Sponsored Content by DSI, a PLG CompanyMay 23 2024Reviewed by Maria Osipova insights from industryJames MencelHead of Drug Substance ServicesDS InPharmatics In this interview, NewsMedical talks to Dr. James Mencel’s Guidance about Scaling Up API Processes.
Working with budget-conscious clients emphasized the need to obtain every bit of information possible from each experiment and operational run. This method was crucial for improving process capacity and readiness in a timely and cost-effective manner, especially when preparing for large-scale operations and stringent requirements. This experience stands out as one of the most important in my career.
In 2016, I joined Design Space Inpharmatics as an API consultant, where I helped customers with API process development, GMP manufacturing, and regulatory document preparation. According to my experience, the chemical development and production teams are fully aware of their critical role in the drug development program and are sincerely devoted to performing their jobs effectively.
Guided by expertise, the team developed a two-part, optimized approach that allowed the essential chemistry to proceed while smoothly incorporating the solvents and conditions from the historical isolation technique. To address complications in scaling up processes, understanding external requirements and verifying their feasibility at scale is important. Many operational aspects can be simulated in the laboratory, while others are more challenging. These problems vary depending on the process.
Robust analytical support is crucial for understanding the chemistry and behavior of the product throughout the manufacturing process. Scale-up failure can result from insufficient analytical examination during process development, as well as an inability to monitor the reaction or other essential process factors for success.
These components serve as the basic blueprint of the intended chemical transformation process, from material input to an isolated product that fulfills specified quality standards. This procedure must be described in terms of the planned scale, available equipment, and other aspects of the scale-up environment.
The points listed above provide a framework for determining the process parameters and adjustments required for the initial scale-up. To ensure the process’s long-term viability, individual process parameters must be studied methodically to determine those that are crucial and require specific boundaries.
Impurity control is a critical area that requires expertise: understanding the introduction or derivation of structurally related impurities, their regulatory toxicity status or ICH M7), and their elimination throughout the chemical process is crucial for setting intermediate and API specifications. This information may highlight the need for additional targeted development of the process.
If the peptide API contains rings or side chain branching, the timing of their introduction is critical. Purification and isolation techniques, such as chromatography and lyophilization, need proper scale adjustments. Reducing time in equipment, which is a key cost factor, is critical. GMP plant reactors are expensive to run, and the objective is to process as much material through a reactor as possible in as little time as possible while manufacturing a high yield of suitably pure product.
How does DSI assist drug substance manufacturers? DSI’s API consultants play an active role throughout the process, collaborating closely with selected chemical development and GMP manufacturing contractors. If requested, we can assist API CMOs in drafting proposal requests, evaluating bids, and recommending contract awardees.
We work to understand the API’s evolving needs and the projected timeframe. This informs our evaluation of the supply chain and chemical process, enabling us to determine what may be required to meet anticipated future API demand. How does DSI assist with drug substance regulatory affairs? Recent regulatory guidance underscores the importance of developing a thorough understanding of the process, including quality control throughout its entirety. This understanding evolves as the process progresses.