Bayer New Facility + Therapy for Parkinson’s Disease
Bayer is nearing the end of the qualification process and is now in the validation phase for their new facility. The facility is projected to be GMP-ready by the end of July. The Project Management group is handling design and project management, while construction and the management of all vendors and contractors is being overseen by Fluor Enterprises Inc. The facility is being used to produce Bemdaneprocel (BRT-DA01), a stem cell-derived investigational therapy for Parkinson's disease owned by BlueRock Therapeutics. Planning for a Phase II study is underway, following encouraging results from the Phase I clinical trial.
Bayer's First Fully Electric Facility Overview
Bayer's first fully electric facility and an end-to-end operation where raw materials are input, and final products emerge. It boasts three floors and the rooftop accommodates solar panels and six heat pumps for the building's heating and cooling needs.
The majority of the first floor is vacant as Bayer is still deciding on its use. Two potential uses considered during planning and construction were office spaces or a Gene Therapy Module production area. The currently occupied spaces include a temperature-controlled material storage space, a Water-For-Injection (WFI) system, a biokill system, and a product storage area. The WFI undergoes a heat cycle for 4 hours to inhibit bacterial growth before cooling for use. The biokill system uses heat to inactivate mammalian cell cultures before they are piped into a neutralization tank and released into the sewage system. The product storage area is used to keep tanks filled with liquid nitrogen for storing Bemdaneprocel at a low temperature.
The second floor houses most of the building's utilities, with the remaining space potentially available for a QC lab or office use in the future. An electric plant steam generator is also present, which supplies steam to the entire facility, thus making it self-sufficient for steam. Space has been reserved in the utility area for future utilities. This utility area is open-air with filters serving as walls.
The third floor houses the Cell Therapy Module space, which includes both single-use drug substances and drug products. The drug substance involves both open and closed processing. Open processing exposes the drug substance to the environment, while closed processing uses equipment to prevent such exposure. The drug product includes an automatic filler inside an isolator to ensure Grade A cleanliness. The vials are inspected after filling before labeling and placement in a storage tank filled with liquid nitrogen.
Manufacturing Process for Bemdaneprocel
Parkinson’s disease results from nerve cell damage in the brain leading to decreased dopamine levels. Bemdaneprocel aims to replace the dopamine-producing neurons, potentially treating, and even curing Parkinson’s disease.
The production process begins with growing a population of stem cells extracted from bone marrow. The cells are initially stored in a 1mL vial. As the cell population multiplies, they are transferred into larger containers. The first few steps are done in open processing until the stem cell population reaches the size of 4 layered T-flasks. Then, the cells are transferred into an automated shaker with 2 sets of multi-layered T-flasks. The stem cells are grown in adherent cell culture, with the cells attached to the surface of the T-flasks. This is done by coating the T-flasks with synthetic polymers. Once the cells are ready to be harvested, they are washed with different solutions to detach from the adhesive. The culture process ends when the desired stem cell concentration is reached. The cells are then frozen in a medium filled with cryoprotectant DMSO (Dimethyl Sulfoxide) to prevent damage during freezing.
To produce bemdaneprocel, the frozen stem cells are thawed and cleaned with solutions to remove DMSO before reformulation. After reformulation, the cells are mixed with DMSO before filling and freezing. Once the patient is ready for the procedure, there is a 24-hour window from thawing bemdaneprocel to injecting it. The final form must pass QC and gain approval from BlueRock Therapeutics before being delivered to the patient. The treatment involves six syringes filled with bemdaneprocel, with three injections on each side of the brain. Bemdaneprocel functions as dopamine-producing neurons in the brain to restore dopamine levels. Further study is required to understand how long bemdaneprocel will last after injection, as there is a chance that the new neurons will also be damaged.
Takeaway
Bayer can reduce production costs and decrease the carbon footprint by 31% compared to a traditional facility by making the new facility fully electric. Could fully electric facilities be the future of biopharmaceutical manufacturing?
The possibilities with stem cell-based therapy are endless. Stem cells can be transformed into different cells to replace damaged ones. Bayer even managed to reformulate stem cells into heart cells. Initially, these heart cells beat differently, but over time, they started beating synchronously, as if communicating amongst themselves. There's still so much we don't understand.
Bayer scientists emphasized the importance of considering patients when developing new therapies. Most patients can't afford these therapies. Therefore, it's vital to find ways to increase drug production while simultaneously reducing production costs.
