FDA Issues Guidance on Clinical Pharmacology for Peptide Drugs

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The guidance document discusses the impact of clinical pharmacology considerations on peptide drug development.

FDA published draft guidance on Dec. 13, 2023 that provides recommendations for the development of peptide drug products submitted in a new drug application. The document describes the impact of clinical pharmacology considerations on a peptide drug’s pharmacokinetics (PK), safety, and efficacy.

The guidance defines a peptide as any polymer composed of 40 or fewer amino acids that can be isolated from animal tissue, produced synthetically, or produced through recombinant expression. According to FDA, there has been an effort to improve absorption, distribution, metabolism, and excretion (ADME) properties of native peptides. These efforts include increasing oral bioavailability, half-life, and conformational flexibility, as well as decreasing general hydrophobicity. Alterations (e.g., cyclization, pseudo-peptide bonds, unnatural 45 amino acids, and peptide conjugations) to the peptide structure have been included to gain more favorable ADME characteristics. Therefore, peptide drugs may exhibit distinct combinations of characteristics regarding their chemistry, pharmacology, PK disposition, and pharmacodynamics (PD), FDA said in the draft guidance document.

Topics discussed in the article include bioanalytical approaches, radiolabeled mass balance studies, and impaired renal function. Considerations for assessing immunogenicity include performing immunogenicity risk assessments, clinical immunogenicity assessments, and immunogenicity clinical impact analysis.


The guidance also addresses characterization of the impact of hepatic impairment, assessing drug interactions, and characterizing QT interval prolongation. Labeling considerations are also covered.

Source: FDA