When looking at materials of contact for drug products, the pharmaceutical industry complies with a variety of regulatory requirements from multiple organizations. This includes tests for extractables, stability trials, and surface resistivity as new products work their way through the new drug application process.

The three primary areas of consideration when selecting a film for use in powder transfer or storage devices include electrical safety, food contact compliance, and regulatory compliance. This article concentrates on the new requirements for materials of contact used in the EU.

2002/72/EC DIRECTIVE AND ITS AMENDMENTS
The 2002/72/EC directive (relating to plastic materials and articles intended to come into contact with foodstuffs) and its amendments, including 2008/39/EC, are also used by the pharmaceutical industry as a guideline.

Compositional compliance to the directive should be considered. All components of the formulation of the film, including the antistat employed for electrical safety, need to be listed as acceptable for use as required by the directive.
By undertaking all necessary migration testing in conjunction with the confirmation that the components of the formulation are included in the directive, one can demonstrate that the safety of the material and its compliance with current EU requirements is achieved.

The “Community Listing” of materials is the listing of acceptable compounds. As such, an “official” Community Listing does not actually exist as a single document, but rather the Community Listing is an agglomeration of the listings provided in 2002/72/EC and as modified by these amendments. Additional amendments and recodification of the Directives on Plastics into a single regulation are planned for publication in 2010. As such, a “Positive List” of permitted additives is not yet in place.

TYPES OF STATIC DISSIPATIVE FILMS
To date, migrating antistats have been of primary use in films for pharmaceutical manufacturing. This chemical additive to a film formulation functions by blooming to the surface of the film in order to attract moisture in the air, which then forms the conductive path for the dissipation of the static charge.

A large variety of migrating antistats, such as amides, amines, and stearates are available for use. However, these are not “smart” antistats and will bloom to the product’s contact side of the film as well as the surface toward the processing suite. To date, antistats have been shown to be acceptable for use in the storage media for drug products by inclusion under 2002/72/EC, through extensive stability trials, and by proof of safe use over years of service.

While migrating antistats are not disallowed by the commission directive relating to plastic materials, some migrating antistats will not be on the list for approval for use past the end of 2009. One such chemical is an amide used in antistatic master batches for static dissipative films. A risk management plan can be developed for the continued use of such chemicals based on historical operations; however, an alternative is to switch to a permanent antistat-based film.

Permanent antistats are polymers that are compounded with other resins during the extrusion process. The resins of the formulation interlink, forming a nonblooming film. As such, the antistat is locked into the film and does not migrate to either the drug product or the ambient surface. Since migratory antistats bloom to the surface, they can not be considered a permanent antistat material.

These regulatory changes take effect in 2010 and are one piece of the overall regulatory compliance puzzle. Whether for drum liners, noncontained Flexible Intermediate Bulk Containers (FIBCs), or flexible containment for product storage, drilling down to the ingredients used in film formulations is prudent. In the end, working with a flexible containment supplier who also developed and controls the film minimizes risk in the manufacturing process.