Top 3 COGS Drivers for Peptide Therapeutics
In the last few years, there has been a renewed interest in peptide therapeutics directed toward a wide range of indications, including diabetes, cardiovascular disease, HIV and cancer. Peptides, compared to other small molecule drugs, offer increased specificity while potentially offering greater metabolic stability and oral availability than protein biologics. These peptide therapies can be manufactured using either recombinant methods or chemical synthesis alone or in combination. Recently, innovative synthesis methods have been described for generating long peptides that can be classified as proteins. For example, Provence Technologies recently synthesized IL-10, consisting of 160 amino acids. The FDA classifies any peptide produced synthetically containing over 100 amino acids as a protein. This blog outlines the three elements that affect costs of producing a peptide therapeutic.
First, a critical factor in the cost of peptides made by chemical synthesis is the product yield per amino acid addition step. A high number of sequential synthesis steps to grow a peptide can prove detrimental to process economics. For example, even a 95% step yield repeated over 20 reactions gives a total product yield of around 36%. In addition, a similar yield challenge exists as the number of peptides to be linked together to form the final product increases. Therefore, gaining the highest possible overall yield is critical to achieving cost-effective processes for longer peptides. One option for longer peptides is to perform a hybrid synthesis where peptide fragments are produced using solid phase synthesis first, then joined using solution phase synthesis to generate the product. Two other significant variables to quantify when considering costs are the coupling reaction time needed per step and the raw materials required. In the case of chemical synthesis, costs are also dependent of whether the process utilizes solution or solid phase synthesis.
Second, costs for recombinant fermentation-based production depend on how much product is produced per batch and fermentor turnaround time. These two factors determine the length of time these batches will keep a manufacturing facility busy. The amount of product produced will depend on the size and number of fermentors used. Recombinant process costs also include downstream separation steps that differ depending on whether the peptide is held within the cells or excreted into the growth medium. Recombinant processes tend to require more up-front investment, but have better economies of scale.
Third, the scale of the manufacturing operation and market demand are key factors. Each of these parameters affects the major cost categories in COGS calculations as outlined in a previous BPTC blog written by my colleague Rick Stock. In many cases, it would be a worthwhile tradeoff to assess quantitatively which method is likely to be the most efficient before making a final manufacturing process selection. Early process development work could both inform the analysis and show how much development work remains for each case. Such an analysis is used to generate the metrics associated with a specific COGS target, and indicate which strategy would likely yield the lowest COGS.
Blog article by: Terence Davidovits