What is an intermediate? What is its relationship with APIs?
When we talk about the pharmaceutical industry, especially the pharmaceutical industry chain, we often hear three key terms: intermediates, APIs, and finished drugs (FDF). Although these three are closely related, they are strictly distinguished. In news, policies, and market reports, we often see words such as "API price increases" and "intermediate supply shortages", but many people are not clear about the true relationship between them.
So, what is an intermediate? What role does it play in the pharmaceutical industry? What is the difference and connection with the APIs we are familiar with?
This article will systematically sort out the concept, classification, function, and relationship of intermediates with APIs for you, and take you to truly understand the "invisible power" behind the pharmaceutical industry.
1. What is an intermediate?
1. Definition: "Transitional product" in the synthesis process
Intermediates refer to intermediate chemical substances produced in the synthesis of APIs. They do not have the final pharmacological function themselves, but exist as intermediates in a series of chemical reactions, and ultimately participate in the generation of pharmacologically active APIs.
In layman's terms, if APIs are compared to a building, then intermediates are semi-finished materials such as cement, bricks, and steel bars used to build this building. Although they are not end products, they are essential building elements.
2. Let's take an example:
Take the common antibacterial drug, cephalosporin APIs, as an example. Its synthesis process generally includes multiple intermediate steps, involving chemical reactions such as cephalosporin nucleus (7-ACA or 7-ADCA), side chain introduction, and intermediate group modification. Each step requires the participation of intermediates, and finally obtains cephalosporin APIs with antibacterial activity, such as cefradine and cefixime.
2. Classification and characteristics of intermediates
According to different classification standards, intermediates can be divided in many ways. The following are several common classification methods:
1. Classification by function
Pharmaceutical intermediates: intermediates used to synthesize pharmaceutical APIs, which are the most common type.
Pesticide intermediates: intermediates used in the synthesis of pesticides.
Dye intermediates: chemical intermediates used in the dye production process.
This article focuses on pharmaceutical intermediates.
2. Classification by synthesis stage
Upstream intermediates: in the early stage of the synthesis process, simple structure, usually low price and large dosage.
Midstream intermediates: complex structure, an important transformation link to the downstream API synthesis.
Key intermediates (KSM, Key Starting Material): intermediates directly connected to the core structure of the API, complex structure, high added value, the focus of quality and process control.
3. Classification by production method
Chemical synthesis intermediates: the most common, synthesized using organic chemical reactions.
Biological synthesis intermediates: produced by microorganisms or enzyme catalysis.
Natural extraction intermediates: certain components extracted from natural products, and then used as raw materials for further synthesis.
III. What is the relationship between intermediates and APIs?
1. "Brotherly relationship" in the chemical chain
APIs (APIs) are the final target products, and intermediates are the only way to this goal. In the actual synthesis path, APIs are often obtained through the step-by-step reaction, modification, purification, and extraction of multiple intermediates.
The relationship between them can be simply expressed as follows:
Raw materials → intermediate A → intermediate B → intermediate C (key intermediate) → API → finished drug
2. Functional differences
Dimension Intermediate API (API)
Intermediate products in the process of functional chemical reactions have active ingredients with therapeutic functions
Is there any efficacy? No, it cannot be used or taken directly Yes, it must meet the pharmacopoeia standards
Market supervision Industrial products can be used as ordinary chemicals to supervise pharmaceutical products, and must meet GMP and other standards
Use scenarios Only used in the synthesis process to directly produce finished drugs
Quality control Industrial or pharmaceutical grade Strict quality standards, batch release management
3. Regulatory differences
Since intermediates are not directly used in clinical treatment, they are generally not included in the scope of drug management and are regarded as fine chemical products in China and most countries. This means:
Its production companies do not necessarily need a drug production license;
Environmental protection and safety standards also vary from place to place;
However, as international regulations (such as ICH Q11) pay more attention to "key intermediates", the production quality of intermediates is gradually being included in stricter regulatory scope.
4. Industrial value and status of the intermediate industry
Although intermediates are not terminal drugs, their industrial value is huge and is an indispensable part of the entire pharmaceutical industry.
1. An important foundation of the global supply chain
China and India have long been the main production bases of global intermediates, especially China, which has significant advantages in price, scale and technology. Therefore, China's intermediate industry has formed a broad support for global API companies.
2. Strategic control points for API manufacturers
Possessing the synthesis process and industrial capabilities of key intermediates is beneficial to API companies:
Control costs;
Ensure stable supply;
Improve R&D flexibility;
Avoid relying on external suppliers to "choke the neck".
3. Large market share and high growth potential
Data shows that the global pharmaceutical intermediate market has reached hundreds of billions of dollars, and with the growth of demand for innovative drugs and complex APIs, the demand for high-end intermediates is rising rapidly.
5. Challenges faced by the intermediate industry
Despite the huge market potential, the intermediate industry also faces many problems:
1. High pressure on environmental protection and safety
Many intermediate synthesis processes involve high temperature, high pressure, strong acid and strong base reactions, which are prone to cause environmental pollution and safety hazards. In recent years, environmental supervision has caused many intermediate companies to suspend production and rectify.
2. Technical thresholds are gradually increasing
Especially for high-end intermediates related to innovative drugs, the synthesis route is complex, and the requirements for reaction selectivity, yield, purity, etc. are extremely high, which ordinary small and medium-sized enterprises cannot meet.
3. International trade barriers
With geopolitical changes, European and American countries have established more technical standards and certification thresholds for Chinese intermediate products, such as "supply chain review" and "product traceability", which puts higher requirements on export companies.
VI. Development trend of intermediates
1. Green process becomes mainstream
The use of green processes such as catalysis, enzyme reaction, and aqueous synthesis to reduce the discharge of three wastes and improve the yield is the key direction of future development.
2. Integrated layout is becoming increasingly important
More and more API or formulation companies have begun to layout intermediate production, realize integrated control from intermediates to API, and improve product quality stability and cost control capabilities.
3. Accelerated domestic substitution of high-end intermediates
Especially in the field of innovative drugs and high-end generic drugs, the independent synthesis capability of key intermediates is becoming an important competitive advantage of domestic companies.
VII. Conclusion: Intermediates are “intermediate”, but their value is not “intermediate”
In the entire pharmaceutical industry chain, intermediates are neither the starting point nor the end point, but the key node connecting raw materials and APIs. It not only determines the quality and cost of APIs, but also affects the overall supply chain efficiency of drugs.
As the pharmaceutical industry develops towards a more complex, high-end, green and compliant direction, the intermediate industry is no longer just a “behind-the-scenes factory”, but has become an important guarantee for pharmaceutical technology strength and industrial security.
To understand intermediates is to understand the “internal structure of the engine” of the pharmaceutical industry; to master intermediate technology is to master the core code of drug quality and cost control.
