Extractables and Leachables Study Approach for Disposable Materials Used in Bioprocessing - Two case studies illustrate a systematic approach. - BioPharm International


Extractables and Leachables Study Approach for Disposable Materials Used in Bioprocessing
Two case studies illustrate a systematic approach.

BioPharm International
Volume 21, Issue 2


All materials chosen for use in a disposable (single-use) bioprocess must pass the specifications in USP 27, monograph c88: Biological Reactivity Tests, In Vivo: Classification of Plastics, Class VI. If the disposable materials require a very long holding time, those materials may need to meet the requirements set forth in ISO 10993–1:2003, Biological Evaluation of Medical Devices Part 1: Evaluation and Testing or in the FDA Blue Book memorandum, Required Biocompatibility Training and Toxicology Profiles for Evaluation of Medical Devices. In addition, materials used in a disposable bioprocess should be fully evaluated in terms of extractables profiles and potential leachables. Routine QC extractables methods should be developed and validated to qualify incoming material components of the disposable bioprocess.

Extractables and leachables studies are only one of many aspects of qualifying materials. Other aspects such as impurity, potency, and mechanical properties, etc., should also be evaluated to ensure that materials used in a disposable bioprocess are compatible with drug product formulations and manufacturing process parameters.

Product quality control can be achieved through well-designed process development, evaluation, and characterization, which begin with the selection of materials used in a manufacturing process. In this article, a roadmap has been presented for a comprehensive extractables and leachables evaluation to establish the suitability of materials used in a disposable bioprocess. Different analytical technologies used to support extractables and leachables studies have their own capabilities and limitations. Depending on the materials used in the disposable bioprocess, specific requirements are needed for the E/L study designs to support the manufacturing process qualification and validation from an E/L perspective. Furthermore, disposable containers designed for low-temperature storage, holding, and processing such as plastic bags made from ultra-low temperature film used in the freeze-and-thaw cycling process-can be evaluated, characterized, and quantified, as demonstrated in the case studies.

New global regulations such as ICH Q8, Q9, and Q10 are steering the pharmaceutical and biopharmaceutical industries to move toward the new paradigm of QbD. The study design approach presented here is based on the importance of a scientific understanding of compounds that could be extracted or leached from disposable materials that make contact with a drug product during manufacturing and product use; the approach is, thus, a means of incorporating quality by design into a disposable biopharmaceutical manufacturing process.


The authors wish to acknowledge the support of their employer, PPD, Inc., and to acknowledge, in particular, Magdalena Mejillano, Tom Rosanske, Donald F. DeCou, Bert Kittner, Louise Caudle, and Joel Galang for their productive input.

Xiaochun Yu is a senior research scientist, Derek Wood is a laboratory manager, and Xiaoya Ding is the director of scientific and technical affairs, all at the cGMP laboratory, PPD, Inc., Wilmington, NC, 910.558.7585,


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