- Different definitions:
The two definitions are as follows:
Intermediate: A material produced during a process step of the drug substance that must undergo further molecular changes or refining to become a drug substance. The 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 require a drug production license, can be produced in ordinary chemical plants, as long as it reaches some levels, it can be used for the synthesis of drugs.
FDA’s summary of the major intermediates is divided into:
a. Hub intermediates: intermediates that can be synthesized by different methods;
b. Key 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 of a chiral atom. Can be understood as the main part of drug synthesis.
c. Final intermediate: the preceding step in the final reaction of the drug substance synthesis.
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. - Differences in certification:
Currently, the FDA requires intermediates to 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.
Submitted by API companies, if the API synthesis route is very simple, such as only one step reaction, FDA believes that 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.
Third, from the perspective of new drug development, the API is a compound that can be safely used in the human body for treatment and diagnosis after sufficient pharmaceutical research; Intermediates are compounds in the process of synthesizing apis and are not necessarily therapeutic or toxic. Note that what is said here is not necessarily, some intermediates in the synthesis process of apis are also apis.
From the perspective of pharmaceutical management, the API should apply for registration with the drug regulatory authorities (the State Food and Drug Administration in China, the FDA in the United States, and the EMA in Europe) in accordance with the law, and obtain the approval number after synthesis in the factory in accordance with GMP; Intermediates are only intermediate products in the process of synthesizing apis, and do not need to obtain a document number. It should be noted that the same compounds as apis do not have a label or are not manufactured in a GMP facility.
For example:
Amoxicillin capsules are called preparations, amoxicillin is called apis, and 6-APA is called intermediates.
Ceftriaxone sodium powder injection is called preparation, sterile ceftriaxone sodium is called raw material, 7-ACA is called intermediate.
V. Relationship between the two: - The specific substances of the two are different
Pharmaceutical intermediates, also known as organic pharmaceutical intermediates, refer to a semi-finished product, which is a product of the production of certain products. The substance refers to the active ingredient of the drug, and is also the basic substance that constitutes the pharmacological action of the drug. An API is a drug active substance configured by chemical synthesis, plant extraction or biotechnology.
2, the production of apis must rely on intermediates
Pharmaceutical intermediate is a chemical raw material or chemical product in the process of drug synthesis, and is also an intermediate product in the process of manufacturing apis. It is a product in the path of synthetic apis, which is produced in the process step of apis, and must go through the next molecular change or refining to become a substance of apis. The API can be directly used as a preparation, and the intermediate can only be used to synthesize the next product, and the API can be manufactured through the intermediate. - Different production requirements
Pharmaceutical intermediates are intermediate products in the process of producing apis, so pharmaceutical intermediates can be produced in ordinary chemical plants. If you want to produce apis, you need to obtain a production license for apis before you can produce them.
To sum up, reliable pharmaceutical intermediates and apis are two very different substances, and the production of pharmaceutical intermediates has a relatively low threshold, while the production of apis needs to meet a higher production threshold. If you want to make apis, you must also have appropriate pharmaceutical intermediates as raw materials.
ABOUT US
About Wisdom DrugsWisdom Drugs Co .,Ltd was founded in Sep. 2011 whose headquarter located in Changzhou Creative Industry Park, having a branch in India. The company’s R&D center is engaged in not only the process development of APIs,pharmaceutical intermediates, poly-peptide compounds and heterocyclic compounds,but also the optimization and production. We are devoted to the synthesis customization and the technology transfer, enabling compounds to be scaled from laboratory to commercial to meet the requirements of different customers.
