An Introduction to Leachables and USP <1664>
Leachables are chemical entities that migrate from one material matrix into another. In pharmaceutical development, leachables typically refers to chemicals from packaging or delivery systems which migrate into a drug product under normal storage conditions, potentially impacting the safety or efficacy of the drug.
The primary United States Pharmacopoeia (USP) chapter directing leachable testing is USP <1664> “Assessment of Drug Product Leachables Associated with Pharmaceutical Packaging/Delivery Systems”. This chapter discusses practical and technical aspects for assessing leachable risk and designing appropriate experiments to monitor leachables.
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)
Specific Testing for Inhalers and Nasal Sprays
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 previously published an inhalation drug device case study, in which a number of concerning chemicals were observed and identified.
Often an extractables (the chemical that can be forced out of a device or packaging) investigation is done in conjunction with, or prior to, a leachables study in order to get a full profiles of the potential hazards of a packaging or delivery system. USP <1663> “Assessment of Extractables Associate with Pharmaceutical Packaging/Delivery Systems” deals with the concept of pharmaceutical extractable testing. Further discussion on <1663> can be found here. Adjacent chapters related to specifically assessing plastics used with pharmaceuticals include USP <661>, <661.1>, <661.2>, and <665>. You can read more about those chapters here.
Leachable Testing at EKG Labs
The amount of information and description in USP <1664> can be overwhelming. Fortunately, EKG Labs is here to help! Understanding this chapter and helping our clients navigate regulatory expectations specific for their product is our forte.
EKG Labs provides leachable testing services for pharmaceutical packaging or delivery systems. We have experience developing and validating a risk-based, product-specific method in order to monitor one or more targeted compounds in even the most challenging matrices. Next month, we’ll be featuring these case studies as the part two to this eblast, but you can get a sneak-peek at some case studies on our website.
EKG Labs is an analytical service provider for the pharmaceutical and medical device industries. Our wide variety of analytical services support product development, regulatory filings, and analytical chemistry investigations. EKG Labs is now a part of the Infinity Laboratories group, a powerful network of state-of-the-art testing facilities that are FDA registered, ISO 17025 accredited, and DEA licensed. With an enhanced focus in the areas of chemical and microbiological sciences, we support pharmaceutical and medical device manufacturers. Our goal is to go Beyond Testing and become a partner in the success of our customers.
To find out more about USP <1664> and how it may impact your product development, please contact us at firstname.lastname@example.org or at 810-354-5229.