GHK-Cu: how it got to PCAC

Origin

GHK is a naturally occurring human tripeptide of sequence glycyl-L-histidyl-L-lysine, identified in human plasma in the early 1970s and catalogued by NCBI as PubChem CID 73587 (PubChem 73587). When complexed with copper(II), the tripeptide forms GHK-Cu, the copper-binding form that has been the focus of most of the laboratory and cosmetic-formulation work. The 2012 Pickart review in Oxidative Medicine and Cellular Longevity described the discovery context and the long-running observation that plasma levels of GHK decline with age PMID 22666519.

Research history

Pickart and colleagues catalogued reports that GHK-Cu interacts with copper homeostasis, modulates oxidative-stress markers, and produces gene-expression signals in cell-culture assays relevant to skin and connective-tissue biology. The 2025 review by Ogórek and colleagues in Molecules surveyed the cosmetic-ingredient literature and outlined methodological considerations for measuring GHK-Cu skin permeation in liposomal formulations PMID 39795193. The cited reviews observed that GHK-Cu has a long history as a cosmetic ingredient in topical skin-care products, but did not point to randomized controlled trials supporting medical-grade therapeutic claims.

The published GHK-Cu literature is concentrated in cell biology, formulation chemistry, and dermatologic-cosmetic contexts. Indexed peer-reviewed human-efficacy trials for systemic or injectable use are limited.

Regulatory journey

GHK-Cu has no FDA-approved drug application. The tripeptide-copper complex appears in cosmetic skin-care products, where claims are limited to cosmetic structure-and-appearance language; cosmetic and drug regulatory pathways are distinct under U.S. law. Compounding pharmacies that wish to use GHK-Cu as a bulk drug substance must rely on the section 503A framework, which permits compounding from bulk substances that appear on FDA’s 503A bulks list or that are the subject of an approved drug application.

FDA’s program page describes the bulks-list nomination workflow and the interim three-category framework — Category 1 (eligible pending rulemaking), Category 2 (significant safety concerns, not eligible pending further evaluation), and Category 3 (insufficient information) (FDA — Bulk Drug Substances Used in Compounding). A number of peptide bulk-drug nominations, including GHK-Cu-related substances, were placed in Category 2 pending advisory-committee review under FDA’s “may present significant safety risks” notice (FDA Category 2 notice).

FDA placed GHK-Cu on the agenda of the Pharmacy Compounding Advisory Committee meeting scheduled for the end of February 2027. PCAC’s role is advisory: the committee analyzes the nomination, hears from the agency’s review team and from the public, and recommends whether the substance should be added to the 503A bulks list. FDA is not required to follow the committee’s recommendation, but PCAC discussions and briefing documents are the central publicly available analysis of nominated substances.

What’s at stake

If PCAC recommends inclusion and FDA agrees, traditional 503A compounders will be able to prepare GHK-Cu under individual prescriptions. If the committee recommends against inclusion — for example, on the basis of immunogenicity concerns, peptide-impurity considerations, or insufficient human evidence — the substance would remain in Category 2, and compounding from the bulk substance would continue to fall outside the 503A safe harbor pending final rulemaking. Cosmetic uses of GHK-Cu are governed by a separate regulatory regime and are not directly affected by a PCAC recommendation. The February 2027 briefing materials are expected to be the most thorough consolidated regulatory record on GHK-Cu released to date; this page will be updated when they are posted.