As of the end of October, 28 deaths resulting from the use of poorly prepared compounded medications by a Massachusetts-based compounding pharmacy have been reported. These deaths have focused increased attention on the role and safety of compounded specialized medicines and dosage forms in the United States.
Pharmaceutical compounding is defined as the combining or mixing of pharmaceutical ingredients to create a customized medication product for a specific patient by a prescriber’s order or prescription. Inherent in this definition is the notion that the final product is not tested for safety and efficacy by data that the FDA normally uses to assess a product. Because pharmacy school curriculums include training in the science and art of compounding, pharmacists are generally well trained in how to compound many medicines. More advanced training is also available for post-graduate pharmacists and pharmacy technicians, by organizations such as the Professional Compounding Centers of America. Although most independently owned and chain pharmacies (eg, Walgreens) do not prepare many compounded products, specialized compounding pharmacies are available that do prepare many compounded products.
Edward A. Bell
The FDA has received reports describing adverse effects from other inappropriately prepared compounded medicines in past years, but the recently reported deaths from poorly prepared injectable methylprednisolone products prepared by the New England Compounding Center has focused increased attention on pharmaceutical compounding (www.fda.gov/Drugs/DrugSafety/ucm323431.htm). The New England Compounding Center (NECC) is a specialized compounding pharmacy located in Framingham, Mass., a suburb of Boston. NECC is no longer operating, as its license to practice was suspended on Oct. 3. The product prepared by NECC that has been reported to result in significant adverse effects is preservative-free methylprednisolone 80 mg/mL, intended for epidural use.
Although commercially manufactured methylprednisolone products of this strength are available from established drug manufacturers, they are not FDA-approved for epidural injection. It is estimated that more than 10,000 patients in more than 20 states may have been exposed to the three lots of contaminated methylprednisolone. Fungal species believed to be the cause of contamination include Exherohilum and Aspergillus. According to a recently published report by the CDC (MMWR, Oct. 12), four categories of fungal infections have been identified from epidural use of the contaminated methylprednisolone product: 1) fungal meningitis; 2) basilar stroke without lumbar puncture; 3) epidural abscess; and 4) septic arthritis of a peripheral joint. Meningitis has been most commonly reported.
Reports of adverse effects have also recently been reported from other contaminated products prepared by NECC, including cardioplegic solution (contaminated with Aspergillus) and triamcinolone acetonide (also intended for epidural administration).
Compounding of specialized medicine products is commonly practiced, and it can play an important role in the pharmacotherapy of numerous diseases states. Compounding can have numerous applications and uses, such as when an individual is unable to use commercially available products because of allergies to dyes or other ingredients in commercial products. In pediatrics, compounding can have many applications: preparation of a liquid dosage form when a commercial liquid product is not available; flavoring of commercial liquid dosage forms to improve taste and administration; preparation of “child-friendly” dosage forms (eg, lollipops, effervescent drinks); or preparation of dosage forms that are gluten-free, sugar-free or casein-free.
Regulation and monitoring of compounding pharmacy practice has been highlighted in recent weeks due to problems identified in the NECC cases. Although the FDA provides oversight for the medication ingredients used in pharmacy compounding, more specific regulation of compounding pharmacy has been assumed by the states.
Assuming that a need for specific medicine product is identified, without the availability of a commercially prepared product, how can a caregiver, patient or health care professional assess the quality of a compounding pharmacy and its products? The state board of pharmacy can provide historical information about a specific pharmacy, as it relates to reports, if any, of poorly prepared products and resultant adverse effects. If the product in need is to be injected, the pharmacy should follow appropriate sterility procedures as outlined by the United States Pharmacopeia.
Although not required for practice, a compounding pharmacy can fulfill specific qualifications for accreditation by the Pharmacy Compounding Accreditation Board. This accreditation demonstrates that the pharmacy complies with nationally accepted quality standards, and the pharmacists and staff have received advanced training in compounding. The NECC had never applied for accreditation through the Pharmacy Compounding Accreditation Board.
American Pharmacists Association. Statement on rare meningitis outbreak (Oct. 11, 2012). Available at: www.pharmacist.com/node/66241. Accessed Oct. 18, 2012.
Galston SK. Federal and state role in pharmacy compounding and reconstitution: exploring the right mix to patients. Statement before the Senate Committee on Health, Education, Labor, and Pensions (Oct. 23, 2003). Available at: www.fda.gov/NewsEvents/Testimony/ucm115010.htm. Accessed Oct. 18, 2012.
For more information:
Edward A. Bell, PharmD, BCPS, can be reached at: Drake University College of Pharmacy, 2507 University Ave, Des Moines, IA 50311; email: email@example.com.