Frequently Asked Questions
1. What are the expectations from regulatory agencies regarding extractables and leachables?
Whether we are discussing pharmaceutical products, ENDS or e-liquids, the topic of extractables and leachables is considered an important regulatory topic.
During the manufacture and subsequent shelf life of a pharmaceutical, ENDS or e-liquid product, it may come into contact with materials associated with processing equipment, packaging and/or delivery device components. During these product contact periods, there is a potential for ingredients or impurities from these materials to leach into the product, and so
a. be delivered to patients/consumers
b. affect the efficient operation of the delivery device
As such, global regulatory agencies have a very real expectation that the development process for the product will include a full assessment of the potential for leachables to be present in the final product, and that a summary of this assessment will form part of the final regulatory submission. Consequently, the extractables and leachables strategy, including the regulatory approach, is an increasingly important part of the overall development process for pharmaceutical, ENDS or e-liquid products.
To further highlight the increasing importance that regulatory agencies place on the subject, there are now a number of regulatory and industry guidance documents specifically dedicated to or which refer to extractables and leachables, including
FDA Guidance for industry (May 1999) - Container Closure Systems for Packaging Human Drugs and Biologics
EMEA Guideline (EMEA/CVMP/205/04) - Guideline on Plastic Immediate Packaging Materials
FDA Guidance for industry (April 2018) - Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) Products - Quality Considerations
FDA Guidance for industry (June 2019) - Premarket Tobacco Product Applications for Electronic Nicotine Delivery Systems USP <661.1> - Plastic Materials of Construction
USP <661.2> - Plastic Packaging Systems for Pharmaceutical Use
USP <1663> - Assessment of Extractables Associated with Pharmaceutical Packaging/Delivery Systems
USP <1664> - Assessment of Drug Product Leachables Associated with Pharmaceutical Packaging Delivery Systems
USP <381> - Elastomeric Closures for Injections
PQRI - Safety Thresholds and Best Practices for Extractables and Leachables in Orally Inhaled and Nasal Drug Products
ICH Q6A - Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products
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