An automated manufacturing process for MP1032
By Dr. Thies Klüßendorf, Senior Chemistry, Manufacturing, and Controls (CMC) Project Manager, MetrioPharm
This is the first article within our series of six covering various aspects of work behind the scenes in the iMPAct project. In today’s article, we explain what to consider when manufacturing MetrioPharm’s medicinal compound MP1032 and the corresponding investigational medicinal drug product as well as which hurdles need to be overcome when preparing for the upscaling of production.
For drugs to reach the patient, they need to be discovered, developed (research and development, R&D), manufactured, and marketed. After an extensive R&D trajectory, the promising new drug candidate and final drug product or dosage form must be produced in sufficient amounts for clinical trials and eventually the commercial market.
Once a potential drug candidate has been identified, it needs to be determined how patients should receive the drug (e. g. injected into the veins or orally by swallowing a pill). During the research and development phase it became clear that MP1032 can be administered orally in the form of a powder mixture filled into gelatin capsules (the final drug product).
Example of an industrial pharmaceutical production line
Early clinical studies required far less capsules than subsequent larger clinical trials or a commercial market supply. The capsules for early clinical trials were initially manufactured manually which limits the drug product supply for greater patient numbers. To supply larger clinical trials with MP1032 capsules and prepare for the potential commercial demand after a granted marketing authorization, an automated manufacturing process of commercial batch sizes of the drug product is necessary. At the same time, the production process of the drug compound MP1032 (a small chemical molecule) itself needs to be scaled up to meet the demands for the larger amounts of capsules.
“If the trial is a success, even larger trials will be conducted, which require even larger amounts of MP1032 capsules. It is my job to ensure that we develop a process to produce these quantities,” says Dr. Thies Klüßendorf.
Challenges of upscaling the drug product
The chemical synthesis of MP1032 is a relatively simple process and no real difficulties with upscaling are expected. However, when changing the manufacturing system from manual to an automated process, Dr. Thies Klüßendorf and his colleagues realized that the formulation of the drug product and specifically the powder mixture (the capsule fill mass) had to be adjusted because its physical characteristics did not allow for automatic capsule filling.
Furthermore, they needed different amounts of MP1032 per capsule to improve patient compliance, and convenience. The current MP1032 capsule used in the clinical trials contains 50 mg MP1032. Patients enrolled in the current clinical trial have to take multiple capsules of MP1032 per day to achieve relevant and effective amounts of drug substance. For future patients it would be much easier to reduce the number of capsules they need to take daily by increasing the amount of MP1032 per single capsule. That would make it easier for patients to adhere to the treatment plan.
As a result of increasing the amount of MP1032, the size of the capsule may also increase. However, Dr. Thies Klüßendorf and his colleagues were able to develop one single new capsule fill mass formulation for MP1032 that can be used to create different strengths of the drug product in an automated manufacturing process. With this new fill mass formulation, they also achieved to keep the capsule sizes small Smaller capsules are easier to swallow and therefore also improve patient compliance and convenience.
“We now have one powder mixture that you can fill into different capsule sizes resulting in different capsule strengths,” explains Dr. Thies Klüßendorf.
Once the drug compound is available in different strengths, different patient groups such as children could also benefit. Children in contrast to adults would require a lower dose.
Our next article: A regulatory strategy for the use of MP1032 in pediatric patients
In our next article we elaborate how and why we prepare the necessary regulatory work to allow for initiation of clinical trials in pediatric patients, and subsequently marketing approval. Children are a vulnerable group and therefore require specific regulatory rules with a careful risk-benefit assessment.
Posted on the 10th of November, 2022.