Struggling with Child Resistance
A petition to the Consumer Product Safety Commission generates a healthy debate.
by Daphne Allen
Deservedly or not, child-resistant packaging isn’t always popular with senior adults. From push-and-turn closures to peel-and-push blisters, child-resistant packaging is often the butt of senior complaints. They want easy-to-open packages.
“The technology used to prevent young children from gaining access to medicines packed in unit-dose packaging is a roadblock for adults,” says Michiel van den Berg, director of global pharmaceutical packaging development for Tekni-Plex Inc. “This is particularly true for older patients who may not have the strength or dexterity to access their medication.”
Nic Hunt, global business director for Rexam Pharma Flexibles, agrees. “There is little attempt at senior friendliness—the focus is totally on child resistance. You can see this by the use of some lidding films that even adults struggle with.”
Child-resistant unit-dose blisters, though, have made great strides toward senior friendliness. Nonetheless, the Healthcare Compliance Packaging Council (HCPC) argues that some fortifications necessary to prove child resistance during the Consumer Product Safety Commission’s (CPSC) test protocol for unit-dose blisters may scare away drug makers that do not want to turn off senior consumers.
FORTRESS: DRUG WITHIN
During protocol testing for unit-dose packages, if a child opens or accesses eight units or a lesser amount that could be considered toxic, the unit-dose package fails. If a drug maker determines that four of its solid oral doses could cause serious personal injury or serious illness, the package will fail if a child can open more than three blister cavities during the test.
“While unit-dose formats can be fortified to pass the current standard, such fortifications can make it difficult for adults to use the package properly,” HCPC released in a press release in late June. “But unlimited amounts of the same product can be placed in a cap-and-vial closure with no consideration as to what happens if a child gets the top off, or if an adult fails to properly resecure the cap after each use. The existing dichotomy creates a disincentive for manufacturers to adopt unit-dose formats for their products.”
HCPC has therefore petitioned CPSC to change the protocol by dropping the “or whichever is toxic” clause, setting the limit at eight units. “CPSC offers no practical definition for the phrases ‘serious injury’ or ‘serious illness,’ nor does the Commission specify exactly how many units of any drug product will cause such reactions with small children,” HCPC said in June. Instead, executive director Peter Mayberry says that HCPC would like to see an objective numerical pass/fail standard. “Such a standard will still require unit-dose formats to have CR fortifications, but it will provide manufacturers with an objective means of determining whether their packages comply with CPSC regulations.”
“Standardization makes product-to- product tests more uniform,” says Hunt. “Changing the test criteria to suit the type of drug makes the tests inconsistent. For highly toxic products, it is clearly necessary to have different levels of package protection, and, as such, an entirely different package and test may be appropriate, rather than an amendment to the current one.”
CPSC is considering HCPC’s request. The commission solicited comments on the petition from manufacturers, doctors, consumers, poison-control centers, and others in a Federal Register notice published on June 16, 2003. The comment period ended on August 15. As of August 21, the CPSC had received 27 comments.
One comment came from KV Pharmaceutical (St. Louis, MO). Robert Brooke, vice president of quality assurance and quality control, wrote that the “current requirements impose an unnecessarily stricter standard of unit-dose packaging [than that] required for bottle packages.” The child resistance testing requirements should be based on an objective standard regardless of the content of the package, similar in nature to [bottles].”
Another comment came from Kenneth C. Stewart and Michelle B. West, the regulatory affairs manager and the marketing director of Alcoa Flexible Packaging. “Approval of this petition will result in significant improvements in safety for children. The ability of child-resistant unit-dose packaging to protect small children from accidental poisonings is obvious from statistical analysis of the history of poisoning by ingested drug products.”
EIGHT IS TOO MUCH
One commenter, Anthony Manoguerra, wrote that he understood that industry “would like a single standard that could be applied across the board.” However, “the only acceptable standard would be no more than one dosage unit in 10 minutes,” he suggested. Manoguerra is director of the San Diego Division of the California Poison Control System.
