Extractables & Leachables

Extractables & Leachables Testing on Primary Packaging 

Primary packaging for biopharma products plays a vital role in ensuring drug product safety.  

Packaging must be a barrier to the external environment and maintain the sterility of its contents. It can also serve to shield the drug product from oxidation, light degradation, and moisture permeation. 

Fulfilling all these functional requirements includes testing of a broad spectrum of components and materials (e.g. plastic containers, metal springs, elastomeric valves and gaskets, adhesives, coatings etc). 

Extractables and leachables testing is an essential component of the drug development process. With a proven track record of testing expertise, our services will ensure your products have a competitive edge for your regulatory success. 

The challenge of Extractables & Leachables Studies on Biologics 

Biopharmaceuticals have become a key driver of growth, revolutionizing the treatment of a broad spectrum of diseases. As the use of biopharmaceuticals continues to increase, so does the demand for specialized testing on their packaging. 

• Compared to small molecule drugs, biologics have more intricate packaging needs, since compounds that can leach from materials coming in contact with the drug product/drug substance could have a direct and significant impact on potency or purity.  
• Single and Multiple Use systems used in product manufacturing and temporary storage packaging need to be evaluated, including container closure systems for the compounds migration, following USP <665> guidelines. 
• A structured Risk Assessment is crucial to the evaluation of manufacturing items and container closure systems of biologics. For example, leachables and large-molecule drug products can impact the chemical integrity of the drug product. These interactions can, in turn, impact drug product toxicity, product efficacy, or product stability.  

Single-use and multiple-use systems E&L Testing 

The use of single-use systems or multiple-use systems (SUS, MUS) to manufacture drugs and biopharmaceutical products has significantly increased. These disposable systems (such as tubing, filters, gaskets, storage bags, etc.) offer many advantages. They facilitate faster, more flexible production and are a cost-effective solution. They also carry a lower cross-contamination risk, enhancing patient safety. 

• The implementation of MUS, in the pharmaceutical and biopharmaceutical process, requires careful consideration in the selection of materials – it is important to avoid the risk of chemical compounds leaching from polymeric components. 
• Both SUS and MUS fall within the scope of USP <665> which will become effectively mandatory in May 2026. 
• The USP <665> and <1665> enable a standardized extraction procedure to determine these potential contaminants using analytical methods, as well as provide guidance on risk assessment approaches. 

Our services 

• Existing data gap analysis and data quality review
  In the case of already existing extractables data, verifying and qualifying the data is important to refining and finalizing the strategic approach. 
• Full risk assessment on the drug manufacturing process items
  We offer a complete analysis of manufacture processes to define the most concerning items in terms of the potential release of extractables. 
• Extractables study design in compliance with the most updated regulation  (<USP 665/1665> and BPOG)  
• Expert toxicological evaluations
  We are able to perform toxicological evaluations on already existing data or on extractables data generated from a new study. To this end, our workflow benefits from a dedicated team of certified and experienced toxicologists. 
• Leachables assessment
  We support with defining the most adequate strategy for primary packaging and drug product assessment, based on our experience and regulatory requirements. 

• USP <665> Plastic Components and Systems Used to Manufacture Pharmaceutical Drug Products and Biopharmaceutical Drug Substances and Products 
• USP <1665> Characterization and Qualification of Plastic Components and Systems Used to Manufacture Pharmaceutical Drug Products and Biopharmaceutical Drug Substances and Products 
• Biophorum Operation Group (BPOG) – standard protocol for Extractables testing on SUS/MUS ICH guideline Q9 on quality risk management 

The importance of toxicological risk assessment for drug products, biologics and medical devices 

Identifying and limiting the risks associated with hazardous materials is imperative to comply with regulatory requirements across the pharmaceutical and medical devices industry. 

A toxicological risk assessment provides the overall interpretation to extractables and leachables studies from a safety perspective. 

A toxicological evaluation must be performed by a qualified toxicologist on the extractable profile derived from the extractable study. Eurofins has the capability to evaluate compounds by referring to both toxicological databases and QSAR methods.  

We offer toxicological analyses on a variety of items, including medical devices, gas pathway devices, as well as pharmaceutical container/closure systems according to standards such as ISO 10993-17 and ISO 18562 and guidance documents from the FDA and PQRI. 

Our dedicated expert team of 40+ toxicologists and consultants at Eurofins Regulatory & Consultancy Services Italy, with a board-certified team, including one European Registered Toxicologists (ERT) and one HAS Consultant, provide top-tier services to meet global regulatory compliance.  

Toxicological risk assessment for drug products and biologics 

• E&L validation plan 
  Implementation of the optimal regulatory strategy based upon the specific drug product and drug substance 
• Data gap analysis and quality review: 
  Evaluation of already generated extractable and leachables data. 
• Change assessment for the evaluation of E&L related impact within the manufacturing process and primary packaging 
• Toxicological risk assessment on the compound of potential concern identified in the E&L studies: 
  Performed by expert toxicologist (including ERT) 
• Permitted daily exposure to evaluate toxicological profile of compounds Includes expert review relevant data and scientific literature, use of in silico methods, QSAR and read-across 
• Evaluation of process related impurities and special impurities such as Nitrosamines 
• Our consultancy team provides technical support for interactions with regulatory agencies and for responding to deficiencies. 
• Expert Technical Support for Regulatory Agency Interactions and Deficiency Responses 

Medical Devices and Combination Products 

Chemical characterization is the first step in the workflow used to establish the biological safety of medical devices, as required by ISO 10993.  

Compounds are intentionally added during device manufacture or can be inadvertently picked up during processing, sterilization, or storage. 

Important phases in your product development lifecycle that may require E&L assessments: 

• Developing new product design concepts 
• Performing verification testing for your design history file  
• Changing raw material suppliers 
• Implementing design or manufacturing process change

Choose Eurofins BPT to help you 

• Determine the most relevant testing conditions for your product and write your protocol 
• Execute your study within a GMP/GLP/ISO  17025 compliant quality system 
• Identify extractable compounds using our proprietary spectral database of over 1,500 non-volatile compounds 
• Assess the toxicological risk of identified compounds according to ISO 10993-17 and the latest update to ISO 10993-18 to provide a report that is ready for regulatory submission

Additional Services Offered 

• Method Development & Validation 
• Stability for Leachables 
• Toxicological Risk Assessments 
• Biocompatibility Testing

Instrumentation 

• Agilent LC/MS TOF and QTOF 
• Agilent/Waters HPLC/UHPLC – including UV/Vis, RI, Fluorescence, ELSD, CAD, and Conductivity detectors 
• Agilent GC/MS – both headspace and direct injection sample introduction 
• Agilent GC/FID/TCD – both headspace and direct injection sample introduction 
• Agilent ICP/MS and ICP/OES 
• Thermo Scientific iCAP ICP-OES 
• Perkin Elmer ICP-OES 
• Bruker Avance 3 (500 MHz) Liquid NMR 
• Bruker Avance 3 (400 MHz) Liquid NMR