We offer a broad range of clinical manufacturing services for replication-competent or non-replicating viral vectors.
We have developed product-specific protocols to produce, purify, test and release measles-, AAV-, lentiviral-, adenoviral-, or VSV-based vector products. Furthermore, we have developed specific protocols for diverse adenoviral vector serotypes. Typically, when a vector can be replicated on a cell line, a clinical manufacturing trajectory starts with the manufacturing of a pre-master virus seed (pre-MVS) under R&D conditions. This pre-MVS is subsequently used to produce a Master Virus Seed (MVS), which in turn is used for production of Drug Substance (DS) production under GMP conditions.
The quality parameters of the pre-MVS are highly controlled to ensure integrity, functionality and yield. When the pre-MVS applies to the pre-set criteria, the pre-MVS material is introduced in a clean room facility. In this facility, cells are cultured to the desired volume and cell density prior to infection with the pre-MVS. The culture is maintained for several days to allow replication of the virus before the material is harvested. If required, purification protocols are executed and subsequently the produced MVS is aliquoted and tested for release. The MVS is the designated starting material for a production campaign.
For each product, a production process can be developed at our R&D laboratories. Read more about our process development capabilities on the process development page.
The next step in the product development trajectory is to perform a process at scale, to demonstrate that the process was successfully developed. All the steps are performed according to the draft GMP batch documentation. This is called the engineering run or shake-down run. The product generated from this engineering run can then be directly used for toxicology testing and early stability studies, contributing to the IND application of the product. Furthermore, the material produced with the engineering run can be used to qualify the product specific assays.
After a successful engineering run the draft GMP batch documentation is updated, and after an approval by our QA department, the production under GMP conditions will be started. All steps of the production process are documented in the GMP batch documentation. The DS will be released using the developed and qualified analytical assays.
When the DS complies with the pre-set criteria, it will be filled in vials and stored under proper storage conditions to create the drug product (DP). This in turn is fully tested according to ICH regulations for DP release, including the developed product specific assays.
The batch documentation for both the engineering and GMP production will be available to ensure a smooth filing for an investigational new drug dossier (IND).
Stability studies will be performed on both DS and DP. At different pre-defined time points samples are taken from temperature-controlled storage and parameters such as infectivity, integrity, and other stability indicating assays. Additional accelerated stability studies can be performed as well.
All our systems and procedures are developed and maintained to ensure compliance to applicable FDA and EMA regulatory requirements and standards. Our Quality Team oversees the entire production process from the validation of equipment to the approval of the documents required to release your product. Overall Quality Review is performed during quarterly meetings with executive management, focusing on adhering to the auditing scheme, critical and major observations (if applicable), numbers of open quality incident reports, changes and CAPAs closure within due date and trends.
At Batavia, we have ample experience to transfer manufacturing procedures to our R&D or GMP laboratories. In each case, we will critically analyze the manufacturing procedures based on protocols, SOPs or batch documentation provided by our customer. Using our extensive experience, we will advise on improvements of the process or, if required, we can perform process development.
We have successfully built a system in which the team of experts developing the processes in an R&D environment, also performs the clinical manufacturing in GMP. This approach has proven to eliminate time consuming and error-prone internal technology transfer processes. Our dedicated team of experts is also closely involved in transferring the manufacturing process to the customer’s late stage or commercial manufacturer.
We operate grade C and D clean room facilities, equipped with a variety of manufacturing platforms. The facilities are supported by GMP materials warehousing and storage areas. Storage of product, consumables and starting material is available at room temperature, at 5°C, -20°C, -80°C and in liquid nitrogen. Our GMP facilities are regularly audited by regulatory authorities and customers. We are proud to host more than 8 audits each year and have passed every audit with flying colors as none of the audits have demonstrated critical observations. For the required stability studies, we have a dedicated storage space for drug substance and drug product.
We have successfully manufactured and released products for both phase-I and phase-II clinical trials, to be conducted in Europe and USA. Our license allows us to deliver diverse replicating and non-replicating viral vectors. We have an outstanding track record for manufacturing and release of clinical products as witnessed by successful IND dossier submissions.