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Extractables & Leachables
(E&L)

A one-stop solution providing an end-to-end service for all your extractables and leachables requirements

The in-depth examination of extractable and leachable substances across all the stages of a drug product or medical device development cycle is fundamental to both the protection of a patient’s well-being and meeting regulatory requirements. We offer tailored E&L studies that combine technical and analytical expertise with integrated toxicological consultancy and regulatory compliance.

What are Extractables and Leachables Studies?

Organic compounds and elemental impurities that leach into a drug product from the manufacturing process, the container closure system (CCS) or packaging materials, and even the delivery mechanism needed for the administration of a drug could be harmful to the patient, cause health issues over time, or adversely impact the efficacy of the active ingredient. 

A wide range of analytical techniques is employed in E&L studies to ensure the detection of all potential leachables. These are then screened to understand their potential toxicological impact on the user. E&L studies move through clearly defined stages, from extracting potential leachable chemical compounds to screening and toxicological risk assessment. Any changes to a product, including in its manufacture or supply chain, may require new E&L studies.


Our scientific experts and toxicologists have years of combined experience conducting E&L studies across a range of pharmaceutical drug product and device categories. 

  • Material characterization screens for raw materials 
  • Orally inhaled and nasal drug products (OINDP) 
  • Parenteral and ophthalmic drug products (PODPs) 
  • Medical devices 
  • Combination products 
  • Pre-filled syringes 
  • Single-use systems and processing equipment 
  • Manufacturing and filling components and containers

Speak to an E&L scientific expert to learn more about we help ensure your products meet regulatory requirements and protect public health.

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Our Extractable and Leachable Testing Services 

Before undertaking an E&L analysis, we complete a comprehensive risk assessment of your materials or device. This will include various factors depending on how the product is intended to be used, such as information on the dosage form, frequency and duration of use, administration route, toxicity classification, manufacturing processes, and the container system material selection. The risk assessment ensures that the correct testing study plans are devised to address the relevant areas of concern for the project. It also ensures transparency in the subsequent testing rationale and analytical methodology chosen for the study.

We always recommend that a consideration of the impact of extractables and leachables on the product, and the users of that product, are committed to at as early a stage as possible in the product life cycle. Late changes to a CCS material can have implications on your project timelines, increasing development costs and causing delays to market introduction and loss of sales. Taking a pragmatic risk-based approach to product design and material selection will help get your product to market sooner.

By leveraging our in-house capabilities across analytical testing, scientific consultancy, and program management, we deliver a fully integrated services approach that allows us to efficiently complete the studies needed to satisfy regulatory requirements and assure patient safety.

Risk assessment and study design

Our scientific affairs and toxicology consultancy teams will undertake Failure Mode and Effect Analysis (FMEA) Risk Assessment of the product, including the formulation, container closure systems (CCS), and packaging materials.

 

The risk assessment will advise the study design; our chemistry consultants will develop a study plan that meets the requirements of your product, allowing a pragmatic but comprehensive assessment of the product for extractable species.

 

Our study designs are tailored to your bespoke needs and specific product lifecycle stage. From material screening and selection to R&D, de-risking your downstream choices, or working towards product regulatory submissions, our integrated services will help move your project forward, troubleshoot problems, and remove roadblocks.

Extractables studies

Our specialized analytical laboratory services team will perform controlled extraction studies (CES) to meet the requirements of the study designs. Utilizing Headspace GC-MS, GC-MS, LC-MS, and ICP-MS, we are able to identify and quantify extractables species associated with the container closure system (CCS). packaging materials, and delivery systems of your product.

 

CES are performed according to USP <1663> principles, the Product Quality Research Institute (PQRI) guidelines, and the ISO10993-18 guidance for Medical Device Chemical Characterization and Extractables and Leachables for Biocompatibility of Materials.

 

With open communications with our scientific development team, you will have access to specialized consultants capable of troubleshooting, problem-solving, and developing analytical solutions

Extractables toxicological assessment

The potential risk to patients, through exposure of the identified species by the administrative route of the product, is assessed by our toxicological consultants. Using in-silico methods, augmented with toxicological in-vivo and/or in-vitro studies, toxicological assessments will identify the extractable species of greatest concern for monitoring as leachables through shelf-life testing of the product.

