Production of Biological Materials
Location: Hutchinson Building, CD-150
Contact phone: (206) 667-5838
Contact e-mail: email@example.com
The facility is designed primarily to produce two types of biological products from established cell lines: (1) clinical grade, intended for intravenous administration in humans and (2) non clinical grade for use in research models. Manufacture and purification of products are performed in dedicated clinical and non-clinical areas of the facility in compliance with regulatory standards.
Production of biological agents includes: monoclonal antibodies, fusion proteins, conjugates, plasmids, formulation of peptide vaccines and various other products derived from both eukaryotic and prokaryotic culture systems. Production amounts can be from mg to gram quantities.
To initiate service or obtain additional information, contact the facility director (x5838). Projects are scheduled following the submission of appropriate service request forms.
Clinical Grade Products
Clinical products are manufactured and tested in accordance with current Good Manufacturing Practices (cGMP) and are produced as part of the Therapeutic Products Program (TPP). Raw materials, intermediate materials and finished components are stored in a manner compatible with clinical manufacture. All manufacturing processes and quality control tests are performed according to approved written procedures. Quality Control (QC) has the authority to accept or reject the product. Product or process nonconformances are documented and referred to management for investigation and resolution. Reserve samples are retained from each lot of finished product. Samples are retained for ongoing stability testing. Facility Production Director, Quality Assurance/Control Unit and appropriate senior staff are responsible for conducting quality audits on an ongoing basis. Production batch records are developed from process development/pilot studies into standardized batch record format. Batch records are reviewed and approved by production staff and management for accuracy, cGMP compliance and product safety. During each production run, supporting documents for production and quality control are compiled and placed in product files for retention in restricted and secured fire proof files.
Facilities and Equipment
The Facility complies with various guidance documents accepted or published by the U.S. FDA including, but not limited to, "Derivation and Characterization of Cell Substrates used for Production of Biotechnological/ Biological Products" (International Congress of Harmonization, Q5D, 1997); "Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin" (ICH Q5A, 1997), "Points to Consider in the Characterization of Cell Lines used to Produce Biologicals" (FDA, CBER 1993), Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use (FDA, CBER 1997), appropriate portions of the Federal Code of Regulations (i.e. CFR 610), and U.S. Pharmacopoeia specifics.
The Facility occupies approximately 2600 square feet and is comprised of areas for nonclinical production, clinical production, development, quality control and support space. The Clinical Production Suite (CPS) is the core of the facility and occupies approximately 1300 square feet divided between two main work areas, production and purification, with related support space for staging, cold room storage, production support and cleanup. Qualified automation systems continuously monitor, control and alarm various aspects within the facility including: energy management, lab data acquisition, lighting, access (security), fire/smoke alarm, and status of air flow and pressurization of individual spaces within the suite. Keycard access to the facility is restricted to Biologics staff and Fred Hutch departments providing support services to the facility. The cGMP facility was constructed according to specifications set by Code of Federal Regulations Title 21, Sections 210 and 211.
Equipment allows production at scales that readiliy exceed the capabilities of most research laboratories and as required provides the added benefit of clinical cGMP compliance that would not otherwise be available to investigators. For production of biological reagents, bulk cell capacity can range up to the equivalent of 100 liters in various culture formats including fully automated fermentor/bioreactor vbessels.
Equipment is available to harvest either bulk-conditioned media or cells depending upon project needs. In most cases bulk conditioned media is harvested followed by purification. Purification may consist of multiple steps including affinity, ion exchange, ultrafiltration and diafiltration.
In conjunction with these capabilities, the facility maintains a separate well equipped quality control laboratory to provide characterization and safety testing capabilities.