We offer a broad range of clinical manufacturing services for replication-competent or incompetent viral vectors.
We have generic viral vector protocols present to produce, purify, test and release measles-, AAV-, lentiviral-, adenoviral-, or VSV-based vector products, as well as specific protocols for diverse AAV- and adenoviral vector serotypes. Typically, when a vector can be replicated on support cell lines, a clinical manufacturing trajectory starts with the manufacturing of a pre-master virus seed (pre-MVS) under R&D conditions.
The pre-MVS is highly quality controlled to ensure integrity, functionality and yield. Based on mycoplasma and sterility testing results, the pre-MVS material is subsequently introduced in a clean room facility. In a clean room facility, cells are cultured to the desired volume and cell density prior to infection (with pre-MVS). The material created by infection is aliquoted, release tested and labelled as master virus seed (MVS), which is the designated starting material for multiple production campaigns.
The next step is to perform an infection with the MVS at final scale to demonstrate that the process was successfully developed. This is called the engineering run. It can be performed in R&D, however it is sometimes advisable to perform the engineering run in the GMP facility. The product generated from this engineering run can then be directly used for toxicology testing and early stability studies.
Typically, an engineering run is followed by a second infection or DNA transfection run to manufacture the drug substance (DS). Finally, DS material is either freshly used or thawed in the clean room facility, vialed 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. As part of the engineering run and GMP production, all steps are documented in batch records to ensure smooth filing for an investigational new drug dossier (IND).
Stability studies will be performed on both DS and DP. At different time points (e.g. T0, T3, T6, T9, T12, T18, T24, T36 months) samples are taken from temperature-controlled storage and parameters such as infectivity, integrity, buffer composition and aggregation are tested.
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.
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 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 B and C clean room facilities. The facilities have dedicated upstream and downstream suites, equipped with a variety of manufacturing platforms. The facilities are supported by GMP materials warehousing and storage areas. Storage is available at room temperature, at 5°C, -20°C, -80°C and in liquid nitrogen, with dedicated space for drug substance and drug product stability testing. 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.
We have successfully manufactured and released products for both phase-I and phase-II clinical trials, to beconducted in Europe and USA. Our license allows us to deliver diverse replication-competent or -incompetent viral vectors. We have an outstanding track record for manufacturing and release of clinical products as witnessed by successful IND dossier submissions.