USP Statement: HHS Peptide Policy Lacks Essential Quality Safeguards

On November 3, 2026, the United States Pharmacopeia (USP) published a public statement titled "USP statement on quality and safety considerations for unapproved peptides" in response to the Department of Health and Human Services (HHS) enforcement discretion policy for 503A compounding with certain peptides (Federal Register notice FR Doc. 2026-22192, filed October 28, 2026, published October 30, 2026).

USP's statement notes that its review conducted in advance of the July 2026 PCAC meeting found that the peptide substances included under the HHS enforcement discretion policy are not sufficiently characterized to support consistent evaluation of their quality, creating a risk to patients.

"Without the clearly established identity and appropriate substance-specific standards and reference materials, the quality of the bulk drug substance cannot be reliably and consistently established," the statement reads.

USP further stated: "In addition, the referenced USP standards in the policy cannot, on their own, provide adequate quality assurance for these peptide substances. They do not establish the substance- and product-specific quality specifications that would come from linking each peptide bulk drug substance to a drug monograph and related reference standard."

The statement concludes by noting that developing USP monographs and reference standards would require scientific information about the identity and quality attributes of these substances as well as official names determined by established naming institutions, and that neither existing nor potential new USP standards replace a regulator's role in determining whether a product is safe and effective.

To understand USP's statement, we need context on what the HHS enforcement discretion policy requires and what USP argues it lacks:

What the HHS Policy Requires (Condition 3)	What USP Says Is Missing
Bulk drug substance from FDA-registered facility with valid certificate of analysis (COA) showing test results consistent with FDA guidance-based criteria for identity, purity, potency, and absence of harmful contaminants (endotoxins, heavy metals, microbial contamination, impurities)	No USP-NF monograph that establishes substance-specific identity and quality specifications for these peptides
Identity requirements per Appendix B: amino acid sequence, chemical structure, molecular weight, molecular formula, and permitted route(s)	No USP Reference Standard for analysts to compare test samples against a known, authenticated reference material
Characterization testing for identity, purity, potency per existing FDA guidance documents	No established bulk drug substance name (USAN, INN, or IUPAC name) that unambiguously defines what the substance is
Referenced USP standards in the policy (e.g., USP <621> chromatography, <467> residual solvents, <232>/<233> elemental impurities, <61>/<62> microbial testing, <85> bacterial endotoxins, <1503> for identity/impurities)	USP states these standards alone cannot provide adequate quality assurance without substance-specific monographs and reference standards

The HHS policy states its intent is to "discourage the continued, widespread use of certain research-use-only peptides supplied by foreign manufacturers that pose a safety risk to US patients" and that "the policy provides patients with a more controlled alternative" via 503A compounding (HHS policy PDF).

However, USP's statement highlights that without the foundational quality infrastructure, that controlled alternative may lack the safeguards needed to ensure consistent quality.

Important: The HHS enforcement discretion policy applies only to 503A compounding pharmacies, federal facilities, and licensed physicians. Holland & Knight confirms the policy does not extend to research-use-only (RUO) active pharmaceutical ingredient (API). RUO catalog procurement is governed by separate frameworks.

USP's statement turns on three technical terms that are central to pharmaceutical quality assurance but often unfamiliar outside regulatory circles. Understanding these terms clarifies why USP is concerned:

Quality Element	What It Is	What It Establishes
USP-NF Monograph	A published standard in the United States Pharmacopeia–National Formulary (USP-NF) that defines the identity, strength, quality, and purity requirements for a specific substance	Official substance-specific acceptance criteria (e.g., minimum purity percentage, maximum impurity levels, specific identity tests such as HPLC retention time or mass spectrum fragments) that analysts and manufacturers must meet
USP Reference Standard	A highly characterized, authenticated physical sample of the substance purchased from USP and used as the benchmark in analytical testing	A known, traceable comparator that laboratories run alongside test samples to confirm identity (does the test sample's peak match the reference?) and quantify purity (how much of the test sample is the target peptide vs. impurities?)
Certificate of Analysis (COA)	A document issued by a manufacturer or third-party laboratory reporting the test results for a specific batch of material	Batch-specific test data (purity percentage, identity confirmation, contaminant levels) that the supplier asserts meets specifications—but those specifications and reference materials used for testing may or may not align with official standards if no monograph or reference standard exists
Established Name (USAN/INN/IUPAC)	An official, unambiguous name assigned by the United States Adopted Names (USAN) Council, the International Nonproprietary Names (INN) program, or the International Union of Pure and Applied Chemistry (IUPAC)	A globally recognized identifier that unambiguously defines the chemical entity, preventing confusion between similar peptides and enabling consistent regulatory tracking

The HHS policy's own testing standard is relevant here. According to the policy's Appendix B testing standards table, the required COA information list includes the "Bulk drug substance (BDS) name (e.g., USAN, INN, IUPAC).

