Packagers help get cervical cancer vaccine to market soon after approval

With Gardasil put on a fast track toward regulatory approval, Merck & Co. Inc. had to mobilize its packaging team so that soon after approval, the new vaccine could be shipped to fill orders. After years of preparation, the packaging team pulled it off. On June 8, FDA approved Gardasil, and within two weeks, Merck had product shipped to physicians’ offices. The vaccine is approved to prevent cervical cancer and vaginal and vulvar precancers caused by human papillomavirus (HPV) types 16 and 18 and to prevent low-grade and precancerous lesions and genital warts caused by HPV types 6, 11, 16, and 18, and is approved for 9- to 26-year-old girls and women.

Colleen Hutter, senior project engineer, Merck Packaging Technology, for Gardasil, says that “the complexity of the project required teamwork.” Such complexity involved developing vials and prefilled syringes as well as the full packaging and labeling lines to support them. Merck developed sophisticated vial and syringe labeling that was a feat to apply, encode, and inspect at top line speeds. Merck also worked diligently to design, build, and validate the packaging lines to prepare for market approval.

For Gardasil, Merck chose new labeling designs that are applied by high-speed labelers. “The NDC [National Drug Code] is encoded and printed by our supplier in RSS [Reduced Space Symbology] in an effort to eliminate medication errors,” Hutter explains. “Each label is designed with two detachable segments.” The new detachable labels are used for both vials and syringes. “We believe we are among the first companies in the U.S. vaccine market to introduce such a label,” she says. “The detachable segments, which are preprinted with product name and printed in-line with lot code and expiration date, are removable for application for immunization recordkeeping.” The label should ease such recordkeeping, as “practitioners often have to record vaccine administration in several places,” Hutter reports. She adds that Merck had worked through its marketing group to develop the labeling with the end-user in mind.

Merck’s packaging team had to keep this innovative label in mind when building the packaging line because it required a double wrap, or what Merck’s team calls the 720 wrap. At Merck’s facility in West Point, PA, the vials are first filled in separate sterile operations and then collected in trays and sent to multiple packaging lines. The vials are then introduced into the high-speed packaging line via a mass accumulator and make their way to a labeling system designed and integrated by Weiler Labeling Systems (Moorestown, NJ). Jason Fox, technical advisor, Merck Sterile and Packaging Operations, says that the line’s elevated speed—600 vials per minute—called for an “up-graded labeling system with integrated inspection.” The challenge was twofold—wrap the lengthy multiple-part label around the vials twice and encode the label with both lot and expiration date three times, all at a rate of 600 vials per minute. “The length of the label was a challenge,” Fox says. “It is one of the longest labels used on a vial.” Fox reports that Weiler Labeling worked to increase the application speed to make the project a success.

For coding, Fox says Merck invested in a high-powered steered-beam laser encoder from Lase Tech (Industrial Dynamics; Torrance, CA). “The laser is the only technology we have found to be capable at this speed,” he says. A reactive varnish on the label changes chemically when marked with the laser to produce a code. Weiler integrated an inspection system from Systech International (Cranbury, NJ) to verify code content, quality, and placement.

The syringes are filled in separate sterile operations at Merck’s West Point facility and printed with a lot-specific data matrix code. The sy-ringes, which feature Hypack glass syringe barrels and elastomeric plunger stoppers from BD Medical-Pharmaceutical Systems (Franklin Lakes, NJ), are collected in tubs for transport to the syringe pack-aging line. All syringe labeling and packaging operations take place on one line at the West Point facility, says Marty Nealey, director, Merck Sterile and Packaging Operations. “Syringes are difficult to handle—once you get your operations in line, they are easier to manage,” he says. The syringes also bear the 720 wrap label, but the line speed is limited to up to 200 syringes per minute. At that speed, “we can use thermal-transfer printing, for lot and expiration-date printing three times,” says Nealey, explaining that the team used such a system from Markem Corp. (Keene, NH).

Bausch + Strobel Machine Co. (Ilshofen, Germany; and Clinton, CT) developed the syringe packaging equipment specifically for Merck. “Several pieces are just being introduced to the market,” says Bruce Rambacher, senior project engineer, Merck Packaging Technology. “Bausch + Strobel engineers were instrumental in making sure that the equipment worked as it should.”

After labeling and plunger rod insertion, the syringe is inserted into a unique passive safety device from Safety Syringes Inc. (SSI; Carlsbad, CA) featuring a needle guard that activates after vaccine delivery. Merck worked closely with SSI to refine the final design based on market research testing and equipment design. The assembled device is coupled with a needle and then automatically fed into a blister thermoformer from Uhlmann Packaging Systems (Laupheim, Germany), reports Nealey. Hutter explains that thanks to the syringe’s luer image, other needles can be used with the luer-lock syringe, based on practitioner preference. The number of unit op-erations on the line totals 12, says Hutter. Rambacher calls the line long—165 ft 93¼8 in., to be exact.

Creating the documentation to support line validation and operation required a team effort, adds Rambacher.

Other technologies play a role in the packaging for Gardasil. Vial caps, syringe plunger rods, and all cartons are color coded to represent Gardasil within Merck’s larger family of vaccines to ease product identification. The plunger rod has also been customized to include the Merck logo to reinforce the branding. Undisclosed anticounterfeiting features are also at work.

Merck also decided to include a comprehensive insert for the patient that separates from the package insert via a perforation.

“It is the largest circular we have ever run for a vaccine,” says Hutter. “We have since implemented it for two other vaccines.” Steve Hess, ex-ecutive director of Merck Packaging Technology, also noted that “the advancement/adoption of the Paperless Labeling Initiative within the industry, which could still supply the patient information in the packaging but would allow the most current information for doctors and other healthcare professionals to be provid-ed electronically, will likely further advance the way information is provided to physicians and their patients.”

Because the vaccine is temperature sensitive, Merck is using qualified thermal shippers to maintain the required product temperature range throughout distribution.
Merck has seen wide acceptance for Gardasil since its approval. The Partnership to End Cervical Cancer (Atlanta), for instance, says that “HPV vaccines hold the promise of helping to eliminate a devastating women’s cancer.”

Gardasil has been approved for use in the United States, Mexico, Australia, Canada, and New Zealand, and has received a positive opinion from the regulatory agency in the European Union.