01 Nov FAQ About Compounding
By: American Pharmacists Association
What is pharmaceutical 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 when commercially available drugs do not meet those needs. A patient may not be able to take the commercially available drug, or a patient may require a drug that is currently in shortage or discontinued.
These are a few examples of the ways a compounding pharmacist can customize medications with a doctor’s prescription to meet a patient’s needs:
- Adjust strength or dosage.
- Flavor a medication, for example to make it more palatable for a child.
- Reformulate the drug to exclude an unwanted, nonessential ingredient, such as gluten or a dye that a patient is allergic to.
- 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, suppositories, or other dosage forms suitable for patients’ unique needs. Compounding does not replicate commercially available drug products.
How is pharmaceutical compounding different from drug manufacturing?
Compounding is the preparation of an individual drug to meet the prescriber’s exact specifications and to be dispensed directly to the patient or the prescriber. Pharmaceutical compounding is performed or supervised by a pharmacist licensed by a state board of pharmacy (see below question on legal oversight of compounding versus manufacturing). Compounded drugs are not for resale by the patient or prescriber.
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 authorized under state and federal law to resell them.
What is a compounding pharmacy?
While all pharmacies do some types of compounding, this is more common or the primary focus of a small portion of American pharmacies. 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 injection into body tissues or the blood).
All licensed pharmacists learn during their four years of pharmacy school to perform basic compounding. In addition, all pharmacies have compounding tools such as a mortar and pestle for grinding materials, graduated cylinders for measuring liquids, scales for weighing solids, spatulas for mixing materials, and pill tiles on which to work. With such tools and applying their knowledge, all pharmacists routinely prepare nonsterile compounded products when requested by physicians.
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 in these pharmacies are more likely to be both sterile and nonsterile. 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?
All pharmacists and pharmacies involved in compounding are subject to oversight by both federal and state authorities.
The practice of compounding is regulated by state boards of pharmacy. Pharmacists engaged in compounding are expected to follow appropriate procedures for the types of preparations that are compounded.
FDA has oversight for the integrity 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 quasigovernmental organization defines the chemical composition of drugs and also issues practice standards. Two standards in particular are relevant to compounding pharmacists.
The USP <797> standard 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 products regardless of setting (for example, hospitals, community pharmacies) and who is performing the compounding (pharmacists, nurses, pharmacy technicians, or others).
USP <795> provides similar guidance for nonsterile preparations that are compounded in health care settings. It describes categories of compounding (simple, moderate, complex); defines terms such as beyond-use date and stability; and provides criteria for compounding pharmacists to follow in preparing various drug preparations.
Compliance with these and other USP standards is considered a standard of practice in pharmacy. Compliance carries the force of law in many states based on statutes or regulations passed by legislatures and boards of pharmacy.
The pharmacy profession recently established an accrediting body for compounding pharmacies. The Pharmacy Compounding Accreditation Board (PCAB) was established by eight pharmacy organizations, including the American Pharmacists Association, and is governed by a Board of Directors made up of representatives of the National Association of Boards of Pharmacy, USP, the International Academy of Pharmaceutical Compounding, and several pharmacy practitioner organizations, including APhA. An onsite survey provides compounding pharmacies the opportunity to demonstrate that they have achieved a superior level of quality assurance recognition for sterile and nonsterile compounded preparations. This provides consumers with a strong indicator of the quality of products they receive from accredited pharmacies.
How would patients know if their medication is compounded? Knowing that, should they take any precautions – 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 can 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.
If a prescription calls for a compounded drug, patients can ask whether the compounding pharmacy is accredited. Lists of accredited compounding pharmacy are organized by state on PCAB’s 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 their compounding knowledge and skills before issuing licenses.
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.
What caused the meningitis outbreak and how could it have been prevented?
Meningitis is inflammation of the tissues in the brain and spine. It is often the result of microorganisms growing in the fluid around the brain and spine. These can be fungi, bacteria, or viruses. In the current outbreak, 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 products. Because the product 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 product was being injected 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 product to many states in large quantities —something that compounding pharmacies are not permitted to do under state and federal laws — the product was not used for a long time in some cases (allowing the fungi to grow), and large number of patients were affected.
Inspections of NECC by the FDA and the Massachusetts State Department of Health have found unsanitary conditions at NECC facilities and violations of the USP<797> standard.
An FDA report described a “greenish black foreign matter” in 83 vials of the implicated steroid. The report also described mold and bacteria in “clean rooms” at NECC — the special areas required under USP<797> for preparation of compounded sterile products.
The Massachusetts Health Department’s report described black particulate matter in vials. The report also noted soiled floor mats as well as a leaky boiler that “created an environment susceptible to contaminant growth.”
The report also found that NECC was distributing large quantities of compounded products “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?
This could be a possible outcome based on the findings of the Congressional hearing. Congress and many state legislatures are looking for the help of APhA and other pharmacy groups to define clearly what constitutes compounding (regulated by the states) and what separates that from pharmaceutical manufacturing (regulated by FDA).
Requiring board certification of pharmacists and/or accreditation of compounding pharmacies to provide complex compounding services could also be a result of the fungal meningitis outbreak.
Are there any alternatives to using a compounding pharmacy?
A health care provider will prescribe a compounded drug only when those commercially available do not meet your needs. If you do not understand why you’ve been prescribed a special formulation, ask your doctor. If you are concerned about taking a compounded drug and you and your doctor agree that you can tolerate the commercial drug, you may also ask if there is any evidence that you will do 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 Allen, 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.
If you are interested in information on the recent fungal contamination, news stories 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.