FDA Reopens Comment Period on HCP Immunogenicity Risk of Follow-on Recombinant Peptides

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FDA announced on Dec. 31, 2024 that it is reopening the comment period for the Federal Register notice (FRN), “Evaluating the Immunogenicity Risk of Host Cell Proteins in Follow-on Recombinant Peptide Products: Establishment of a Public Docket: Request for Information and Comments”, published on July 25, 2024 (89 FR 60436) (2), because the FRN has received high interest from industry. The comment period will remain open until March 3, 2025 (1).

The December 31 notice establishes a public docket under which substantive comments from interested parties can be submitted on evaluating the immunogenicity risk of host cell proteins (HCPs) in follow-on peptide products. FDA is specifically interested in comments that address suitable methods to detect, identify, and control HCPs in commercial lots of recombinant peptide products (including information on achievable residual amounts of HCPs in the drug product) as well as in-vitro, in-silico immunogenicity assessment (IVISIA) of host cell proteins in recombinant peptide products.

Comments can be submitted electronically or in writing. If sent electronically, comments, including any attachments, should be submitted to the Federal eRulemaking Portal at https://www.regulations.gov. Comments and any accompanying attachments will be posted to the docket unchanged, according to FDA. “Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else's Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on https://www.regulations.gov,” FDA states in the December 31 notice (1).

Comments that contain confidential information not for public consumption should be submitted as a written/paper submission only.

For written/paper submissions, comments should be submitted by mail, hand delivered, or sent by courier to: Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. For comments submitted in writing, FDA will post the comments, as well as any attachments—except for information submitted that is marked and identified as confidential.

FDA also instructs that all submissions received must include the Docket No. FDA-2024-N-2980 for “Evaluating the Immunogenicity Risk of Host Cell Proteins in Follow-On Recombinant Peptide Products; Request for Information and Comments.”

Written/paper submissions that are confidential should be submitted in two copies, with one copy including the information marked as confidential. FDA recommends using a heading or cover note that states “THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.” The agency will review this copy, including the claimed confidential information, in its consideration of comments, while the second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https://www.regulations.gov.

“Although follow-on recombinant peptide products can rely on FDA’s findings of safety and effectiveness for a listed drug that is a peptide product, differences in recombinant expression systems used during the peptide production could result in quality attribute differences, including in the host cell protein profile, which in turn, could contribute to differences in immunogenicity risk between a follow-on peptide product and the relied upon listed drug,” FDA states in its announcement. Public comments will help the agency develop recommendations for evaluating and mitigating the immunogenicity risk associated with differences in HCP profiles between the follow-on and listed drug.

For more information about the open docket, including what information to include when submitting comments, see the Federal Register notice(1).

References

1. FDA. Evaluating the Immunogenicity Risk of Host Cell Proteins in Follow-On Recombinant Peptide Products; Reopening of the Comment Period. Notice, Federal Register, 89 FR 107147, 2024-31365.
2. FDA. Evaluating the Immunogenicity Risk of Host Cell Proteins in Follow-On Recombinant Peptide Products; Establishment of a Public Docket; Request for Information and Comments. Notice, Federal Register, 89 FR 60436, 2024-16356.