Reprinted Courtesy of Equine Veterinary Management Magazine (Summer 2005)
LEGAL EASE//EVM SUMMER 2005
Click here for a .pdf version of this article in Equine Veterinary Management magazine.
Gain insight on the new AAEP guidelines on compounding drugs with this in-depth report.
BY DENISE E. FARRIS, ESQ.
On the surface, veterinary compounding–that is, preparing a multi-ingredient drug from generic or trade-name pharmaceutical products for animal use under veterinary care–appears to be a straightforward practice. However, it remains a hotly contested issue in both courts and administrative halls, and among practitioners and their clients and patients.
Recognizing that compounding continues to serve a useful, albeit controversial, function, the American Association of Equine Practitioners recently published a set of guidelines, which, it’s hoped, will clarify the existing compounding confusion. Here, we’ll identify those guidelines (see page xx), as well as give you their legislative and legal precedent.
According to the International Academy of Compounding Pharmacists, there are many situations that might require pharmacists to compound medications for animal patients. These include:
- Discontinued products. Under this scenario, a pharmacist may compound commercial medications that have been discontinued from the market for reasons other than safety or effectiveness, therefore otherwise unavailable.
- Product integrity. A pharmacist may use bulk active pharmaceutical ingredients (APIs) to compound medications in cases where using a commercially available, finished product as the ingredient source could add unnecessary excipients to the medication and increase the risk of contamination or yield a product that isn’t concentrated enough to offer proper compliance.
- No alternative therapy. One of the more common scenarios; here, a pharmacist compounds medications using bulk APIs when there’s no commercial alternative to treat the disease state or condition treated by the compounded medication.
- Patient compliance. Also prevalent in the veterinary industry; in this case, a pharmacist compounds medications for animal patients to make it easier for horse owners to administer medications to their horse. This compounding often involves flavoring a medication or changing the dosage form.
Some scenarios involving compounding are so subtle they might not be immediately recognized. Veterinary compounding might refer to combining two injectible medicines into one syringe application. Or, it can apply to the administration of potassium bromide to a patient that suffers from severe brain seizures and would otherwise die without it. Or, it might refer to an Internet product represented to be antibiotic that upon further testing proves otherwise.
It’s these contradictory applications–met by equally contradictory regulations–that have given rise to the current confusion over compounding, its legitimacy, effectiveness and exposures.
A Complex History
To understand the context for compounding drugs as it relates to equine veterinary medicine, we first must look at the history and legal precedents of the practice in human medicine.
Compounding has been an integral part of the development and ongoing practice of pharmacology since mankind first discovered medicinal use of certain plants and minerals. As such, compounding was and continues to be taught as part of the standard curriculum at most pharmacy schools.
The practice recognizes that it’s possible to custom-create specific medications for specific patients that wouldn’t otherwise be commercially available, such as medication for a patient who’s allergic to an ingredient in a mass-produced product. Accordingly, compounding regularly has been allowed and regulated by the various states as part of their regulation of pharmacies.
The historical and beneficial utilization of compounding in human pharmacology was recognized as recently as 2002 by the United States Supreme Court in the case of Tommy G. Thompson, Secretary of Health and Human Services, et. al. v. Western States Medical Center, et. al. In that decision, the Supreme Court held that a statutory ban on advertising compounded drugs–as set out in 21 USCS §353a of the Food and Drug Administration Modernization Act of 1997–represented an unconstitutional violation of compounding pharmacies’ free-speech rights under the First Amendment, where compounding was legally permissible and commercial advertising served a useful function in disseminating information about the product.
Although this recent Supreme Court case was based on First Amendment issues related to commercial free speech and arguably deals with compounding in human medicine, it contains a concise history of the evolution of compounding and its relevant regulations, which also apply to compounding in veterinary medicine.
The case defines “drug compounding” as “a process by which a pharmacist or doctor combines, mixes, or alters ingredients to create a medication tailored to an individual patient’s needs.” The case explains the treatment of compounding under the federal Food, Drug and Cosmetic Act of 1938, which regulates drug manufacturing.
Under the FDCA, “No person shall introduce or deliver for introduction into interstate commerce any new drug, unless an approval of an application filed [with the FDA]…is effective with respect to such drug.”
A “new drug” is defined as: “Any drug…not generally recognized, among experts qualified by scientific training and experience to evaluate the safety and effectiveness of drugs, as safe and effective for use under the conditions prescribed, recommended, or suggested in the labeling thereof.”
Section 360b of the FDCA applies the regulations to animal drug compounding by stating: “No one may sell a new animal drug, or feed containing a new animal drug, without the approval of the Food and Drug Administration.”
