any patients must abstain from animal-derived ingredients (ADI) or prefer animal-free (AF) medications due to health, dietary, religious, animal cruelty, or climate change reasons. Based on some estimates, 75% of popular medications may contain ADI (active or inactive ingredients; heparin, thyroid hormone, gummies, gelatin capsules, etc.); ADI are also present in a diverse set of medical products, such as bioprosthetics (e.g., porcine heart valves), surgical mesh, and most vaccines. This poses a problem not only in acute medical care (e.g., medications/devices used during surgery) but also in ambulatory settings.

According to a recent report from the Centers for Disease Control and Prevention, as many as 450,000 individuals in the US may have a health condition known as alpha-gal syndrome (AGS). Patients with AGS can have a potentially life-threatening reaction to galactose-α-1,3-galactose, an oligosaccharide expressed on glycoproteins and glycolipids of nonprimate mammals (e.g., pork, beef, rabbit, lamb) and products made from mammals (including gelatin, cow’s milk, milk products). According to a recent survey of 559 AGS patients, 50% had experienced an anaphylactic reaction due to health products that include alpha-gal.

The practical challenges of obtaining an animal-free medication can be showcased using the popular drug atorvastatin. Once prescribed, a pharmacy can legally dispense a prescription for atorvastatin with any of the 40-plus generic suppliers to the US market. Typically, prescribers or pharmacists are not checking for ADI, and the origin of ingredients (animal, plant, synthetic) may not be known from the package insert. Depending on which generic is dispensed, the risk of a serious anaphylactic reaction cannot be ruled out [Table 1]. This applies for over-the-counter (OTC) products too. Diphenhydramine, a standard-of-care in the management of AGS, is available from multiple manufacturers and in multiple dosage forms. Ironically, many of them contain animal-derived ingredients (e.g., gelatin, magnesium stearate) which in themselves could trigger adverse effects [Table 1] in some AGS patients.

As such, 91.8% of AGS patients have had to modify their use of medications, with 18.1% contacting the drug manufacturer 12 times or more. Unfortunately, even drug manufacturers are at times unable to provide this information, leaving patients vulnerable to potentially serious allergic adverse effects. In a recent assessment of medical information departments at the top 20 pharmaceutical companies, 40% of them were unable to provide an accurate response regarding ADI in their own medications.

Further, a particular supplier’s active or inactive ingredients may not conform to the patient’s dietary, religious, or other preferences. Approximately 5% of the US consider themselves vegan or vegetarian and around 10% of the population consists of individuals from the Jewish, Hindu, Buddhist, or Muslim faiths. In 2018, the American Medical Association approved a policy (H-100.947) urging manufacturers to include all ingredients and components present in medical products on the product label, including both active and inactive ingredients, and denote any derived from an animal source. According to their report, 70% of physicians lacked awareness regarding the presence of ADI in medications. This lack of awareness stemmed from inconsistent reporting, difficulties in obtaining accurate information, and occasional inaccuracies. Nevertheless, 70% of physicians acknowledged the importance of informing patients who might object if such medications are prescribed.

Unfortunately, not much progress has been made, prompting a Citizen Petition to the US FDA asking for transparency around medications. The Citizen Petition to the FDA requests regulatory action to 1) require drug and dietary supplement manufacturers to clearly label whether ingredients used in their products are animal derived (e.g., magnesium stearate, plant-based versus animal-based); 2) revise existing regulations and policies to require manufacturers to replace ADI with plant-based and/or synthetic ingredients when other alternatives are available (e.g., HPMC capsules versus gelatin capsules); and 3) allow labeling of drugs and dietary supplements to include an accurate and truthful certification symbol denoting that the product(s) are free of ADI (e.g., animal-free).

Given that active and inactive ingredient suppliers can implement changes with every lot, third-party auditing and subsequent certification can ensure a commitment from the manufacturer to only use animal-free active and inactive ingredients. A “certified animal-free” (AF) seal on the product would allow for easy product identification [Table 1]. Adequate labeling and transparency would have a direct impact on patient safety, inclusion of patient preferences, and an indirect but positive impact on animal cruelty and climate change.

It is promising that novel cell-free expression technology is being developed (such as vivoXPRESS®) for instances where using Chinese hamster ovary cells has been the norm for the development of monoclonal antibodies. Embracing manufacturing and labeling of animal-free medications is an underrecognized and important step to promote diversity and inclusion, patient advocacy, and environmental, social, and governance (ESG) initiatives at drug manufacturing companies. Until transparent labeling is required, prescribers are encouraged to use certified animal-free products, authorized government resources, or drug manufacturers’ medical information department to identify AF medications.

References available upon request.

Table 1: Animal-Free Atorvastatin and Diphenhydramine

**Independently “Certified Animal-Free”; no animal-derived ingredients utilized in any batches.

**Independently “Certified Animal-Free”; no animal-derived ingredients utilized in any batches.