How To Set Up A Compounding Pharmacy

Compounding is the procedure of combining, mixing, or altering ingredients to create a medication tailored to the needs of a patient (FDA, 2022).^{^ane} Compounding is most often practiced past a licensed pharmacist, a licensed physician, or a person under the supervision of a licensed chemist (FDA, 2022).^² The traditional compounding process begins with a prescription created past the prescriber responding to a patient need. The prescriber customarily chooses the active ingredient(due south), dosage form, dose, dosing intervals, and road of administration when writing the prescription. The prescriber may also choose inactive ingredients, especially in cases where a patient has a documented allergy to an inactive ingredient, such every bit peanut oil. This is followed by the compounding pharmacist preparing (east.g., formulating) and dispensing the medication to the patient.

Compounded medications may offering therapeutic alternatives for patients with unique medical needs that cannot be met past U.S. Food and Drug Administration (FDA)-approved drugs (FDA, 2022; Gudeman et al., 2022; USP, 2022). For example, compounding can provide customized formulations to (1) create alternate dosage strengths or forms, and (two) omit components of FDA-canonical drugs to which a patient has an allergy. Compounding can also fill gaps in cases of shortages and discontinuations of FDA-approved drug products (Glassgold, 2022; USP, 2022).

Patient populations that take traditionally benefited from customized compounded formulations include pediatric patients, people at the end of life who may have difficulty swallowing pills or capsules, or people with certain specific medical atmospheric condition for which a current FDA-canonical medication does not exist (Kochanowska-Karamyan, 2022; USP, 2022). Compounding differs from pharmaceutical industry drug manufacturing in that the volume of drugs prepared and prescriptions dispensed is small in relation to FDA-approved medications. Meet the section "The Compounding Market: Supply and Demand" in this chapter for insights on the recent growth of the compounding marketplace.

COMPOUNDING: TYPES AND SETTINGS

Currently, the regulation of compounding—including rules related to the assart and prohibition of compounding—is addressed at the federal level under the Federal Food, Drug, and Cosmetic Act (FDCA).^ⁱⁱⁱ Compounding tin can utilise FDA-canonical drug products as a starting point, and change them in some way, such every bit combining or diluting them. Compounding can also start with bulk substances (active pharmaceutical ingredients [APIs]) and combine them with excipients (inactive ingredients) to produce the final compounded training. In addition, compounded drugs are prepared either every bit sterile or nonsterile preparations. In sterile compounding, drug formulations are prepared in a clean-room environment using aseptic techniques to ensure preparations are free of microorganisms. Sterile compounding is used primarily for injectable, implant, and ophthalmic preparations. In nonsterile compounding, drug formulations are prepared in a clean surround but without aseptic techniques required. Nonsterile compounding is used primarily to set up oral and topical (skin) formulations: capsules, solutions, suspensions, ointments, creams, and suppositories. Both sterile and nonsterile drug formulations are produced within a wide range of pharmaceutical and medical settings.

Compounding can occur in community pharmacies, physicians' offices, and hospital pharmacies; these are referred to in this study as 503A compounding pharmacies. Compounding, particularly in smaller, contained customs pharmacies, remains an of import component of pharmacy do (McPherson et al., 2006). In fact, studies suggest that the grooming of compounded formulations at community pharmacies may strengthen the patient–pharmacist relationship, improve pharmacists' professional satisfaction and perceived quality of patient intendance, and imbue pharmacists with a greater responsibility to provide patient-centered intendance (McPherson and Fontane, 2010; Yancey et al., 2008).

Public testimony to the committee provided additional insights into the expanding compounding market. Based on submitted testimony, certain 503A compounding pharmacies no longer function primarily every bit community pharmacies just rather equally large corporations that dispense compounded preparations to thousands of patients beyond state lines.^{^four}

In 2022, Congress created a new category for compounding drugs in larger amounts at specialized compounding facilities, referred to in this report as 503B outsourcing facilities. Given that certain requirements are met, these compounding facilities can produce and ship big volumes of drugs across state lines and produce compounded preparations for third parties, such as hospitals, clinics, and dr. offices without a prescription (Glassgold, 2022).^⁵

In either compounding setting (503A compounding pharmacy or 503B outsourcing facility), the United states of america Pharmacopeia (USP) provides environmental guidelines, suggesting that compounded drugs should exist developed in designated areas that are adequately designed to support the sterile or nonsterile processes, including providing proper storage for those preparations and the appropriate conditions (e.1000., designated temperature, light, moisture, ventilation, and security) (USP, 2022). Box 2-i provides details almost the regulations for allowable compounding under the FDCA.

