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Meeting patient needs and achieving high quality are common goals for all stakeholders.
It is frequently said that there are several sides to every story, especially when the story results in strongly held opinions and even emotions, as does the discussion of the role and scope of a compounding pharmacy in manufacturing quality drugs.
There are many stakeholders in compounding pharmacy. Certainly, regulatory authorities are stakeholders, who play a key role in ensuring quality to protect patients. Pharmacists, much like physicians, nurses, and other health professionals, have always been licensed or registered by state authorities. In the case of pharmacists, the regulatory body has been the respective State Boards of Pharmacy. However, as will be discussed in this article, the regulatory roles and responsibilities have been shifting, and FDA has become a stakeholder. Regulators want patients to have the right drug, at the right dose, within the right quality requirements.
For healthcare providers who prescribe, there is a need to customize dosages for many patients. These healthcare providers also become stakeholders. Although personalized medicine may be viewed as a more recent topic, many products have been customized (i.e., compounded) to address a variety of needs. Perhaps the prescription needs to be adjusted for a pediatric dose and none is commercially available; perhaps it needs to be compounded as a liquid so it can be given via a naso-gastric tube; perhaps it needs to be free from preservatives to be administered intrathecally (into the cerebral spinal fluid); perhaps it needs to be adjusted for a specific dose, such as heparin subcutaneously, or for any of a myriad of reasons. Some of those reasons can be for ingredients in the commercial presentation that the patient is allergic to, such as dyes, or the need to be gluten-free. For these reasons, healthcare providers who prescribe will seek to find a means to help the patient get the right drug at the right dose and will want it to be the right quality.
For patients, there is a need to get better, or at least feel better, quickly. Patients become stakeholders when they want to have a medication intervention rather than a surgical intervention; most will want to have only one eye drop to apply daily rather than three; most will want to have as many of their medications as possible administered through one intravenous (IV) administration set rather than have multiple injections or multiple lines; most parents will want to have a pleasantly flavored liquid medication to give their child rather than try to get him to swallow a tablet. And although it might not seem important to the average person, despite the small amount that may be present in the commercial presentation, some patients will object because it is not vegetarian (or vegan), or kosher, or sugar-free. Of course, the patient is going to want the right drug at the right dose and for it to be a quality product.
For the pharmacist that is a compounder, these desires are an opportunity to practice their profession. Rather than just count or pour, and type a label, they are making a special product for a patient the way pharmacists did in the early part of the 20th century. Compounding was the rule rather than the exception until some of those early compounders, such as Eli Lilly and Silas Burroughs, expanded their pharmaceutical compounding business from a neighborhood pharmacy to a pharmaceutical manufacturer. As those new pharmaceutical manufacturers began producing standardized products, such as penicillin tablets and sulfanilamide elixir in the 1930s and 1940s, a shift in pharmacy practice began to occur. Hospital pharmacists have long compounded sterile IV solutions to physicians’ orders. Almost every IV hanging next to a patient contains some additive; a liter bag of normal saline solution (0.9% sodium chloride) might have additions made including potassium chloride, multiple vitamin injection, and sodium bicarbonate. These are not medications but are electrolytes to ensure the patient stays in balance while recovering. There are, however, solutions that are so large and complex that instead of being administered through an IV, a central line is placed into a major vein. Some of these are total parenteral nutrition products (TPNs) for severely ill patients who cannot take any nourishment by mouth. TPNs are comprised of high sugar content, high fat content solutions to which as many as 24 individual electrolytes and medicines are added. Because of the complexity, a prescribing physician will consult with a nutritionist to find the right balance, and ask for daily blood tests to find the right amount of electrolytes to add, so the formulation changes from day-to-day. And yes, the compounding pharmacist is going to want to be certain that the product being prepared is the right drug(s), the right dosage, and the highest quality that can be made.
Pharmaceutical manufacturers, who may have started out as a compounding pharmacy 150 years ago, are now stakeholders making efforts to minimize compounding by creating products that meet more specific patient needs. For example, unlike most pharmaceuticals that are only available in one or two strengths, a medication used for blood thinning is dosed on almost a daily basis for many patients based on blood clotting tests; it is available in nine strengths, and even then, some patients will use a tablet splitter to get the correct dose. Large volume parenteral (LVP) manufacturers have long worked toward offering a variety of solutions, with liter bags formulated to include 40 mEq potassium chloride (a frequent additive) and piggy-back bags (smaller IV bags that are used to add to the flow of a larger IV bag) that have premixed medication. As a result, a nursing station on a medical/surgical ward may have a daunting array of combinations of liter IV bags offering different combinations and concentrations of saline, dextrose, lactated ringers, and potassium chloride offered by the pharmaceutical manufacturer. And of course, the pharmaceutical manufacturer works to ensure that the right drug(s) and the right dosage are available and correctly labeled for use and that the quality is correct.