Making the failure level one, not eight, would put blisters on a par with bottles, since a single opening is a failure, write Hugh Lockhart and Laura Bix, professor and assistant professor, respectively, at Michigan State University. “If the subjectivity of toxicity levels is truly the driving force behind this petition, HCPC should err on the side of safety and make the failure level one, not eight. This will take the subjectivity that is uncomfortable for the manufacturers away and not allow a potentially toxic dose to be considered acceptable under the test protocol.”
Most professionals from poison-control centers who commented agreed that eight doses of some drugs could be harmful, even fatal. “Many prescription drugs are toxic with ingestion of [fewer] than eight dosage units,” wrote James Mowry, director of the Indiana Poison Control Center in Indianapolis. In addition, “There are medications used today [that] are hazardous to toddlers in even a single-dose administration,” wrote Steven Marcus, executive director of the New Jersey Poison Information and Education System.
Instead of a numerical pass/fail standard, Pfizer proposes that the failure rate be set at “the amount that may produce serious personal injury or serious illness,” wrote Marc Wilenzick, senior corporate counsel for Pfizer. In addition, protocol testing “should not be necessary if a unit package contains a nontoxic amount of a substance, regardless of the number of units in the package.”
|Graphic Packaging offers the Pick and Peel for a child-resistant, senior-friendly blister.|
“We believe an assessment needs to be made for each product we market,” adds Rich Hollander, Pfizer’s senior director of packaging services.
There appeared to be a general consensus on the types of drugs that could harm children, even in small doses. Eight units doses of “Clonidine, Sulfonyureas, Lomotil, Isoniazid, calcium channel blockers, antipsychotics,” and others “would pose a risk to a toddler,” wrote Suzanne Doyon, medical director of the Maryland Poison Center. These were also referenced by other poison-control center professionals.
Some of these drugs, as well as others like methadone, nifedipine, and carbamazepine, were part of a study by the European Association for the Coordination of Consumer Representation in Standardisation. The group is against HCPC’s petition as well as the draft European standard EN 14375: Child-Resistant Non-Reclosable Packaging for Medicinal Products, Requirements and Testing. That standard states that if a child removes more than eight units from a unit-dose package in 10 minutes, the package is a failure. The study concluded that a small number of ingested tablets of some pharmaceuticals can seriously damage the health of a child; in certain cases, less than one pill can kill a child; in a large proportion of moderate to severe poisonings fewer than eight units could be involved.
Mayberry understands that there are classes of drugs that could cause serious illness with fewer than eight tablets. “But if only one or two doses of a product can be toxic, it’s unconscionable that these same products could be dispensed in 30- or 60-count bottles,” he says. “There’s no control the bottle will be properly reclosed.”
Instead, he argues that CPSC should list these drugs as hazardous and mandate that they be placed in individual units with a CR test protocol rating of F1. He points to FDA’s argument in defense of its unit-dose packaging requirement for iron-containing products: under the Poison Prevention Packaging Act (PPPA), unit-dose packaging can be mandated because there are several types of unit-dose packaging. He adds that, while HCPC suggested setting the standard at eight units, the important thing is setting an objective numerical standard, “so long as it is more than one.”
Some of the petition respondents opposed to HCPC’s petition explained that they believe that blister packaging can help reduce child poisonings. “We agree that unit-dose packages can be more child-resistant than cap-and-vial closure systems because children may access fewer units of medication per breach,” wrote Lockhart and Bix.
“I agree that child-resistant unit-dose packaging is preferable to child-resistant cap and vial packaging,” wrote Manoguerra.
Pfizer’s Wilenzick wrote that “Pfizer agrees that the public health and safety would benefit from an increase in the use of unit-dose formats.” In addition, “Unit-dose systems need not be resecured after each use, and, therefore, their child-resistance properties are not dependent on proper adult usage.” Since each dosage is in its own cavity, each must “be removed one at a time, slowing children down and allowing more time for adult intervention, or for children to lose interest.”
Doyon cited the success of FDA’s regulation requiring unit-dose packaging for high-concentration iron products. “This novel regulation has resulted in a dramatic reduction of pediatric emergency department visits related to iron ingestions. More importantly, it has resulted in a reduction in pediatric iron fatalities in the United States. Blister packaging works!”
|Alcan Packaging Pharma Center suggests its bend-and-tear blister design for child resistance and adult friendliness.|
But these blister supporters don’t want to see the protocol test relaxed. “Lowering the acceptance criteria for unit-dose packaging, as HCPC has argued, is not the proper way to encourage manufacturers to use it,” say Bix and Lockhart.
