Compounding and related issues (Proceedings)
Individualized drug therapy increasingly is being recognized as an important aspect of health care for both human and veterinary medicine. Consequently, veterinarians must reach beyond FDA-approved veterinary products to provide the current standard of veterinary care to their patients. The lack of commercially - available drug formulations often leads the veterinarian to prescribe or dispense a product specifically designed and compounded for their patients' medical needs. Compounding has been defined by the National Association of Boards of Pharmacy (Model State Pharmacy Act) as the preparation, mixing, assembling, packaging, or labeling of a drug or device, as the result of a practitioner's prescription drug order (or initiative) and based on the practitioner /patient/pharmacist relationship (http://www.iacprx.org/index.html, accessed July 2004).
The last two descriptors – prescription driven and in the context of a veterinary (client) patient relationship- are vitally important but often unrecognized or ignored descriptors of the definition.
Clearly, compounding is and always has been a critical component to the provision of individualized drug care to the small animal patient. However, the sole justification for prescribing or dispensing a compounded preparation relates to the patient: no commercially available preparation is available which will meet the needs of the patient. Cost is NOT a justifiable reason for pursuing a compounded product. Many reasons exist for the veterinarian to use compounded products judiciously. These include legal and ethical reasons. Among the reasons are the lack of oversight by any state or (with the most recent federal court rulings) federal government oversite of the compounded product. Accordingly, no assurance can be provided regarding the quality, safety or efficacy of compounded product. Use of a compounded product may put the practitioner in a situation where civil liability (rather than criminal liability) is a concern. Transdermal gels offer an example of both the best and worst considerations regarding the availability of novel drug delivery systems that are compounded. Just because a product can be made does not mean it will work (or that it is safe); standard of care criteria upon which liability issues are based are likely to no support decisions that support compounding if an alternative approach is available.Among the important aspects to recognized regarding compounding is their difference from generic products. Generic products are approved products that contain the same ingredients, in the same form as the pioneer product (or another already approved generic product). As such, generic products undergo full FDA approval. However, although not related to compounding, it also is important to recognized that while generic drug preparations in general behave the same as the pioneer drug, this is true only for the target species. In other words, if two generic forms of a human drug (eg, zonisamide) exist (A vs B), both A and B can be expected to behave the same as zonisamide in the person. However, neither A nor B should be expected to behave the same in the dog (if it is a human generic drug) nor should A be expected to behave the same as B in the dog. If, however, it is a canine generic, then the expectation would be that the drug would behave the same in the dog.
It is important to recognize the Congress has not given the FDA the power to regulate compounding, or even the compounded products. The act of compounding is regulated at the state level; however, Boards of pharmacy are quite variable in their regulations, sometimes in conflict with the federal laws. The FDA regulates fixed dosing forms which might be used to compound a preparation but does not regulate the end product, nor does it regulate bulk substances which might be used to compounde a product. The majority of bulk substances come from Asia. Already, contamination of bulk substances has been internationally recognized (contamination with cyanuric acid of the contaminate melamine for pet food products; contamination of heparin with hypersulfated glycosamine glycans). Although a reputable compounding pharmacy will assure a paper trail exists for products that they use, even certificates of analysis can be falsified or modified. The availability of bulk substances facilitates the manufacturing (rather than compounding) of compounded products that several nationally recognized pharmacies implement. Pharmacies that do such manufacturing place labels on the products that easily are mistaken for approved labels (e.g, KBroVet®). Among the difficulties of the FDA in controlling such manufacturing is, again, limitations set by congress not only in activity but in fines. Further, pharmacies that are found to be in violation of state (rather than Federal) laws simply move to another state.
Quality assurance of the product should be of concern. Whereas approved animal or human drugs have undergone rigorous, scientific testing to ensure drug safety and efficacy for the patient, compounded products have not. Although pharmacists are directed to compound from written protocols and to maintain written records of compounding activities, currently pharmacists are not required to assure accuracy in product preparation, including product stability. Although a reputable pharmacy may randomly check accuracy of selected drugs, this act currently is voluntary and will be limited to selected drugs and aliquots. Although guidelines exist for establishing expiration dates of compounded products, dates are not necessarily based on scientific data and may not be followed. The risks associated with failed delivery (too much or too little) of a compounded product are added to risks associated with the approved finished dosing form of a drug. The more sophisticated the preparation, the more likely adverse events will occur because of diminished or excessive drug delivery.