EXTRACTABLES AND LEACHABLES
The Risks of Single-Use Bioprocess Containers
Charles Ducker, PhD, Michelle Kolodziejski, MS,
Mai Jacques, PhD, Jennifer Roark, Andrew Blakinger, and Thomas Lehman, PhD
Eurofins Lancaster Laboratories Submitted: 08/25/2014 Accepted for Publication: 09/23/2014 Extractables and Leachables
The screening of the final packaging components of human drug products for extractables and leachables has become commonplace in the 15 years since the FDA released their Container Closure Systems for Packaging Human Drugs and Biologics. With the increase in prevalence of single-use systems for biomanufacturing, these components require the same scrutiny. The regulation applicable to bio-processing/manufacturing components (CFR Part 211.65) states: “Equipment shall be constructed so that surfaces that contact components, in-process materials, or drug products shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements.”1,2
Drug applications to the FDA are expected to provide a safety evaluation, based
on the extractables and leachables profile, of the highest risk components that are in closest contact with the drug. For biologics these components not only include the final container/ closure system but also components associated with the biomanufacturing process.
In an article in BioProcess International, Bestwick and Colton defined extractables and leachables as:
• •
Extractables: Chemical compounds that migrate from any product contact material when exposed to an appropriate solvent under exaggerated conditions of time and temperature.3
Leachables: Chemical compounds, typically a subset of extractables, that migrate into the drug formulation from any product contact material—including elastomeric, plastic, glass, stainless steel or coating components—as a result of direct contact with the drug formulation under normal process conditions or accelerated storage conditions and are found in the final drug product.3
Dr. Charles Ducker is a Principal Chemist for Eurofins
Lancaster Laboratories’ Method Development and Validation group where he performs
extractables and leachables testing using LC/MS- TOF, LC/MS/MS, GC/MS, and ICP-OES technology. Specializing in LC/MS analysis, Dr. Ducker has
13 years of experience in the biotech industry and has served as the lead scientist for two significant drug discovery and development programs
during his career. Dr. Ducker has 10 peer reviewed publications and earned a PhD in Biochemistry/ Molecular Biology from The Pennsylvania
State University, as well as a BS in Biology from Millersville University.
As will be discussed in this article, the containers used in biomanufacturing can themselves be a source of contamination as a result of leachable compounds. These leachables may result from anti-oxidants, stabilizers, or plasticizers used in the manufacture of the single use system. In addition, since the materials are polymeric in nature, residual monomers, oligomers or polymeric fragments may also be observed as leachables.4
To demonstrate that a bioprocessing/manufacturing component will not adversely affect the manufacturing process, an initial extractables screening study is typically performed.
The
extraction experiment is designed to exaggerate the conditions of real-time use. Due to the shorter contact time with the drug product overly aggressive conditions are not always appropriate for extracting the components of bioprocess systems, such as bioprocess bags, filters, and tubing.5,6
Use of aggressive extraction techniques may result in the breakdown of the polymer or component (eg, blistering the film of a bioprocess bag).
Single-Use Systems Most single-use products are constructed of polymeric materials that can introduce leachables into the manufacturing process.
These leachables can affect the safety and efficacy of the 1 American Pharmaceutical Review | Biopharmaceutical Supplement 2014
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