Learn what extractables and leachables are, how they differ, and how they are tested in the pharmaceutical industry.
Extractables and Leachables (E&L) are critical in ensuring the safety, efficacy, and quality of pharmaceuticals by identifying potential contaminants. Extractables are chemical compounds that can be released from packaging or process materials under aggressive conditions, while leachables are those that actually migrate into the drug product under normal storage or use conditions, potentially impacting its safety and quality.
These impurities can arise from packaging materials, manufacturing equipment, and drug delivery systems, posing potential risks to patient health. In this blog, I will discuss what extractables and leachables are, how they differ, and how they are tested in the pharmaceutical industry.
Extractables are chemical compounds that can be drawn out (extracted) from packaging or device components when exposed to aggressive solvents under exaggerated conditions such as high temperature or extended time.
Purpose of Testing: Extractables studies are typically conducted early in development to identify all potential compounds that could migrate into the drug product.
Leachables are chemical compounds that actually migrate into the pharmaceutical product under normal storage, handling, and use conditions over time.
Purpose of Testing: Leachables are evaluated in the final drug product to assess real-world patient exposure and toxicological risk.
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| Feature | Extractables | Leachables |
|---|---|---|
| Definition | Compounds that can be extracted under forced conditions | Compounds that do migrate into the product under normal use |
| When Tested | Early development | Late-stage development and stability studies |
| Conditions | Aggressive (e.g., high temp, solvents) | Realistic (e.g., product formulation, storage) |
| Purpose | Risk identification | Risk confirmation and control |
| Sample Matrix | Packaging/device materials | Final drug product |
E&L studies are critical for:
Conducted using aggressive extraction techniques:
Conducted under real-time or accelerated stability conditions using the actual drug product:
Key guidelines and standards include:
Extractables and leachables testing is not just a regulatory checkbox—it’s a patient safety imperative. By identifying and controlling E&L impurities, pharmaceutical manufacturers can ensure that packaging, devices, and storage systems do not compromise product safety, stability, or efficacy.
As drug delivery systems become more complex (e.g., inhalers, prefilled syringes, biologics), robust E&L testing strategies are more important than ever.
Related:
Extractable substances are compounds that can be pulled out of a material under aggressive, often non-physiological conditions (e.g., using strong solvents, heat).
Leachable substances are compounds that actually migrate from a material under normal use conditions (e.g., during storage or contact with a drug product).
Extractables in drug substances are chemical compounds that can be released from packaging, manufacturing components, or delivery systems when exposed to aggressive conditions.
Leachables are compounds that actually migrate into the drug product under normal storage or use conditions.
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