1. Different definitions
(1) Intermediate: a material produced in the process steps of the API that must undergo further molecular changes or refining to become the API. The intermediates can be separated or not separated.
(2) Active Pharmaceutical Ingredient (API) (or Drug Substance) - Active pharmaceutical ingredient: any substance or mixture of substances intended to be used in the manufacture of a pharmaceutical product and, when used in a pharmaceutical product, becomes an active ingredient of the pharmaceutical product. Such substances have pharmacological activity or other direct effects in the diagnosis, treatment, symptom relief, management or prevention of disease, or can affect the function and structure of the body.
As can be seen from the definition, the intermediate is a key product of the previous process of manufacturing the API and has a different structure from the API. In addition, the pharmacopoeia has the detection method of the bulk drug, but there is no intermediate.
2. Differences in certification
(1) Intermediates (FDA) At present, the FDA requires that intermediates must be registered, CEP is not, but the CTD file must have a detailed process description of the intermediate. In China, there is no mandatory GMP requirement for intermediates.
(2) The API is submitted by the API enterprise, if the API synthesis route is very simple, such as only one step reaction, FDA believes that the risk control is insufficient, it is very likely to extend the inspection of intermediates. Intermediate management is generally in accordance with ISO or combined with Q7a, with quality system management.
