FDA Weighs in on Popular Peptides

In about a week, the committee that advises the FDA on pharmacy compounding will hold a public meeting on several peptides that are popular in sports medicine and do-it-yourself physical improvement/wellness circles. The meeting will address whether the individual peptides that are the subject of the meeting can legally be used by compounding pharmacies to make products for individual patients.  

Why FDA Is Reviewing These Peptides

Under current law, compounding pharmacies are limited to manufacturing drug products using bulk drug substances:  

1. That are subject to an applicable US Pharmacopeial or National Formulary monograph,

2. Are components of FDA-approved drugs, or 

3. Appear on a list developed by the Secretary of Health and Human Services on the basis that there is a clinical need and safety is verified.

The list is referred to as the 503A Bulks list. The upcoming meeting will evaluate whether the following peptides should be added to the 503A Bulks list: TB-500, Semax, MOTS-c, KPV, Epitalon, Emideltide, BPC-157.  

It is generally considered that the advantage of having products manufactured by compounding pharmacies is that it ensures that the bulk drug substances are tested for sterility, potency, and purity. Having a reliable source of drug substance for the compounded products can protect individuals from relying on questionable online purveyors. Presence on the 503A Bulks list, while falling far short of an FDA approval, also provides a pathway for providing a product when there is no available FDA-approved alternative. What the 503 list does not do is to provide any surety on the efficacy of a product against therapeutic conditions.  

Compounded drugs containing substances that do not meet any of the three criteria listed above are considered to be unapproved new drugs, and may be the subject of warning letters or regulatory enforcement actions.

The Peptides Under Review and Their Proposed Medical Uses

The seven peptides under review are popular in sports medicine for muscle growth, improving endurance, reducing inflammation, and/or enhancing recovery. However, in six of the seven cases, these peptides are not being reviewed by the advisory committee specifically for those uses. Instead, the peptides were submitted for review for use in the medical conditions for which they are most commonly associated. In one case (MOTS-c), the peptide is being reviewed for both the medical conditions for which it is associated as well as its effect on well-being (i.e., metabolism and longevity):

• TB-500: wound healing

• Semax: cerebral ischemia, migraine, trigeminal neuralgia

• MOTS-c: insulin resistance, obesity, osteoporosis, vascular calcification, muscle/fat metabolism, longevity

• KPV: wound healing, inflammatory conditions

• Epitalon: insomnia

• Emideltide: opioid withdrawal, chronic insomnia, narcolepsy

• BPC-157: ulcerative colitis

FDA's Initial Assessment and Recommendations

The advisory committee will provide its recommendations about listing the individual peptides on the 503A list at the meeting to be held on July 23 and July 24. This decision will rely on the committee’s own review of the available data, any public comments, and advice provided by the FDA as the results of its own review.  

The decision by the committee is not yet known, but the FDA has published summaries of their findings and recommendations. Across all seven peptides, the FDA recommended against listing.  In each case, the recommendations made by the FDA were dependent on:  

1. The physical and chemical characterization of the peptide; including stability and impurities

2. The history of use of the peptide

3. The evidence for efficacy

4. Any concerns about its safety

5. Clinical need

The most common objections to listing were inadequate clinical evidence of efficacy and safety, and determination that there were already FDA-approved products available to treat the specific disease(s).  

What Happens Next?

Ultimately, it will be the FDA that makes the final determination regarding listing the peptides on the 503A Bulks list once the advisory committee has made their recommendations. The overall negative tone of the published FDA findings suggests that there will be significant hurdles to listing irrespective of the findings of the advisory committee. This is consistent with FDA’s overall approach to new products. It's not just safety that matters; the product’s efficacy is equally important.