Genetic Engineering & Biotechnology News

JUL 2017

Genetic Engineering & Biotechnology News (GEN) is the world's most widely read biotech publication. It provides the R&D community with critical information on the tools, technologies, and trends that drive the biotech industry.

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Genetic Engineering & Biotechnology News | | JULY 2017 | 27 hold only a specified amount of drug. Intarcia's lead investigational asset to treat type 2 diabetes, ITCA650, is a product candi- date that combines the Medici pump and the peptide exenatide. ITCA650, which is under- going NDA review, delivers up to 60 mg of exenatide per day for a period of six months. Intarcia anticipates that its platform could be used to deliver other drugs besides exenatide. If a drug is to be delivered via the Medici pump, however, it not only needs to maintain accurate potency, it must also solu- bilize sufficiently in Intarcia's storage matrix. Even with those constraints, many drugs in many different categories qualify for use with a Medici pump. "Also possible are peptide and peptide- drug combinations, where the peptides have been optimized for high potency and excellent pharmacokinetic properties," Dr. Feldman adds. "Given recent advances in peptide technology, Medici is suitable tech- nology for many peptides [to treat] many chronic indications." In addition to having expertise in peptide discovery and delivery, Intarcia has a col- laboration in place with the Swiss biotech company NuMab for the discovery of potent antibody fragments for treating metabolic and immunoinflammation disorders. More recently, Intarcia has teamed with the Gates Foundation on an HIV prevention regimen involving a small-molecule drug. The com- pany is also participating in a peptide pro- gram with California Institute for Biomedi- cal Research. Processing Considerations Contract manufacturing is at least as significant for peptide manufacturing as it is for small-molecule drugs and biologics. With the renewed interest in peptide drugs, solid-phase peptide synthesis has become a specialty capability for contractors who typi- cally run multiproduct facilities. With that competency comes the potential for product cross-contamination; contamination is of particular concern given the potency of some peptide drugs. Robert Geiger, Ph.D., vice president for quality at CMO AmbioPharm, notes that the production of peptides, given the nature of peptides and their production processes, poses lower cross-contamination risks than the production of other drug types. "Most peptides are, fortunately, very soluble," he points out. "I've seen maybe two in the last 15 years that were not. That makes life eas- ier for quality groups when switching from product to product." High solubility presents cleaning and cleaning validation functions with fewer problems. Processes that permit easy cleaning can speed up changeovers, provided appro- priate analytical methodology exists to verify the appropriate cleanliness level. Chemical definition, which exists to a far lesser degree with mAb, is another factor in favor of peptide processing. Whereas anti- bodies are expressed in living organisms— which confer a multitude of post-translation- al modifications—peptides are synthesized. With peptides, input equals output. Since every synthesis step and building block is known, maintaining a library of known and potential side products and contaminants is much easier for peptides than for proteins. "There are many more unknowns with mAbs," Dr. Geiger notes. Optical purity is a factor that mAb man- ufacturers hardly think about, but this can affect peptide manufacturing. AmbioPharm purchases its peptide building blocks as protected, synthetically generated amino acids. Unlike nature, which synthesizes pro- tein-based cell culture media and feed com- ponents perfectly, chemical asymmetric syn- thesis always creates some small percentage of the wrong mirror-image stereoisomer. Keeping the concentration of stereoisomers as low as possible assures optical purity and product quality. Analytics is crucial for determining optical purity as well. "Older reverse-phase HPLC methods might not distinguish between the correct entity, a product or starting material, and another, isomeric entity that possesses one or more 'reverse' chiral centers," warns Dr. Geiger. "This is one area where you can't cut corners." He adds that the optical purity of starting materials is not so much an issue as is reliable supply. Bioprocessing

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