Reliable API manufacturing units for small molecule drugs need to be evaluated on multiple factors, such as the manufacturing process, technical expertise, quality control, and many more. On the above-mentioned factors, reliable API manufacturing depends on and is necessary in the manufacturing company. This blog deals with all the factors necessary to find a reliable API manufacturer for small-molecule drugs.
Understanding Small Molecule API Manufacturing
Small molecule Active Pharmaceutical Ingredients have a lower molecular weight, i.e., 900 Daltons. The small molecule API manufacturing involves a multi-step chemical synthesis designed to be stable, scalable, and orally bioavailable.
The generalized stages involved in small molecule API manufacturing are mentioned below:
Route Scouting and Process Development
Before the whole manufacturing process of a medicine starts, process chemists understand the products that need to be manufactured, the reaction conditions, raw materials needed, reagents needed, and the process followed. This stage is basically the preparation stage.
Raw Material Sourcing and Qualification
The quality of the raw materials is very important as it determines the quality of the final product. Hence, the reagents, solvents, and intermediates should be of high quality. Next, testing of the raw materials is done to determine their purity.
Chemical Synthesis or Reaction Stage
The raw materials are added to reactors to form the molecular structure required for further processes. Then, using the in-process controls to monitor the progress of the reaction. At the end, the intermediates are isolated and purified or telescoped to increase the efficiency of the intermediate.
Purification
The next step is to purify the intermediate by processes like crystallization, filtration, and distillation. Then, the most important step in the process is to define the physical properties, such as the polymorph form, as it affects the stability of the drug. Then, the final step, washing, is done to separate the API crystals from the mother liquor.
Isolation and Drying
In this process, the API crystals are separated and dried. Drying is the process of removing the residual solvents using vacuum tray technology or ANFD. Drying is very important as it avoids dehydration.
Physical Transformation
This process involves a milling stage in which the particle size is reduced, which ensures uniform absorption. The next step is particle engineering, in which the drug particle is examined based on its shape. The drug needs to be fixed according to the way it looks and behaves, like crystalline or amorphous.
Quality Control and Packing
Next rigorous testing, such as analytical and stability, is done on the API formed to know its purity, potency, and impurity profiles. Then pack the API to save it from moisture, light, and air.
Regulatory Compliance
You must follow the guidelines in every step of the manufacturing of an API. Study the cGMP rules very carefully and then proceed towards the main reaction process. A detailed record of every batch and the SOPs is really important. Compiling the data is also an important part of the Drug Master File for the regulatory authorities.
Key Factors to Evaluate in a Reliable Small Molecule API Manufacturer
Selecting a small molecule API manufacturer includes evaluating it based on the following factors:
Regulatory Compliance and Regulatory Standards
This includes the audit history, reputation, GMP certificates, documentation, and DMFs, and data integrity are the regulatory standards every company should have.
Technical Expertise and Manufacturing Capabilities
In depth knowledge of the chemical processes, is capable to scale the desired quantity of small molecule API manufacturing, in-house R&D capabilities, apply the principles of Green Chemistry, the quality control laboratory have advanced tools for impurity profiling, polymorphism determination, and particle size analysis are few of the technical amd manufacturing related standards that you need to look for in a small molecule API manufacturing.
Supply Chain Reliability and Risk Management
Analyzing the stability and diversity of the raw material sourcing, understanding the geopolitical risks and shipping timelines, and analyzing their ability to handle disasters are the pointers related to supply chain reliability that need to be seen in a manufacturer.
Quality Management System
The QMS needs to be well optimized for deviation management and change control, and the manufacturer should follow all the environmental and safety standards in the small molecule API manufacturing.
Transparency
The manufacturing company should be transparent enough to maintain communication with its technical, regulatory, and project management teams. This makes sure the small molecule API manufacturers are reliable.
Certifications, Compliance, and Regulatory Standards
A small molecule API manufacturer needs the following documentation and certifications:
- Manufacturing license
- Approval for new Drug/API
- Site Registration
- Test License
- GMP and Quality Standards(Schedule M, ICH Q7 guidelines, WHO GMP certification, and data integrity)
- Drug Master File
- Site Master File
- Certificates of analysis
- Stability Data
- ISO Certificates
- Pollution Control
- Registration in foreign markets
These were some of the documents and certificates that need to be prepared and be aware of to be a small molecule API manufacturer.
Manufacturing Capabilities and Technical Expertise
For a small molecule API manufacturer, they must follow all the guidelines associated with production. These manufacturers need to be well aware of the following manufacturing capabilities and technical expertise:
Key Manufacturing Capabilities
- The manufacturers should be able to produce API with a wide range of sizes, weights, and volumes of the products that a facility can manufacture.
- The manufacturers should be proficient in handling collaborative robots and autonomous guided vehicles to make the manufacturing process even more efficient.
Key Technical Expertise
- The machinery used should be repaired continuously to maintain the efficiency of the machines.
- Continuously analyze the production data to improve performance and ensure compliance.
Quality Control Systems and Documentation Practices
Quality Control systems and documentation practices are very important for a small molecule drug API manufacturer. The following quality control systems and documentation practices are necessary:
Core Components of Quality Control and Documentation include the following:
- Standard Operating Procedures (SOPs)
- Quality Manuals and Policies
- Records and Reports
- Validation Protocols & Calibration Records
Documentation Control Practices
- Document Control System
- Version Control
- Unique Identification
- Audit Trails
- Accessibility and Security
- Regular Reviews
Supply Chain Reliability and Scalability
Small molecule API manufacturer needs resilient and geographically diversified supply chains. Here are the pointers that explain the supply chain reliability and scalability.
Strategies for Supply Chain Reliability
- To reduce the geopolitical or regional supply shock, source the raw materials from multiple sources.
- Evaluating the supply risk management, checking and monitoring the supply chain based on reliability, safety, and following all the rules and regulations well.
Scalability for API Manufacturing
- Using the advanced technology to enhance efficiency, reduce footprint, and make the scaling process faster.
- Using the facilities capable of handling complex reactions and having the ability to scale these complex reactions.
The small molecule API manufacturers need to have procedures, standards, documentation, certifications, and a proper methodological strategy. The APIs are very critical and need to be very carefully prepared to avoid higher impurity profiles and other destruction factors.
Frequently Asked Questions
What is small molecule API manufacturing?
Small molecule API manufacturing is a multi-step chemical synthesis process used to produce low molecular weight active pharmaceutical ingredients that are stable, scalable, and orally bioavailable.
What is the typical molecular weight of small molecule APIs?
Small molecule APIs generally have a molecular weight of less than 900 Daltons, making them easier to synthesize and formulate compared to large molecule drugs.
What factors should be considered when choosing a small molecule API manufacturer?
Key factors include technical expertise, regulatory certifications, manufacturing capabilities, supply chain reliability, transparency, and strong quality control systems.
What certifications should a reliable small molecule API manufacturer have?
A reliable manufacturer should have GMP certifications, Drug Master File (DMF), Site Master File, ISO certifications, stability data, and regulatory approvals for domestic and international markets.
