal directly with ANVISA is true and vice versa.
3. The company registration review form is available at https://tinyurl.com/3ne7uacz
4. Updated CADIFA List of Petitions is available at: https://tinyurl.com/552h7kv4
5. The suggestion for naming the CTD module 3.2.S files for APID submission, is available at https://tinyurl.com/jbcexfwd, and from a CADIFA template https://tinyurl.com/jy25zhp4
6. Clarification on where to place the studies that qualify the acceptance criteria for impurities and degradation products can be found in section “3.2.S.3.2 Impurities”.
This update of the CADIFA manual was intended to clarify the system for registering companies to apply for APID. However, even with these clarifications and details, a lot remains unresolved.
As soon as the API regulatory framework was published, international manufacturers were first excited because they thought they could get their CADIFAs independently and no longer customize their DMF according to the requirements of each drug manufacturer and their respective interpretations of the law. A year later, what should be the great advantage of the regulatory framework of the API, still has no prediction of when it will happen.
In addition, it established a direct relationship between ANVISA and the API Manufacturer, but without establishing a legal provision on how this relationship can be brokered by a local representative/company to facilitate communication. I personally have already reached out three times, requesting clarification on this issue, and the response was that they made a legal consultation and there is still no feedback.
Unfortunately, the truth is that this regulatory framework of the API did not convince the regulated sector of its usefulness because:
For API manufacturers it only created the need to register and deal directly with ANVISA without the counterpart of the drug manufacturer's independence.
For companies with local production, APID is linked to the registration of their medicine, but they cannot intervene in this process.
For companies with vertical production that manufacture the API and the medicine, APID/CADIFA only created one more bureaucratic step, since the API will only be used in their product.
For the company that obtains the license to market a product in Brazil that is not the international holder of the drug, it created a complication because API manufacturers may not want to submit the APID either due to lack of interest, or due to a contract with other companies in Brazil to which the API is already sold. And, as I've seen happen in the past, it ends up compromising the international agreement with the drug manufacturer and the deal to be undone.
ANVISA's intention to optimize administrative resources with the implementation of a single DMF analysis for all drug manufacturers that make use of the API is commendable and, at the same time, guarantee the quality of the API used in Brazil. However, COIFA urgently needs to find a way to equalize the above issues so that the regulatory framework of the API can be implemented, bringing the expected benefits.