" Footnote 2 states that analytical testing "may be conducted utilizing either established compendial procedures or appropriately validated non-compendial (in-house) procedures" and that "the COA should also include information on any reference standards utilized during testing," with reference-standard characterization for identity and purity per ICH Q7.

The assay row specifies HPLC/RP-HPLC "based on comparison with an established quantitative reference standard.

" In other words, the policy asks for a BDS name and reference-standard information on the COA, while USP states that no official name or USP Reference Standard exists for these six substances.

What This Means for COA Interpretation

A COA shows what tests were performed and what values were recorded for a specific batch. But a COA's reliability depends on:

• What reference standard the laboratory used: If no USP Reference Standard exists, the lab may use an in-house standard, a commercial standard from a supplier, or a standard synthesized in-house. The traceability and purity of that standard are critical but often not disclosed on the COA.
• What acceptance criteria were applied: If no USP monograph exists, the manufacturer or lab sets its own specifications. Those may be reasonable, stringent, or lenient—but they are not official.
• Whether the substance is unambiguously defined: If no established name exists, different suppliers may use the same label (e.g., "BPC-157 Acetate") for materials with different counterion ratios, salt forms, or impurity profiles.

In our analysis, this means that without these three foundational elements—monograph, reference standard, and official name—a COA alone cannot reliably establish quality in a consistent, reproducible way across different manufacturers and testing laboratories.

For laboratories purchasing research-grade peptides, this underscores the importance of asking suppliers:

• What reference standard did the testing laboratory use?
• Is that reference standard traceable to a recognized authority (e.g., USP, NIST) or is it an in-house standard?
• What acceptance criteria were applied (not just "≥98% purity," but what method and what threshold)?
• Can you provide the full analytical report, not just the summary COA?

See our guides on how to read a peptide COA and how to verify COA authenticity for detailed checklists.

The HHS enforcement discretion policy (Federal Register FR Doc. 2026-22192) imposes 10 conditions that 503A compounders must meet. USP's statement does not reference the policy's specific conditions; its concerns bear most directly on Condition 3 (characterization and COA requirements). Here is how we map USP's concerns onto the policy's conditions as editorial analysis:

HHS Policy Condition	Our mapping (USP does not reference specific conditions)
Condition 1: Peptide must be on Appendix A (six peptides: BPC-157, TB-500, epitalon, KPV, MOTS-c, semax)	USP notes these six peptides do not have USP-NF monographs, USP reference standards, or established names (USAN, INN, IUPAC)
Condition 2: Identity per Appendix B (amino acid sequence, chemical structure, molecular weight, molecular formula, route limits)	Appendix B provides structural information, but USP states that "without the clearly established identity and appropriate substance-specific standards and reference materials, the quality of the bulk drug substance cannot be reliably and consistently established"
Condition 3: Characterization from FDA-registered facility with valid COA (identity, purity, potency, absence of contaminants per FDA guidance)	USP states that the referenced USP standards in the policy cannot, on their own, provide adequate quality assurance without substance-specific monographs and reference standards linking to the peptide
Condition 4: Original manufacturer (not repacker) registered with FDA, CGMP-compliant, lists facility location on COA; repacker must validate	Not addressed by USP
Conditions 5–10: Adverse event reporting, labeling ("compounded drug, not for resale"), single API, oral bioavailability documentation where applicable, FDA 510(k)-cleared syringe only, all other FDCA requirements	Not addressed by USP

In short: the HHS policy imposes procedural and documentation requirements, but USP argues that without the foundational quality infrastructure (monograph, reference standard, official name), those requirements cannot ensure consistent, reliable quality.

The HHS enforcement discretion policy was published in the Federal Register on October 30, 2026 (Volume 91, Number 209, Pages 68526-68527). The public comment deadline is November 13, 2026 (two weeks after publication).

Comments can be submitted via regulations.gov docket HHS-OASH-2026-0496. Stakeholders—including compounding pharmacies, patient advocacy groups, analytical laboratories, pharmacy associations, and quality standards organizations like USP—can submit comments addressing the policy scope, the peptides covered, the conditions imposed, or the adequacy of quality safeguards.

