Are Compounded Medications Safe and Regulated?

Compounded medications are custom-prepared formulations intended to meet specific patient needs when commercially available, FDA-approved products are unavailable or unsuitable. Compounding is performed by specialized pharmacies and may involve altering dosage forms, excluding allergens, or creating specific strengths not otherwise available.[1] While compounding can address important clinical gaps, it introduces unique safety and regulatory considerations.
​
​Regulatory Framework and Oversight
​
Compounded drugs are not FDA-approved and do not undergo premarket review for safety, efficacy, or manufacturing quality. Instead, oversight is divided between state boards of pharmacy and, for certain facilities, the FDA. The Drug Quality and Security Act (DQSA) of 2013 established two categories of compounding facilities: 503A pharmacies, which compound patient-specific prescriptions and are primarily regulated by state boards, and 503B outsourcing facilities, which may compound larger quantities for office use and are subject to FDA inspection and current Good Manufacturing Practice (cGMP) requirements.[2][3][4][5][6][7][8][9][10] The United States Pharmacopeia (USP) sets standards for compounding quality, with chapters <795> and <797> addressing non-sterile and sterile compounding, respectively. Most state boards of pharmacy now incorporate USP standards into their regulations, though the degree of enforcement varies.[9][10]
​
​Safety Concerns and Historical Context
​
Compounded medications have been associated with significant safety incidents, most notably the 2012 fungal meningitis outbreak linked to contaminated steroid injections from a compounding pharmacy, which resulted in over 60 deaths and hundreds of infections.[2][3][5][7][8] This event highlighted the risks of inadequate sterility, subpotency, and contamination, especially with high-risk sterile products. The DQSA was enacted in response, increasing federal oversight and establishing the 503B outsourcing facility category to improve quality and accountability for large-scale compounding.[2][3][4][5][7][8][10]
​
Despite these reforms, compounded drugs remain exempt from the FDA’s rigorous approval process. They may lack batch-to-batch consistency, standardized labeling, and robust post-marketing surveillance. The American Diabetes Association explicitly recommends against the use of non-FDA-approved compounded GLP-1 and dual GIP/GLP-1 receptor agonists due to concerns about content, safety, quality, and effectiveness.[6] Compounded products may only be prepared when the FDA-approved product is on the official shortage list, and only by facilities meeting 503A or 503B requirements.[6][8]
​
​503B Outsourcing Facilities
​
503B outsourcing facilities are permitted to compound larger quantities of medications, including sterile injectables, and are subject to FDA inspection and cGMP standards. These facilities play a critical role in addressing drug shortages and providing access to medications when commercial products are unavailable.[11][12] However, challenges remain, including variability in inspection frequency, lack of a finalized 503B bulk drug substance list, and ongoing concerns about quality assurance.[11][8][12] The FDA’s Compounding Incidents Program and MedWatch reporting system are key components of post-market surveillance for compounded drugs.[13]
​
​Clinical Implications and Best Practices
​
Clinicians should be aware that compounded medications may carry higher risks of contamination, dosing errors, and variability in potency compared to FDA-approved products.[3][5][6][1][10] When prescribing compounded GLP-1 or dual GIP/GLP-1 receptor agonists, it is essential to:
​
- Confirm that the product is being compounded in response to a documented shortage of the FDA-approved medication.[6][8]
​
- Prefer 503B outsourcing facilities that comply with cGMP and are subject to FDA oversight.[11][2][3][4][5][6][7][8][10][12]
​
- Ensure the compounding pharmacy follows USP <797> standards for sterile preparations.[9][10]
​
- Educate patients about the potential risks and lack of FDA approval for compounded products.[6][1]
​
- Report any adverse events to the FDA’s MedWatch system to support ongoing surveillance and safety improvements.[13]
​
​Summary
​
Compounded medications, including compounded GLP-1 and dual GIP/GLP-1 receptor agonists, fill important clinical needs but are associated with increased safety risks and regulatory complexity. The current consensus, as articulated by the American Diabetes Association and supported by regulatory and clinical literature, is to avoid non-FDA-approved compounded incretin products except in the context of documented shortages, and to use only facilities that meet the highest standards of quality and oversight.[6] Ongoing vigilance, adherence to regulatory requirements, and transparent communication with patients are essential to minimize risks and ensure patient safety.[13][11][2][3][4][5][6][7][8][1][9][10][12]
​
​