Process Scale-up of Generic Drug

For both oral solid preparation or injection, the FDA clearly requires a scale-up study of the product and provides sufficient experimental data to prove the quality of the product after optimizing and validating the prescription process. To ensure the quality consistency of generic drug with that of the Reference Listed Drugs (RLDs), the scale-up studies should be performed on the same production line. The FDA requires pharmaceutical companies to provide results of the process scale-up research as an important reference for the consistency evaluation. Alfa Chemistry provides process comprehensive services of scale-up optimization and validations, and delivers test and analysis results in the consistency evaluation to prove the consistency of quality and/or efficacy of your final production.

Figure 1. The development process of a generic product. (Al-Tabakha, M. M.; Alomar, M. J. 2020)

Purpose of Process Scale-up Studies

• Further optimization of process parameters
• Verify that the quality of the generic products after the scale-up production is still consistent with that of the RLDs
• Prove the rationality and feasibility of the process route

Figure 2. Laboratory-scale batches of generic drugs. (Crasto, A. M. 2013)

Our Services

Alfa Chemistry conducts at least two batches of scale-up. The first batch is used to confirm the target process parameters and select the equipment, and the second one is carried out to validate a series of quality attributes including relevant analytical method and quality standard research.

Process Scale-up

We scale up the production of several batches using the proposed prescription process to:

• Evaluate whether the laboratory-scale process route is suitable for industrial-scale production
• Further optimize the process conditions including each reaction and unit operation
• Calculate the material balance
• Determine the process flow and operation method
• Calculate the heat and mass transfer
• Determine quality standards and analytical methods based on data of scale-up process
• Determine the specifications or standards for the starting materials, reagents or organic solvents
• Determine the cost of raw material, operating hours and production cycle

Scale-up Validation

After the scale-up is completed, our experts provide additional process validation services. In the consistency evaluation, the results of process validation will be used to prove the reliability and reproducibility of the process under the selected conditions.

• Stability tests of 3 to 5 pilot-scale batches
• Quality studies and validation of analytical methods
• Structure confirmation: ¹²C NMR, ¹H NMR, mass spectrometry, infrared spectroscopy, ultraviolet spectroscopy, etc
• Cleaning validation

Alfa Chemistry's Equipment for Process Scale-up

• Scalable lab system designed for scalability from start to finish
• Application of consistent equipment that has been certified with high efficiency and success of the scale-up
• Ensure consistency during the scale-up process

Our Advantages

• Provide comprehensive quality comparison research of products and reference preparations
• Optimize the production process based on the report of scale-up
• Study the feasibility of the process for commercial production
• Review and improve the synthetic process route
• Perform accurate comparisons in a fast, accurate and repeatable manner