Pharmacy Law CE Column

By Shari L. Miller, MA, CPhT, JD, attorney at Shari L. Miller, Attorney, PLL

Compounding

Introduction:

Compounding has experienced resurgence in popularity in health care, and lately the practices of certain compounders have come under great scrutiny. This article will briefly address the history of compounding, the reasons for the renewed popularity, general principles of good compounding, and the current legal and regulatory climate governing compounding.

History:

Traditional pharmacy compounding, according to the Food and Drug Administration, is the extemporaneous combining, mixing or altering of ingredients by a pharmacist in response to a physician's prescription to create a medication tailored to the specialized medical needs of an individual patient, whether human or animal. Pharmaceutical compounding has a long history spanning more than 5,000 years. It is the foundation for the current pharmaceutical industry, which came into existence in the mid-1900s. Formulas and methods for treating diseases have been found in pharmacy history books.¹ The standards for quality and uniformity of pharmacy formulas for compounded medications began in Italy in 1580 and were known as "pharmacopoeia," which literally means "drug-making."² There were many pharmacopoeias established in various geographic jurisdictions in Europe. In the United States, the U.S. Pharmacopeia, or USP, was created in 1820 by a group of physicians with the objective of establishing uniform standards for the medications they prescribed.¹ In the mid-1900s, drug manufacturing became mechanized, and today we see mass production of most commonly used medications. However, there is an ongoing need for the creation of medications tailored to meet a specialized medical need of a person or animal, which compounding fulfills.

Traditional compounding creates a relationship between the prescriber, the patient and the pharmacist to provide customized, safe and effective medications for individual patients.³ Traditional compounding typically occurs when an FDA-approved drug is unavailable or a licensed healthcare provider decides that an FDA-approved drug is not appropriate for his or her patient's medical needs. Examples include specially formulated hormones, unavailable chemotherapy drugs and allergy medications for pets. According to the FDA, pharmacy compounding involves making a new drug for which safety and efficacy have not been demonstrated with the kind of data that the FDA requires to approve a new drug. In virtually all cases, the FDA regards compounded drugs as unapproved new drugs.⁴ The recent news concerning large-scale production of a tainted compounded product has again raised the issue of whether or not the production was traditional compounding or pharmaceutical manufacturing. Currently, there are no limits on the amounts of compounded products that a pharmacy can prepare before falling under FDA regulations for pharmaceutical manufacturing.³ The FDA does have the legal right to inspect compounding pharmacies, and it requires that ingredients be purchased from FDA-registered distributors or manufacturers, but this oversight is considerably less than the compliance with the strict FDA regulations required for pharmaceutical manufacturing.³

Regulatory oversight of compounding pharmacies

State pharmacy boards have primary jurisdiction over compounding pharmacies. The FDA also asserts that it has authority over compounding pharmacies but that it is limited by statute and court decisions. The FDA interpretation that a compounded medication is not an approved drug has been challenged in the courts across the country.⁵ Notably, a federal district court in Texas ruled that "millions of Americans have conditions that off-the-shelf, one-size-fits-all pharmaceuticals cannot meet. For them, customized, compounded medicines - prescribed by physicians and prepared by licensed, trained pharmacists - are the only way to better health."⁶

In response to the recent meningitis outbreak, members of Congress are considering introducing legislation to strengthen the FDA's authority over compounding pharmacies. Some lawmakers noted that the law "did not intend for a compounding pharmacy to be permitted to operate as a small drug manufacturer."⁷ State boards of pharmacy have generally regarded preparing and shipping large volumes of compounded medications without patient-specific prescriptions as crossing the line into manufacturing.³ The federal government also has launched a criminal investigation into the compounding practices at the pharmacy responsible for preparing the tainted products. Pharmacists should pay close attention to new legislation and regulations on both the federal and state levels that may be introduced to address the practice of compounding.

USP chapters to aid compounding pharmacies

Today in light of the recent news about dire consequences from contaminated compounded medications, there are two particularly relevant chapters in the USP - chapters 795 and 797 - for pharmacists who are performing compounding activities. Chapter 795 provides guidance on applying good compounding practice in the preparation of nonsterile compounded formulations for dispensing and/or administration to humans or animals. It was updated effective May 1, 2011, and included new material on categories of compounding (i.e., simple, moderate and complex), as well as new definitions for terms and criterion for compounding each drug preparation. The pharmacist's responsibilities in compounding drug preparations are to dispense the finished preparation in accordance with a prescription or a prescriber's order or intent and to dispense those preparations in compliance with the requirements established by the board of pharmacy and other regulatory agencies.⁸

Chapter 797 provides procedures and requirements for compounding sterile preparations. It describes conditions and practices to prevent harm to patients that could result from microbial contamination, excessive bacterial endotoxins, variability in intended strength, unintended chemical and physical contaminants, and ingredients for inappropriate quality in compounded sterile preparations.⁸

There are other important chapters, including 1160, which provides general guidance and assistance to pharmacists in performing the necessary calculations when preparing or compounding any pharmaceutical drug; 1163, which describes a quality assurance program as a system of steps and actions that must be taken to ensure the maintenance of proper standards in compounded preparations; and 1176, which provides information about acceptable balances and volumetric apparatus used to weigh or measure medicinal and other substances required in prescriptions or in other pharmaceutical compounding.⁸ USP chapters that are numbered under 1,000 are enforceable, whereas chapters numbered 1,000 or greater are advisory. However, many states include all or portions of the USP in their pharmacy rules and regulations. It is important for the compounder to be familiar with the rules and regulations that govern that state.

General practice tips

The pharmacist who compounds the medication should be available to discuss the compounded medication with the patient and the prescriber. The compounding pharmacist is advised to review and follow the guidelines in the USP chapters regarding proper compounding practice, including these responsibilities from chapters 795 and 797:

• Personnel are adequately skilled, educated, instructed and trained to perform and document their functions;
• Ingredients have their correct identity, quality and purity;
• Opened or partially used containers are properly stored;
• Water-containing nonsterile compounded sterile products are sterilized within six hours;
• Correct compounding procedures are used;
• Components are clean, accurate and appropriate;
• Potential harm from added substances is evaluated prior to dispensing;
• Appropriate packaging is selected for sterility and stability;
• Compounded preparations are of acceptable strength, quality and purity, with appropriate packaging and complete labeling, and prepared in accordance with good compounding practices, official standards and relevant scientific data and information;
• Critical processes are validated to ensure that procedures, when used, will consistently result in the expected qualities in the finished preparation;
• The compounding environment is suitable for its intended purpose and maintains the sterility or purity of items;
• Appropriate stability valuation is performed or determined from the literature for establishing reliable beyond-use dating to ensure that the finished preparations have their expected potency, purity, quality and characteristics at least until the labeled beyond-use date;
• There is assurance that processes are always carried out as intended or specified and are under control;
• Compounding conditions and procedures are adequate for preventing errors;
• Adequate procedures and records exist for investigating and rapidly correcting failures or problems in compounding, testing or in the preparation itself; and
• Compounding is separate from quality evaluations.⁸

Conclusion

Traditional compounding is a valuable pharmacy activity that provides safe and effective medications that help millions of American address vital healthcare needs, as well as reduce costs.³ Pharmacists who engage in compounding activities are strongly encouraged to follow the appropriate USP guidelines concerning proper compounding practices.

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