FDA Determination of Qualification Limits Peptide-related Impurities of - Products to Inform Guidance

Position: FDA Determination of Qualification Limits for Peptide-related Impurities of Follow-on Products to Inform Guidance
Organization

U.S. Food and Drug Administration (FDA)

Reference Code

FDA-CDER-

Final date to receive applications

1/1/2027 3:00:00 PM Eastern Time Zone

Description

• Applications will be reviewed on a rolling-basis.

FDA Office and Location

A research opportunity is available within the Food and Drug Administration (FDA) in The Center for Drug Evaluation and Research (CDER), located at White Oak, Maryland.

The Center for Drug Evaluation and Research (CDER) performs an essential public health task by making sure that safe and effective drugs are available to improve the health of people in the United States. As part of the U.S. Food and Drug Administration (FDA), CDER regulates over-the-counter and prescription drugs, including biological therapeutics and generic drugs. This effort covers more than just medicines.

Research

Project

This project will concentrate on establishing Immunogenicity-Based Qualification Thresholds for Peptide and Protein Impurities as well as assessing HLA-Restricted T-Cell and Anti-Drug Antibody Risk. Per regulation, follow-on peptide and protein therapeutics approved under the 505(j) and 505(b)(2) pathways may not require new clinical trials when bioequivalence and qualitative comparability to the reference product are demonstrated. However, differences in product quality attributes (including sequence variants and process/product-related impurities) may alter immunogenicity risk and affect safety, pharmacokinetics, pharmacodynamics, and efficacy.

Current FDA guidance (e.g., the 2021 guidance for certain highly purified synthetic drug products referencing rDNA origin drugs) provides analytical qualification limits for impurities but does not establish thresholds based on immunogenicity risk. This creates regulatory uncertainty for industry applicants and reviewers. The proposed project addresses this gap by experimentally defining impurity qualification thresholds that incorporate immunogenicity risk and mechanistic understanding of HLA-restricted T-cell activation.

Learning

Objectives:

• Identify Impurity-Derived Neoepitopes via Immunopeptidomics
• Define Functional T-Cell Activation Thresholds In Vitro
• Elucidate HLA-Restricted Mechanisms of Drug-Specific T-Cell Responses
• Validate Translational Relevance in Humanized HLA Mouse Models

Mentor

The mentor for this opportunity is Sujin Hwang (sujin.hwang.gov). If you have questions about the nature of the research, please contact the mentor.

Anticipated Appointment

Start Date:

2026/2027.

Start date is flexible and will depend on a variety of factors.

Appointment Length:

The appointment will initially be for one year, but may be renewed upon recommendation of FDA and is contingent on the availability of funds.

Level of Participation:

The appointment is full time.

Participant Stipend:

The participant will receive a monthly stipend commensurate with educational level and experience.

Citizenship Requirements:

This opportunity is available to U.S. citizens, Lawful Permanent Residents (LPR), and foreign nationals. Non-U.S. citizen applicants should refer to the Guidelines for Non-U.S. Citizens Details page of the program website for information about the valid immigration statuses that are acceptable for program participation.

This program, administered by ORAU through its contract with the U.S. Department of Energy to manage the Oak Ridge Institute for Science and Education, was established through an interagency agreement between DOE and FDA. The participant will receive a monthly stipend commensurate with educational level and experience. Proof of health insurance is required for participation in this program. Participants do not become employees of FDA, DOE or the program administrator, and there are no employment-related benefits.

Completion of a successful background investigation by the Office of Personnel Management is required for an applicant to be on-boarded  can complete a background investigation only for individuals, including non-US Citizens, who have resided in the US for a total of three of the past five years.

FDA Ethics Requirements

If an ORISE Fellow, to include their spouse and minor children, reports what is identified as a Significantly Regulated Organization (SRO) or prohibited investment fund financial interest in any amount, or a relationship with an SRO, except for spousal employment with an SRO, and the individual will not voluntarily divest the financial interest or terminate the relationship, then the individual is not placed  additional requirements, see FDA…