Two crucial USP chapters include USP <1663> “Assessment of Extractables Associated with Pharmaceutical Packaging/Delivery Systems” and USP <1664> “Assessment of Drug Product Leachables Associated with Pharmaceutical Packaging/Delivery Systems”. These chapters are for informational purposes, but discuss practical and technical aspects for assessing extractable/leachable risk and designing appropriate experiments to monitor extractables/leachables. (Additional USP chapters that directly relate to E&L studies include USP <661.1>, <661.2>, and the drafted <665>. You can read more about those chapters here.)
USP <1663> essentially describes the “who, what, when, where, why, and how” of extractables testing including:
- Definitions for the language used when talking about extractables
- Who is responsible for extractables studies
- Functions of extractable studies
- Potential sources of extractables
- Discussion on:
- Choosing extraction media
- Extraction temperatures and times
- Extraction stoichiometry (sample preparation and surface area-to-volume extraction ratios)
- Extraction techniques
- The process of characterizing extracts
- Preparing extracts for analysis
USP <1664> essentially describes the “who, what, when, where, why, and how” of leachables testing including:
- Definitions for the language used when talking about leachables
- Background information on what leachables are and why they matter
- Who is responsible for leachable studies
- Functions of leachable studies
- Safety thresholds
- A lengthy discussion on leachables study design
- Analytical thresholds and their importance in method development
- Possible sample preparations
- Parameters for method validation
- Linking extractable studies to leachable studies
- Considerations for simulation studies
- Inorganic leachables (elemental impurities)
USP <1664.1> is a more recent chapter that addresses specific considerations for leachables in orally inhaled and nasal drug products (OINDP). Though these products contain both drug and device components, they are viewed as drugs from a regulatory perspective. They are considered high-risk dosage forms because of the increased likelihood that the drug product will interact with packaging components (often polymeric). EKG Labs has extensive experience performing extractable and leachable studies on OINDP products. We recently published an inhalation drug device case study, in which a number of concerning chemicals were observed and identified.
The amount of information and description in USP <1663> and <1664> can be overwhelming. Fortunately, EKG Labs is here to help! Understanding these chapters and helping our clients navigate the regulatory expectations specific for their product is our forte. Our team has years of experience guiding companies through the analytical portion of their product development. We have spent years executing extractables and leachables studies on a wide variety of products, from pharmaceutical packaging, to combination drug/device products, to medical devices, to raw materials (you can read a number of case studies on our website).
EKG Labs takes pride in keeping up-to-date with the latest USP revisions and is able to provide appropriate consulting and analytical services for companies seeking to conform to USP standards. To find out more about USP <1663> and <1664> and how they may impact your product development, contact us at 810-354-5229.
About EKG Labs
EKG Labs is an analytical service provider for the pharmaceutical and medical device industries. Our analytical services support product development, regulatory filings, and analytical chemistry investigations. EKG Labs operates out of Innovative Technology Enterprises (ITE) at the University of Missouri, St. Louis (UMSL).