Frequently Asked Questions About Pharmaceutical Compounding
What is compounding, and why is it necessary?
Compounding is the creation of a pharmaceutical preparation—a drug—by a licensed pharmacist to meet the unique needs of an individual patient (either human or animal) when a commercially available drug does not meet those needs. A patient may not be able to tolerate the commercially available drug, the exact preparation needed may not be commercially available, or a patient may require a drug that is currently in shortage or discontinued. The U.S. Pharmacopeia Convention (USP) formally defines compounding as “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 order, or initiative based on the practitioner/patient/ pharmacist/compounder relationship in the course of professional practice.”
Following are a few examples of how a compounding pharmacist can customize medications based upon a doctor’s prescription to meet a patient’s needs:
- Customize strength or dosage.
- Flavor a medication (to make it more palatable for a child or a pet).
- Reformulate the drug to exclude an unwanted, nonessential ingredient, such as lactose, gluten, or a dye to which a patient is allergic.
- Change the form of the medication for patients who, for example, have difficulty swallowing or experience stomach upset when taking oral medication.
Compounding pharmacists can put drugs into specially flavored liquids, topical creams, transdermal gels, suppositories, or other dosage forms suitable for patients’ unique needs. Compounding does not include making copies of commercially available drug products, as this is not allowed by law.
How is pharmaceutical compounding different from drug manufacturing?
Traditional compounding is the preparation of a medication to meet the prescriber’s exact specifications and to be dispensed directly to the patient, pursuant to a valid prescription for that patient. Pharmaceutical compounding is performed or supervised by a pharmacist licensed by a state board of pharmacy (see question below on legal oversight of compounding versus manufacturing). Manufacturing is the mass production of drug products that have been approved by the Food and Drug Administration (FDA). These products are sold to pharmacies, health care practitioners, or others who are authorized under state and federal law to resell them.
What is a compounding pharmacy?
While most pharmacies offer some level of compounding, most compounding is done in pharmacies that have made the investment in equipment and training to do so safely and efficiently. The preparations offered by these compounding pharmacies can be nonsterile (ointments, creams, liquids, or capsules that are used in areas of the body where absolute sterility is not necessary) or sterile (usually intended for the eye, or injection into body tissues or the blood).
All licensed pharmacists learn during their training and education to perform basic compounding. In addition, most pharmacies have some compounding tools, such as a mortar and pestle for grinding materials, graduated cylinders for measuring liquids, balances for weighing solids, spatulas for mixing materials, and ointment slabs on which to work. With such tools and through applying their knowledge, all pharmacists routinely prepare nonsterile compounded preparations when requested by prescribers.
Of the approximately 56,000 community-based pharmacies in the United States, about 7,500 pharmacies specialize in compounding services. This means the pharmacists in those facilities spend most or all of their time compounding special preparations for patients. Preparations made in these pharmacies are more likely to include both sterile and nonsterile dosage forms. Compounding also takes place in hospital pharmacies and at other health care facilities.
Who regulates compounding pharmacies? Do compounding pharmacies follow the same regulations as drug manufacturers? Why or why not?
The practice of compounding is regulated by state boards of pharmacy. Community and hospital compounding pharmacists are allowed exemptions to the Federal Food, Drug, and Cosmetic Act of 1938 if they comply with the regulations outlined in Section 503A. All pharmacists and pharmacies engaged in compounding are subject to oversight by both federal and state authorities.
Pharmacists engaged in compounding are expected to follow applicable standards and regulations for the types of preparations that are compounded. FDA has oversight for the integrity and safety of the drugs (called Active Pharmaceutical Ingredients, or APIs, by FDA) used in compounded preparations. The Drug Enforcement Administration (DEA) has oversight for any controlled substances used in the preparation of compounded medications. Controlled substances include narcotics such as hydrocodone, amphetamines, and similar drugs, and drugs such as those used for anxiety and sleep disorders.
In addition, the United States Pharmacopeial (USP) Convention issues standards that apply to compounding. This private, nonprofit organization defines the chemical purity of drugs and also issues practice standards. USP develops standards for the identity, quality, strength, and purity of medicines, dietary supplements, and food ingredients that may be used in compounding preparations. These standards in particular are relevant to compounding pharmacists.
USP General Chapter <797> is a national standard for the process, testing, and verification of any compounded sterile preparations. It provides guidance on preventing microbial contamination and other variances in compounded sterile preparations, regardless of setting (e.g., hospitals, community pharmacies) or who is performing the compounding (pharmacists, nurses, pharmacy technicians, or others).
USP General Chapter <795> provides similar guidance for nonsterile preparations that are compounded in health care settings. It describes categories of compounding (simple, moderate, complex), defines concepts such as beyond-use date and stability, and provides criteria for compounding pharmacists to follow in preparing various drug preparations.
USP General Chapter <800> is a new standard developed by USP that establishes practice and quality standards of hazardous drugs to minimize the exposure to hazardous drugs within health care settings. This standard aims to promote worker safety (pharmacists, pharmacy technicians, veterinarians, veterinary technicians, and many others), patient safety, and environmental protection. This standard was published on February 1, 2016, but will not be officially implemented until July 1, 2018. The current list of hazardous drugs is available from the National Institute for Occupational Safety and Health (NIOSH).
