Development and Manufacture of Therapeutic Proteins through Fermentation Technology

Therapeutic proteins are a fast growing segment of the pharmaceutical industry. These include native proteins, recombinant and fusion proteins, peptides and antibody fragments, many of which are manufactured through microbial fermentation. Building on 30 years of experience, SAFC offers contract development and manufacturing of fermentation-derived therapeutic proteins from pre-clinical to commercialization.

SAFC employs microorganisms up to Risk Group 2 and operates at Bio-safety level 2 large scale. Project specific master and working cell banks are safely deposited in temperature-controlled bio-storage. Strains, handled under strict aseptic procedures, are identified and characterized for homogeneity (absence of foreign growth), viability and productivity. Native or recombinant proteins may be recovered from the fermentation broth (secreted) or the biomass (e.g. intracellular, periplasmic, soluble, or in inclusion bodies). Yields are optimized through both upstream and downstream process development. SAFC has broad experience in microbial fermentation, including but is not limited to:

   Bacteria (e.g. Escherichia coli, Staphylococcus aureus, Clostridium species)

   Streptomycetes (e.g. Streptomyces species, Actinomyces species)

   Filamentous Fungi (e.g. Nigrospora species, Aspergillus species)

   Yeast (e.g. Saccharomyces cerevisiae, Pichia pastoris)

   The state-of-the art GMP fermentation facility in Jerusalem, Israel features:

–   Fully automated equipment

–   Cleaning and sterilization/sanitization in place (CIP, SIP) systems

–   Sanitary grade piping equipped with filters

–   Uniform fermentor geometry and pilot/ production purification system consistency to ensure robust and scalable
processes

   Class 100,000 (ISO 8) Manufacturing suite:

–   Fermentors - 100 L / 1,000 L / 4,000 L

–   Continuous disc stack centrifuge

–   Automatic piston discharge high-speed centrifuge

–   High-pressure homogenizer

–   Temperature-controlled, stirred processing tanks up to 4,000 L

   Class 10,000 (ISO 7) segregated purification suites:

–   GE Uniflux™ tangential flow ultra/diafiltration, Unicorn™ software

–   Millipore® Liquid BioChromatography production and pilot-scale systems

–   BPG QuickScale high-performance columns

   Lyofast 5 pharmaceutical freeze dryer (Lyophilizer)

SAFC partners with Pfēnex Inc. to provide customers with a cutting-edge expression technology system. With SAFC’s world-class contract manufacturing services and purpose-built facilities, the partnership facilitates a more comprehensive offering in the area of vaccine components and support development of conjugate vaccines. The Pfēnex expression technology also aids in the production of fermentation-derived recombinant proteins. To learn more about SAFC’s partnership with Pfēnex, click here: Pfēnex Expression Technology platform.

Dedicated Quality Assurance (QA) and regulatory affairs personnel are in place to handle:

   Document review and approval (e.g. MMF, SOPs, batch records, product release)

   Equipment qualification including 21CFR part 11 compliance

   Validation of manufacturing processes and cleaning procedures

   Investigation of non-conformances

   Change control implementation

   Corrective And Preventive Action (CAPA)

   Personnel training and qualification program

   Drug Master File (CTD-DMF) filing with the regulatory agencies (e.g. FDA, EMEA)

Therapeutic proteins analytical tests are compliant with Pharmacopoeia (EP/USP) methods and ICH guidelines. Managed via a validated Informatics System for Quality Control (QC) analytical data (SAP-QM), our services include:

   Analytical methods development and validation

   Testing of raw materials, in-process control, and final product release

   Stability testing

   Cleaning efficiency testing

   Selected protein analysis tests:

>> Download the print version of this page Fermentation Insert (1.08 Mb PDF)

>> Additional High-Potent Fermentation Capabilities

>> View the Israel Facility

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