For the first 50 years following enactment of the FDCA, the FDA generally left regulation of compounding drugs to the states. As a result, some states required all licensed pharmacies to offer compounding services. Other states allowed pharmacists to provide compounded drugs to patients only upon receipt of a valid prescription from a doctor or other medical practitioner licensed to prescribe medication. Where the regulations varied from state to state, pharmacists continued to provide patients with compounded drugs subject to various interpretations of the FDA regulations, and without FDA approval of those drugs.
The FDA eventually became concerned that some pharmacists were manufacturing and selling drugs under the guise of compounding, thereby avoiding the FDCA’s “new drug” requirements. The FDA could’ve elected to implement criminal or administrative sanctions against the prescribing veterinarians or pharmacies providing compounded medications. However, recognizing the benefit of compounding in specific circumstances, the FDA elected instead to implement procedures that restricted compounding pharmacies access to bulk drug ingredients necessary for the compounding process.
Thus, in 1992, in response to what it perceived to be a growing abuse and circumvention of FDA manufacturing regulations, the administration issued a Compliance Policy Guide, which announced that the FDA may “in the exercise of its enforcement discretion, initiate federal enforcement actions…when the scope and nature of a pharmacy’s activities raises the kinds of concerns normally associated with a manufacturer and…results in significant violations of the new drug, adulteration, or misbranding provisions of the Act.”
Several years later, Section 503a of the Food and Drug Administration Modernization Act of 1997 was enacted to specifically address the FDA’s concern of mass-manufacture of compounded medications. Under this section, compounded drugs were exempt from FDA-approval requirements, but only where the providers of those drugs refrained from advertising or promoting particular compounded drugs, and only where the manufacturing was in quantities small enough to meet the “one patient, one prescription” test. (ep)
Thus, in the above historical context, the amount of bulk ingredients on hand for the manufacture of a compounded medicine gave rise to the appearance of “mass manufacture” more akin to new drug development rather than single-patient or single-circumstance compounding.
The stringent requirements of the FDCA drug-approval process is the underlying basis for the current compounding confusion. Under testing and approval regulations of the FDA, new medications–called “pioneer drugs”–undergo a rigid testing process designed to determine whether the drug is safe, effective, and susceptible to side effects in both the short and long terms.
In determining whether or not a drug is safe, the manufacturer is required to submit the drug to extensive safety studies. This testing analyzes potential side effects and effects of overdosing before a product is introduced into the market. The testing also confirms that the manufacturing of the drug is subject to stringent industry standards to ensure ongoing purity and safety. Finally, the drug is monitored over a period of time to ensure there are no undisclosed long-term side effects in terms of patient reaction to the drug or the manner in which it’s administered.
Obviously, the detail involved in the development and FDA approval of pioneer drugs, is extensive, time consuming and costs in the millions. Companies devoting time, resources and money to new drug development are entitled to recoup their investment through lucrative and protected drug patents. However, these patents are time-limited. When the patents expire, competitors are allowed to use similar formulas to create generic substitutes.
Although bypassing the years of testing involved in pioneer-drug development, generic drugs still require compliance with all FDA manufacturing standards to preserve integrity, purity and consistency. Yet both forms–pioneer and generic–are FDA-approved drugs.
In comparison, the compounded drug is not FDA-tested, not FDA-approved and not subject to any form of manufacturing oversight that serves as a standard for purity, integrity, consistency and safe application. For this reason, the use of compounded drugs is a form of “last hope” treatment in situations where no FDA-approved pharmaceutical is available to adequately address the presenting medical situation. And this is why such medications are subject to stringent requirements that ensure they won’t be passed onto an unsuspecting marketplace in the guise of an FDA-approved substance.
New AAEP Guidelines
With these principals in mind, the new AAEP guidelines can serve as a reliable roadmap in determining when–and when not–to rely on compounded medications in your practice. These guidelines suggest that you should verify that the use of compounded medications is covered under your existing liability policy and whether such coverage is subject to special restrictions.
These guidelines also suggest that–as a regular practice–you shouldn’t prescribe compounded medications without fully disclosing their unique characteristics to the client. To comply with the latter suggestion, you can simply provide the client with a copy of the guidelines for their review, secure his or her signature, date the form and then permanently place the form in the client’s file.
Following is a paraphrased version of the recently released AAEP’s Drug Compounding Task Force Position Paper. For the original version, visit www.aaep.org.
Recognize the differences between FDA Pioneer Drug, Generic Drug and Compounded Drug:
* FDA Pioneer Drug:
A drug that has undergone the scrutiny of blinded controlled studies to demonstrate safety and efficacy in accordance with federally mandated Good Laboratory Procedures. The active ingredient and product were manufactured under federally mandated Good Manufacturing Practices in federally inspected plants. Therapeutic consistency, product quality, accurate drug shelf life and scientifically substantiated labeling are all federally mandated on these products.
