WASHINGTON, DC—Compounding sterile medications for parenteral use, such as allergy drugs, in a private physician’s office is potentially subject to almost as much scrutiny and regulation as are visited upon commercial preparers of such medicines.
Otolaryngologists, with their many allergy patients, are among the specialists most affected by these rules, regulations, and standards. These standards have been established in order to reduce some of the 17 billion adverse medical events that occur each year in the United States. Of that number, 44,000 deaths result from medical error, of which mistakes in mixing and compounding allergy medicines are a part.
USP: The Gold Standard
Steven M. Houser, MD, Assistant Professor of Otolaryngology at Case Western Reserve University in Cleveland, told the miniseminar audience that the US Pharmacopeia (USP) is the gold standard of vial mixing. He said that although USP is not a government entity, it does have enforcement power, and it is the basis for procedure and safety in compounding sterile medications for parenteral use. USP has five major criteria in this area:
- Preventing microbial contamination (maintaining sterility).
- Removing excessive bacterial endotoxins from the medications.
- Eliminating variability in the strength of correct ingredients.
- Preventing unintended chemical and physical contamination.
- Using only correct types and qualities of ingredients in sterile preparations.
To achieve these objectives, USP has developed a manual that covers in minute detail the steps to be taken and the correct procedure to be followed for compounded sterile preparations (CSPs). Chapter 797, Pharmaceutical Compounding—Sterile Preparations, pertains to private physician offices, and it is with this document that most of the miniseminar was concerned.
Chapter 797 went into effect on January 1, 2004, and covers a wide range of topics about compounding sterile preparations, labeling, and storage. The standards are enforced by the Food and Drug Administration and state boards of pharmacy. The Joint Commission on the Accreditation of Healthcare Organizations (JCAHO) has adopted the USP guidelines, but JCAHO is interested mostly in hospital pharmacies, which, in many cases, check and test procedures in physicians’ offices.
CSPs are administered to patients via application, implantation, infusion, inhalation, injection, insertion, instillation, and irrigation. There are four categories of CSPs: low risk, medium risk, high risk, and immediate use. Physician office preparation falls into the medium risk category.
CSPs are defined as biologics, diagnostics, drugs, nutrients, and radiopharmaceuticals, all of which are manufactured sterile products that must be prepared in a physician’s office according to the manufacturer’s instructions.
The most critical component in preparation of CSPs is maintenance of sterility—in the compound itself and in the area where it is mixed. This pertains to both the physical plant and facilities and the personnel themselves. USP standards include the following in the office of a physician who prepares and mixes allergy vials:
- An anteroom where personnel wash their hands in a prescribed manner and don sterile garb. It is also a transition room that provides assurance that pressure relationships are constantly maintained so that air flows from clean to dirty areas and that reduces the need for heating, ventilating, and air conditioning.
- Attention to the beyond-use date (a certain number of days after the preparation was compounded), at which time it must be discarded.
- A ventilated biological safety cabinet for personnel and products, having an open front with inward airflow for personnel protection and filtered laminar airflow for product protection.
- A buffer area or room where preparation and staging of components take place.
- A clean room in which the compounds are mixed.
- Disinfectant, a chemical agent that destroys disease-causing pathogens.
- Appropriate labeling on all containers used to mix the compounds, as well as those that contain the compounds themselves, with name, ingredients, date mixed —and by whom they were prepared.
- Terminal sterilization for sealed containers to achieve a predetermined sterility level. This is usually accomplished by steam under pressure or autoclave.
Compounding personnel are responsible for ensuring that CSPs are accurately identified, measured, diluted, and mixed, and are correctly purified, sterilized, packaged, sealed, labeled, stored, dispensed, and distributed. These performance responsibilities include maintaining appropriate cleanliness and conditions and providing labeling and supplementary instructions for the proper clinical administration of CSPs.
Compounding supervisors must ensure, through either direct measurement or appropriate information sources, that specific CSPs maintain their labeled strength within USP-designated limits, or within 10% if not specified, until their beyond-use dates. All CSPs should be prepared in a manner that maintains sterility and minimizes introduction of particulate matter.
A written quality assurance procedure includes the following in-process checks that are applied, as appropriate, to specific CSPs: accuracy and precision of measuring and weighing; the requirement for sterility; methods of sterilization and purification; safe limits and ranges for strength of ingredients, bacterial endotoxins, particulate matter, and pH; labeling accuracy and completeness; beyond-use date assignment; and packaging and storage requirements. When appropriate and practical, the dispenser must obtain and evaluate results of testing for identity, strength, purity, and sterility before a CSP is dispensed. Qualified, licensed health care professionals who supervise compounding and dispensing of CSPs are required to ensure that certain objectives are achieved.
The regulations (not the synopsis outlined here) are long and detailed and might instill some trepidation in the heart of one reading them. But, not to fear, said Sandra Lin, MD, of the Department of Otolaryngology—Head and Neck Surgery at Johns Hopkins Hospital in Baltimore. “The rules are fairly easy to follow, and the safety standards are there to protect our patients and ourselves. What’s more, Chapter 797 is open to interpretation, and as long as you have your own office guidelines based on 797—and follow them scrupulously—you should be fine.”
Number of deaths from methicillin-resistant Staphy-lococcus aureus (MRSA)infection in 2005, the last year for which data are available.
Number of MRSA infections in the United States in 2005.
Source:Centers for Disease Control and Prevention
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