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New FDA Draft Guidance: Clinical Pharmacology Considerations for Peptide Drug Products

  • 1.  New FDA Draft Guidance: Clinical Pharmacology Considerations for Peptide Drug Products

    Posted 09-11-2023 08:13

    The introduction is interesting in that it not only defines what will be considered a 'peptide' but also why certain peptides and their formulations are considered drugs and the responsibility of CDER and not other divisions of the FDA:

    The term peptide, for purposes of this guidance, refers to any polymer composed of 40 or fewer amino acids.2 In general, if a peptide meets the definition of a drug and does not otherwise meet the statutory definition of a "biological product"3 or a "device,"4 it would be regulated as a drug under the FD&C Act and be subject to all the "drug" requirements under the FD&C Act and FDA's regulations, including the requirement that new drugs must be approved under section 505(c) of the FD&C Act before they can be marketed in interstate commerce.5 However, peptide drug products can have product characteristics that may be similar, in certain respects, to biological products, and as such, this guidance includes references to other FDA guidances on biological products that discuss scientific principles that could also be applicable to peptide drug products.

    Peptides can be isolated from animal tissue, produced synthetically, or produced through recombinant expression, and often serve as signaling molecules for many physiological functions. Recent drug development efforts have focused on improving the absorption, distribution, metabolism, and excretion (ADME) properties of native peptides, such as increasing oral bioavailability, increasing half-life, decreasing general hydrophobicity, and increasing conformational flexibility to increase selectivity of the intended target. To obtain more favorable ADME characteristics in patients, peptide drug products under development have included certain alterations to the peptide structure and/or incorporated new formulation strategies (e.g., liposomes). These structural alterations can include cyclization, pseudo-peptide bonds, unnatural amino acids, and peptide conjugations (e.g., PEGylation). As such, peptide drug products can exhibit distinct combinations of characteristics of both small and large molecules regarding their chemistry, pharmacology, pharmacokinetic disposition, and pharmacodynamics (PD). Of note, this guidance does not focus on the development of any particular peptide drug product. Any questions about regulatory requirements for a particular peptide drug product should be addressed to the appropriate FDA review division.

    The guidance also describes the requirements for bioanalytical assays, radiolabeled mass balance studies, renal and hepatic impairment studies, immunogenicity testing, QT interval prolongation studies, and DDI studies. 

    The information on the draft guidance and how to comment can be found here, where a link to the actual guidance is provided. 



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    Mark Arnold Ph.D., FAAPS
    Westampton, NJ
    [email protected]
    Bioanalytical Solution Integration
    LinkedIn: https://www.linkedin.com/in/markearnoldphd/
    Website & Blog: Bioanalysis & Biomarkers <bioanalysisandbiomarkers.blogspot.com>
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    </bioanalysisandbiomarkers.blogspot.com>


  • 2.  RE: New FDA Draft Guidance: Clinical Pharmacology Considerations for Peptide Drug Products

    Past President
    Posted 09-11-2023 08:27

    Thanks Mark. I was also reading this draft guidance over the weekend.  Very interesting.

    Cheers

     

    Joe

    ***************************************************************

    Joseph W. Polli, PhD, FAAPS

    Senior Director, Project Specialist, Nonclinical Safety and DMPK

    ViiV Healthcare

    406 Blackwell Street

    Suite 300

    Durham NC 27701

    [email protected]

    M:  1-919-448-1016