Extractable & Leachable Studies

Regulatory requirements are dynamic and important to drug product packaging. Primera’s goal is to always remain current with regulations and work diligently to provide services that are important to our clients and help facilitate their submissions.

Extractables and leachable studies are required by many governmental agencies such as FDA & EMA and assist in our understanding of compatibility between drug packaging or manufacturing components and the drug product. Migration of leachable substances from packaging (container closure systems) or manufacturing components into the drug products can create a patient health hazard and present drug quality issues. Toxicological as well as drug product degradation can be a result of the leachable impact to the drug product.

Extractable studies involve the extraction of container closure systems and manufacturing components (where appropriate) with solvents under exaggerated (stress) and controlled conditions. The extractable study provides a profile of the possible leachables that can be found in the leachable study.

Leachable studies involve the analysis of drug products which have already been exposed to packaging materials, manufacturing components, and delivery devices. Finished products from stability programs, under accelerated and long term conditions, are the most commonly used samples for leachable analysis.

Primera’s E&L studies typically consist of:

Pharmaceutical packaging materials/container closure systems (i.e. vials, stoppers, I.V. bags)
Manufacturing components (i.e. filters, tubing, manifolds, gaskets, sealing rings)
Delivery devices (i.e. syringes, nozzles).

Primera has vast experience with many closure systems, drug delivery systems and manufacturing components. Through the years, we have built a comprehensive database of various components that make us efficient in the identification of both extractables and leachables. If compounds are not identified in our database, Primera will utilize highly experienced scientists to identify compounds with our state-of-the-art LC-MS/MS’s or our HRMS (Orbitraps), GC-FID or MS and ICP-MS.

Primera’s Process of Extractable and Leachable Studies

Primera works closely with our clients to design an Extractable and Leachable Study (E&L) that provides crucial information about their product. With many years of experience in designing and performing these studies, we can provide guidance for the recommended stress conditions and testing.

Protocols will be prepared that utilizes Product Quality Research Institute (PQRI), GMP, and USP guidance to assess the potential extractables and leachables. Although these studies can be done concurrently, Primera strongly recommends that they are done separately.

Our process includes:

Protocols that are reviewed and signed by both Primera and the Sponsor
Development of an AET(Analytical Evaluation Threshold) which is documented in the protocol per maximum daily dose of each specific drug product.
A variety of analytical techniques (HS-GC-FID, GC-MS, LC, LC-MS and ICP-MS) that is used for E&L testing of volatile, semivolatile, organic and elemental substances.

Simulation studies that reflect the expected product conditions (controlled conditions) can be customized to fit a client’s specific E&L needs.

When potential leachable substances are identified, Primera will work with our clients and their partners for in vitro toxicological risk assessment to facilitate regulatory filing of extractable leachable study results.

We can provide GMP method development and validation for the leachables of concern for monitoring in stability and product release programs.

Extractable & Leachable Studies

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