Downstream Services

Downstream Process Development  

GBI's downstream process development group has over twelve years experience in developing and refining purification processes. With an extensive background in the purification of monoclonal antibodies (including IgG, IgA and IgM subclasses) and recombinant proteins from mammalian, microbial, and plant and animal transgenic systems, GBI can quickly develop a purification process for clients that will maximize yields for the target molecule, meet required purity levels, and be compliant with the regulatory requirements for product's development status.  GBI has experience with affinity, ion exchange, hydrophobic interaction, and MEP chromatography processes.  Our experience includes UF processes using TFF technologies in both flat plate and hollow fiber formats.  Viral clearance techniques employed include low pH inactivation and nanofiltration.  We work closely with filtration media providers to develop a filtration process that works within the confines of your process and product requirements and provides the necessary viral removal. 

As the product proceeds through its clinical evaluation, GBI can optimize and refine the purification process including the testing and establishment of parameter limits.  When the product reaches phase three clinical testing and beyond, GBI will have developed a process that can be transferred for commercial manufacturing and ready for qualification runs with a minimum of problems. 

Viral clearance studies are managed by GBI using a contract biological safety testing organization.  GBI can perform the necessary scale down validation to assure that the process transferred to the testing organization is representative of the full scale process.  GBI can provide an on site scientist at the testing organization to assure that your process is run according to its requirements to avoid comparability questions on the results.  The scale down validation and viral clearance studies are assembled into one package for submission to regulatory agencies or other manufacturers.

 
Protein Modification and Conjugation  
 
GBI has both the expertise and experience in protein modification utilizing either chemical conjugation or enzymatic digestion. 
 
Conjugation of antibodies with other molecules is a specialty of GBI's development and manufacturing groups. Whether the conjugate is a drug toxin, chelating agent for radio isotopes, adjuvants such as Aluminum Hydroxide-Antibody conjugate, or other antibodies, GBI has the ability to develop and perform them at GMP compliant manufacturing scales for clinical applications. The development group fully understands the issues involved with these processes such as incorporation levels, active site masking and isotope uptake and stability. The manufacturing group has utilized these processes in the production of multi-gram lots of conjugated antibodies that have been administrated in clinical trials throughout the world.

Antibody modification through enzyme digestion is another GBI staff specialty. The production of Fab and F(ab')2 fragments and their subsequent purification can be achieved to a client's specifications. These processes are GMP compliant and scalable to multi-gram lot sizes for clinical applications.