Proposed Vial Mixing Standard May Have Adverse Effects for Otolaryngologists

TORONTO-Standards proposed by the United States Pharmacopeia (USP) for the compounding of sterile medication could be applied to vial mixing in the office. This would represent a radical change that won’t make many otolarygnologists happy, according to panelists at the recent annual meeting of the American Academy of Otolaryngic Allergy (AAOA).

Although the changes would represent a significant effect on practice, not many otolaryngologists seem to be aware of them, yet they could actually happen, panelists warned.

One of the significant problems with the proposed USP standards is that they state that mixing must be performed in a dedicated clean room with a laminar flow hood. The specially built rooms would cost an estimated minimum of $21,000-a figure that some participants at the AAOA speculated would be significantly higher in reality. The standards would apply to physicians of all specialities who perform sterile medication compounding.

Aside from the cost, another key issue panelists discussed is how the standards would affect otolaryngologists if they are adopted by regulatory agencies.

Indeed, when it comes to vial mixing performed by otolaryngologists who provide patients with immunotherapy, there is no evidence showing any safety problems with the way things are done now, according to Sandra Lin, MD, Assistant Professor of Otolaryngology at Johns Hopkins University School of Medicine in Baltimore. She is working to make sure that any standards or regulations will be both relevant and evidence-based for otolaryngology practice.

The USP and Its Standard

As background, Dr. Lin explained that the USP is a nonprofit, volunteer standard-setting organization. Generally, standards are needed to ensure quality, safety, and the correct use of medications, she said.

The USP is not a regulatory agency and has no enforcement powers, yet the FDA does adopt USP standards if a specific USP monograph exists for a product. However, many state boards of pharmacy do follow USP guidelines, and the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) adopts many of them too, Dr. Lin said.

The vial mixing standard of concern, USP-797 Sterile Compounding Rules, was issued in the spring of 2004 and addressed everything from the need for mixing to be done in a clean room to risks, the length of time for which compounds can be stored, employee training, and what centers should have in their written procedures.

According to a recent JCAHO publication regarding USP-797, an organization must follow state laws if they have their own, or have guidelines based on expert opinion and scientific evidence, said Dr. Lin.

Compliance Requirements

Compliance with the standards would require extensive training of staff, plus yearly written tests and observation visits by expert personnel to confirm adherence to procedures. Environmental monitoring, including monthly air sampling, would also be needed. Further, mixed vials would have to be discarded after one week, instead of the typical 12-week remixing that is now common.

Estimates for building a clean room start at about $150 per square foot. Such rooms need stainless steel frames, specialized airflow systems, HEPA air filtration, humidity control, and more.

There would be costs behind building the room, training and certifying staff, and the frequent remixing, and questions arise about how to bill or get reimbursed for vials mixed outside if a center has no clean room.

This seems like a lot of trouble and cost for the otolaryngology profession, especially taking into account that there is no evidence in the medical literature showing an increase in infection from immunotherapy from the way mixing is done currently.

There are no papers published on the topic of infections and immunotherapy, Dr. Lin said. To determine whether there was a risk to patients, Dr. Lin and colleagues launched their own study on the topic. Findings were presented by Chase Lay, MD, a resident in otolaryngology at Southern Illinois School of Medicine in Springfield, Ill.

About 10 million immunotherapy injections are administered annually, and vials are prepared in the office. Yet, there is a lack of literature showing patients are at significant risk of local or systemic infection, Dr. Lay said.

A retrospective chart review was done of 284 patients who received a cumulative 13,576 injections from the years 2000 to 2006. Vials were prepared under sterile techniques in designated space without use of a ventilated hood or clean room, he said.

For the study, researchers examined data pertaining to the antigens that were in the vials, the date of mixing and injection, injection site, and whether there were any local or systemic reactions-and, if there were, their causes, treatments, and outcomes.

A total of 23 local reactions in 11 patients occurred, but there were no systemic reactions, patients had no fever or other indication of iatrogenic infection from the injections, and no antibiotics were given. The findings suggest that current mixing practices do not pose an infectious risk for patients, he said.

Additional Immunotherapy Issues

In another presentation on the panel, Byon Yeatts, a principal at the health care consulting company DK Pierce & Associates in Kennebunk, Maine, provided highlights from two studies on immunotherapy and practice by the US Department of Health and Human Services Office of Inspector General (OIG), an office whose overall mission is to detect fraud, waste, and abuse in health care.

The study showed that when it comes to immunotherapy in general, there have been some problems related to issues other than safety of the compounds. One was the 2002 Antigen Preparation report, which provided recommendations for practice expense re-evaluation and Medicare education for providers. The other was the 2006 Immunotherapy for the Medicare Beneficiary report, which stated a need for a national Medicare policy on immunotherapy.

Both OIG reports indicate the need for standardized immunotherapy and antigen preparation, he said.

The OIG reports found that 20% of patients getting immunotherapy had no need for the treatment; 13% of patients received immunotherapy despite having contraindications, and 15% had inappropriate allergy testing performed. In addition, 22% of patients continued getting immunotherapy beyond clinical norms and without justification and another 22% received improperly prepared allergy shots that were provided too frequently or in an inappropriate setting.

AAOA Task Force in Action

In the meantime, spurred on by Dr. Lin, the AAOA has created a task force to educate otolaryngologists about the issue, lobby against otolaryngologists having to do immunotherapy mixing under the new standards, and to create vial mixing guidelines specifically for otolaryngologists.

The AAOA task force is working with the Joint Council of Allergy, Asthma and Immunology (JCAAI) task force, and members are in discussions with the USP about possible revisions or exemptions to the proposed standards.

Dr. Lin is also planning further studies relating to vial mixing environments and patient safety. While otolaryngologists suspect mixing vials in the office is safe, actual evidence is always a good thing to have. In addition, she encouraged otolaryngologists at the AAOA to get involved in the process. If we don’t create guidelines for ourselves, someone else will, she said.

©2006 The Triological Society