Views: 88 Author: Site Editor Publish Time: 2023-04-20 Origin: Site
When it comes to the pharmaceutical industry, intermediates and APIs are two terms that are commonly used. Intermediates refer to the chemical compounds that are produced during the manufacturing process of a drug, which later undergo further processing to become the active pharmaceutical ingredient (API).
APIs, on the other hand, are the final products that are used in medications to treat various diseases and conditions. While they are related, intermediates and APIs serve different functions and play distinct roles in the drug development process. In this article, we will explore the difference between intermediates and APIs in the context of the pharmaceutical industry, as well as their relationship to one another.
ICH Q7A defines both as follows:
A material produced in the process steps of the raw material drug that must undergo further molecular changes or refinements before it can become a raw material drug. Intermediates may or may not be isolated.
Pharmaceutical intermediates are actually some chemical raw materials or chemical products used in the process of pharmaceutical synthesis. This kind of chemical product does not require a drug production license, and can be produced in ordinary chemical factories. As long as it reaches a certain level, it can be used in the synthesis of drugs.
The FDA's summary of the main intermediates is divided into:
a. Hub intermediates: intermediates that can be synthesized by different methods;
b. Key intermediate: usually the intermediate in which an important part of the molecule is formed for the first time. Such as: the first introduction of chiral atom intermediates into molecules with stereoisomerism. It can be understood as the main part of drug synthesis.
c. Final intermediate: the previous step in the final reaction of the synthesis of the API.
Active Pharmaceutical Ingredient: Any substance or mixture of substances that is intended to be used in the manufacture of a drug and, when used in a drug, becomes an active ingredient of the drug Element. Such substances have pharmacological activity or other direct effects in the diagnosis, treatment, symptom relief, treatment or prevention of diseases, or can affect the function and structure of the body.
It can be seen from the definition that intermediates are the key products of the previous process of making APIs, which are different in structure from APIs. In addition, there are detection methods for raw materials in the Pharmacopoeia, but not for intermediates.
The difference in certification:
At present, FDA requires intermediates to be registered, while CEP does not, but CTD documents must have detailed process descriptions of intermediates. In China, there is no GMP mandatory 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, and it is very likely to extend the inspection of intermediates. Intermediate management is generally in accordance with ISO or combined with Q7a, and quality system management is sufficient.
From the perspective of new drug development,
The API is a compound that can be safely used in the human body for therapeutic diagnosis after sufficient pharmaceutical research; while the intermediate is a compound in the process of synthesizing the API, which does not necessarily have therapeutic effect or toxicity . Note that what is said here is not necessarily the case. Some intermediates in the synthesis of APIs are also APIs.
From the perspective of pharmaceutical management
Raw materials should apply for registration to the drug regulatory authority (the State Food and Drug Administration in China, the FDA in the United States, and the EMA in Europe) according to the law, and comply with GMP after obtaining the approval number.
Synthesized in the plant; and the intermediate is only an intermediate product in the process of synthesizing the raw material drug, and does not need to obtain a document number. It should be noted that the compound that is the same as the API is not an API if it has not obtained a document number or is not produced in a GMP plant.
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 in the production of certain products.
The raw material drug refers to the active ingredient of the drug, and it is also the basic substance that constitutes the pharmacological action of the drug. API is a pharmaceutical active substance formulated by chemical synthesis, plant extraction or biotechnology.
The production of raw materials must rely on intermediates
Pharmaceutical intermediates are chemical raw materials or chemical products in the process of drug synthesis, and are also intermediate products in the process of producing raw materials. A substance that must go through the next step of molecular change or refinement before it can become an API.
The bulk drug can be directly used as a preparation, while the intermediate can only be used to synthesize the next step product, and the bulk drug can be produced only through the intermediate.
Different production requirements
Pharmaceutical intermediates are intermediate products in the process of producing raw materials, so pharmaceutical intermediates can be produced in ordinary chemical plants. And if you want to produce raw materials, you need to obtain a production license for raw materials before you can start production.
To sum up, reliable pharmaceutical intermediates and raw materials are two completely different substances. The threshold for making pharmaceutical intermediates is relatively low, while the production of raw materials needs to meet higher production thresholds. If you want to make raw materials, you must also have suitable pharmaceutical intermediates as raw materials.