By Kalah Auchincloss, SVP & Deputy General Counsel, Greenleaf Health, Inc.
and Cynthia Schnedar, EVP, Greenleaf Health, Inc.
More than seven years after the passage of the Compounding Quality Act (“CQA”), certain drug compounding facilities continue to illegally compound “essentially copies” of FDA approved drugs. Compounded drugs are different than traditional manufactured drugs because compounded drugs do not undergo the rigorous FDA approval process. This not only puts patients directly at risk but also undermines incentives to seek FDA approval in the first place, further endangering the public.
The FDA premarket approval process is recognized worldwide as the gold standard. As Congressman Frank Pallone explained in 2019, “American patients should take comfort in the knowledge that drug products approved by the FDA are among the most rigorously reviewed in the world.” We must continue to maintain this standard by ensuring that compounding is an exception to the FDA approval process, done in accordance with the law—only when it is medically necessary for patients, as Congress intended.
The FDA review process is indeed rigorous, daunting, and expensive. FDA approval signals that adequate tests demonstrate the product is safe and effective for use under the conditions prescribed in the drug’s proposed labeling, and that the methods used to manufacture and package the product will preserve the drug’s identity, strength, quality, and purity.
In contrast, compounded drugs are manufactured and distributed to patients without FDA approval under the authority and requirements of the CQA. For example, drugs compounded in registered outsourcing facilities are exempt from the pre-approval requirements of the FD&C Act and certain labeling requirements.
Because compounded drugs are not approved by FDA before coming to market, they pose a higher risk to patients. FDA has identified numerous serious adverse events associated with compounded drug products, often due to bacterial, fungal or other contamination, sub- or super-potency, or other dangerous mistakes made during compounding. This includes more than 60 deaths and 750 cases of infection associated with a contaminated injectable drug product manufactured by the New England Compounding Center in 2012 (an event which, in part, prompted the passage of the CQA).
Outsourcing facilities do have to meet many statutory conditions to qualify for the exemptions from pre-market approval and labeling, including that outsourcing facilities may not compound “essentially a copy” of an FDA-approved drug. That prohibition, along with the other listed statutory conditions, are intended to limit the circumstances in which a compounded drug may be lawfully used—generally for patients “whose medical needs cannot be met by an FDA approved drug.”
Compounding by outsourcing facilities can fulfill an important niche when there is no approved drug available, but as former Commissioner Scott Gottlieb explained, “[o]ur policies regarding these provisions carefully balance preserving access to compounded drugs for patients who need them, while preventing compounders from undermining the drug approval process or unnecessarily exposing patients to risks associated with unapproved drugs.”
This careful balancing act works only when compounders follow the law and the FDA enforces it. Unfortunately, outsourcing facilities continue to violate the law, compounding essentially copies of FDA-approved drugs, as demonstrated by three examples. First, Emerphed™—an FDA approved ready to use version of Ephedrine sulfate used during surgery for patients suffering from severe hypotension—is often replaced with a compound version. Second, Hope Medical Enterprises markets an FDA-approved product with sodium thiosulfate injection for treating acute cyanide poisoning and as an off-label treatment for patients with renal disease experiencing calciphylaxis. However, a compounded version is also available. Third, FDA has approvedFIRVANQ®, an oral vancomycin hydrochloride solution for treating gastro-intestinal symptoms associated with certain bacterial infections, and yet a compounded copy is available in place of theFDA-approved drug.
The impact of ignoring FDA approved drugs for compounded copies is clear—patients who have the option of an FDA approved drug are instead unnecessarily exposed to compounded, unapproved drugs at significant risk to their safety. Not to mention the damage this substitution of an unapproved drug for an approved drug does to incentives to seek FDA approval in the first place. Why would a rational company invest the financial resources, effort, and time to reach for the FDA “gold standard” of approval if outsourcing facilities could freely market unapproved, compounded copies of the drug a traditional manufacturer has labored to bring to market?
Some outsourcing facilities argue that they should be permitted to compound copies of approved drugs if the facility starts with an FDA approved product, rather than compounding from the bulk ingredient. In our view, that goes against both the plain language and the intent of the CQA, regardless of the starting source. The focus is rightly on the end product in order to ensure that the safest and most effective product – the approved version of the drug – is available to the patient.
We understand, and support, FDA’s efforts to encourage the development of a robust outsourcing industry, but copying approved drugs has serious negative consequences on public health. We remind compounding facilities of their obligation to follow the law and stop compounding copies of FDA approved drugs. We also urge the Agency to step up its enforcement of the “essentially a copy” prohibition to stop this dangerous activity.
Ms. Auchincloss and Ms. Schnedar are consultants at Greenleaf Health, Inc. Ms. Auchincloss has served as an expert witness for Nexus Pharmaceuticals, Inc. and Hope Medical Enterprises, Inc. in the litigation mentioned in this article. These companies are clients of Greenleaf Health.