原料药工艺研发 API Process Research & Development

5.
6. 7.
To verify the consistency in quality & quantity.
To establish all the regulatory requirements. Cost effectiveness.
⊛ A systematic and prospective approach during R&D is key to achieving a successful prospective validation and scale-up.
01 02 03 04 05 06 07 08 09 Patent infringement Inconsistent quality of raw material Cost of raw material Hazardous or non regulated raw materials (Material safety) Unsafe or environmentally hazardous reactions (Process Safety) Difficult-to-achieve levels of purity (e.g., for enantiomers Difficult-to-handle processes Polymorphism-related issues. Stability of intermediates or products
Process Adaptability
Modify the process techniques to fit the process in manufacturing environments
1. Avoid evaporating the solvents to dryness because it is difficult to follow such procedures in the plant.
Inconsistent Quality of Raw Materials
With the help of purchase department, find out the right vendor who can supply the raw materials consistently as per specification and as per quantity required. a)For general/common raw materials, it advisable to purchase from the existing approved vendors (Especially approved by plant)
Process Development : “Any improvement in existing process is called Process
Development”
“Research and development is one of the means by which business can experience future growth by developing new products or processes to improve and expand their operations”
Cost of Product
Major components in the cost of product are
Raw material s Packaging materials
Manufacturi ng cost
Labour
cost
Product Cost
R&D chemists can help reduce process expenses by: 1. Suggesting cheaper alternative reagents or synthetic routes; 2.Reducing raw material consumption (e.g., by optimization of raw material qty & yield improvement ); 3.Shortening process time cycles; 4.Recycling materials, if possible.
The Ultimate Goal of Process Development is to Scale-Up
Product Milligram Qty Gram Qty
High Quality
Low Cost
Reproducible
Product
Kilogram
Tons
Purpose of API Development
2. Develop a suitable technique such as crystallization or precipitation should be developed because, in such cases, the product can be isolated by centrifugation or filtration in the plant. 3. Purification by column chromatography should be avoided on plant scale because this technique have the limitation.
1.To study & establish the process control. 2. 3. 4. To study the safety issue of process. Identify the problematic issue for scale-up. To address the patent issues.
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⊛ These activities are important and are frequently under scrutiny by the Food and Drug Administration.
Prerequisites
1.The data generated in an R&D laboratory must be accurate, reproducible, and dependable. 2.Therefore, it is imperative to establish and follow standard operating procedures (SOPs) for important activities such as the qualification and calibration of instruments and equipment (e.g., weighing balance, standard weights, pH meter, temperature indicators, and reference standards). 3. It also is necessary to keep proper detailed records of these qualification and calibration activities and other laboratory experiments, observations, and related analytical data.
Process Considerations
Prepare for the complete literature report about the API and the action plan about its possible future developments.. Challenges to overcome at this stage include……
• Reaction Condition • Work-up • Drying condition
• Impurity profile & limit of them
Note : The infringement or FTO analysis should be done by patent department.
b) It is important to conduct vendor audits and approval to ensure consistent quality and supply of raw materials.
c) Vendors should be selected according to criteria such as their market recognition, record, ability to supply consistent quality materials in time, and customer orientation. d) Certificates of analysis (CoA) and MSDS of the materials should be obtained from vendors. Such information is useful while designing the specifications of raw materials .
Processing Industry
Leather
Paint
Nutraceuticals etc Paper & pulp Textile
What is process research & development ?
Process Research :
“Investigating and development of new process based on chemistry is called Process Research”.
•Study /compare the action plan for infringement analysis.
Synthesis Route Operation Polymorph • Intermediate • Final Product Impurities
• Starting Materials • Intermediates • Reagent used • Solvent for reaction & work-up
Patent infringement Analysis
•After completing the literature study, study the patent thoroughly •Chalk –out action plan (Reaction scheme, Polymorph etc)
What is Process Chemistry?
“Chemistry used in processing industry to develop the robust process is called Process Chemistry .”
Pharmaceutical
Petrochemicals
4.Purification of a product should be achieved by means of crystallization or selective precipitation .
5. Reactions involving low temperatures or high pressures could be difficult to handle in the plant, and an alternative route should be considered . Methods of handling viscous materials in a plant also must be taken into account because the large surface area of plant equipment and piping can pose problems during material transfer.