By Alan Horowitz
The tops of injectable drug vials are small, but they have become a fairly large battleground, where drug companies and the United States Pharmacopeia (USP) are currently pitted against one another. The conflict, which has been years in the making, involves what to print on the tops, if anything.
The tops in question are called ferrules and cap overseals. Ferrules are crimped metal shells that attach elastomeric stoppers to vials as a seal, and cap overseals are plastic caps which cover the ferrules and stoppers. The USP wants to change the labeling on ferrules and cap overseals in its General Chapter <1> Injections Labeling on Ferrules and Cap Overseals Section, and the pharmaceutical industry does not agree with the proposed changes.
The USP’s proposed changes would restrict labels on the ferrules and cap overseals to cautionary statements relating to imminent, life-threatening situations only. Examples of such statements are: “Warning — Paralyzing Agent” or “Dilute Before Using.” These statements are to be printed in a contrasting color and be clearly visible under ordinary conditions of use. When cautionary statements are not warranted, the cap overseal is to be left blank.
Other important but less urgent information would need to be located on other areas of the vial. Such information includes the manufacturer’s name and logo, lot number, and product name. Under the existing rules, manufacturers are free to put on the ferrules and cap overseals information they think important, and this often results in labels that contain the manufacturer’s name, logo, drug’s name, and/or drug’s strength.
Behind this proposed change is the USP’s belief that limiting the labels on vial tops to only cautionary labels and leaving all other tops blank, makes the cautionary labels stand out by reducing clutter, thus enhancing patient safety. Matthew Grissinger, director of error-reporting programs at the Institute for Safe Medication Practices, says that if ferrules and cap overseals contain a wide variety of information, important messages are easy to “gloss over and not see.” He likens it to a road with many speed-limit signs versus a road with a few well-placed signs. Where there are many, drivers tend to ignore them, in effect not see them, while a road with a few signs makes each one stand out. A healthcare practitioner who opens a drawer filled with vials and their cap overseals is apt to notice those with imminent life-threatening warnings if the remaining cap overseals are blank, or so the thinking goes.
“Your mind plays a trick on you when you expect something. This is when we accept information that agrees with our hypothesis and reject information that does not; this is called confirmation bias,” says Marjorie Shaw Phillips, medication safety pharmacist at MCGHealth (which is the clinical arm of the Medical College of Georgia) and a member of USP’s Safe Medication Use Expert Committee. A busy health professional might think they are grabbing the right product based on size, shape, color, and a vial being in the right place, when, in reality, what they are grabbing is different from what they expected. There is no substitute for carefully reading labels, notes Phillips, but without some kind of visual cue that looks different, “we might not even realize we have not read the label thoroughly,” she says.
The industry agrees ferrule and cap overseal printing/labeling is an issue of patient safety, only it thinks safety is enhanced with less restrictive labeling requirements. “This space [on the ferrules and cap overseals] is used to prevent medication errors,” says Debbie Thomas, global VP of regulatory affairs at West Pharmaceutical Services and cochair of the Consortium for the Advancement of Patient Safety or CAPS (www.caps-edu.org), an industry-sponsored group set up to promote patient safety and the industry’s position regarding ferrule and cap overseal labeling. Examples of labeling she thinks promote patient safety but would not be allowed under the proposed rules include dosages and such warnings as “Keep Refrigerated” or “Adult Dose Only.”
And the language of the standard is also problematic, she says. The industry questions what makes for an “imminent” life-threatening situation. “If there’s a life-threatening condition but it’s one that may occur in or after 48 hours, does that mean it should not be on the cap?” asks Thomas.
Where’s The Proof?
It is the contention of Frederick J. Balboni Jr., executive director of CAPS, that while the proposed changes may sound plausible, there is no proof that the current USP General Chapter <1> standards have caused any problems. “There is no data to support either side,” he says. CAPS currently has under way a human factors project that, according to Balboni, includes a literature review, a survey of healthcare practitioners, and a human factors phase that, together, will produce a clearer picture of whether such restrictive labeling as proposed by the USP is likely to be effective. The study was expected to be completed at the end of March 2010. “I am looking forward to seeing this data. Right now there’s an absence of it,” says Balboni.
In addition, the industry contends that the new labeling will take away supplemental anticounterfeiting measures currently used by the industry. According to Thomas, some view the use of product names and logos as a form of advertising and feel that this valuable space should not be used for such purposes. Her response: “It’s not advertising. The use of logos and product names provides additional anticounterfeiting measures. The printing on the ferrules and cap overseals is hard to duplicate because of the technology involved.” It’s not correct to view such labels as advertising, she says, because healthcare practitioners do not choose products based on cap overseal labels. This is an audience that knows what medications it wants, and the printing on the ferrules and cap overseals provides a means to accurately identify those medications and thwart potential counterfeiters.
Mistakes Have Occurred
Supporters of limiting information on caps overseals say that mistakes have happened, and that better labeling could have prevented them. “There have been a number of cases reported where there have been close calls, injuries, and deaths where high-risk medications, such as paralyzing agents, have been given mistakenly,” says Phillips.
Such reported mistakes prompted the changes, she says. “Drug companies had company logos and names [on cap overseals] which we did not think essential,” Phillips says. “We thought it better that only important safety messages be used, so they are the last information seen before a drug is prepared and administered.”
Shawn Becker, director of healthcare quality standards at USP, has been leading that organization’s ferrule and cap overseal labeling efforts. “Four different expert committees at USP looked at the ferrules and cap overseal labels,” says Becker. “There was a lot written on the tops of vials, and they were being confused by healthcare practitioners. Our expert safe medication use committee felt that cautionary statements only should appear on caps and ferrules.”
She notes that the environments where injectables are often used, such as ambulances and emergency rooms, are chaotic and tense, and when a healthcare practitioner in such a situation looks at medication vials and sees multiple colors and information on caps and ferrules, there can be confusion with mistakes resulting. Limiting what is there makes it easier for the practitioner to pick the correct medication and be warned about any imminent danger, says Becker.
As for the industry’s concern about counterfeiting, Becker notes: “We hear that, but there are a lot of different ways that manufacturers and others deal with counterfeiting. You can hide a logo or description that can’t be seen by the naked eye, for example. We are not suggesting they can’t place anticounterfeiting measures on other parts of the vial, [but] there are other mechanisms available besides putting them on the cap and ferrule.”
Changes to cap overseals and ferrules were first proposed in 2004. Since then, there have been various postponements. Currently, the proposed changes are out for public comment, which are due April 15, 2010. At that time, the USP will look at the comments to determine if changes are needed to the proposal. If no substantive comments are received, the USP will publish the proposed changes, and they will become official. If the comments that come back are substantive, then adoption of the changes will be put off for further discussion.