* Generic drug:
A generic drug is bioequivalent to a brand-name drug in dosage form, efficacy, safety, strength, route of administration, quality and intended use. Generic drug labels display an ANADA # or ANDA # signifying FDA approval of a generic animal drug or human drug, respectively. Generic drugs and their active ingredients also must be manufactured under GMP in federally inspected plants.
* Compounded drug:
Any drug manipulated to produce a dosage-form drug (other than that manipulation provided for in the directions for use on the labeling of the approved-drug product).
- Understand that use of bulk drugs in the preparation of compounded medications is, under strict interpretation of the Federal Food Drug and Cosmetic Act, illegal because it results in the production of an unapproved new animal drug. Preparation, sale, distribution and use of unapproved new animal drugs are in violation of the Act.
However, the preparation of compounded medication from bulk drugs may be permissible in medically necessary situations but only where there’s no approved product available, the needed compounded preparation can’t be made from an FDA-approved drug, and where the compounding involves only FDA-approved drugs in compliance with federal extra-label drug use regulations subject to the rules and regulations set forth by the appropriate governmental regulatory bodies that pertain to the country or province where the veterinarian practices.
- Legal compounding requires a valid veterinarian-client-patient relationship, with its use limited to unique needs in specific patients, limited to situations in which a physiological response to therapy or systemic drug concentrations can be monitored, or situations for which no other method or route of drug delivery is practical.
- Remember that compounded drugs haven’t been evaluated by the FDA approval process for safety, efficacy, stability, potency and consistency of manufacturing. For this reason, you:
> Cannot assume that compounded drugs are consistent from one batch to another.
> Cannot assume that the compounded drugs contain the stated amount of drug substance or the desired drug substance.
> Cannot assume that the compounded drugs are safe and efficacious for the intended use.
- Remember that compounding pharmacies operate in a dynamic regulatory situation; laws, regulations and guidelines might vary widely from state to state. For this reason, make sure the compounding pharmacy you use is licensed in the state in which you practice.
- Proactively seek to educate yourself on regulations concerning compounded medications.
- Beware of pharmacies using trademarked brands in their literature to promote “look-alike” compounded products.
- Beware of firms that appear to disregard federal, state and local laws, regulations and guidelines concerning disposition of compounded drug products.
- Understand that compounding drugs to mimic licensed, FDA-approved drugs is illegal.
> You cannot use compounded “look-alikes” as substitutes if there’s an FDA-approved product in the appropriate dosage form that can be used for the specific patient indication.
> A decision to use compounded products in lieu of appropriate FDA-approved products is illegal and may jeopardize the patient and the veterinarian’s liability insurance.
- Contact your state pharmacy boards concerning the reselling of compounded products–some state boards reportedly require compounded drugs to be dispensed at cost; others allow a regular markup.
- Consider the legal, ethical and clinical ramifications when making recommendations concerning the use of compounded medications for their patients. You should:
> Provide information about the benefits and risks of compounded drugs, as it’s important to an owner’s decision about therapy.
> Understand the concept of “Standard of Care.” One acts below the standard of care when he/she fails to exercise the level of care, skill, diligence and treatment that’s recognized as the standard of acceptable and prevailing veterinary medicine.
- Understand your professional liability policy may or may not respond to allegations of negligence arising from the use of compounded drugs. If you’re insured with AVMA-PLIT, you can review comments at www.avmaplit.com.
- Don’t miss the opportunity to form a relationship with a pharmacist experienced in compounding who, when medical necessity exists for a specific patient, can produce the best possible compounded product and discuss related product expectations. (bug)
Denise E. Farris is a litigator practicing equine, insurance, defense and construction law in the Kansas City area. She’s a nationally known equine-law attorney and, in addition to writing numerous articles, has been a featured speaker at local, state and national symposiums, including the National Equine Law Practitioner’s Conference, the National Farrier’s Convention, the National Multiple Trail Users Conflict Symposium and the North American Trail Ride Conference. She’s an avid equestrian who competes in endurance and competitive-trail riding events.
DISCLAIMER: This article provides general coverage of its subject area. It’s provided free, with the understanding that the author, publisher and/or publication do not intend this article to be viewed as rendering legal advice or service. If legal advice is sought or required, the services of a competent professional should be sought. The author and publisher shall not be responsible for any damages resulting from any error, inaccuracy or omission contained in this publication.
© Denise E. Farris, Esq. All rights reserved. This article may not be reprinted or reproduced in any manner without prior written permission by the author. Contact: The Farris Law Firm, LLC, 20355 Nall, Stilwell, KS 66085; (913) 685-3192; FAX (913) 685-3292; e-mail, firstname.lastname@example.org.