BOX ii-one

Allowable Compounding Nether the Federal Food, Drug, and Cosmetic Act.

THE Complication OF COMPOUNDING

There is a unique fine art and science behind compounding drugs. It is the compounder's responsibility to prepare the compounded drug preparation with the proper dose of the API and the appropriate quality and purity of all ingredients while maintaining sanitary, and if necessary, aseptic conditions when preparing a compounded drug preparation. The compounder must as well provide the patients and their families with the proper instructions through articulate labeling or face-to-confront consultation (USP, 2022). See Box 2-2 for an overview of the importance of a Master Formulation Record as a component of quality control during the conception of a drug.

BOX two-2

Master Conception Record Co-ordinate to USP <795> for Compounded Nonsterile Preparations.

For the evolution of more complex compounded formulations, a professional specializing in conception scientific discipline may exist needed. Formulation science is critical in the development, manufacturing, and testing of chemical (including pharmaceutical) products and preparations. Such conception experts apply established science and are able to guide decisions about quantities and combinations of active and inactive ingredients, incorporate quality procedures, and test for stability. This level of expertise is peculiarly essential for the development of circuitous medications (eastward.g., sustained released medications, pellets). Of critical importance, a compounding pharmacist often does non take the same training or experience as a conception scientist, nor access to the same data for evaluation and determination of quality, stability, and effectiveness.

Seemingly small variations in compounding processes, such as the order in which ingredients are added, the temperature at which the formulation is prepared, or the fourth dimension allotted to mixing ingredients, tin lead to significant differences in the performance of the resulting drug preparation (Chang et al., 2022). Unlike manufacturing protocols for drugs that FDA approves to reliably ensure that a safety and effective production results every time, compounding procedures are not standardized nor tested for their power to produce safe and constructive drug preparations. For example, delivery of active ingredient doses above the desired therapeutic level could upshot from miscalculation, including too much API in the formulation, or from poor-quality formulation resulting in an erratic and unpredictable release rate; the latter has been observed with compounded pellet formulations (Jiang, 2022).

Polypharmacy, when a single patient is simultaneously taking multiple medications to care for one or more than medical status, too as potential drug–drug interactions, add together to the considerations pertinent to the compounding procedure. While concerns for drug–drug interactions are not unique to compounding, the combination of multiple drugs into a single dosage form without prior testing for safety and effectiveness is of concern, especially for formulations that include multiple drugs within a like therapeutic class. For example, compounders should business relationship for the fact that testosterone can exist direct metabolized to estradiol, and that patients receiving a combination of testosterone and estradiol may inadvertently receive a higher dose of estradiol than intended (Ishikawa et al., 2006).

Preparation and Oversight for Compounders

While standard pharmacy school curricula generally include some basic training in compounding, additional grooming and certification are needed to go skilled at compounding, peculiarly for formulations that are circuitous or contain multiple active ingredients. Compounding pharmacists would also benefit from education that extends across the basic skills, just relatively few have specialized grooming or higher certification (Schommer et al., 2008). Organizations such as the Professional Compounding Centers of America and the American College of Apothecaries offer classes, both live and online, and certification programs. Starting in the fall of 2022, the Lath of Chemist's shop Specialties began offering an test for pharmacists to go accredited in Compounded Sterile Preparations, though the specialty has all the same to receive official recognition (Lath of Pharmacy Specialties, 2022).

Many states await compounders to adhere to standards of practice established by USP (The Pew Charitable Trusts and NABP, 2022):

to minimize damage, including death, to human … patients that could result from (i) excessive microbial contamination, (2) variability from the intended strength of correct ingredients …, (iii) physical and chemic incompatibilities, (four) chemical and concrete contaminants, and/or (five) use of ingredients of inappropriate quality. (USP, 2022)

However, because USP has no power to enforce practice compliance, it is upwardly to the state legislature or state pharmacy boards to prefer, oversee, and enforce the quality standards for compounding fix by USP. Such oversight varies significantly from state to state.

