Genotoxicity & Impurities
Extractables and leachables (E&L) toxicological assessment
Packaging, delivery devices and single-use manufacturing components can release chemicals into a product. We help design extractables and leachables (E&L) studies, set the thresholds that decide what needs to be identified, and carry out the toxicological assessment that shows whether patients are protected.
- Guideline basis USP ‹1663›/‹1664›, PQRI thresholds, ISO 10993-17/-18; ICH Q3E (draft)
- Typical inputs Materials of construction, product details, E&L study data
- You receive Toxicological safety assessment report
Overview
About Extractables & Leachables
Extractables are compounds that can be released from a material under exaggerated conditions; leachables are those that actually migrate into the product under normal conditions of use. Laboratory studies identify and quantify them. A toxicological assessment then decides whether each compound, at its worst-case daily exposure, is acceptable.
The analytical evaluation threshold (AET) links the two: it defines the concentration above which compounds must be identified and assessed, based on a safety concern threshold and the product’s dosing. We set these thresholds, review study designs and assess the results.
Use cases
When this service helps
New container-closure system
Demonstrate the safety of a new bottle, blister, vial or stopper.
Inhalation, injectable and ophthalmic products
Higher-risk dosage forms where E&L scrutiny is greatest.
Single-use manufacturing systems
Assess process-equipment leachables in biologics and sterile manufacture.
Medical devices and combination products
Chemical characterisation and toxicological risk assessment of device constituents.
Scope
What the service covers
- Risk-based assessment of packaging and component materials
- Safety concern threshold (SCT) and analytical evaluation threshold (AET) calculation
- Input to extractables and simulation study design
- Review of analytical reports for completeness and identification confidence
- Toxicological assessment of each extractable or leachable above the AET
- Extractables–leachables correlation and worst-case exposure estimation
- Device constituent assessment under ISO 10993-17 where applicable
Who does what
Extraction studies and chemical analysis are performed by a specialist E&L laboratory of your choice. Globaxa sets the thresholds, reviews the study and prepares the toxicological assessment.
What is an AET?
The analytical evaluation threshold is the concentration in an extract or product above which a compound should be identified and reported for toxicological assessment. It is derived from a safety concern threshold (a daily exposure considered negligible) and converted to a concentration using the product’s dose and the number of doses per container.
Methodology
How we work
A defined sequence, agreed with you at the start, so you always know what happens next and what we need from you.
- Assess the materialsMaterials, contact conditions and dosage form determine the level of risk.
- Set thresholdsSCT and AET are calculated for the product’s dosing and route.
- Review the studyWe review study design and analytical results for adequacy.
- Assess each compoundExposure is compared with a compound-specific or threshold-based limit.
- ReportA toxicological assessment ready for the dossier or design history file.
Deliverables
What you receive
Threshold and strategy memo
SCT, AET and recommended study approach.
Study review comments
Gaps in study design or identification that need addressing.
Toxicological safety assessment
Compound-by-compound assessment with an overall conclusion.
Technical basis
Guidelines we work to
- USP ‹1663› and ‹1664›Assessment of extractables and of leachables associated with pharmaceutical packaging and delivery systems.
- PQRI recommendationsSafety and qualification thresholds for orally inhaled and nasal products and for parenteral and ophthalmic products.
- ISO 10993-18 and ISO 10993-17:2023Chemical characterisation of device materials and toxicological risk assessment of device constituents.
- ICH Q3E (draft)A harmonised ICH guideline on extractables and leachables reached Step 2 in 2025 and is not yet final; we track its progress (information current as of October 2026).
What we need from you
- Materials of construction and supplier information for each component
- Product composition, dosage form, route, dose and duration
- Storage and contact conditions
- Extractables and leachables study reports, if available
Please share confidential information only after an NDA is in place — we are happy to sign one first.
Market and jurisdiction considerations
E&L expectations are highest for inhalation, parenteral and ophthalmic products in the US and EU. Other authorities increasingly ask for E&L justification of packaging, especially for new container-closure systems. ICH Q3E, once final, is expected to harmonise expectations further.
FAQs
Extractables & Leachables: frequently asked questions
Do you perform the E&L testing?
No. Testing is done by an accredited E&L laboratory you appoint. We help define what the laboratory should do and assess what it finds.
Is E&L required for oral solid products?
Expectations are lower for oral solids in standard packaging, but a documented risk-based justification is still advisable, particularly for new materials.
Can you assess leachables that are potentially mutagenic?
Yes. Leachables with structural alerts are assessed using ICH M7 principles, including (Q)SAR where appropriate.
Talk to us about Extractables & Leachables
Share your product, target market and timeline. We will review your requirement and propose a defined scope.
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+91 99894 74590 - Emailbd@globaxa.in
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