How CDMOs Should Vet a GMP Extractables and Leachables Testing Partner

Introduction:

Choosing the right GMP Extractables and Leachables Testing partner is a critical decision for contract development and manufacturing organizations (CDMOs) responsible for product quality, patient safety, and regulatory compliance. Packaging components, manufacturing equipment, tubing, filters, elastomers, and drug delivery systems can introduce chemical substances into a drug product during manufacturing, storage, or administration. Without an appropriate testing strategy, these substances may create safety concerns, affect stability, or delay regulatory approval.

Selecting an analytical laboratory takes more than checking whether it offers mass spectrometry or chromatography. The laboratory must demonstrate suitable analytical capabilities, a documented quality system, risk-based study design, reliable data management, and the ability to generate scientifically defensible results.

A well-qualified partner can identify contamination risks early, support material selection, strengthen your extractables and leachables assessment, and provide the data needed for regulatory submissions. An unsuitable partner may miss important compounds or deliver reports that need substantial rework.

This guide explains how CDMOs should evaluate a GMP E&L testing partner using practical technical, regulatory, quality, and operational criteria. Regulatory status is current as of October 2026.

Summary:

• GMP compliance matters: A suitable extractables and leachables (E&L) testing partner should understand Good Manufacturing Practice (GMP), data integrity, analytical method validation, and pharmaceutical quality requirements.
• Evaluate analytical capabilities: Look for complementary techniques such as GC-MS/MS, LC-MS/MS, LC-HRMS, ICP-MS, and FTIR to identify and quantify potential contaminants across different chemical classes.
• Review regulatory expertise: The laboratory should understand relevant USP chapters, ICH guidance, FDA expectations, and requirements for packaging, manufacturing equipment, and delivery systems.
• Assess risk-based study design: Testing should reflect the drug product, route of administration, patient exposure, container-closure system, and manufacturing process.
• Verify data integrity: Review audit trails, electronic records, instrument qualification, SOPs, deviation management, and quality oversight before selecting a partner.
• Prioritize toxicological interpretation: Identified compounds must be evaluated against appropriate safety thresholds and patient exposure, not just listed.
• Look beyond price: Scientific depth, documentation quality, communication, and support for regulatory submissions are essential selection criteria.

1. What Should CDMOs Look for in a GMP Extractables and Leachables Testing Partner?

CDMOs should choose a partner that combines relevant instrumentation, qualified personnel, documented quality systems, risk-based study design, and regulatory documentation experience. The laboratory’s capabilities should match the drug product, materials, route of administration, and intended regulatory use.

Assess these areas before starting qualification:

• Experience with pharmaceutical packaging and container-closure systems.
• Knowledge of manufacturing components and single-use systems.
• Methods for volatile, semivolatile, nonvolatile, and elemental substances.
• Validated or appropriately qualified analytical procedures.
• Documented instrument qualification, calibration, and maintenance.
• Traceable sample handling and chain of custody.
• Procedures for deviations, out-of-specification results, and CAPA.
• Scientifically justified reporting thresholds and toxicological assessments.
• Experience preparing reports suitable for quality and regulatory review.

The central question is whether the laboratory can produce reliable, interpretable, traceable evidence that addresses the specific risks of your product and process.

2. How Do You Verify GMP Compliance and Quality Management Systems?

Ask for documented evidence of the quality system rather than accepting a claim of GMP compliance. Not every laboratory performing pharmaceutical analysis operates under GMP conditions, so confirm that the proposed testing will run under the agreed quality framework.

Key quality-system elements to review

Also establish whether the laboratory can provide raw data, chromatograms, mass spectra, integration records, audit trails, and supporting calculations on request.

Data integrity in GMP Extractables and Leachables Testing

Electronic records should be managed according to applicable requirements, including 21 CFR Part 11 where relevant. Records should be attributable, legible, contemporaneous, original, accurate, complete, consistent, enduring, and available.

Important distinction: GMP status, accreditation, and quality certifications are not interchangeable. ISO/IEC 17025 accreditation demonstrates competence within an accredited scope but does not automatically establish that every activity is performed under pharmaceutical GMP. Verify the actual scope and regulatory suitability of the proposed work, including inspection history and how past observations were closed.

3. Which Analytical Instruments and Technical Expertise Should a Qualified E&L Laboratory Have?

A qualified lab needs complementary techniques, because no single instrument detects and characterizes every relevant chemical substance. It should show that its platform covers the expected chemical classes and sample matrices.

The right combination depends on the materials, extraction conditions, target analytes, and intended use of the results. A GC-MS method may suit volatile compounds released from polymeric components, LC-HRMS may suit nonvolatile additives, oligomers, and degradation products, and ICP-MS is needed where elemental contaminants are relevant.

