Finding a Niche
The pharmaceutial technologies and services group of Cardinal Health (www.cardinalhealth.com/pts) uses a patented gene product expression technology, GPEx, to insert genes and create stable mammalian cell lines with high gene copy numbers.
GPEx employs retroviral vectors to deliver genes coded as RNA that are reverse-transcribed to DNA and integrated into host cell genomes. It enhances protein yields to permit efficient pilot plant and large-scale production of Mabs and other therapeutic proteins. By inserting multiple copies of genes of interest, Cardinal Health can reportedly create cell lines that express as much protein as traditional gene transfection methods in half the time.
The GPEx technology originally was developed by Gala Biotech to make transgenic cows using retroviral vectors discovered by the late Nobel laureate Howard Temin at the University of Wisconsin-Madison. Cardinal Health acquired the company in 2003.
We noticed that the cultured cells used to make the retroviral particles express high levels of proteins, especially antibodies, says Paul Weiss, president of Cardinals biopharmaceutical development center.
Weiss describes Cardinal Health as a CMO plus because the GPEx technology optimizes cell lines for clients so that clients can then either remain with Cardinal Health or take the improved cell lines elsewhere. Because of its diversified capabilities, Cardinal Health can take a clients gene for an antibody, create or optimize a cell line, produce bulk protein, perform FDA biosafety testing, develop a stable formulation, and fill and finish the final product in vials, ready for dosing of patients.
Cambrex Bio Science Walkersville (www.cambrex.com) recently signed an agreement for the manufacture of Gerons (www.geron.com) GRNVAC1 telomerase vaccine (see GEN, March 1, 2006, p. 46). Gerons production process is being transferred to Cambrex, which will carry out the cGMP manufacture of the product, a therapeutic cancer vaccine composed of autologous dendritic cells, loaded ex vivo with telomerase mRNA.
We will leverage our cell therapy expertise and cGMP-manufacturing capabilities to enable Geron to advance the development of GRNVAC1 in the clinic, adds Shawn Cavanagh, Cambrex senior vp and general manager, bioproducts.
According to Cambrex officials, the companys manufacturing facilities provide a number of support services that might be required to produce human cells for therapeutic use, including autologous cells of varying shelf life for shipment to the U.S. and Europe; allogeneic cells, including sourcing, production of cell banks, and expansion to product quantities; and stem cell production via both master and feeder cell-banks.
Cambrex is equipped for and has experience with flasks, roller bottles, beads, and cell factories, including tissue engineered formats to meet specific customer requirements, says a company spokesperson. U.S.-based suites currently comply with ISO Class 7 (Class 10,000) classification to meet U.S. requirements, and suites with ISO Class 5 (Class B) compliance for European needs are expected to be available shortly. European suites meet all current European GMP regulatory standards, according to the firm.
The CMO team at Avid Bioservices (www.avidbio.com) is flexible to accommodate each client, says Richard Richieri, senior vp of bioprocess development and manufacturing.
In addition to standard batch and fed-batch processes, Avid offers perfusions (continuous cultures) that maintain high cell densities. Depending on the cell line, perfusions can generate as much material in a day as a fed-batch process produces in two weeks. When perfusion works, it has tremendous process economics, explains Richieri.
Avid Bioservices started in 2002 as a wholly owned subsidiary of Peregrine Pharmaceuticals (www.peregrineinc.com) to perform in-house biomanufacturing, then expanded to serve outside clients. One client recently received API approval for Avid to manufacture its commercial materials. Ever since we passed that inspection, weve been getting more Phase III clients, says Richieri.