There are various reasons compounded medications are necessary: either because the patient cannot tolerate the commercially available drug or its excipients; the exact dose, strength, or route is not commercially available; or the patient may need a medication that is currently in shortage or discontinued.
The United States Pharmacopeia (USP) Convention formally defines compounding as “the preparation, mixing, assembling, altering, packaging, and labeling of a drug, drug-delivery device, or device in accordance with a licensed practitioner's prescription, medication order, or initiative based on the practitioner/patient/ pharmacist/compounder relationship in the course of professional practice.”¹
Compounding pharmacists can put drugs into specially flavored liquids, topical creams, transdermal gels, suppositories, or other dosage forms suitable for patients’ unique needs. Compounding does not include making copies of commercially available drug products, since this is not allowed by law unless there is a Food and Drug Administration (FDA) declared shortage, like the one for GLP-1 receptor agonists, e.g., Ozempic, Wegovy, and Mounjaro.²
Semaglutide and tirzepatide were initially on the FDA’s list of drugs in shortage, which meant these drugs could be approved for compounding if other criteria were also met. In October 2024, tirzepatide (Mounjaro and Zepbound) was removed from the drug shortage list. However, due to concerns that the drug remains in short supply, the FDA continues to allow its compounding by delaying enforcement actions against compounders.³ At the time of this writing, the FDA delayed enforcement of its regulations until February 18, 2025, for state-licensed pharmacists and physicians compounding, and until March 19, 2025, for outsourcing facilities.4
Compounding pharmacies have received heavy media attention lately, thanks to GLP-1 receptor agonists that have become popular for their weight loss effects.
There are some situations in which you may need to turn to a compounding pharmacy, and when you do, some careful research should be conducted before selecting one. Here are some questions you should think about when considering compounded medications for your patients.
► Is drug compounding the same as drug manufacturing?
Most pharmacies offer some level of compounding, typically for nonsterile preparations that are meant to be used in areas of the body where sterility is not necessary. The key differences between drug compounding and manufacturing include:
- Personalization: Compounding is patient-specific, while manufacturing is mass produced.
- Regulation: Compounding is more loosely regulated, focusing on individual cases, while manufacturing is strictly regulated by the FDA, with stringent quality control and Good Manufacturing Practices (GMP) in place to ensure the safety, efficacy, and consistency of products.
- Volume: Compounding is small-scale and customized, while manufacturing involves large-scale production.
► How are compounding pharmacies regulated?
The practice of compounding is regulated by state boards of pharmacy. Community and hospital compounding pharmacists are allowed exemptions to the 1938 Federal Food, Drug, and Cosmetic Act if they comply with the regulations outlined in Section 503A of the Act. All pharmacists and pharmacies engaged in compounding are subject to oversight by both federal and state authorities. 503A-designated compounding pharmacies, such as those that compound according to prescriptions specific to certain patients, are required by state boards of pharmacy to comply with USP and other guidelines.
Section 503B of the Act defines some compounding pharmacies as those with outsourcing facilities that may manufacture large batches with or without prescriptions and can be sold to healthcare facilities for office use only.²
Pharmacists involved in compounding are required to adhere to the relevant standards and regulations for the types of preparations they create. The FDA oversees the safety and integrity of the drugs (referred to as Active Pharmaceutical Ingredients, or APIs) used in compounded medications. The Drug Enforcement Administration (DEA) regulates the use of controlled substances in compounded drugs, which include narcotics like hydrocodone, amphetamines, and medications for anxiety and sleep disorders. However, there are no agencies regulating the medications that are being produced by compounding pharmacies.
Additionally, the USP sets standards that govern compounding practices and defines the chemical purity of drugs and establishes practice standards. They also develop criteria for the identity, quality, strength, and purity of medicines, dietary supplements, and food ingredients used in compounding, which are particularly important for compounding pharmacists to follow.5
Compounding pharmacies can obtain accreditation through the Accreditation Commission for Health Care (ACHC), which follows a specific set of standards that concentrate on the quality and consistency of medications produced to assure patient safety. Although ACHC accreditation is voluntary, it ensures the pharmacy meets the most rigorous review and inspection measures in the industry.6
► Do I need to tell patients their medication is compounded?
Patients should be aware they are receiving a compounded drug. Typically, these medications are labeled by the compounding pharmacy and include the pharmacy’s information.
Patients may ask whether the compounding pharmacy is accredited. The Pharmacy Compounding Accreditation Board’s (PCAB) website lists accredited compounding pharmacies by state.6 You can also refer patients to the FDA BeSafeRx website to ensure they are safely buying prescription medicines online.7
► I have seen more FDA warnings about compounded medications. Why?