Questions to ask during technical qualification

• Which instruments are in-house, and which tests are outsourced?
• Can the laboratory detect and quantify compounds at justified analytical evaluation thresholds (AET)?
• How does it identify unknown compounds when reference standards are unavailable?
• Are extraction blanks, procedural blanks, and system suitability checks included?
• How are matrix effects, recovery, carryover, and interferences evaluated?
• Can it distinguish tentative from confirmed identifications?
• How does it develop and validate targeted methods for compounds of concern?

A strong laboratory explains why the selected methods are appropriate and how their limitations will be managed, rather than simply listing instruments.

4. Which Regulatory Standards and Guidance Should the Partner Know?

A suitable partner understands the framework applicable to your product and its packaging or manufacturing system, and shows it through justified protocols, traceable decisions, and clear reporting. Ask prospective laboratories how they apply each guidance document to your project.

Applicability depends on the product, component, jurisdiction, and current regulatory status, so verify current editions before finalizing a protocol. A lab that presents draft ICH Q3E as final is misreading its status.

The partner should also treat extractables and leachables as related but distinct. Extractables are substances released from a material under defined laboratory extraction conditions. Leachables are substances that migrate into the drug product under actual or simulated conditions of use. An extractables study establishes a potential chemical profile, and a leachables assessment determines what actually migrates and whether levels raise safety or quality concerns.

5. Why Does Risk-Based Study Design and Material Knowledge Matter?

Because generic extraction conditions applied to every component may fail to represent actual risk. A reliable partner builds the protocol from the product’s intended use, material composition, manufacturing process, and patient exposure.

The design should account for:

• Drug product composition, including solvent systems, pH, and surfactants.
• Route of administration: oral, ophthalmic, inhalation, topical, or parenteral.
• Contact duration, storage conditions, and shelf life.
• Material type, additives, processing aids, and supplier information.
• Manufacturing equipment, filters, tubing, bags, seals, and transfer components.
• Temperature, contact time, surface-area-to-volume ratio, and extraction medium.
• Effects of sterilization, irradiation, or other processing steps.
• Patient population, daily exposure, and toxicological considerations.

Product type changes the design. Freeze-dried products raise their own questions about stoppers, vial interactions, and reconstitution, so look for experience with extractables and leachables in lyophilized drug products. Complex molecules also behave differently, so a partner handling extractables and leachables testing for peptide injectables should show it understands peptide adsorption and low-level interference. Generic programs add timeline and comparability pressure, which is where experience in E&L testing for generic injectable drugs helps.

Example: single-use manufacturing components

A CDMO making an injectable biologic may use polymeric bags, tubing, connectors, filters, and elastomeric components. A suitable partner helps prioritize them by contact conditions, material composition, processing history, and patient exposure, and should be familiar with single-use systems and GMP extractables and leachables (E&L) testing.

A practical workflow:

1. Inventory product-contact components and collect available material documentation.
2. Conduct a risk assessment to identify components needing further evaluation.
3. Define justified extraction conditions and analytical screening methods.
4. Identify and characterize relevant extractable compounds.
5. Decide whether simulated-use or product-specific leachables studies are needed.
6. Evaluate identified substances against exposure and toxicological criteria.
7. Document conclusions, uncertainties, and any risk-mitigation measures.

The laboratory should explain why the extraction conditions are appropriate and how results will determine whether further testing is necessary.

6. How Should You Review Method Validation, Detection Limits, and Unknown Identification?

Confirm that the methods are suitable for their intended purpose, with adequate sensitivity, specificity, accuracy, and precision, and that they can meet the study’s reporting thresholds. Ask the laboratory to explain how it establishes:

• Method detection and quantification capabilities.
• Analytical evaluation thresholds and reporting limits.
• Recovery and precision for representative analytes.
• Blank contamination and background subtraction procedures.
• Calibration strategy and reference-standard suitability.
• Identification criteria for unknown compounds.
• Data-processing rules and integration practices.
• Handling of results below reporting limits or with uncertain identities.

Why unknown identification matters

E&L investigations often find compounds outside any predefined target list, such as polymer additives, antioxidants, processing residues, oligomers, and degradation products formed during storage or manufacturing.

High-resolution mass spectrometry supports identification through accurate mass, isotope patterns, adduct evaluation, and tandem MS fragmentation. Accurate mass alone does not establish an unequivocal identity. A robust process documents the evidence behind each proposed structure, communicates confidence appropriately, and recommends reference-standard comparison or orthogonal techniques where needed.

Be cautious about reports that offer long lists of proposed identities without explaining confidence, analytical limitations, or the basis for quantification.

7. What Toxicological and Patient Safety Expertise Is Required?

The partner should interpret findings in the context of patient exposure and toxicological risk. Detecting a substance does not by itself establish a safety concern, because identity, concentration, exposure, route of administration, and toxicological properties all matter.

