Meet the Expert: Marije, GMP Scientist
Many customers want to know how much time it will take to move a candidate viral vaccine or viral vector product from bench to bed. The next question often is what shortcuts can be taken to move even faster. Having strong preclinical data from in vivo experiments, showing excellent efficacy of the candidate product, does not suffice to allow rapid testing in human subjects. In reality, getting from ‘bench-to-bed’ involves an enormous amount of work. For example, often both the production and purification processes used during the research phase do not meet the strict Good Manufacturing Practices (GMP) requirements. Thus, these processes need to be re-designed. In addition, one must demonstrate that the intended production process is robust. This means that it should always result in a product within a narrow quality bandwidth.
To develop a GMP compliant production process, you need expert knowledge in regulatory requirements. At Batavia, the team that designs and develops a production process in an R&D environment, also manufactures the final product in GMP. This set-up ensures that the involved team keeps GMP regulations in mind while developing a process. Moreover, this approach has proven to avoid risky and time-consuming tech transfer processes from development into GMP. It results in high quality documentation – no or low amount of deviations in production batch records – and an outstanding track record of successful GMP manufacturing campaigns.
I will discuss four examples to demonstrate the challenges of a CDMO in the manufacturing of virus-based products in a GMP environment.
The first example regards the materials used, such as starting material, disposables, medium and buffers. A GMP compliant process uses materials that are fully traceable. This means that any plasmids, virus seeds, cell lines and other raw materials used in the process need to be GMP compliant and are provided with certificates such as for sterility, mycoplasma and TSE/BSE to document their quality.
The second example is that not every virus product is suitable for sterile filtration during downstream processing. Some viruses, such as measles virus, are relatively large, making it impossible to perform a final sterile filtration. Consequently, an aseptic process is needed for the production of measles virus seeds. An aseptic process needs validation before execution of the actual virus seed production. The validation process simulates the entire USP as well as the DSP process. Instead of normal medium, the simulation process uses bacterial growth promoting medium, such as TSB. Generally, manufacturing of a minimum of three consecutive batches constitutes a validation of the process. This includes the testing of the entire processed volume including a growth promotion test to confirm the growth promotion capabilities of the medium.
When working with biological agents of increased biosafety level in a GMP environment there is often an additional challenge. In these cases, you are not only obliged to work under GMP conditions to protect the product, but also need to adhere to strict safety precautions to protect the operators and the environment from getting contaminated. For instance, the obligatory Personal Protective Equipment (PPE) required for working with poliovirus, does not always accommodate the GMP regulations. In general, PPE, such as mouth masks and gowns protect the operator from exposure, where GMP compliant gowning material minimizes the introduction and generation of particles inside the cleanroom. Hence, it is challenging to compose a gowning regime meeting both GMP as well as biosafety requirements.
The last example is the vesicular stomatitis virus (VSV) vector. This vector is gaining popularity due to its oncolytic properties. However, the native virus is a great danger for cattle. An outbreak of vesicular stomatitis virus can therefore cause significant economic loses. Hence, one of the requirements for working with vesicular stomatitis virus is that the cleanroom needs to be fumigated afterwards. Fumigation of the cleanroom with H2O2 has a major impact on the environmental monitoring of the cleanroom as well as the gowning areas, making it a necessity to clean the entire facility before any other production campaign can be initiated.
To ensure a high success rate in manufacturing virus-based clinical products, it is key to thoroughly understand regulatory requirements. We always go the extra mile to minimize risks for our customers. This allows smooth transition to the clinic within budget and timelines.
Batavia Biosciences offers a broad range of clinical GMP manufacturing services for all major classes of biopharmaceuticals. We are dedicated to help bring biopharmaceuticals to the market at higher speed, with reduced costs, and with a higher success rate. Batavia Biosciences has vast experience in process development and GMP manufacturing. Our experienced scientists, technicians, and in-house QP are well equipped to take on any challenge associated with clinical GMP manufacturing.