“The PPPA has been the single most effective measure that has reduced deaths in children from drug and other poison ingestions. We cannot accept a standard that relaxes the level of protection and places children at risk,” wrote Manoguerra.
Mayberry counters that adopting a numerical standard doesn’t make the package easier to get into. “The package will still need fortification. The change would simply remove the major obstacle cited by manufacturers— the need to determine what number of units causes ‘serious illness or injury.’ They don’t have to make that determination when using bottles.”
Renard Jackson, executive vice president/packaging services of Cardinal Health and chairman of HCPC, stresses that HCPC is not trying to lower testing standards. “We just want to ensure that the use of blisters is not prohibited by the current test protocol.”
Companies like Graphic Packaging Corp., Colbert Packaging Corp., and Alcan Packaging Pharma Center Inc., too, want more unit-dose blisters to be used, since that is one of their core businesses. However, these three package providers do not advocate changing the unit-dose test protocol. Scott Denley, marketing manager for Alcan Packaging Pharma Center, says that the standard for bottles should be changed. “If, for example, four doses of a drug can be toxic, then, under the current regimen, a bottle should not be allowed to contain more than three tablets or capsules.”
“We do not believe that less testing, as the petition allows for, is in the best interest of society,” adds Christopher Madison. He is sales and marketing manager of healthcare packaging for Graphic Packaging. “Many items today are toxic, which could cause serious injury or death to a 25-lb child if only one unit were accessed. Customers and their products are all different and must be treated that way.”
“We work on packages for products where just one pill could be toxic,” adds Glenn Grosskopf, vice president of product development for Colbert Packaging. “We aim for zero failures.”
These companies and others are hard at work in search of the child-resistant, senior-friendly blister. “We tailor our cards to satisfy both child-resistant and senior-effective balance. We have them tested to prove the design is adequate, and when needed, we redesign and retest,” says Madison. Graphic Packaging’s most popular solution is its Pick and Peel design.
Two new designs are also in the works for Graphic Packaging. The first offers dual protection on the front and back blistercard surfaces. “The second is a special laminate, a new generation of blistercards, which we believe will replace much of the market in the near future,” says Madison. “You would not know it’s a child-resistant card by looking at it, since the features are laminated internally on the board.”
Colbert recently went back to fine- tune one of its child-resistant designs. “In a preliminary test, PharmaDial received zero failures in the first five minutes of protocol testing,” explains Grosskopf. “But a child did get into the package during the second five minutes by using back molars to pull out one of the blisters. By design, PharmaDial’s raised blister was formed as a wing-nut to make it easier for seniors. On the redesigned PharmaDial, the excess blister material was eliminated but the design is still easy for seniors to turn. Colbert Packaging is planning to go back into protocol testing in September.”
Rondo/Dividella’s TopPak Box Wallet recently underwent protocol testing, and vice president of sales and marketing Mike DeCollibus reports that it passed with an F1 rating. “All the child resistance is in the outer package,” he says. “Blisters are hot-glued to one or two of the flaps, and the paperboard closes up like a box.” Dividella can provide the TopPak premade, paperboard converting and gluing systems for assembling TopPak, or a blister packaging and paperboard converting line with input from its sister company, Klöckner Medipak.
In addition to its current child-resistant offerings, like peel-push, tear-open, and peel-open designs, Alcan Packaging continues to advocate the development and use of multiple-step opening features, says Denley.
Material choices may also play a role in child resistance. “High-moisture-barrier multiple-layer film structures based on PCTFE are very difficult to puncture or cut,” says Tekni-Plex’s van den Berg. “By using a PCTFE-based film and by ensuring appropriate blister wall thickness after thermoforming, the dosage can only be dispensed via the intended child-resistant feature.”
Other options are Cardinal Health’s Slide Pack and E-Z Tear, and MeadWestvaco’s DosePak and SurePak, carded blisters that involve multiple opening steps. Cardinal Health is also developing another design.