Previous articles in this series discussed how peptide synthesis has aided in developing a wide range of effective vaccines and therapeutic agents. This has been made possible by the ability to synthesize peptides with high purity and on a large scale. However, the nearly infinite number of sequence combinations, which frequently include modified amino acids, places significant demands on synthesis optimization.
SPPS is the sequential addition of protected amino acid derivatives to a growing peptide chain, which includes deprotection and washing steps to remove unreacted groups and side products. You would produce only the full-length peptide if you completed every single step. However, this is extremely rare, regardless of how well a protocol is optimized. Significantly, the risk of side reactions and incomplete reactions means that peptide purity becomes a critical issue in the application context.
Introduction
Peptide product demand has skyrocketed over the last decade. Due to limited resources, manufacturers are struggling to keep up with demand. As demand grows, manufacturers strive to improve peptide purity while lowering costs. However, as technology advances, the world of peptide synthesis is expanding faster than ever. The environmental impact of large-scale peptide production has been positive.
According to Mimoun Ayoub, vice president of strategic development and global business at Peptisyntha (a Solvay company), manufacturing approximately 20 kilograms of the 18-residue peptide generates about 300 metric tons of solvents and a significant number of other forms of waste.
These waste materials are amplified for companies that handle large amounts of peptides at any time. This is complicated further by the time and logistics required for waste separation, storage, and disposal.
Although recycling solvents may benefit large peptide products, you should conduct a cost-benefit analysis. However, even though all solvents exiting the production units are mixed, they are later separated by distillation. This process costs a lot of money and increases the space required for analysis, testing, and production.
Dr. Ayoub believes that the purity of the synthetic product is critical to lowering production costs because crude peptide purification is the primary factor driving peptide costs. Some of the most effective peptide synthesis strategies are discussed below in this article.
Are you Using Long Peptides or Protein?
Synthetic challenges to the system are increasing as the number of therapeutic peptides increases. Dr. Hazel Moncrieff, a senior group leader at GMP peptides, mentioned this factor. According to her, errors are caused by adding amino acids to a growing peptide strand compound as the peptide length increases. They have the potential to reduce the final product’s quality significantly.
A choice of resin is critical in producing long peptides because it increases the solubility of the peptide during formation while reducing aggregation. Another essential consideration is using anti cyclic citrullinated peptide, grouping post-synthesis products, and the need to correct analytical processes such as LC/MS and UPLC to separate impurities from full-length peptides.
Despite the separation system, these impurities elute with a full-length molecule because they lack the complete amino acid construct.
Take Note of Every Detail
Increased customer demands and the evolution of synthesis and purification technology are two significant factors driving CMO innovation. Jan Pawlas, a Ph.D. holder and member of the PolyPeptide Group (PPG) process development and support team, identified two major trends: increased focus on the economic aspects of peptide manufacturing and increased demand for faster delivery.
According to Dr. Pawlas, an efficient and well-developed solid-phase synthesis process is beneficial for small and medium-scale production and very efficient for large-scale production of complex peptides with intricate side chains.
One critical step is to streamline the production phase and achieve an efficient conversion to produce high purity crude synthetic peptides. However, to reduce the cost of peptide synthesis, you need an experienced and knowledgeable base that allows a CMO to shorten development time and instead opt for a synthetic route.
Understand Market Strength
Peptide manufacturing projects have recently increased due to the expanding pipeline at Bachem facilities. According to Mills, the number of ongoing development projects (preclinical to phase III) has risen from 120 in 2009 to 138 in 2010. The number of Phase III projects increased from 16 to 25.
According to Science Direct, the peptide industry was worth $15 billion in 2011, and experts predict that by 2027, it could be worth $47 billion. When synthesizing peptides, it is critical to understand the market flow.
The peptide industry thrives in some continents, such as North America and Europe, far more than in others.
Applying Six Sigma
Peptide manufacturing involves approximately 50 steps, which introduces a large margin of error and increases the possibility of process optimization. 96 to 98 percent of product yield is accounted for by synthetic peptides. In contrast, using the 50-step process for manufacturing peptides results in little or no product yield at the end of production.
Didier Monnaie, Ph.D., project leader at Lonza and Six Sigma Black Belt, explains. “To correctly manufacture peptides, an average yield of 99 percent at each process is required, with little margin for error.” He described Six Sigma’s four to five-year implementation at his department’s peptide manufacturing facility.
A well-designed process with proper documentation and process parameters would reduce the possibility of errors occurring during production.
Bottomline
The world of peptide synthesis is expanding at an incredible rate. As the demand for pure peptides grows, more and more companies are shifting to producing synthetic peptides. However, the product’s quality may deteriorate from time to time. However, as shown in the article, many scientists, organizations, and departments are pushing their limits to produce synthetic peptides correctly.