Statements from pharmacy associations, including the American Higher of Clinical Pharmacy, American Club of Wellness-System Pharmacists, and National Association of Boards of Chemist's shop, echo the considerations outlined earlier in this affiliate. While all of these organizations recognize the importance of drug compounding, they likewise express concern regarding the lack of standardized, well-studied formulas; the scarce education and information on compounding provided to patients, prescribers, compounders, and regulators; the lack of show on the rubber or effectiveness of compounded bioidentical hormone therapy (cBHT); and the increasing exposure of patients to compounded preparations that pose greater hazard than FDA-approved drug products. (See Chapters 6 and vii for a give-and-take on the available bear witness on the bioavailability, safety, and effectiveness of compounded hormone preparations.)

THE COMPOUNDING Marketplace: SUPPLY AND DEMAND

Compounding was the primary route by which medications were produced until early in the twentieth century, when the advent of large-calibration pharmaceutical manufacturing led to a decreased reliance on compounding (Newton, 2003; Sundberg, 1997). However, over the past few decades, the increasing demand for personalized medical care—coupled with the lack of regulations and oversight for the development of compounded medications—has catalyzed a resurgence in compounding and engaged a much broader patient population than traditionally intended (Gameiro et al., 2022; Gudeman et al., 2022; Oroszlan, 2022).^⁶

The growing demand for compounded drugs is too reflected in their use to care for a wide spectrum of weather condition beyond a range of therapeutic areas, including men's and women's health, pain management, sports medicine, dental care, veterinary intendance, pediatrics, hospice intendance, and in their utilize in the fields of allergy, dermatology, immunology, otolaryngology, oncology, ophthalmology, neurology, and rheumatology (Glassgold, 2022; McPherson et al., 2022; NABP, 2022).^⁷ Public health officials take become concerned nigh this expansion of the compounding market because it increases the number of patients with the potential to be exposed to drugs that accept non undergone the same rigorous production processes and quality controls every bit FDA-approved drugs (FDA, 2022).^{^viii}

Compounding Services and Data on General Use

Given its rise in popularity over the past two decades, compounding has go an increasingly lucrative industry. Unfortunately, it is difficult to identify publicly available, evidence-based estimates of the number of drugs compounded, the types of drugs compounded, the number of pharmacists and physicians who compound, or the size of the compounding market (Glassgold, 2022). This lack of data likely results from the lack of federal reporting requirements and centralized information collection, too as variable insurance coverage for a wide range of compounded medications (NASEM, 2022). Specifically, there is no requirement for 503A compounding pharmacies to written report or publicly advertise the presence and/or extent of their compounding capabilities (east.grand., nonsterile or sterile; pocket-sized focus versus chief specialty). Although outsourcing facilities must study their 6-month compounding totals to FDA, only some 70 facilities have registered voluntarily and identified themselves as outsourcing facilities, and it is likely that other nonregistered facilities exist and are operating in violation of Section 503A without appropriate oversight for the compounding they perform.^{^ix} The resulting information shortage poses challenges for risk–do good assessment and public health policy related to compounded drug preparations.

With this context in listen, the National Council for Prescription Drug Programs estimates that at that place are more than than 32,000 pharmacies nationwide that broadly depict some compounding activities under their offered services (The Pew Charitable Trusts, 2022). In terms of specialization, the American Pharmacists Clan estimates that just effectually 7,500 of the approximately 56,000 customs-based U.S. pharmacies specialize in providing compounding services, pregnant the pharmacists in those facilities spend virtually or all of their time compounding special preparations for patients (American Pharmacists Association, 2022). The Alliance for Pharmacy Compounding reports that 1 to 3 percentage of prescriptions in the United States are for compounded drugs (APC, due north.d.). Additionally, a 2022 Letco Medical survey of more than four,000 chemist's shop compounders found that nearly 40 percentage of those surveyed worked in pharmacies solely dedicated to compounding (APC, northward.d.).

