Pharmaceutical and Medical Packaging News Magazine
PMPN Article Index

Originally Published February 1998

SPOTLIGHT

Blisters in 1998: New Opportunities Emerge

by Karen G. Beagley, Midwest Editor

Are blisters booming? Maybe not at this moment, but there are several regulations and market developments that are pushing many manufacturers toward blisters. While some regulations are expected to expand the blister marketplace, others are likely to motivate companies to reengineer existing blister package designs and employ different materials. In addition, the increased number of clinical trials will probably step up demand for blisters. Without a doubt, blister packaging activity will be amplified in 1998.

CHILD RESISTANT AND SENIOR FRIENDLY

In June 1995, the U.S. Consumer Product Safety Commission (CPSC; Washington, DC) voted unanimously to issue a final rule modifying the child-resistant packaging test protocols of the Poison Prevention Packaging Act of 1970. "These changes revise the testing method, which will make closures adult-friendly and easy to open while maintaining their child resistance. The rule change[s] the makeup of test panels[,] substituting senior adults, ages 50—70, for younger adults. This will give a more realistic picture of the ability of normal adults to use child-resistant packaging properly than the current panel of 18 to 45 year olds," according to a statement issued by CPSC.

Photo courtesy of Acuity Imaging Inc./Packaging Coordinators Inc.

The big news now is that as of January 22, 1998, CPSC began compliance testing using the new senior adult testing protocol, which means CPSC representatives can pull packages off the shelves or make establishment inspections. "This was an important ruling," says Ken Giles, spokesperson for CPSC. "Twenty percent of the children being poisoned by pharmaceuticals were [poisoned by] their grandparents' medicines. The older adult population were not effectively opening and then closing their prescription medicines."

So what can manufacturers do if their blister package is child resistant but can't be opened by the senior test panels? "Manufacturers that have claimed child-resistant packaging have all the child test data," says Richard Ward, vice president and director of consumer product testing, Perritt Laboratories (Hightstown, NJ). "Now companies have to deal with the senior test panel. Changing the directions on the package to read 'Open with scissors' or 'Cut here' enables the packages to be opened by the senior test panel. We do not recommend using a scissors icon on the package showing where to cut. A child will recognize that icon, go get the scissors, and be able to get into the blister. We advocate 'Say it, don't show it.'"

Of course, blister packages will need to be reengineered so they can be cut open with scissors. "I think we need a newer, better design giving an area where the person can cut the blister and get to the medicine," Ward says.

"Over-the-counter drugs are increasingly coming out in blisters because of the child-resistant and convenience factors," says Dan Gerner, president, Packaging Coordinators Inc. (Philadelphia).

"There has been a trend toward child resistant even before it was dictated," says Bernie Conlon, vice president of sales, Romaco Inc. (Morris Plains, NJ). "Peel-and-push blisters are child resistant and now the big issue is to make them senior friendly."

STABILITY TESTING REQUIREMENTS

This past January 1, the International Conference on Harmonisation's (ICH) Technical Requirements for the Regulation of Pharmaceuticals for Human Use took effect. The requirements deal with stability testing for packages and have been adopted by FDA. Specifically, the guidelines change the accelerated stability test from 3 months at 38°C, 90% relative humidity to 6 months at 40°C, 75% relative humidity.

The blister industry is taking a variety of approaches to ensure that products will withstand the more stringent testing procedures. "We are seeing a trend toward using higher-barrier films that will meet these stability testing guidelines," explains Knud A. Christiansen, the director of pharmaceutical films at Klöckner Pentaplast of America (Princeton, NJ). "The testing conditions are much more severe now. The same drug that passed before won't necessarily pass in the same package under the new stability testing."

An all-aluminum blister package from Teich Packaging Inc.

Increasingly, companies are seeking out newer materials that can hold up to the more rigorous testing procedures. "We are seeing pharmaceutical companies looking more seriously at cold-formable foil to meet the more demanding tests," says Dave Sciubba, healthcare sales manager, Hueck Foils LLC (Manasquan, NJ).

Burt Zirin, the president of Teich Packaging Inc. (Northbrook, IL), comments: "There is more usage of high-barrier cold forming aluminum for moisture-sensitive drugs to meet ICH's stability-testing guidelines. There are lots of good materials available to meet these needs."

However, the IHC requirements are only some of the factors driving companies to look at alternative materials for blister packaging. "Pharmaceutical companies are changing materials to meet ICH's guidelines and for other reasons such as price and ease of use. PVDC with different laminations is becoming more popular," says Bob Misher, executive vice president, Blis-Tech Inc. (Fairview, NJ). "Foil/foil packages have been big in Europe and they seem to be coming here."

EUROPEAN MARKET

The European market for blisters is larger than that in the United States. "The European market uses more blisters than we do, whether they're for prescription or over the counter," says Hugh Lockhart, professor, Michigan State University School of Packaging (East Lansing, MI). "They use more-opaque materials, which they claim are less attractive to children. Their culture has been more accepting of blisters as the preferred method of packaging."

