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DDCM- What are the most demanding requirements by ANVISA?




In early May, COPEC / ANVISA took an excellent initiative, they made a presentation on the main reasons that generate demands in the DDCM. Based on this presentation, and on our experience of outlining DDCMs, we have made a list of the most demanding requirements and we will provide some tips to avoid them.

We divided it into 3 blocks: Requirements of the organizational and administrative part, the part of the Dossier of the Experimental Medication, and the Clinical part. Today we will cover the first two:


1) Requirements on the organizational and administrative part:


ANVISA reported minor inattentions that cause delay in analysis and rework, which can be easily avoidable, such as:


Problems in electronic media:


· Missing electronic media

· Files without textual search capability (total or partial) Files whose copy / paste function is not satisfactory.

· Incomplete folders on electronic media

· Texts containing errors or Reference Source not found.


Problems related to information inconsistencies in the process:


· Different storage conditions listed in the experimental medicine dossier and FAEC (Clinical Trial Presentation Form)

· Divergence in the Countries where the trial is planned: ClinicalTrials.gov x FAEC x FP (Petition Form) DDCM

Problems related to document organization and translation Documents without index

· Indexes that are not reliable where the information is located.

· Formatting errors (number of tables, pagination) and their respective mentions during the process

· Mention of tables, figures or documents that are not part of the process.

· Truncated tables, unreferenced acronyms that cannot be interpreted

· Ordering documents

· Translation errors

· Outdated versions

· Different medications header x body of the document

· Outdated forms after compliance with requirements

· Requirements on the Experimental Medication Dossier


Active Pharmaceutical Input


· As for Active Substance / IFA, the requirement items correspond to 23% and the main issues involve two blocks:

· Impurities, degradation products and residual solvents Flowchart / Equipment / Batch sizes

· IFA stability tests not performed (ex: characterization):

· Expected tests not performed (without justification) Insufficient data to cover the expiration date.


2) Experimental Medicine:


Responsible for 30% of the requirements, the main reasons for which are:

· Questions about stability, mainly insufficient data that do not cover the expected time of use during the clinical study, lack of stability of use and not performed planned tests without due justification.

· Doubts about the manufacturing process with requests for clarification on the design of equipment and batch sizes, as well as greater detail of the Flowchart, critical steps and changes in the production process.

· In quality control the main questions are about the evaluation of impurities / specification limits.


As can be seen, the technical and administrative requirement points are similar to those received when registering the product, and the companies have the technical knowledge, but also have flaws in the assembly.


On the organizational side, there are quite simple and avoidable mistakes, but with the rush and tight deadline to meet the agreed submission date, they end up passing. An important tip to avoid technical requirements is to understand the purpose of each item in the document and, when the item is already structured, question whether the arguments and documentation presented corresponded to the item's objective. If you have doubts, certainly, so will the ANVISA technician.


A reflection that companies need to make is if 2 or 3 more days to produce a thorough verification in the process is really a delay or a gain of time, since it avoids certain strict requirements and time loss in the analysis of the process. Is the most important thing to meet a deadline at any cost or to meet quality parameters?


In the final assembly of the process, it is essential to have a specialist who has a good technical knowledge of the areas that make up the DDCM, but above all be able to have a global view of the project in order to make a thorough verification of the information, ensuring that they are present in a coherent and understandable in all parts of the dossier.


Remember: a DDCM must tell the story of the technical and clinical development of the experimental product within the script that ANVISA expects to receive.


In the next article, we will comment on the main clinical reasons for the DDCM's demand.

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