Brazil Report: New Rules Challenging for New Registrations
21 March 2012 
Registrations in Brazil have always been a challenge, especially for companies seeking to expand their product portfolios. In addition to regulatory barriers, there are political ones as Brazil employs a non-tariff barrier for new entrants. A non-tariff barrier uses the World Trade Organization to investigate anti-dumping claims and countervailing duties. These barriers effectively repress new entrants to the market.
Registration of generic technical products are evaluated by a joint committee of three pesticide regulatory agencies: ANVISA, IBAMA and the Ministry of Agriculture. The registration is ultimately granted by the Ministry of Agriculture. This process requires about two years to complete. For example, most of the registrations that were approved in 2011 were submitted in 2009, and the approval of current submissions tend to take longer due to the number of submissions in the queue.
Since 2006, when Brazil issued a decree approving the guidelines for technical product equivalency, more than 200 registrations of technical products and 160 formulated products linked to these technical products were approved, resulting in an intense competition, and consequently, some deflation of the prices of crop protection products. As a result of price deflation, some generic companies started facing financial difficulties and started looking for partnership opportunities with well-capitalized foreign companies.
Technical product registration based on equivalency is evaluated in three phases based on a five-batch sample and physic-chemical tests (Phase I); acute toxicological and mutagenicity tests (Phase II); and sub-chronic and other tests (Phase III). A product that has been confirmed for equivalency in the first phase goes forward to the following phase(s).
According to registration authorities, 40% of all approved registrations were evaluated on Phase I. Many applicants decide to not go forward with the acute toxicological and mutagenicity tests until they learn from the regulatory authorities whether the product would be approved in Phase I.
If a company decides to wait to conduct toxicological and mutagenicity testing until Phase 1 approval is granted, the applicant could save some money, but obviously the process can be delayed significantly. And there is a second downside to waiting for Phase 1 results: The selected sample to perform these tests should have the same impurity profile of the sample of the five-batch study that has the worst impurity profile. Thus a very detailed review of the five batches, impurity profile and all information of the product of reference should be done in order to anticipate if the equivalency could be approved on Phase I, and for the cases of Phase II evaluations, to define the appropriate sample for testing.
In December 2011, there were more than 340 technical product registration submissions in the queue for evaluation, plus 117 under evaluation for a total of approximately 460 submissions. Even though these numbers might be not relevant in markets like in Argentina, India or China, they are significant in Brazil, especially where companies with proprietary data dominate more than 80% of the market share. This prompted Brazilian regulatory authorities to make important changes in regulations in order to standardize proceedings, to avoid companies submitting incomplete data packages and to speed up registration evaluations. In other words, it became much more difficult, complex and expensive than before.
New Rules, New Obstacles
Two important new rules issued in 2011 are having a direct impact on generic product registrations, and they are still raising many uncertainties for those who have ongoing applications or who are completing dossier packages for first submission.
The first new rule was passed June 16 by ANVISA, RDC #25, which makes it mandatory for all submitted data packages and efficacy studies to be in Portuguese. The two outcomes of this rule are potential delays during the translation process, and secondly, cost and accuracy of translations of very technical dossiers.
The second new rule was passed Sept. 21 – a joint provision passed by ANVISA, IBAMA and the Ministry of Agriculture. The “Guidance for the technical and administrative procedures for the evaluation of the determination of equivalence of technical products” established several changes in the five-batch studies as well as proceedings regarding report amendments, samples for toxicological and mutagenicity studies and the screening of the samples.
Some of the new guidelines regarding the five-batch report:
■ Validation of analytical methods and the batch analysis must be performed with the same equipment and test facilities
■ Balance mass: minimum of 98%
■ Analytical scan showing the impurities profile of the analyzed product (3D)
■ Must be oriented by theoretical discussion of formation of impurities, issued by the manufacturer
■ Must adopt the respective analytical standards to each impurity to be searched instead of analogue standards
■ Only one amendment shall be accepted
■ Toxicological and environmental relevant impurities must be identified and quantified
It was also established that the registration data packages that were not completed according to this new guideline could be amended, or companies would be granted additional time to complete them. Among the more than 340 registration submissions in the queue for evaluation, more than 280 were considered ineligible for registration, and most of these were companies that asked for additional time to complete the data package. Of the remaining 60 submissions, some companies missed the deadline to request for additional time – and there is the risk that these submissions can still be rejected. Ultimately, very few submissions were considered eligible for evaluation.
In addition to the new criteria, there are several submissions for which data packages cannot be completed because batch samples have expired during the approval process. Thus, new studies should be presented to replace the old ones. Besides the high cost to resubmit the dossier, the possibility of requiring new GLP data is a lengthy process these days as CROs around the world are backlogged.
For new submissions, the data package should follow these new guidelines, and those that are not in full compliance will be rejected. In these cases, rejections are automatic and companies will not have the opportunity to update their data packages. They will be forced to begin the process again.
In conjunction with the new rules, new interpretations of them could muddle approvals. The products most vulnerable to interpretive denial are formulated products.
Technical Grade Approvals
According to government records, about 25% of the technical product registrations based on equivalency were rejected until now.
Most prevalent reasons for rejections of tech:
■ Studies performed in laboratories without GLP compliance
■ Missing study reports in the submitted data package
■ Submissions did not prove equivalency to registered
active substances
■ Same manufacturer with different five-batch results of the same active ingredient with different registration submissions
■ Banning of active ingredients
It appears that some of the listed reasons for rejections seem to be easily avoided. However, some companies still misunderstand Brazilian regulations. It may be suggested that some of them are new, foreign players that lack a clear understanding of the comprehensiveness of the regulations. On the other hand, the majority of rejections have been handed down to established, Brazilian companies with long history in pesticides business.
The good news is that 2011 was a record year for technical-grade approvals based on equivalency. However, as new regulations continue to be interpreted, it appears that new submissions will have a difficult road ahead without proper attention to detail and formality.
Flavio Hirata is a registration consultant for AllierBrasil in Sao Paulo. He is an editorial advisor to Farm Chemicals International and a frequent contributor to FCI’s magazine, website and Trade Summits. He is a certified agronomist and holds a master’s degree in business administration.
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