Other data provide additional insights into the scope of the compounding world. From 2005 to 2022, the number of Medicare patients receiving a compounded drug increased 281 pct (HHS OIG, 2022). Similarly, a study of individuals with private insurance institute an increase of 27 percent in compounded drug apply between 2022 and 2022 (McPherson et al., 2022). A 2022 survey of 494 patients institute that almost 80 per centum of people who received compounded prescriptions did so through mail-gild pharmacies, and that amid those surveyed, compounded prescriptions were being used to supersede rather than supplement other drug(s) (McPherson et al., 2022).

Information on compounded drugs are likewise available from national workers' bounty claims. Compounding is a growing trend in workers' compensation programs; prescriptions for compounded drugs increased almost v-fold between 2007 and 2022, from half dozen,416 to 30,669 (Walls et al., 2022). Several surveys of pharmacists and prescribers accept sought to elicit information about the use of compounded drugs, but the data obtained has been limited considering of low response rates (McPherson et al., 2022; Ness et al., 2002; Warner and Tuder, 2022).

Insurance claims data also show that the number of beneficiaries receiving compounded drugs increased by 281 percent, from 73,368 in 2006 to 279,873 in 2022 (HHS OIG, 2022). A retrospective analysis of prescription claims information constitute that the prevalence of eligible members using compounded drugs increased by some 27 percentage between 2022 and 2022, with one.four percent of eligible members using compounded drugs in 2022. The number of claims for compounded drugs also increased by some 34 per centum (from 486,886 to 653,360) during the same period (McPherson et al., 2022).

Market Reports

Several individual marketing reports take estimated the global marketplace revenue for compounded preparations to fall betwixt $2 and $nine billion. Those analyses all predict growth in the next few years, ranging from 3 to 7 percent. A caveat is that these estimates come from private marketing reports and are based on data sources that are publicly unverifiable (e.g., Bourne Partners, 2022; Global Market place Insights, 2022; Market Inquiry Engine, 2022; Ugalmugale and Mupid, 2022a,b; Zion Market Research, 2022). Other unverifiable analyses have estimated the global market place for compounding pharmacies in 2022 to be $8.5 to $ix billion, with the 503B market place estimated at $1.five billion (Bourne Partners, 2022; Global Marketplace Insights, 2022; Zion Market Inquiry, 2022). These analyses projection that past 2022 to 2024, the global compounding marketplace will reach $x to $14 billion, with a compounded annual growth rate of 4 to 6 percent (Bourne Partners, 2022; Global Market Insights, 2022; Market Inquiry Engine, 2022; ReportsnReports, 2022; Zion Market Research, 2022).

Given the evidence for the substantial use of compounded drugs and the minimal federal and land oversight and protection for patients, there is crusade for serious concern that an increasing number of drugs used in the U.s. are consumed without assurance for their quality, safety, and effectiveness. Affiliate 3 reviews the current federal and state-level regulatory framework to minimize risks related to the use of compounded preparations, and Chapter seven discusses the scientific evidence on the prophylactic and effectiveness of compounded bioidentical hormone preparations, and related adverse events.

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1: In an effort to provide additional guidance, the U.s.a. Pharmacopeia (USP) offers a more detailed definition of compounding: "the preparation, mixing, assembling, altering, packaging, and labeling of a drug, drug-delivery device, or device in accordance with a licensed practitioner's prescription, medication society, or initiative based on the practitioner–patient–chemist–compounder relationship in the form of professional exercise" (USP, 2022).
2: At times throughout the written report, the terms compounder and pharmacist are used interchangeably to describe certain professional person practices related to compounding.
3: See Chapter three for an overview of the federal and state-level regulations and oversight for compounding preparations.
4: Open up session testimony, November 2022.
five: Under federal law, 503B outsourcing facilities may also compound for patient-specific prescriptions. See the Federal Food, Drug, and Cosmetic Act. 21 U.S. Code Chapter 9.
six: See Chapter 3 for an overview of the federal and state-level law, regulations, and oversight for compounding preparations.
vii: A discussion on the trends in the marketing of cBHT preparations tin can exist found in Chapter 8.
eight: Chapter iii provides an overview of how policies and regulations have dealt with marketing for compounded drugs.
9: These points are discussed in greater detail in Affiliate 3 of this report.