Reducing Particulates: Mitigating the Risk of Recall through Material Compatibility

The pharmaceutical industry has traditionally used glass as a primary material for containment systems due to a variety of characteristics that enable generally safe and efficient drug storage. However, there are many risks associated with glass. In a recent draft guidance, “Immunogenicity Assessment for Therapeutic Protein Products,” the United States Food and Drug Administration (FDA) called attention to issues commonly associated with container closure systems, including:

• Denaturation and aggregation of proteins at glass-air interfaces

• Glass delamination and particulate formation in certain drug formulations

• Protein aggregation associated with silicone-lubricated containers

• Leachables from container components

These issues may affect the therapeutic activity of the drug product, and the recommendations come at a time when such issues have led to an increase in the number of recalls. For instance, in 2011, 10 drug product recalls were caused by glass particulates in the drug product solution. The pace continued in 2012 with recalls of 19 lots of four different injectable oncology products caused by the discovery of glass particles. The direct and indirect costs of a drug product recall may result in the loss of millions, and may also affect a company’s reputation, market share, and consumer trust. Although recalls caused by glass breakage and particulate peaked in 2011, the issues persist, and patient safety may be affected.

To help solve fundamental incompatibilities that may exist between a drug formulation and its primary container, manufacturers are exploring and adopting alternative materials of construction, such as cyclic olefin polymers, that may help assure stability during a drug product’s shelf life.

To maintain the safety and efficacy of a drug product, pharmaceutical manufacturers should partner with packaging manufacturers to help evaluate material compatibility and select the optimal primary containment and/or delivery system for the drug product. Factors to evaluate include:

• Chemical interaction between the drug and its primary containment system

• Dimensional consistency of the containment system

• Any potential alteration in the physical properties of the drug

• Functional characteristics of the packaging system during the rigors of processing, storage, and distribution

Many biotech and sensitive drug products have unique requirements, and polymer systems provide key solutions for patient safety and compliance. There are a variety of products on the market that can help mitigate risk from particulate. Barrier films for elastomer components may help to reduce potential extractables and leachables formation. For materials that are sensitive to glass or that may require larger dose volumes, cyclic olefin polymers may offer a solution. Cyclic olefin polymers (COPs) provide an alternative to traditional glass that can be molded to a variety of shapes to provide containment throughout the drug product’s lifecycle as well as large-volume dosing needs. Such choices early in development may also aid decisions later in the manufacturing cycle. COPs also offer improved dimensional tolerance and design flexibility, so innovative container/device combinations can be considered to help optimize overall system design based on the needs of the patient. In addition, cyclic olefins can be molded to suit innovative delivery devices, offering differentiation in the market. An insert needle prefillable syringe, such as the Daikyo Crystal Zenith 1mL Insert needle syringe, may be required for a drug product with metal and silicone oil sensitivities.

Collaborating with a single partner with diverse expertise in primary packaging, delivery systems, custom design, and analytical testing early in the drug process can help at a variety of stages. Packaging manufacturers who also provide analytical laboratory services can offer product recommendations to the latest alternative technologies and provide prescreen stability work early in the process to ensure that the containment materials do not react with the drug product. Working together, pharmaceutical and packaging companies can develop containment solutions that may help to reduce issues caused by particulate.

Kevin E. Cancelliere is director, PDS Marketing, West Pharmaceutical Services.