The FDA drafted new recommendations regarding the fill size for vials of injectable drugs and biologic products this summer, which prompted a response from the American Society of Anesthesiologists.
In a letter to FDA Commissioner Margaret Hamburg, ASA President Jane Fitch, MD, said the anesthesiology group “strongly supports the FDA’s recommendation that a drug product’s vial fill size be appropriate for the labeled use and dosing of the product,” and proposed working with the FDA and sponsors in implementing guidance on the issue. “Critical anesthesia drugs are still in shortage, and the availability of appropriately sized vials will help limit waste.”
The FDA drafted the new recommendations out of concerns that potentially unsafe handling of injectable drugs has led to an increase in vial contamination and an increased risk for the transmission of bloodborne illnesses among patients, according to a notice in the Federal Register. ASA was one of 15 groups or individuals to comment on the guidance during an open period this spring, said FDA spokesperson Jeff Ventura.
“ASA would appreciate the opportunity to work with the FDA and sponsors to implement guidance on labeled vial fill size, and in particular to identify the usual or maximum dose for a drug product,” the ASA letter said. “Physician anesthesiologists have unique knowledge of the typical doses of drug products and how they are used every day in operating room settings and pain clinics. Working together, we can take significant steps to help mitigate drug shortages and protect patient safety.”
The draft guidance, intended for new drug applications, biologics license applications and new packaging supplements, said that manufacturers must follow United States Pharmacopeia standards to fill each injectable product container with a volume that slightly exceeds the label, to permit withdrawal and administration of the drugs. Deviations from the recommendations should be justified with content-testing data. Sponsors also should determine the appropriate packaging sizes during product development, considering how vials are likely to be used. In deciding vial fill size, the FDA said manufacturers should consider the following:
· Single-dose vials should not contain a significant volume beyond what would be considered a usual or maximum dose.
· Health care providers should not be routinely required to use more than one vial to administer a typical single dose of the drug.
· Multiple-dose vials should contain no more than 30 mL of drug.
As of press time, the ASA had not received a response, said Beverly Philip, MD, the ASA’s vice president for scientific affairs and a professor of anesthesia at Harvard University, Boston. She was not concerned.
“I think the FDA deserves credit for working hard to try to solve these drug shortages and the drug safety issues,” Dr. Philip said. “Within their regulatory limits, they are working with the medical professional organizations and the pharmacy organizations to make progress on these.”
Two categories of anesthetic drugs have been problematic regarding vial size, Dr. Philip told Anesthesiology News. One is propofol, generally packaged in vials of at least 20 mL. Physician anesthesiologists may need just a small 5- or 10-mL dose to provide brief anesthesia to insert a block, she said. Additionally, if there are only a few minutes left on a longer procedure and one vial of propofol has been used up, the physician anesthesiologist may need to open a second vial just to use a small percentage of it.
At larger hospitals like hers, leftovers can be repackaged by the pharmacy under a sterile hood in a sterile room. But “that may not be an option for smaller facilities,” she said, who might have to waste the remainder. “Having small-vial flexibility will help make sure that anyone who uses propofol will use it as cleanly as possible.”
The other category is pain medicine: Physician-anesthesiologists may need just a few milliliters of contrast material to inject local anesthetic under x-ray guidance, but vials contain much more.
Mr. Ventura said the FDA could not discuss the guidance as it is being reviewed and edited, “nor can we estimate when said review will be completed.”
Dr. Philip said that’s a fair comment: “I have every expectation that the ongoing positive dialogue between ASA and the FDA is going to continue. We are really both on the same side of this issue, and they’ve been very interested in making it work.”