Extractable and leachable substances in disposable components

Use of disposable systems in the processing of pharmaceutical products continues to grow along with their track record for saving time and money during production. Disposable systems employ single-use vessels, bags, tubing and connectors in place of traditional stainless steel or glass components in the manufacturing system. One of the ways that disposables save time is by minimizing the need for cleaning and associated validation. However, manufacturers still need to demonstrate that the disposables, which are typically made of plastic, do not cause adulteration of their product by leaching unwanted substances out of the components.
Chemist Michelle Kolodziejski analyzes client’s disposable
bags for extractables and leachables for potential contamination
of the pharmaceutical product.
By applying their expertise in extractable and leachable testing to disposables, analysts at Lancaster Laboratories are helping clients verify that there are no adverse effects from the use of these components in their production process. Extractable compounds are those that can be extracted from a component under exaggerated conditions and have the potential to contaminate the drug product. Leachable compounds are a subset of extractables that leach into the drug product from the component as a direct result of contact with the formulation under normal conditions.

In order to test a disposable for extractable and leachable compounds, a protocol must be developed that considers both the construction materials of the disposable and the manufacturing process where it will be employed. “It’s critical that there’s a collaborative approach to developing the protocol with information from the disposable vendor, laboratory and the manufacturing area,” says Dr. Jon S. Kauffman, director of Method Development and Validation and Biopharmaceutical Services. He adds that a toxicologist may also be needed to help with risk assessment and establish safe exposure levels because the use of disposables is still an emerging technology in pharmaceutical manufacturing.

Extraction of potential contaminants under normal and exaggerated conditions, such as high temperature, must be simulated to develop test solutions. The test solutions are then analyzed for a wide range of contaminants using techniques that provide qualitative data for use in identifying the source of any positive results. Typical analytical techniques used to screen the resulting extracts and leachates include liquid chromatography/mass spectrometry (LC/MS) to detect non-volatile compounds, gas chromatography/mass spectrometry (GC/MS) to detect volatile and semi-volatile compounds and inductively coupled plasma (ICP) or ICP/MS to detect metal compounds.

Lancaster Labs has extensive experience using mass spectrometry as a tool to identify unknown compounds. In addition to information from commercially available libraries of spectra, analysts at Lancaster Labs are building their own library of spectra specifically containing compounds extracted or leached during studies of various disposable components. By purchasing standards, generating the mass spectra and maintaining a historical file of the information, analysts are gaining expertise with the specific contaminants that may be present when various disposable materials are used.

Lancaster Labs offers a variety of services to support the use of disposables, including extractable and leachable analysis, protocol writing, and stability storage. For more information, please contact Pharmaceutical Business Development at (717) 656-2300.