Although some peptides have emerged in the field of wellness and medical innovation, pursuant to the 2019 implementation of the Biologics Price Competition and Innovation Act[1], very few peptides can be compounded. Peptides are defined as having less than 40 amino acids, but greater than 40 amino acids constitutes a biologic, which cannot be compounded unless the pharmacy has a biologics license. However, 503(a) facilities are not able to acquire a ‘biologics license’, and therefore, cannot compound biologics.
Categories of Peptides
Peptides that can be compounded are either: FDA-approved or are FDA GRAS (Generally Recognized as Safe) status,[2] have a USP monograph, appear on the 503A Bulks List, or have been placed in Category I of the interim 503A Bulks List.[3] Examples of peptides that meet these criteria are NAD+ and sermorelin. Since most other peptides do not currently meet any of those conditions, it remains important for compounders to be certain of the regulatory status of any peptides they intend to compound. In addition to the Bulks List, FDA has a listing of ingredients, some of which are peptides that present safety issues and should not be compounded.
Sourcing Active Pharmaceutical Ingredient (API)
After a determination of the regulatory status of whether a particular peptide can be compounded, it is equally important that peptide APIs be carefully sourced. Any supplier must be listed with FDA as an API manufacturer and provide a Certificate of Analysis.[4] Peptides that are ‘research use only’ (RUO) cannot be used in human or veterinary compounding. For human use, the API must be ‘pharmaceutical grade’, and not ‘food grade’ or ‘RUO.’
FDA Enforcement
It is possible to see many sites selling peptides over-the-counter (OTC) with multiple disclaimers that they are for RUO and not intended to diagnose, treat, cure, or prevent any disease. FDA has pursued enforcement action especially where it can be shown that the products were actually intended for human use, where for example, therapeutic claims were made or where the products were sold together with diluent and syringes. FDA has stated such disclaimers were a ruse to avoid FDA scrutiny for selling misbranded and adulterated products in violation of the FD&C Act.[5] There have also been some warning letters pertaining to compounding of peptides. The prohibition on compounding peptides is selectively enforced. The warnings have mostly been issued if certain claims were made or if the facility has had other violations such as incorrect BUDs, insanitary conditions, product strength exceeding label claims, high doses with side effects reports, or sold OTC (without a prescription). Most recently, FDA issued a warning letter targeting thymosin alpha 1 which was being offered to treat COVID-19 and ‘RUO’ GLP-1s sold OTC.[6]
The Future
Robert F. Kennedy Jr. posted a now infamous tweet shortly before the election:
“FDA’s war on public health is about to end. This includes its aggressive suppression of psychedelics, peptides, [emphasis added] stem cells, raw milk, hyperbaric therapies, chelating compounds, ivermectin, hydroxychloroquine, vitamins, clean foods, sunshine, exercise, nutraceuticals and anything else that advances human health and can’t be patented by Pharma…..”
On the highest level, this seems to imply a reversal of the policies pertaining to suppression of products which do not comply with all FDA regulations. While it remains to be seen if regulatory scrutiny for this class of products will remain high, peptide compounding must adhere to USP 797/795 and always align with local, state and federal laws and regulatory considerations.
How Frier Levitt Can Help
It is critical that pharmacy compounders perform due diligence and consult legal counsel before they engage in compounding peptides. Frier Levitt attorneys, including our pharmacist-attorneys, have a deep bench of compounding knowledge and regularly advise clients in the compounding space. Contact us for assistance.
[1] 42 U.S.C. § 262.
[2] However, pursuant to FDA Guidance “Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application (Jan 2018), 503(a) and 503(b) facilities may still mix, dilute or repackage. While repackaging is considered compounding under the USP definition, it is not compounding under the FDA Guidances.
[3] Meaning the substance is eligible and was nominated for inclusion (but not yet included) on the Bulks Drug List and does not present significant safety risks).
[4] The Pharmacy should request third-party stability and endotoxin testing from the API supplier to ensure patient safety
[5] 21 U.S.C. §301 et seq.
[6] FDA stated that thymosin is not approved to treat any condition and cannot be compounded.