Compliance with these and other USP guidelines is considered the minimum standard of practice in pharmacy.
Pharmacy Compounding Accreditation
Pharmacy Compounding Accreditation is a service of the Accreditation Council for Health Care (ACHC) that assesses the nonsterile and sterile pharmacy compounding process as defined by a specific set of standards that concentrate on the quality and consistency of medications produced.
How would patients know if their medication is compounded? Knowing that, should they take any precautions, or do anything differently?
Ask. A patient can receive compounded drugs from a typical community pharmacy or a specialty compounding pharmacy, or compounded drugs can be administered by doctors or other health professionals in clinics or medical offices. Patients should ask the person administering a medication or the pharmacist dispensing a prescription whether it was prepared in a compounding pharmacy or manufactured by a drug company. A widely accepted standard of practice is to label all compounded preparations with information stating the medication has been “compounded.”
If a prescription calls for a compounded drug, patients can ask whether the compounding pharmacy is accredited. Lists of accredited compounding pharmacies are organized by state on the Pharmacy Compounding Accreditation Board’s (PCAB) website.
Does a compounding pharmacist have special training?
Compounding is a central activity to the practice of pharmacy. Pharmacists are taught in pharmacy school how to properly compound medications, and many states test pharmacists’ compounding knowledge and skills before issuing them a license.
Pharmacists who practice in the 7,500 pharmacies that specialize in compounding services have generally had advanced training in compounding after they graduated from pharmacy school. No state currently requires a particular type of training, and no nationally recognized specialty exists for pharmaceutical compounding. Specialized training in pharmacy compounding processes is available through several of the active pharmaceutical ingredient (API) suppliers serving the needs of the compounding pharmacy community.
The Board of pharmacy Specialties also offers a Compounded Sterile Preparations Pharmacy Specialty Certification (BCSCP) for pharmacists who are responsible for ensuring that sterile preparations meet the clinical needs of patients. The American Pharmacists Association is approved by BPS as a provider for recertification of BCSCP.
When is a compounding pharmacy necessary?
A health care provider will prescribe a compounded drug only when commercially available drug products do not meet your needs. If you do not understand why you have been prescribed a special formulation, ask your prescriber. If you are concerned about taking a compounded drug and you and your prescriber agree that you can tolerate the commercially available drug, you may also ask if there is any evidence that your outcome will be better on the compounded formulation.
Where is more information about compounding available?
APhA has made available on this website the introductory chapter of a leading book it publishes on compounding pharmacy. Author Loyd V. Allen Jr., a recognized expert in pharmaceutical compounding and editor of the International Journal of Pharmaceutical Compounding, provides detailed information about many topics, including those presented in these FAQs.
For additional information about compounding pharmacy, contact IACP, PCAB, USP, the National Association of Boards of Pharmacy (NABP) or the appropriate state board of pharmacy.
If you are interested in information on new regulations, news stories, and practice standards in compounding pharmacy, these are available on APhA’s “Just the Facts” page. The FDA and CDC websites provide up-to-date information, lists of affected facilities and states, treatment guidelines, FAQ statements and other resources to assist health care providers and the public in addressing this issue.
What caused the meningitis outbreak, and how could it have been prevented?
In 2012, patients developed fungal meningitis after receiving injections into the spinal column of a product prepared by the New England Compounding Center (NECC), according to the Centers for Disease Control and Prevention (CDC) and FDA.
A number of things went wrong with these preparations. Because the compounded preparation was a suspension (with visible particles) rather than a solution (a dispersion of the drug at the molecule level), the liquid could not be filtered in a way that would have removed bacteria and fungi. Because the preparation was being injected directly into the spine, no preservative or other additives that might have prevented fungal growth could be added. The drug itself was a type of steroid, and these agents decrease the body’s response to microorganisms, and this might have prevented some patients from fighting off the fungi on their own. Finally, because NECC was distributing the preparation to many states in large quantities—something that compounding pharmacies are not permitted to do under state and federal laws—some of these preparations remained unused for a long time in some cases (allowing the fungi to grow), and a large number of patients were affected.
Inspections of NECC by FDA and the Massachusetts State Department of Health found unsanitary conditions at NECC facilities and violations of the USP<797> standard as well as local law.
The report also found that NECC was distributing large quantities of compounded preparations “apparently for general use rather than requiring a prescription for an individual patient.” State law requires a prescription for compounding and dispensing medication.
“Manufacturing and distributing sterile products in bulk was not allowed under the terms of its state pharmacy license,” the report said. “If NECC was appropriately licensed as a manufacturer with the FDA, the company would have been subject to additional levels of scrutiny.”
Congressional hearings on November 14–15, 2012, examined what went wrong in the NECC case, the role and responsibility of regulators, and what can be done to prevent another such outbreak in the future.
Will the outbreak lead to reconsideration of or changes in current policy/regulations?
The Compounding Quality Act of 2012 was a direct outcome of increased regulation over compounding. This landmark legislation is also called the Drug, Quality and Security Act (DQSA) of 2013. The first section, Title I, is concerned with compounding. Title II deals with Track and Trace rules.
The DQSA established for FDA clear authority over certain aspects of compounding. The Act also created a new entity, called Outsourcing Facilities. Section 503B of the FD&C Act was added by this bill to govern outsourcing facilities.