While compounded preparations are supposed to contain FDA-approved ingredients, the formulations as prepared at compounding pharmacies are not reviewed by the FDA for purity, safety, or effectiveness. In 2023, the FDA received reports that some compounders were using salt forms of semaglutide, such as semaglutide sodium and semaglutide acetate, but neither are FDA approved, therefore there is no evidence that they are safe or effective.
Unlike commercially prepared medications that are pre-dosed, minimizing the risk of errors, compounding pharmacies prepare the dose manually, which can lead to miscalculated dosing. The FDA has received reports of dosing errors with compounded injectable semaglutide products, which can lead to potentially serious side effects like nausea, vomiting, headache, or acute pancreatitis. Some patients have required hospitalization as a result.
Many patients who received vials of compounded semaglutide lacked experience with self-injections, according to the adverse event reports. Unfamiliarity with transferring medication from a vial into a syringe, coupled with confusion between different units of measurement (e.g., milliliters, milligrams, and “units”) may have also contributed to dosing errors.
Some compounded versions of semaglutide that are being mixed with other drugs or different ingredients have become more popular. However, the FDA has issued a warning stating that these compounded options may not be safe.8
Compounded drugs pose a higher risk to patients than FDA-approved drugs because compounded drugs do not undergo FDA premarket review for safety, quality, or effectiveness. Compounded drugs should only be used for patients whose medical needs cannot be met by an available FDA-approved drug.
Additionally, there are growing concerns with counterfeit prescription medications from online pharmacies. The Centers for Disease Control and Prevention (CDC) recently released a statement warning the public of this issue after the U.S. attorney’s office announced charges against 18 defendants in a scheme to manufacture and distribute millions of deadly counterfeit pharmaceuticals through fake online pharmacies.9
► What if I find an issue with a compounded drug, such as a medication error?
The FDA encourages pharmacists, healthcare providers, and patients to report adverse events and medication errors associated with compounded products to the FDA’s MedWatch Adverse Event Reporting program: https://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-…. You can also report websites that you think are illegally selling medicine. To do so, download and complete the form at https://www.fda.gov/media/85598/download?attachment, then submit it via fax to 1-800-FDA-0178.
Monica Ludwick, Pharm.D. is a Senior Risk Management and Patient Safety Specialist. Questions or comments related to this article should be directed to MLudwick@CAPphysicians.com.
References
¹Serumaga, Brian. (2017) “USP Compounding Standards” [Presentation]. Accessed November 12, 2024. https://www.usp.org/sites/default/files/usp/document/get-involved/stake…
²U.S. Food and Drug Administration. (2024, December 18). “Compounding When Drugs Are on FDA's Drug Shortages List.” U.S. Food and Drug Administration. Accessed November 12, 2024. https://www.fda.gov/drugs/human-drug-compounding/compounding-when-drugs…
³U.S. Food and Drug Administration. (2024, December 19). “FDA Clarifies Policies for Compounders as National GLP-1 Supply Begins to Stabilize.” Accessed November 12, 2024. https://www.fda.gov/drugs/drug-safety-and-availability/fda-clarifies-po…
4U.S. Food and Drug Administration. (2024, December 19). “Declaratory Order: Resolution of Shortages of Tirzepatide Injection Products (Mounjaro and Zepbound)” [Letter]. https://www.fda.gov/media/184606/download?attachment
5American Pharmacists Association. “Frequently Asked Questions About Pharmaceutical Compounding.” Accessed November 12, 2024. https://www.pharmacist.com/Practice/Patient-Care-Services/Compounding/C…
6Accreditation Commission for Health Care. “Compounders Rely on PCAB Accreditation” [Webpage]. Accessed November 12, 2024. https://www.achc.org/pcab/
7U.S. Food and Drug Administration. “BeSafeRx: Your Source for Online Pharmacy Information.” Accessed November 12, 2024. https://www.fda.gov/drugs/quick-tips-buying-medicines-over-internet/bes…
8U.S. Food and Drug Administration. “FDA's Concerns About Unapproved GLP-1 Drugs Used for Weight Loss.” Accessed November 12, 2024. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-a…
9Centers for Disease Control and Prevention. (2024, October 3). “Potential public health risk among individuals ordering counterfeit prescription medications from online pharmacies” [Press Release]. https://www.cdc.gov/media/releases/2024/s1002-counterfit-prescription-online-pharmacies.html