Scaling Up to Market
The need to scale up oligo synthesis as compounds in development move through the pipeline creates challenges for maintaining product quality. The demand for large-scale synthesis is particularly strong in the RNA sector, “however, scales have still not approached those of DNA,” says Dr. Fettes.
“This is likely due to the early clinical phase of the compounds and purported increased efficacy of the drugs. As scales increase, focused process-development activities, rather than novel chemistries, are key to maintaining good product quality. Even as the number of RNA compounds is increasing rapidly, many DNA compounds hold a lot of promise such as antisense, aptamers, immunomodulators, decoys, and DNAi.”
At “TIDES,” Dr. Fettes will be participating in a discussion entitled “Manufacturing RNA Oligonucleotides: Can One Hydroxyl Really Make That Much of a Difference?” While the core principles governing successful DNA and RNA production are basically the same and include developing scalable models and implementing Design of Experiments (DoE) methods, “the manufacture of RNA is a more complex process involving the synthesis of two strands with deprotection chemistry that requires careful process control.”
“The management of these parallel processes to maintain equivalent process performance requires predictive development work,” says Dr. Fettes. To ensure that risk-management tools and DoE are integrated across the organization and throughout process and analytical development and manufacturing, “Avecia recently added personnel that have extensive experience in Lean and Six Sigma to drive operational excellence.”
In other recent news, Biosearch Technologies(www.biosearchtech.com) received a worldwide license to the noncoding DNA patients owned by Genetic Technologies (GTG; www.gtg.com.au), granting the oligonucleotide-synthesis company the rights to manufacture and distribute oligos, probes, and primers for research use under GTG patents. The license covers all genomes and includes SNP genotyping and allelic discrimination.
Houston, TX-based CytoGenix (www.cytogenix.com) developed a synthetic cell-free process for large-scale production of biologically active DNA and an expression vector for producing single-stranded DNA sequences inside target cells.
In August, the company broke ground on a new 20,000 sq.ft. facility that will house its offices, laboratories, and DNA production plant and will enable expansion of the company’s internal drug-development programs toward clinical testing and its ability to produce GMP DNA products for customers.