1. Different definitions:
ICH Q7A and ICH Q7A are defined as follows:
Intermediate: A material produced in the process of an API that must undergo further molecular change or refinement before becoming an API. Intermediates can be separated or not separated. Pharmaceutical intermediates are actually some chemical raw materials or chemical products used in the process of drug synthesis. This chemical product does not need a drug production license, can be produced in ordinary chemical plants, as long as it reaches some levels, can be used for drug synthesis. FDA classifies major intermediates into: a. Hub intermediates: intermediates that can be synthesized by different methods; b. Critical intermediate: Usually an intermediate in which an important part of a molecule is formed for the first time. For example, a molecule with stereoisomerism first introduces an intermediate to a chiral atom. Can be understood as the main body of drug synthesis. c. Final intermediate: the preceding step in the final reaction of API synthesis.
Active Pharmaceutical Ingredient (API)(or Drug Substance) — Active pharmaceutical ingredient (API)(or drug substance) — Any of a substance or mixture of substances intended to be used in the manufacture of a drug product and, when used in a pharmaceutical product, to be an active ingredient of the drug 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, intermediates are the key products of the previous process to make the API and have a different structure from the API. In addition, the pharmacopoeia has the detection method of active drug, but there is no intermediate.
2.Differences in certification: Currently, FDA requires that intermediates must be registered, while CEP is not. However, detailed process description of intermediates should be included in the CTD file. In China, there is no mandatory GMP requirement for intermediates. 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 the intermediate. Intermediate management is generally in accordance with ISO or Q7a, quality system management can be.
3. From the perspective of new drug development, API is a compound that can be safely used in human body for treatment and diagnosis after sufficient pharmaceutical research. Intermediates are compounds in the process of synthesizing apis, which may not be therapeutic or toxic. Note that some of the intermediates in the synthesis of apis are also apis.
Iv. From the perspective of pharmaceutical administration, API should be registered with the drug regulatory authorities (the State Food and Drug Administration in China, FDA in the United States, and EMA in Europe) in accordance with the law. After obtaining the approval number, the API should be synthesized in a factory that complies with GMP. However, intermediates are only intermediate products in the process of synthesis of active drug without the need to obtain the document number. It should be noted that the same compounds as apis are not licensed or manufactured in GMP facilities. For example, amoxicillin capsules are called preparations, amoxicillin is called apis, and 6-APA is called intermediates. Ceftriaxone sodium powder is called preparation, sterile ceftriaxone sodium is called API, 7-ACA is called intermediate.
V. Relationship between the two:
1. The specific substances of the two are different. Medical intermediates are also known as organic medical intermediates, which refer to a semi-finished product and a product of the production of some products. The active substance refers to the active ingredient of a drug, which is also the basic substance constituting the pharmacological action of a drug. An API is a drug active substance that is configured by means of chemical synthesis, plant extraction or biotechnology.
2.The production of API must rely on intermediates. Pharmaceutical intermediates are a kind of chemical raw materials or chemical products in the process of drug synthesis, as well as intermediate products in the process of API production. It must undergo a further molecular change or refinement before it becomes a substance of the API. While the API can be directly used as the preparation, the intermediate can only be used to synthesize the next product, through which the API can be manufactured.
3.Production requirements Different medical intermediates are intermediate products in the process of producing apis, so medical intermediates can be produced in ordinary chemical plants. If you want to produce the API, you need to obtain the production license of the API before you can produce it. To sum up, reliable medical intermediates and apis are two completely different substances, and the production of medical intermediates has a relatively low threshold, while the production of apis needs to meet a higher threshold. In order to make an API, it is necessary to have a suitable pharmaceutical intermediate as the raw material.
Post time: Nov-14-2022