How the FDA, ICH, and EMA Regulate Peptide and Protein Drug Quality — a Complete Overview | Research

The takeaway

Peptide and protein drugs now represent about 25% of the global drug market, and this review summarizes the FDA, ICH, and EMA guidelines that govern their testing, stability, and quality control.

25% of the global drug market
Peptide and protein therapeutics have grown from a single drug (insulin, 1921) to roughly one-quarter of all pharmaceutical sales worldwide

What the researchers found

Peptide and protein drugs now account for approximately 25% of the global pharmaceutical market. The FDA, ICH (International Council for Harmonisation), and EMA (European Medicines Agency) have each established specific guidelines for the analysis, stability testing, and quality control of peptide and protein therapeutics. The review summarizes these frameworks and advocates for tailored bioanalytical workflows for each individual peptide or protein drug, since each has unique stability and characterization requirements.

Why it matters

As peptide drugs explode in popularity (from insulin to semaglutide and beyond), understanding how they're regulated ensures quality and safety. This review provides a comprehensive overview of the regulatory landscape across the three major regulatory bodies, which is essential for drug developers, compounding pharmacies, and anyone evaluating peptide drug quality.

The numbers in context

~25% of global pharmaceutical market · Regulatory bodies: FDA + ICH + EMA · Growth since insulin approval (1921) · Physical + chemical characterization required

How the study worked

Regulatory review article summarizing guidelines from the FDA, ICH, and EMA regarding the analysis, stability testing, quality control, and formulation requirements for therapeutic peptides and proteins.

What this study cannot tell us

This is a review of existing regulatory frameworks, not an experimental study. Guidelines are inherently evolving documents — some details may change as regulators update requirements. The review focuses on the three major Western regulatory bodies and may not cover regulatory frameworks in other major markets (e.g., China's NMPA, Japan's PMDA) in equal depth.

How to read the evidence

This is a regulatory review article, not a clinical or experimental study. It accurately summarizes existing guidelines from authoritative regulatory bodies and is valuable as a reference document rather than for its evidence grade.

When this study was published

Published in 2025, this is a current review reflecting the latest regulatory guidelines. However, regulatory frameworks are continuously updated, so specific requirements may evolve.

The bigger picture

With GLP-1 drugs driving record pharmaceutical revenues and hundreds of peptide drugs in development pipelines, regulatory quality standards have never been more important. This review arrives at a critical time when compounding pharmacy-made peptides are under intense scrutiny (e.g., compounded semaglutide and tirzepatide). Understanding the regulatory framework helps distinguish between properly manufactured peptide drugs and those that may lack adequate quality testing.

Questions still open

Are current regulatory guidelines keeping pace with the rapid expansion of peptide therapeutics, including novel formats like stapled peptides and peptide-drug conjugates?
How do compounding pharmacy quality standards compare to the FDA/EMA manufacturing requirements outlined here?
Should peptide drug regulation be harmonized globally, given that different regions apply different guidelines?

Common questions

Why do peptide drugs need special quality testing compared to regular pills?

Peptides are large, complex molecules that can degrade, change shape, or lose activity much more easily than small-molecule drugs. They're sensitive to temperature, light, pH, and time. Regulatory agencies require extensive stability testing, purity analysis, and activity verification specifically because peptides are so fragile — a degraded peptide could be inactive or even harmful.

Do the FDA, ICH, and EMA all have the same peptide drug requirements?

They share common principles through ICH harmonization efforts, but each agency has its own specific guidelines and emphasis areas. This review summarizes all three frameworks and highlights where they overlap and differ, arguing that drug developers need to understand all of them — especially for drugs sold in multiple markets.

Read the original research

Regulatory Guidelines for the Analysis of Therapeutic Peptides and Proteins.

Journal of peptide science : an official publication of the European Peptide Society, 31(3), e70001

View on PubMed ↗Publisher’s paper ↗

Citation

Elsayed, Yomnah Y; Kühl, Toni; Imhof, Diana. (2025). Regulatory Guidelines for the Analysis of Therapeutic Peptides and Proteins.. Journal of peptide science : an official publication of the European Peptide Society, 31(3), e70001. https://doi.org/10.1002/psc.70001