Some companies are turning to plasticizer-free, biologically inert materials to replace the use of PVC.
By Jenevieve Blair Polin, Contributing Editor
The impetus driving demand for IV bags made of materials other than polyvinyl chloride (PVC) is twofold. First, the incineration of PVC reportedly generates dioxin; therefore, European environmental regulations limit its use when there are acceptable alternatives. Second, concern about the possible deleterious effects of phthalate plasticizers often used to soften PVC—specifically diethylhexyl phthalate—has increased the pressure to find alternatives. Manufacturers have responded with several materials that are available as film or as finished bags.
Ethylene vinyl acetate. Stedim (Concord, CA, and Aubagne, France) was one of the pioneers in the development of PVC-free IV bags. The company introduced IV bags made of monomaterial ethylene vinyl acetate (EVAM) in Europe in 1979. These EVAM bags were developed primarily for total parenteral nutrition (TPN) because of concerns about PVC extractables interacting with the lipids of TPN solutions. EVA bags, however, cannot withstand autoclaving, which is the standard method of sterilization for many parenteral drugs supplied in PVC bags. This drawback prevented their more widespread use in pharmaceutical applications. EVA bags are used in pharmaceutical applications where the products are filled aseptically and do not need to be terminally sterilized. Also, EVA bags are used where low temperatures are required.
Polypropylene. "We saw in our market research that people who were going to be replacing PVC were not going to want to replace their current sterilization methods," explains Michael L. Troedel, director of sales and marketing for Pactiv Corp.'s Flexible and Medical Packaging Group (Lake Forest, IL). Polypropylene-based bags, which are autoclavable, have broken through this barrier.
Propyflex from Pactiv is a three-layer coextruded flat or tubular film consisting of polypropylene and styrene ethylene butylene styrene. Propyflex bags won a 2000 Medical Design Excellence Award in a program sponsored by Canon Communications LLC, the publisher of PMP News. Pactiv supplies the film as rollstock to converters or supplies premade bags.
In March 2001, Pactiv announced a global strategic partnership for medical packaging with Rollprint Packaging Products Inc. (Hartford, CT, and Chicago). This partnership may eventually result in the domestic manufacture of Propyflex bags, which currently are made in Pactiv's plant in Germany.
This January, Stedim introduced Stedim 100 polypropylene-based autoclavable film. The bag chamber as well as the ports and port tubes are made of the same polypropylene-based material. The components are assembled and heat-sealed, then the heat of the autoclave cycle produces a tight mechanical fit. This bonding takes place without solvents, which can be a source of extractables. "We wanted the material contact surface to be as inert or pure as it could be," explains Matt Crowley, sales and marketing manager, IV drug delivery products, for Stedim.
Copolyester ether. All polypropylene bags contain other materials added to make them more flexible and durable. "Straight polypropylene," Pactiv's Troedel summarizes, "is too brittle and stiff." One happy marriage is that of polypropylene or other polyolefin resins to a copolyester ether, Ecdel elastomer, available as resin from Eastman Chemical Co. (Kingsport, TN). B. Braun, Abbott, and Cryovac have all developed monolayer or multilayer films incorporating Ecdel elastomer. When used in multilayer films, Ecdel as the outer layer provides toughness, clarity, and flexibility, explains Cary Clubb, Eastman's marketing communications manager. In tensile strength, modulus, elongation, and tear strength, Ecdel is superior to PVC, adds Doris Hobbs, Eastman's business market manager, medical.
The Excel system from B. Braun, which incorporates Ecdel elastomer, has been available in the United States since the late 1980s. "Just to come up with the film alone, we had to go through hundreds of candidate films," Steve Smith, director of product engineering for B. Braun, remembers.
Like the Stedim 100 system, the Excel system relies on heat-sealing rather than solvents to bond the film to the ports and other components. "Even the medication site, which is normally rubber, has a diaphragm in the molded component to ensure that the only things the solution comes into contact with are made of the same materials as the inner layer of the film," Smith stresses.
B. Braun supplies Excel film to Fresenius Kabi (Uppsala, Sweden) for construction of a multichamber bag, which won a 2001 Medical Design Excellence Award. Fresenius in turn has contracted with Donegal HealthCare Ltd. (Donegal, Ireland) to manufacture the bags. The Fresenius three-chambered bag keeps three TPN component solutions separate until the seals are broken immediately before use. It therefore may be stored for 24 months at room temperature, unlike traditional packages that have a short shelf life and require refrigeration. Stedim has similarly extended the shelf life of TPN mixtures with a dual-chamber EVA bag.
With the Duplex system unveiled early this year, B. Braun introduced a new level of sophistication in IV packaging. The Duplex system, which won a 2002 Medical Design Excellence Award (see news story, p. 12), is a dual-chambered bag with extremely high barrier properties. One chamber contains powdered antibiotic; the other, the sterile liquid that will serve as the diluent. At the point of care, the nurse breaks the intervening seal to reconstitute the drug. Running simultaneous aseptic powder and liquid fills in flexible containers requires state-of-the-art equipment, cautions B. Braun's Smith. "It wasn't just product development but also process development, equipment development—the entire scope was quite difficult," he recalls. This package, which offers considerable labor savings to hospitals, has been so well received that demand has outstripped supply. "We have to limit the hospitals that can get it," Smith says. Cefazolin is the first drug supplied in this format; however, B. Braun plans to make other antibiotics available in this package soon.