CPHI Milan 2024: Navigating CMC Challenges for GLP-1 and Oral Peptides

During CPHI Milan, Andrew Lewis, PhD, chief scientific officer at Quotient Sciences, sat with Pharmaceutical Technology® Europe to discuss the chemistry, manufacturing, and control (CMC) challenges encountered during the development of glucagon-like peptide 1 (GLP-1) and oral peptides.

Lewis noted that a poor correlation seems to exist between the performance of oral peptides in preclinical animal studies and humans. “So, the approach we've pioneered at Quotient is to really tightly integrate our drug product manufacturing and clinical testing … by tightly integrating them, not only does it mean that we can rapidly advance [oral peptide products] into the clinic, but it also enables us, through the use of adaptive CMC clinical strategies, to modify formulations in response to emerging clinical data,” he stated.

Lewis also said that GLP-1s present tolerability challenges, and that this is true of this class of drugs as a whole. Permeability challenges can be addressed by the use of permeation-enhancing technology combined with modified release formulations, which may also enhance control of the pharmacokinetic profile and, hopefully, manage adverse events. “I think it's probably worth pointing out as well that, for oral peptides, they are particularly [used] with permeation enhancers. They are specific. They're very different formulations [from] a standard tablet formulation. You typically will require quite large amounts of permeation enhancers, so they make up a significant percentage of the formulation,” he explained. “Many of these permeation enhancers are quite waxy, [while] some of them are [somewhat] semi-solids.” These characteristics make permeation enhancers generally poorly compressible. In addition, they exhibit poor flow, which can make tableting or granulation difficult.

“There [are] certainly specific formulation and manufacturing processability challenges with oral peptides,” Lewis said. “Peptides behave very differently to small molecular weight drugs.”

Click above for the full interview.

You can visit Quotient Sciences at Booth A90 in Hall 7. CPHI Milan is being held from Oct. 8–10, 2024 in Milan, Italy.

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