LEGAL PEPTIDE COMPOUNDING GUIDE503A & 503B Regulatory Compliance

January 2025 Update

DISCLAIMER: This document is for informational purposes only and does not constitute legal advice. Regulatory status of peptides changes frequently. Always verify current FDA guidance and consult legal counsel before compounding. Document compiled: January 2025

TABLE OF CONTENTS

1. Legal Pathways for Peptide Compounding

2. Category 1 Peptides (Can Be Compounded)

3. Previously FDA-Approved Peptides

4. Category 2 Peptides (Prohibited)

5. PCAC December 2024 Outcomes

6. Compliance Requirements

7. Complete Reference List

1. LEGAL PATHWAYS FOR PEPTIDE COMPOUNDING

Under FDA regulations, a peptide can be legally compounded by 503A pharmacies if it meets ONE of these criteria:

Pathway	Description
1. FDA-Approved	Is a component of an FDA-approved drug product
2. USP/NF Monograph	Has a United States Pharmacopeia or National Formulary monograph
3. 503A Bulks List	Appears on the official 503A Bulks List (21 CFR 216.23)
4. Category 1	Is in Category 1 of the interim 503A Bulks List (under evaluation, no significant safety concerns)

Source: FDA Bulk Drug Substances Used in Compounding (https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding)

2. CATEGORY 1 PEPTIDES (CAN BE COMPOUNDED)

The following peptides appear on Category 1 of the FDA's interim 503A Bulks List as of September 27, 2024. FDA does not intend to take enforcement action against compounders using these substances.

Peptide	Restrictions	Clinical Uses
Vasoactive Intestinal Peptide (VIP)	None	CIRS/mold illness, inflammatory conditions, pulmonary hypertension
NAD (Nicotinamide Adenine Dinucleotide)	None	Cellular energy, anti-aging protocols, addiction recovery, cognitive function
NADH (NAD Disodium Reduced)	None	Same as NAD
GHK-Cu (Copper Peptide)	NON-INJECTABLE ONLY	Topical: photoaging, hair loss, wound healing
Glutathione	Under ongoing evaluation	Detoxification, oxidative stress, mold toxicity treatment

Primary Source: FDA 503A Bulk Drug Substances List (September 27, 2024) - https://www.fda.gov/media/94155/download

Additional 503B Category 1 Peptide:

Peptide	Prior FDA Approval	Clinical Uses
Gonadorelin Acetate	LutrePulse (discontinued)	Ovulation induction (hypothalamic amenorrhea), hypogonadism, fertility protocols

3. PREVIOUSLY FDA-APPROVED PEPTIDES

These peptides can be compounded under the "component of FDA-approved drug" pathway. They either have current FDA approval or were previously approved and discontinued for reasons OTHER than safety or efficacy concerns.

Peptide	FDA Status	Clinical Uses
Sermorelin	Previously approved (Geref, NDA 020443) Discontinued 2008*	GH deficiency (pediatric/adult), age-related GH decline, body composition optimization
Oxytocin	FDA-approved (Pitocin)	Labor induction, postpartum hemorrhage, off-label autism protocols
Vasopressin/Desmopressin	FDA-approved (DDAVP)	Diabetes insipidus, bleeding disorders
Leuprolide	FDA-approved (Lupron)	Prostate cancer, endometriosis, precocious puberty
Octreotide	FDA-approved (Sandostatin)	Acromegaly, carcinoid tumors
Tesamorelin	FDA-approved (Egrifta) - BRAND ONLY	HIV lipodystrophy (specific indication only)
Calcitonin	FDA-approved (Miacalcin)	Osteoporosis, Paget's disease

*Sermorelin was discontinued by manufacturer in 2008 for commercial reasons, NOT safety or efficacy concerns. Per FDA PCAC Briefing Document: "Only sermorelin (Geref, NDA 020443) was approved for the treatment of short stature associated with GHD in pediatric patients."

4. CATEGORY 2 PEPTIDES (PROHIBITED)

WARNING: The following peptides are classified as Category 2 (Bulk Drug Substances that Raise Significant Safety Risks) and CANNOT be legally compounded by 503A or 503B facilities. FDA has stated it would consider taking action against a compounder for compounding drug products with this bulk drug substance.

