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Why are 24% of drug registrations still rejected?




Why are 24% of drug registrations still rejected?

Last Thursday, 05/21, Gustavo Mendes of ANVISA presented the main reasons for the denial of registration and post-registration in 2019 in an online meeting. Most reasons are not surprising because they are old acquaintances of the regulated sector:

· Analytical validations lead the ranking sometimes for simple issues such as non-compliance with mandatory items (for example, linearity without all points or not covering the entire range of quality control specifications). But the main issues are related to selectivity, which, as explained, generate problems in issues involving degradation products related to RDC 53/15 and RDC 166/2017, with special emphasis on the first;

· Stability studies: absence of photostability without justification, absence of analysis at times without justification, absence of analysis of degradation product or other important parameters, study with failed analyzes without justification, and presentation of accelerated stability without long term in progress;

· Certificate of Good Manufacturing Practices: CBPF is not obtained before the analysis of the registration process is completed;

· Bio-exemption study: failure of the study due to the absence of the drug's solubility tests and, surprisingly, for the pharmaceutical form, oral solution for not using excipients with the same function as those of the reference medicine;

· Inadequate Quality Control specifications without proper discussion to support the adopted parameters and, mainly, not to relate the specifications with potential for impurities arising from the synthesis route and the degradation profile;

· Groove problems: adoption of groove when the reference does not have it (or vice versa) and absence of quality control analysis of the separate parts of the tablet in the case of functional grooves;

· API manufacturer not approved.


For innovative medicines, the following reasons are added:

· Disapproval of bioequivalence studies where bio is the only pivotal study and the company is unable to support pharmacokinetic differences to demonstrate safety and effectiveness.

· Absence of rational or safety and effectiveness study;

· Not linking Specific Clinical Trial Dossier - DEEC to DDCM. But some reasons can be surprising and lead us to think about why some companies still insist on submitting processes without basic items that only take the time of technicians who could be analyzing processes with chances of registration:

· Absence of a bioequivalence or pharmaceutical equivalence study;

· Absence of quality control documentation from the importer;

· Absence of the open part of the Drug Master File for th IAPI;

· Absence of documentation of the packaging material;

· Absence of description of the manufacturing method;

· Not meeting requirements.


For post-registration the reasons are basically the same as those for registration for technical documentation plus:

· Absence of the amendment for conditional approval provided for in 219/18;

· Manufacturing of lots in an unapproved location;

· Justifications for post registration are not accepted.


ANVISA's speeches point out that companies need to improve their ability to argue in the elaboration of justifications about the absence of documents and deviations found, as well as rationals to support their claims. It was also clear that well-planned and well-organized processes save time for ANVISA and companies that will no longer have to comply with unnecessary requirements. In this sense, Gustavo Mendes informed that GGMED is standardizing the analysis of processes to reduce the difference in analysis between technicians and that it intends to intensify the alignment with the regulated sector on the presentation of technical information in dossiers in order to reduce the requirements and rejections, which are still very high and occur in around 24% of the processes.


It brings great satisfaction to observe the maturity of ANVISA in the analysis of the processes, with the adoption of a partnership posture and aimed at approval, trying to understand the reasons for the failures and help the regulated sector to overcome them. Fortunately, the time of lack of dialogue and summary rejections is behind us.

Questions on the topic? Forward to our email contato@inovatie.net.br




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