Good Manufacturing Practice
The manufacturing stage forms an integral and legally required part of the drug development process which leads from the development of innovative therapies to their clinical application. Both the medicinal product itself and the manufacturing process are subject to strict regulatory requirements, all of which must be met by the finished product. This system of quality assurance guidelines is generally referred to as ‘Good Manufacturing Practice’.
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A manufacturing process which is tested to ensure that its products are of a consistently high quality is a crucial requirement which must be met before drugs can used in patients as part of a clinical trial. It is a key step in translating innovative drug discoveries into drugs ready for clinical application. This intensive form of regulation aims to ensure a consistently reproducible level of quality for use in patients. Charité currently holds manufacturing authorizations for multiple GMP manufacturing sites which differ in terms of their product focus. All of these sites are subject to regular inspections by the competent authority and comply with the high standards required.
Berlin Center for Advanced Therapies
Advanced therapy medicinal products (ATMPs) are drugs which are intended for use in humans. Rather than the synthetic substances which are intended to relieve symptoms, these are biological drugs which aim to restore a patient’s health. Often referred to as ‘living drugs’, they break with the principles of conventional drug development and open up entirely new treatment options for previously incurable disorders.
The Berlin Center for Advanced Therapies (BeCAT) is dedicated to the development of ATMPs for patients with high medical needs. It has a manufacturing authorization for various T cell products (ReSHAPE). BeCAT has a state-of-the-art GMP facility which enables the manufacture of all types of ATMPs for use as investigational medicinal products, including in combination with biomaterials and 3D-printed systems.
- Manufacture of ATMPs for clinical test samples
- Comprehensive product characterization and standardization
- Assay development and validation
- GMP-compliant quality management system
- GMP-compliant manufacturing site (GMP certificate and manufacturing authorization) with 4 state-of-the-art cleanrooms for aseptic manufacturing (grade A in B)
- 2 preparation rooms (cleanroom, grade C)
- Online monitoring system for the monitoring of more than 150 quality-relevant parameters (pressure, temperature, humidity, particles, incubators, refrigerators)
- High-quality equipment for cell isolation (positive and negative selection) and cell expansion
- Freezing equipment
- Cryogenic storage capacity for quarantined products and products approved for release
- Irradiation device
- 10-color flow cytometer suitable for IVD applications, offering a range of phenotyping methods and functional assay techniques
- Various established cell counting methods, e.g. using the CASY cell counter
- Access to a qualified high content screening device
- All devices used for manufacturing and monitoring are subject to regular maintenance and (re-) qualification
- All methods and processes used are validated
Cell culture laboratory for clinical trials | ECRC GMP Facility
In addition to containing a clean room suite with three manufacturing lines, the Cell Culture Laboratory for Clinical Trials (ZKP) also functions as a containment level 2 gene technology facility, which closely monitors compliance with all relevant requirements to ensure correct operation. Processes are planned, prepared, and performed to comply with all relevant quality and safety aspects which apply to the areas of manufacturing and quality control. The ability to continually develop and implement new process steps relies on the facility’s members of staff and their high levels of accuracy, reliability, and expertise.
The ECRC GMP Facility also provides services to external drug manufacturers, such as microbial monitoring and sterility testing.
- Design of drug manufacturing processes
- Transfer of manufacturing processes for developed cell therapeutics (ATMP, immune and gene therapies) to GMP manufacture
- Completion of applications and securing of all authorizations required for the manufacture of investigational medicinal products pursuant to Section 13 of the Medicinal Products Act (§ 13 AMG)
- Manufacture, storage, and transport of investigational medicinal products for human use which are intended for phase I/II clinical trials
- Cell culture systems: Flasks, cell factory systems and bags
- Bioreactor-based systems and automated systems: the Xuri Cell Expansion System W25 (cell culture bags), the CliniMACS Plus Instrument (depletion or enrichment) and – shortly – the CliniMACS Prodigy (cell culture chamber)
- Heat sealing technologies for closed systems
- Blood culture systems BACTEC 9050 and FX40 for sterility testing in compliance with Ph. Eur. 2.6.27
- Test microbe production for microbiological monitoring of cleanrooms, sterility testing, etc.
- Cryopreservation in bags and vials, gas-phase storage using liquid nitrogen and cell banking management
- GMP production unit specialized in aseptic manufacturing of cell therapeutics for innovative therapies (ATMPs)
- Site with two cleanrooms of grade A in B (cell cultures) and a cleanroom of grade C (tissue preparation)
- Associated quality control testing: sterility, microbiology, flow cytometry, particle monitoring, qPCR for quantification of vector copy numbers in transduced cells
- Maintenance of reference microbes in compliance with the European Pharmacopoeia (Ph. Eur.)
- Own nitrogen stores