A comprehensive assessment may involve:

• Converting analytical concentrations into estimated patient exposure.
• Evaluating maximum daily exposure under relevant use conditions.
• Comparing results with applicable safety thresholds.
• Assessing compound-specific toxicological data.
• Considering route-specific and population-specific risks.
• Identifying data gaps and the need for additional testing.
• Documenting assumptions, uncertainties, and rationale.

A low-level compound with a concerning toxicological profile may need further evaluation, while a detected substance can be acceptable when exposure is well characterized and supported by safety evidence. Clarify whether assessments are performed by qualified specialists within the laboratory or by a qualified external provider, and define responsibilities, deliverables, and review procedures before the study begins.

8. What Should a Strong E&L Report Contain?

It should let your quality, analytical, toxicology, and regulatory teams understand what was tested, how, what was found, and what it means. A list of compound names and concentrations is rarely enough.

• Study objective, scope, and material description.
• Sample identification and chain-of-custody information.
• Extraction conditions and justification.
• Analytical methods and instrument details.
• Method performance and acceptance criteria.
• Blank results, controls, and system suitability findings.
• Compound identification evidence and confidence levels.
• Quantitative results, units, reporting thresholds, and limitations.
• Chromatograms, mass spectra, and supporting data.
• Toxicological evaluation or a clear reference to the associated assessment.
• Deviations, investigations, and their impact on conclusions.
• Conclusions, residual uncertainties, and recommendations for further work.

The report should clearly separate confirmed findings from tentative identifications. For regulatory readiness, confirm the laboratory can answer technical questions, supply supporting data, and retain records for the agreed period.

9. How Should a CDMO Audit the Laboratory?

Audit proportionally to the risk and regulatory use of the work, using a document review, remote assessment, on-site audit, or review of previous relevant studies.

Ask for relevant completed projects, redacted reports, and examples of how unexpected findings were investigated. Judge references by relevance to your work, not as proof of universal competence.

Red flags

• The lab will not allow an on-site or remote audit.
• Unidentified peaks are dismissed instead of investigated.
• Sample reports lack raw-data references or blank controls.
• Subcontracting is not disclosed.
• Timelines are promised before materials and product are reviewed.
• Draft ICH Q3E is presented as final, or ignored entirely.

10. How Do Cost, Timelines, and Scientific Value Compare?

Compare proposals on scope, technical suitability, documentation, and total project risk, not price alone. A cheaper proposal may omit key techniques, unknown identification, confirmatory testing, or toxicological interpretation.

Request a quotation that specifies:

• Number and type of components or samples.
• Extraction conditions and replicate strategy.
• Analytical platforms and screening scope.
• Targeted versus non-targeted analysis.
• Identification and quantification deliverables.
• Method development or validation requirements.
• Toxicological assessment responsibilities.
• Reporting format and raw-data availability.
• Milestones, review cycles, and change-order terms.

Include the cost of repeat testing, delayed development, extra regulatory questions, and inadequate documentation. The best partner delivers the required evidence and quality documentation within a realistic, agreed timeline.

11. Practical Scorecard for Selecting a GMP E&L Laboratory

A weighted scorecard lets you compare laboratories consistently and document the rationale for selection. Adjust the weightings to your project’s risk, complexity, and regulatory requirements.

Score each criterion from 1 (inadequate evidence) to 5 (strong, documented evidence), then multiply by the weighting. The score supports, but does not replace, technical judgment. A laboratory with an attractive total should still be rejected if it fails a critical requirement such as data integrity, analytical suitability, or a mandatory quality-system expectation.

Conclusion:

Selecting the right partner for GMP Extractables and Leachables Testing requires a comprehensive assessment of analytical capabilities, quality systems, regulatory expertise, risk-based study design, toxicological interpretation, and documentation standards. CDMOs should verify these through documented evidence, technical discussions, supplier qualification, and risk-appropriate audits.

A strong E&L partner does more than detect chemical substances. It helps explain their origin, establish how reliably they were identified, evaluate their significance, and provide traceable scientific evidence for development and quality decisions.

For CDMOs working with injectables, biologics, complex formulations, polymeric components, or single-use manufacturing systems, early engagement with an experienced analytical partner can surface material-related risks before they affect timelines or submissions.

ResolveMass Laboratories Inc. supports pharmaceutical analytical characterization through mass spectrometry and complementary analytical approaches. When evaluating an E&L project, discuss the required analytical scope, material types, identification objectives, and documentation needs to determine the right testing strategy. Confirm the specific GMP scope and availability of E&L services directly with the laboratory.

Frequently Asked Questions:

Reference

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About the Author

Priyal Darji