 

Our toxicology team can help identify potential gaps in existing data packages and advise on the remedial action needed to fix any shortcomings. This can be through retrospective risk assessment or advising on further CES in order to close potential gaps in the extractables assessments that may be viewed as deficiencies by regulatory authorities.

Leachables method development and validation

Our scientific development team has a wealth of experience in the analysis of trace organics from complex matrices. Their knowledge and insight are ideally suited to meet the demands of developing methods for the determination of identified leachables. They are adept at providing methodology that is fit for purpose, accurate, precise, and robust. Methods will be stability indicating to ensure no unforeseen issues during stability studies.

 

Methods are validated according to the intended use, with ICH Q2 guidelines providing the basis of our validation procedure. The stability data generated is reported with high confidence that it can be used for accurate stability trending and prediction.

Leachables shelf-life studies

With 60,000 liters of multi-zone ICH stability storage, our laboratory operations team is able to manage stability studies as part of an E&L project. 

 

Near real-time reporting through our LabHQ Laboratory Information Management System and client portal enables you to track samples, obtain live status updates, and view results and reports as if we are an extension of your in-house laboratory team.

 

Project management support from our dedicated program management office will ensure timelines are adhered to and communication is proactive and seamless to ensure a completely integrated approach.

 

Through tracking the identified species and screening for unknowns, our chemistry team can advise on the likely sources and outcomes of any unexpected peaks noted during the stability assessment.

 

Learn more about our stability storage and analysis services.

Leachables toxicological evaluation

Our toxicology consultants are able to provide a comprehensive toxicological assessment report for your product. They utilize data generated during the leachables stability study along with data from the original extractables assessment. The report will give a full understanding of the toxicological profile of your product, any risk to the patient and/or users, and satisfy your regulatory submission requirements.

 

They can also advise on any potential gaps in your regulatory submission and propose remeditative studies to close data gaps.

Our E&L Services for Early-Stage Product Development

 
Extractable studies early in a development project can help inform the appropriate material selection for the container closure system, and medical device components, to mitigate possible toxicological red flags later. Our E&L and toxicology experts specialize in material selection consultancy to help you make the right decisions as early as possible. These early-stage development studies include. 

  • Desk-based research 
  • Literature review of existing data
  • Extractables studies
  • Material selection consultancy

We also offer extractable studies as part of our Product Realization Service.  

Read more about our Toxicology Consultancy Services. 

 

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Aligned with Accepted Industry Principles 

E&L studies are designed with consideration to the accepted industry principles such as those laid out in the following guidelines.

  • Product Quality Research Institute (PQRI) 
  • BioPhorum Operations Group (BPOG)
  • United States Pharmacopeia (USP) requirements  (e.g., extractable and leachable USP chapters <665>, <1665>, <1663>, <1664>, and <1664.1>) 
  • European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA) extractables and leachables guidance
  • ISO 10993 Biological Evaluation of Medical Devices

Speak to an Expert

Discuss your project with one of our scientific experts and find out more about how we can help accelerate your product to market to maximize your success.



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Testing Services Resources

Learn more about how we can help bring your product to market through our high-quality analytical testing services.  

Pharmaceutical-Services---Extractables-and-Leachables

Pharmaceutical Services - Extractables and Leachables

The evaluation of extractables and leachables (E&L) is an essential component of the pharmaceutical development process.

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Whitepaper:-The-Use-of-Risk-Assessments-to-Optimize-your-Extractables-and-Leachables-Strategy

Whitepaper: The Use of Risk Assessments to Optimize your Extractables and Leachables Strategy

Extractables and leachables (E&L) risk assessments are valuable processes that can identify and highlight the risks of potential leachables from both the container closure system and the manufacturing processes. The risk assessments also include the level of risk that leachables might present to user safety and product quality. Download this Whitepaper to learn more.

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Toxicology-Advice-and-Consultancy-Services

Toxicology Advice and Consultancy Services

Our team of in-house toxicologists reviews and evaluates toxicological data on a wide range of chemicals to produce independent expert opinions on risk assessment. We then advise on the strategies to mitigate or reduce those risks to protect corporate reputation and public health.

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Industry Insight and Expert Opinion

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