There are those who disagree with the way ANVISA will control the Active Pharmaceutical Ingredient (APIs), but it is difficult to disagree that controlling the quality of inputs is fundamental.
But why is the API so important?
API is the most important component of any medication, being responsible for its therapeutic action and for unwanted side effects (toxic effects).
Every chemical substance usually has toxicity. The presence of impurities means additional toxicities to the drug.
The impurity profile of an API is the set of synthetic impurities and degradation products and is directly related to its production process. Controlling the presence of each impurity means directly controlling the quality of the API.
Small changes in the synthesis route can alter its quality (presence of impurities) and thus affect its effectiveness.
Important properties of the API can be changed by modifications in the manufacturing process. For example, modifications of the solvents used in purification processes by recrystallization can alter the crystalline characteristic of the API (existence of the so-called polymorphism). There are examples of APIs that have different solubilities for different polymorphs, which may impact the effectiveness of solid dosage forms.
But what is ANVISA actually proposing?
ANVISA intends to create two documents: the Active Pharmaceutical Ingredient Dossier (APID) and the Adequacy Letter of Active Pharmaceutical Ingredient Dossier (ALAPID).
The APID must be sent to ANVISA by its holder (API manufacturer) between 180 and 60 days before the submission of the medication registration petition when there is a need to protect intellectual property or as an integral part of the registration petition when there is no need for registration. protection of intellectual property. The only provision for submitting APID, that is not linked to a registration dossier, is at the request of ANVISA, in cases of public interest or risk of shortage of API in the country.
The items required for APID are fully aligned with the content required in module 3.2.S of the CTD format (Common Technical Document - registration dossier format accepted by more than 50 countries). This makes negotiation much easier to obtain information from international API manufacturers, as they are already familiar with the format and content being demanded by ANVISA.
After due analysis and adequacy of the APID information, Anvisa will issue the Adequacy Letter of the Active Pharmaceutical Dossier (ALAPID) that can be used in the registration or post-registration petition.
An important point is that ANVISA will start to demand the certificate of Good Manufacturing Practices for all manufacturers of APIs. ANVISA is disclosing that, as they have established one of the risk matrix and will accept inspection reports from other agencies, less than 20% of international API manufacturers will need to be inspected and therefore they will be able to handle the inspections. We shall hope they're right!
A final issue that calls my attention is that the GMP request must be made by the company that manufactures the drug that will use the API.
The fact is that companies will have to adapt and present information in the new format covering all the proposed new requirements, even though in terms of content, ANVISA has already been charging most of the information through requirements.