RE:RE:Volumei found the following comments from the cc the most interesting. a lot of companies are caught flat footed and behind the eight ball when it comes time to produce product. oncy has been producing for a number of years, have used the same company, and have had prior fda inspections and approvals for their process.
the fact they are ramping up product production as well as producing single use product says more to me about their confidence in the future than anything else said in the cc.
this was hageman's contribution:
Key takeaways from my section are we have a well-established product supply chain for pela, we have made numerous batches of material at increasing scale and pela has a long shelf life. We have been working with a high quality contract manufacturing organization for some time and we are investing in optimized manufacturing scale up and validation so that we are ready to support product registration. For a bit of background, pela drug substance is produced in a simple eight step process and stored in bulk at -80 degrees Celsius. Finished drug product can be stored at -80 or -20 degrees Celsius. Pela material has a long shelf life with ongoing drug substance stability out pass 10 years plus an established drug product expiration period of six years from date of product filling.
Pela is made by our Contract Development and Manufacturing Organization or CDMO MilliporeSigma SAFC located in the San Diego area. Master and working cell banks and virus banks are established and validated. All raw materials are sourced from qualified suppliers and the process operating parameters are well defined. We have been working with this organization, formerly known as Sigma-Aldrich, for more than 15 years with consistent staffing at both organizations. The MilliporeSigma site has a well-established quality management system and our protocols and procedures are well aligned. In addition, the site produces GMP materials for other organizations, including commercial products, and has completed nine successful inspections including the FDA and other health authorities.
They have handled numerous biologics over the years and are a leader in bio vector manufacturing, so they are familiar with assets like pela. Stable staffing, a well-established quality management system, and working with the CDMO that has been FDA inspected are all very important for consistency, quality and risk management, which are always top of mind in manufacturing. In the fourth quarter of 2023, we initiated a new GMP production campaign with the drug substance process transitioned to single use equipment and scaled up to a 200 liter bioreactor, increasing the purified batch size to about 12 liters of bulk drug substance. The first GMP batch has been completed and once routine manufacture has been established, our next step will be the validation batches.
Our successful track record in scale up and consistent production gives us confidence that our investment in the next level of pela drug substance batches will go well as we continue this work in 2024 and 2025. In conjunction with the scale up, we also optimized some upstream elements of the process, including a change in detergent to align with European long-term guidelines. Thankfully, this switch won't impact the purified drug substance or product. The detergent is cleared through the purification steps and the final pela product concentration and formulation remains the same. In addition to drug substance manufacture in the fourth quarter of 2023, we also completed a second automated drug product fill in a full isolator system. This provides an aseptic environment for filling and high level of sterility assurance and also allows for larger quantities per lot, reducing the cost of goods.