Prohibited Peptide	Common Marketing Claims
BPC-157	GI support, tendon/ligament healing, anti-inflammation
Thymosin Beta-4 Fragment (TB-500)	Tissue repair, wound healing
GHK-Cu (INJECTABLE only)	Anti-aging (topical permitted)
Cathelicidin LL-37	Antimicrobial, immune support
Dihexa Acetate	Cognitive enhancement
Emideltide (DSIP)	Sleep regulation
Epitalon	Telomere extension, anti-aging
Ibutamoren Mesylate (MK-677)	GH secretagogue
Kisspeptin-10	Reproductive hormone modulation
KPV	Anti-inflammatory peptide
Melanotan II	Tanning, sexual dysfunction
Mechano Growth Factor (PEG-MGF)	Muscle growth
MOTs-C	Metabolic regulation
Semax (heptapeptide)	Cognitive enhancement, neuroprotection

Source: FDA 503A Bulk Drug Substances List, Page 3 (September 27, 2024) - https://www.fda.gov/media/94155/download

5. PCAC DECEMBER 2024 OUTCOMES

In September 2024, FDA removed several peptides from Category 2 after nominators withdrew their nominations. These peptides were then reviewed by the Pharmacy Compounding Advisory Committee (PCAC) for potential inclusion on the 503A Bulks List. All were REJECTED.

Peptide	PCAC Meeting Date	Outcome
Ipamorelin (free base/acetate)	October 29, 2024	REJECTED - Not recommended
Ibutamoren Mesylate	October 29, 2024	REJECTED - Not recommended
Kisspeptin-10	October 29, 2024	REJECTED - Not recommended
Thymosin Alpha-1	December 4, 2024	REJECTED - Not recommended
CJC-1295 (all forms)	December 4, 2024	REJECTED - Not recommended
AOD-9604	December 4, 2024	REJECTED - Not recommended

Key Implication: These peptides remain prohibited for compounding. Removal from Category 2 was procedural (nominations withdrawn) but PCAC rejection means they will NOT be added to the approved bulks list.

Sources: FDA PCAC December 4, 2024 Meeting Transcript - https://www.fda.gov/media/185641/download; Alliance for Natural Health USA (December 6, 2024)

6. COMPLIANCE REQUIREMENTS

API Sourcing Requirements:

• API supplier must be listed with FDA as an API manufacturer

• Each bulk drug substance must be accompanied by a valid Certificate of Analysis (CoA)

• Peptides labeled 'Research Use Only' (RUO) CANNOT be used in human compounding

• For human use, API must be 'pharmaceutical grade' - NOT 'food grade' or 'RUO'

• Compounding must adhere to USP 797/795 standards

• All applicable state and federal laws must be followed

Research-Only Peptide Warning: FDA has stated that "Research Use Only" disclaimers on peptides sold with diluent and syringes are "a ruse to avoid FDA scrutiny for selling misbranded and adulterated products in violation of the FD&C Act." Enforcement actions have targeted such sellers.

Source: Frier Levitt - Regulatory Status of Peptide Compounding in 2025 - https://www.frierlevitt.com/articles/regulatory-status-of-peptide-compounding-in-2025/

7. COMPLETE REFERENCE LIST

Primary FDA Sources:

1. FDA 503A Bulk Drug Substances List (September 27, 2024) - https://www.fda.gov/media/94155/download

2. FDA 503B Bulk Drug Substances List (March 21, 2025) - https://www.fda.gov/media/94164/download

3. FDA Interim Policy Guidance (January 7, 2025) - https://www.fda.gov/media/174456/download

4. FDA Bulk Drug Substances Overview - https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding

5. FDA PCAC Briefing Document (Ipamorelin) - https://www.fda.gov/media/182088/download

6. FDA PCAC December 4, 2024 Meeting Transcript - https://www.fda.gov/media/185641/download

7. Federal Register - Interim Policy (January 7, 2025) - https://www.federalregister.gov/documents/2025/01/07/2024-31546/

Secondary Legal/Industry Sources:

8. Frier Levitt - Regulatory Status of Peptide Compounding in 2025 (April 3, 2025) - https://www.frierlevitt.com/articles/regulatory-status-of-peptide-compounding-in-2025/

9. Fagron Academy - Interim 503A and 503B Bulks Lists Revisions - https://www.fagronacademy.us/blog/industry-update-503a-and-503b-bulks-lists-new-revisions

10. Alliance for Pharmacy Compounding (A4PC) - January 29, 2025 - https://a4pc.org/news/2025-01/fda-releases-final-interim-guidance-on-bulk-drug-substances-for-both-503as-and-503bs

11. Lexology/Reed Smith - FDA Removes Peptides from Category 2 (October 1, 2024) - https://www.lexology.com/library/detail.aspx?g=2e55b76a-3173-4e04-beda-bf021202f18d

12. Alliance for Natural Health USA - PCAC Meeting Outcome (December 6, 2024) - https://anh-usa.org/fda-strikes-another-blow-against-compounded-medicines-peptides-rejected-at-latest-pcac-meeting/

Document prepared for educational purposes. Regulatory status changes frequently. Always verify current FDA guidance at https://www.fda.gov/drugs/human-drug-compounding/ before compounding decisions. Consult qualified legal counsel for compliance questions.