The European community also has stronger environmental reasons for using blisters, and manufacturers are penalized for introducing excessive material into the system. "In Europe, a blister is cut to a minimal size," says Tom McMurray, director of package engineering, Warner-Lambert (Morris Plains, NJ). "They are just more frugal in their use of materials. Blisters come in the preferred multiple for the specific country. For example, Italy prefers multiples of seven."

Another environmental aspect of the widespread use of blisters in Europe is the move away from PVC. "Europe uses polypropylene for blisters; they feel very strongly about the potential for undesirable by-products you can get as a result of burning PVC," explains Lockhart.

CLINICAL TRIALS

Another growth area for blisters is clinical trials. With the increasing incidence of clinical trials, many of which require complex regimens, more pharmaceutical companies are employing blisters. "We use blisters from a convenience and compliance standpoint," says Gary Puzio, clinical supplies manager, Phase IV research group, Schering-Plough (Kenilworth, NJ). "For a dose range study where the patient is taking four tablets a day or a placebo, the only way to do it is in a blister. It is hard to tell a patient to take one tablet from this bottle, then one from this bottle, etc. With a blister, all the medication is there, easily marked."

Romaco Inc.'s blister packaging machine can produce more than 300 blister packs per minute.

One issue that clinical trial companies are considering is whether blister packages should be subject to CPSC's child-resistant/senior-friendly regulations. "I have talked with CPSC, and they have said that if the package goes into the person's home, then it is subject to the same regulations as other packaging," says Stan Johnson, chief of integrated quality management, VA Cooperative Studies Program, Clinical Research Pharmacy Coordinating Center (Albuquerque). "During most of our studies, the patients take the medications home with them. For a limited clinical trial it is not worth the time and expense of conducting the tests for child-resistant and senior-friendly features. Previously, the FDA requirements had a provision absolving clinical trials from some of the regulations. With CPSC, there doesn't seem to be the latitude we need."

According to CPSC, all medications that end up in a home environment are subject to the child-resistant/senior-friendly regulations. "The manufacturer of the package is responsible for the testing to ensure that it is in compliance," says CPSC's Giles. "Pharmaceuticals must be in child-resistant packages, which also must meet the senior-friendly guidelines, unless a doctor or patient specifically asks for a non-child-resistant package."

IRON SUPPLEMENTS AND
THE METHAMPHETAMINE CONTROL ACT

Two regulatory developments relating to iron supplements and methamphetamine manufacturing may affect future growth of blister packaging. FDA's final rule of January 1997, titled Iron-Containing Supplements and Drugs: Label Warning Statements and Unit-Dose Packaging Requirements (21 CFR parts 101, 111, and 310), took effect on July 15, 1997. One provision of the ruling calls for unit-dose packaging for iron-containing products that contain 30 mg or more of iron per dosage unit.

"There have been some companies that have had to take iron products off the market because they were not in unit-dose packaging," says Matt Neumann, vice president of operations, Uhlmann Packaging Systems (Towaco, NJ). "We are seeing a move toward blisters having to be in compliance. Even though this ruling is already in effect, some companies did not have the time to get their iron into blisters."

On October 3, 1996, President Clinton signed into law the comprehensive Methamphetamine Control Act of 1996. The law broadens control over certain chemicals used in the production of methamphetamine, increases penalties for the trafficking and manufacture of methamphetamine and listed chemicals, and expands regulatory controls to include the distribution of certain lawfully marketed products that incorporate ephedrine, pseudoephedrine (PSE), and phenylpropanolamine (PPA).

The law subjects transactions involving PSE and PPA to the registration, recordkeeping, and reporting requirements of the Controlled Substances Act. The law creates a safe harbor exemption for the retail sale of ordinary over-the-counter products that contain PSE and PPA, according to a statement from the Nonprescription Drug Manufacturers Association (NDMA; Washington, DC).

"In order to be included in the safe harbor, the product must meet two requirements: 1) the package must contain not more than 3 g of the base ingredient, and 2) the product must be in blister packs of not more than two tablets per blister (unless use of the blister pack is technically impossible, such as for liquids). For those products not packaged in accordance with the safe harbor exemption as of Oct. 3, 1997, pharmaceutical retailers are required to register with the Drug Enforcement Administration if they sell more than 24 g in a single transaction and to keep records of such transactions," according to NDMA's statement.

"Basically, what this means is that if a retailer wants to avoid all the paperwork involved in registering, the retailer should sell the products in blister packaging," says Joe Doss, senior vice president and director of public affairs, NDMA. "The law is designed to stop the unscrupulous manufacture of an illegal drug from these substances. This would make it more difficult to have to open each blister package to get the required amount of drug."

CONCLUSION

This year will definitely bring both challenge and opportunity to companies using blister packaging. Packaging engineers have been called upon to develop creative solutions for meeting CPSC's child-resistant, senior-friendly requirements. With additional regulatory developments, such as the ICH testing guidelines and the rule on iron supplements, we are likely to see more blisters, along with the use of innovative materials and designs.