Extractables and Leachables for Bioprocessing Single-Use Disposables

Risk-based extractables and leachables (E&L) studies of plastic single-use disposable systems (SUS) used in bioprocessing that can help you to assess and control risks due to leachables from SUS components

Risk-based extractables and leachables (E&L) studies of bioprocessing using plastic single-use disposable systems (SUS) help to ensure safe, effective, and high-quality final biopharmaceutical drug product or vaccines. The application of single-use technologies in the bioprocessing industry are increasing. These processing materials include disposable media bags, tubing, connectors, sampling systems, elastomer parts (e.g., gaskets, O-rings), buffer containers, mixing systems, bioreactors, membrane adsorbers and perfusion and tangential flow filtration cassettes. These single use technologies are constantly being redesigned and improved enabling more useable, more effective (fewer contamination risks, lower cleaning, and validation costs), and more compliant products with improved extractables/ leachables profiles. With increasing innovation and application of single-use systems, it is important to demonstrate continued regulatory compliance and compatibility with the production process/product to ensure safe, effective, and high-quality final biologic drug products or vaccines manufactured by these processes and extractables testing is a key element of SUS equipment design.

Extractables Studies for Single-use Systems
These studies can be challenging, however, our extractables and leachables scientists based at our GMP laboratory in Reinach, Switzerland, use stepwise risk-based approach that meets regulatory expectations and enables robust data generation. Typically, we design an E&L study and method set-up to include a comprehensive analysis of the extractables and leachables including both volatile and non-volatile compounds. The extractables study would involve multiple techniques (e.g. (HS)-GC-MS, GC-MS, LC-MS or ICP-MS) where the Analytical Evaluation Threshold analysis (AET) values/design would follow recommendations from industry Guideline documents such as those from the BioPhorum Best Practices Guide for Extractables Testing of Polymeric Single-Use Components Used in Biopharmaceutical Manufacturing (BPOG protocol, May 2020), USP<665> standard or <1665> guidance (Sept, 2020) but also with reference to PQRI for PODPs (2013), CDER from FDA (2008), EMA, or biocompatibility according to ISO 1099366 as appropriate to the application and region of interest. The BPOG protocol/ BioPhorum best practice for SUS extractables testing data and leachables evaluation are widely used by end-users to assess and control potential risks presented by the SUS components.

Extractions with both organic and aqueous solvent and formulation/placebo are required to establish the “picture” under the worst-case conditions. Analytical screening methods should be comprehensive and cover volatiles, semi-volatiles & non-volatiles. Through our stepwise approach to extractable/leachable studies, the data we generate supports the assessment of potential leachables present in the final product and help you to determine whether leachables are present at levels that cause safety concerns.
Our experts have over 25 years’ experience in specialised analytical and toxicology assessment for extractables and leachables across many product types such as pre-filled syringes, large volume parenteral products, transdermal delivery, orally inhaled and nasal drug products (OINDP), single use and disposable medical equipment, printed packaging, and bioprocessing equipment.

Our knowledge of polymer, plastic, and packaging materials, allows us to identify components from the most complex polymer formulation including adhesives, additives and stabilizer ingredients and their degradation products. Our consultants provide a first-class evaluation and assessment of existing E/L data gaps, and through strategic screening or quantitative studies, we offer the right study for your product. Comprehensive evaluation and safety assessment review of laboratory E/L study data is performed by our in-house toxicologist consultants.

Total Quality Assurance
Through our Total Quality Assurance expertise, the robust data we generate, can help identify extractable species and reduce risks associated with selection of single-use bag-tubing-combinations for your production line. With increasing innovation and application of single-use systems it is important, more than ever, to ensure continued regulatory compliance and compatibility of the production process/product to enable approvals of single-use manufactured commercial products that are safe, effective and of high quality.
Need help or have a question? +41 61 686 4800

Need help or have a question?

+41 61 686 4800
+41 61 686 4800