What Comments Might Address

Given USP's statement, we can anticipate several comment themes:

• Request for monograph development: Comments may urge USP and FDA to prioritize development of USP-NF monographs and reference standards for the six peptides, providing the infrastructure USP argues is missing.
• Request for clearer specifications: Comments may ask HHS or FDA to specify exactly what analytical methods, reference standards, and acceptance criteria compounders and manufacturers must use to demonstrate identity and purity.
• Concerns about COA variability: Comments may highlight that without official standards, COAs from different manufacturers may use different test methods and reference materials, making it difficult for compounders, regulators, and patients to compare quality across suppliers.
• Requests for interim measures: Comments may propose interim quality measures (e.g., third-party certification programs, registries of approved testing laboratories, or manufacturer audits) until official monographs and reference standards are developed.

503A Bulks List Rulemaking

The enforcement discretion policy is an interim measure while FDA conducts rulemaking to potentially add these peptides to the official 503A bulks list (21 CFR 216.23). According to Holland & Knight legal analysis, the policy does not add these peptides to the 503A Bulks List; H&K advises readers to monitor forthcoming FDA rulemaking.

If FDA proposes to add any of the six peptides to the 503A bulks list through formal rulemaking, that proposal will include a separate Federal Register notice and comment period.

At that stage, USP's concerns about quality infrastructure would likely be raised again—and FDA would need to address how quality will be assured without monographs and reference standards, or announce plans to develop them.

What RUO Buyers Should Do

The HHS enforcement discretion policy and USP statement focus on 503A compounding pharmacies—not research-use-only catalog suppliers. However, the quality assurance principles USP raises (the need for reference standards, established names, and substance-specific specifications) apply equally to RUO procurement.

Laboratories sourcing peptides for research should:

• Ask suppliers what reference standard was used for identity and purity testing.
• Request full analytical reports, not just summary COAs.
• Compare COAs from multiple suppliers to identify inconsistencies (e.g., different purity methods, different impurity profiles).
• Document procurement decisions, including why a particular supplier and batch were chosen.
• Maintain batch-to-batch records and link them to experimental protocols.

See our RUO documentation checklist for detailed guidance.

This analysis synthesizes primary regulatory documents and expert legal commentary. All claims are sourced as follows:

• USP Statement (November 3, 2026): United States Pharmacopeia, "USP statement on quality and safety considerations for unapproved peptides." https://www.usp.org/news/usp-statement-on-quality-and-safety-considerations-for-unapproved-peptides (retrieved November 4, 2026).
• Federal Register Notice (October 30, 2026): Department of Health and Human Services, "Enforcement Discretion Policy Regarding 503A Compounding Using Certain Peptide Bulk Drug Substances," FR Doc. 2026-22192, Docket No. HHS-OASH-2026-0496, 91 FR 68526-68527. https://www.govinfo.gov/content/pkg/FR-2026-10-30/html/2026-22192.htm
• HHS Policy Document (Appendix B): https://www.hhs.gov/sites/default/files/hhs-503a-peptide-enforcement-discretion-policy-appendix-b.pdf
• Holland & Knight Legal Alert (November 4, 2026): Sara M. Klock, Michael J. Werner, Sarah Starling Crossan, Andrew I. Namkung, "HHS Issues Interim Enforcement Discretion Policy for Compounding of 6 Peptides." https://www.hklaw.com/en/insights/publications/2026/11/hhs-issues-interim-enforcement-discretion-policy-for-compounding
• Foley & Lardner Legal Commentary: "Peptides: HHS Announces Limited Enforcement Discretion for Compounding of Six Peptides." https://www.foley.com/insights/publications/2026/10/peptides-hhs-announces-limited-enforcement-discretion-for-compounding-of-six-peptides/
• McDermott Will & Emery Legal Commentary: "Peptides First, Paperwork Later: HHS Clears Six for Compounding Ahead of Bulks List Rulemaking." https://www.mcdermottlaw.com/insights/peptides-first-paperwork-later-hhs-clears-six-for-compounding-ahead-of-bulks-list-rulemaking/
• Federal Food, Drug, and Cosmetic Act, Section 503A: 21 U.S.C. § 353a.

Related PurePep Vital Content

• HHS Peptide Enforcement Discretion Policy (Oct 2026) — Full Analysis
• Research Peptide Regulatory Timeline (2023–2026)
• How to Read a Peptide Certificate of Analysis (COA)
• How to Verify Peptide COA Authenticity
• Peptide Testing Labs: Third-Party Analytical Services
• 503A vs. 503B Compounding: Educational Guide
• BPC-157 Research Page | TB-500 | Epitalon | KPV | Semax | MOTS-c
• Certificate of Analysis (COA) — Glossary Definition