It is evident from the perspectives of the prescribing health professional and the patient that there are exceptions to the commercially available medications based on needs. Certainly, these are a minority of the prescriptions being filled; but that minority deserves to have the same access to quality care, and the prescribers and the compounding pharmacists believe that compounded prescriptions are the answer. It is also true that the pharmaceutical manufacturers seek to provide products that meet the needs of the patients, but to meet the needs of all patients could be a logistically daunting task. All these stakeholders, including the patient, want to have the right drug, at the right dose, within the right quality requirements.
Perhaps it is this last element, quality, that colors not only opinions but emotions surrounding the story of compounding pharmacy. The quality discussion will begin with regulators, but they are not the only stakeholders in the realm of quality. It was mentioned earlier that the respective State Boards of Pharmacy were the regulators of pharmacy, but that has shifted. FDA has historically had little impact on the practice of pharmacy. It was the meningitis outbreak from contaminated compounded injectables from the New England Compounding Center in 2012 and the passage of the Drug Quality and Security Act (DQSA) the following year, where new roles and responsibilities for FDA in the practice of pharmacy expanded significantly (1).
Despite the expanded role that FDA has in compounding pharmacy, pharmaceutical manufacturers may not believe that compounding pharmacists are being held to the same quality requirements that they are held to. That could be true in some circumstances. Many 503A and 503B compounding pharmacies do an outstanding job in their compounding operations. Some, however, might not be meeting the standard. In many ways, they are analogous to the doctor who is bedside with a patient, and wanting to draw a dose from a vial, draws the volume of the dose from room air and injects that volume of air into the vials so that the dose can be removed from the vial without ‘suction’ pulling against the plunger. Ever wonder what the quality of the air might be in a patient’s room? And suppose that was a multidose vial. Or the nurse who opens an ampule to withdraw a dose, and because the dose was not the entire ampule, puts a piece of tape across the ampule to ‘save it’ for the next dose. So it doesn’t matter whether the product has been made by a pharmaceutical manufacturer or a compounder when it comes time for the dose to be administered by a physician or nurse.
One solution to this quality problem is ensuring that those people, who when asked would certainly say they are interested in quality and wouldn’t do anything to harm the patient, know not just the ‘what’ but the ‘why.’ Understanding basic microbiology and how it applies to the working environment, including elements such as laminar airflow and aseptic technique, are important. This understanding of microbiology needs to begin with the basics as a foundation. One basic tenet is understanding the difference between sanitizing and sterilizing. In sanitizing, a surface or material is cleaned, and the soils with many (but not all) contaminants are removed. In sterilizing, however, a proven method to destroy organisms is employed. Practitioners need to understand what might defeat cleaning and sterilization, as some think that cleaning doesn’t need to be scrupulous because the sterilization cycle will ‘take care of it.’ In addition, it is crucial to appreciate that, despite all of the technology and aids such as the laminar airflow systems, gowning, preparation of sterile water for injection, and sterilization of components and tools, the person performing the tasks is the greatest risk of contamination.
Everyone wants to help the patient, and everyone wants quality. All perspectives include these goals. To achieve both, all stakeholders need to work together to understand the ‘why,’ because everyone has a piece of the process and it all comes together when administered to the patient. The way to achieve the ‘why’ is through education and training. There are technological solutions, such as better cleanroom design and robotics among others, but whether at the compounder or the patient’s bedside, it comes down to the person performing the manipulation of the drug product. And this is true for every perspective and stakeholder.
1. FDA, “Human Drug Compounding,” fda.gov (April 26, 2021).
Chris Smalley is a compounding pharmacy advisor, firstname.lastname@example.org.
Vol. 46, No. 4
When referring to this article, please cite it as C. Smalley, “Understanding Pharmaceutical Compounding from Multiple Perspectives,” Pharmaceutical Technology, 46 (4) 2022.