Filter Extractables and Leachables Risk Assessment

Document type	Risk Assessment
Topic area	Drug Product
Level	Advanced
Updated	September 2026

This is a ready-to-use risk assessment for mapping a filter manufacturer’s generic extractables dataset onto the actual product and process, and deciding whether the manufacturer data alone is sufficient justification or a product-specific leachables study is warranted. Replace every <<FILL: ...>> placeholder with your own specifics and route it through your normal document control, review, and approval. A worked filled specimen follows. Verify each cited reference against the current source before you rely on it.

Document control header

Field	Entry
Document title	Extractables and Leachables Risk Assessment for `<<FILL: filter / single-use component>>`
Document number	`<<FILL: e.g. EL-2026-03>>`
Version	`<<FILL>>`
Effective date	`<<FILL>>`
Component / manufacturer / part number	`<<FILL>>`
Document owner	`<<FILL: e.g. Extractables/Leachables Lead>>`

1. Purpose

This assessment maps the filter manufacturer’s extractables dataset onto the real contact time, temperature, and product chemistry this component will actually see in the process, and decides whether that mapping is sufficient justification or whether a product-specific leachables study is required.

2. Scope

Dimension	Decision
Component(s) assessed	`<<FILL>>`
Process step(s)	`<<FILL>>`
Route of administration	`<<FILL: IV, subcutaneous, intrathecal, ophthalmic, other>>`
Manufacturer extractables dataset reference	`<<FILL>>`
Out of scope	`<<FILL: e.g. downstream container closure, covered separately>>`

3. Responsibilities

Role	Responsibility
Extractables/leachables lead	Performs the mapping, drafts the risk assessment and conclusion.
Formulation / process development	Confirms actual contact time, temperature, and formulation chemistry inputs.
Toxicology (if a product-specific study is triggered)	Sets or reviews safety thresholds for any identified leachable.
Quality Assurance	Approves the conclusion and any decision to proceed on manufacturer data alone.

4. Manufacturer extractables data summary

Field	Entry
Extraction conditions used by manufacturer	`<<FILL: model solvents, contact time, temperature>>`
Conservative vs. representative design	`<<FILL: state how manufacturer conditions compare to your actual process in severity>>`
Compounds identified and quantified	`<<FILL: reference the manufacturer's report>>`
Protocol followed	`<<FILL: e.g. BioPhorum extractables protocol, or manufacturer's own method>>`

5. Actual process conditions

Parameter	Manufacturer study condition	Actual process condition	More or less severe?
Contact time	`<<FILL>>`	`<<FILL>>`	`<<FILL>>`
Temperature	`<<FILL>>`	`<<FILL>>`	`<<FILL>>`
Product chemistry (organic solvent, pH, ionic strength)	`<<FILL>>`	`<<FILL>>`	`<<FILL>>`
Surface-area-to-volume ratio	`<<FILL>>`	`<<FILL>>`	`<<FILL>>`

6. Risk factors driving a product-specific study

Factor	Present?	Notes
Long product contact time relative to manufacturer study	`<<FILL: Yes/No>>`	`<<FILL>>`
Elevated process temperature	`<<FILL: Yes/No>>`	`<<FILL>>`
Organic solvent or high concentration of an extraction-driving component	`<<FILL: Yes/No>>`	`<<FILL>>`
Small-scale process with worse surface-area-to-volume ratio than commercial scale	`<<FILL: Yes/No>>`	`<<FILL>>`
Low-tolerance route of administration (intrathecal, ophthalmic)	`<<FILL: Yes/No>>`	`<<FILL>>`

Any “Yes” above is a trigger to weigh seriously toward a product-specific study; more than one trigger present makes manufacturer data alone difficult to defend as sufficient justification.

7. Conclusion and decision

Field	Entry
Manufacturer data sufficient alone?	Yes / No
Basis for decision	`<<FILL>>`
If No: product-specific leachables study scope	`<<FILL>>`
Toxicological evaluation needed for any identified compound?	`<<FILL>>`

8. References

BioPhorum Extractables Protocol (current edition). USP General Chapter <1663>, Assessment of Extractables Associated with Pharmaceutical Packaging/Delivery Systems. USP General Chapter <1664>, Assessment of Drug Product Leachables Associated with Pharmaceutical Packaging/Delivery Systems. PDA Technical Report No. 26, Sterilizing Filtration of Liquids.

Confirm the current version of each reference before issue.

9. Revision history

Version	Date	Author	Summary of change
`<<FILL: 1.0>>`	`<<FILL>>`	`<<FILL>>`	Initial issue.

10. Approvals

Role	Name	Signature	Date
Author (E&L lead)	`<<FILL>>`
Reviewer (Formulation/Process Dev)	`<<FILL>>`
Approver (QA)	`<<FILL>>`

Filled specimen

Extract for an example single-use bioreactor bag and final sterilizing filter train used in a lentiviral vector process. Company, product, and numbers are illustrative.

Parameter	Manufacturer study condition	Actual process condition	More or less severe?
Contact time	24 hours (accelerated, aggressive model)	6 hours actual bioreactor hold	Manufacturer study more severe
Temperature	40 C	37 C	Manufacturer study more severe
Product chemistry	Model solvents (water, ethanol/water, isopropanol)	Aqueous cell culture medium, no organic solvent	Manufacturer study conservative, real matrix simpler
Surface-area-to-volume ratio	Commercial-scale bag geometry	Same commercial-scale geometry	Equivalent

Risk factors: none of the five triggers in section 6 present; actual process conditions are less severe than the manufacturer’s deliberately aggressive study design on every axis assessed, and the surface-area-to-volume ratio matches commercial scale rather than a worse small-scale ratio. Conclusion: manufacturer extractables data sufficient alone; no product-specific leachables study triggered. Decision documented and approved by QA, with the mapping table above retained as the basis should the process, scale, or contact time change.

Common inspection findings this risk assessment prevents

Manufacturer extractables data filed as the leachables conclusion with no mapping to actual process conditions.
A small-scale process assumed to be covered by a commercial-scale extractables dataset with no surface-area-to-volume comparison.
A route-of-administration risk factor (intrathecal, ophthalmic) not weighted any differently than a routine IV infusion filter.
A decision to skip a product-specific study made informally, with no documented basis a reviewer can follow.
The BioPhorum protocol or an equivalent named framework never cited, so the mapping methodology looks ad hoc.

How to adapt this risk assessment

Set your document number and component identifiers in the header.
Populate section 5 from your actual process data, not from the manufacturer’s marketing summary.
Score every factor in section 6 honestly; a single “Yes” is enough to warrant a serious look at a product-specific study.
Route any identified compound needing a toxicological evaluation through your normal safety assessment process before closing the assessment.
Confirm every reference in section 8 against the current published version before issue.