Extractables & Leachables Testing 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.

Biologics are complex and sensitive to their environment and require advanced packaging to protect their therapeutic benefits. Compared to small molecule drugs, biologics have more intricate packaging needs, since the compounds released from the materials could have a direct and significant impact on the potency or causing contamination. Often the drug delivery of these products requires moreover specialized packaging that are able to maintain the physical-chemical properties of the drug during transportation and storage.

Biologics are typically produced in medium-small quantities and are transported in bulk to the fill & finish site. Single and Multiple Use system used in the product manufacturing and temporary storage packaging needs to be evaluated as well as for container closure systems for the compounds migration, following USP <665> guidelines.

The manufacturing items and container closure systems of biologics presents unique challenges due to the complexity and sensitive nature of this category of drugs, that need to be carefully evaluated through a structured Risk Assessment. Leachables may cause conformational changes in the protein or may cause the protein to aggregate. Large-molecule drug products may also chelate inorganic leachables. These types of interactions can increase the toxicity of the drug product, reduce the product’s efficacy, or affect the product’s stability. It is, therefore, important to fully evaluate the E&L risks to ensure quality and safety of these products as well as avoid costly delays in getting a product to market.

We offer exceptional, risk-mitigating solutions with testing and regulatory expertise to ensure the safety of these life-changing drugs. We are pioneering this open field, not yet defined and harmonized under a regulatory overview. Our dedicated team has also developed a new approach to asses the interaction between E&L and active substace of biological finished products. 

• Evaluation of the customer’s available data
  to check for integration for the E&L regulatory compliance
• Extractables study – From design to laboratory execution
  • Choice of the right components/materials to be tested
  • Extraction solvents to be applied in the extractables generation step
  • Extraction conditions (time and temperature to be used in the study)
  • Analytical techniques to be applied to cover all the potential released compounds
  • Definition of the correct reporting threshold (Analytical Evaluation threshold) to avoid both unfounded concerns and loss of alerts.
• Fingerprint approach - Extractables studies focused on specific items
  (e.g. the label which could be subjected to changes). This service is used in order to prevent the need to redo another extractables study.
• Leachables studies – comprehensive study to meet regulatory requirements
  • Targeted leachables screening - to search for specific compounds with potential toxicological concerns
  • Non targeted leachables screening – to screen for potential compounds missed in the extractables step (this is a mandatory requirement from FDA)
  • Limit Test method validation
  • Full method validation (ICH Q2R1 and Q2R2)
• Assessment of the interaction between E&L and active substance of biological finished products
• Detection of unidentified impurities

Despite the fact that Extractables and Leachables framework is well-known and more standardized for small molecules, a comprehensive approach to investigate the interaction between these impurities and biological products is not yet defined nor harmonized.

Nevertheless, the characteristics of biological products make them more prone to react with leachables, raising concerns about the potential interactions. As they are generally present in low concentrations the main challenges are being able to detect them and assess their impact on drug product quality and safety.

Our dedicated team has developed a new approach to asses the interaction between E&L and active substace of biological finished products. Read our whitepaper to learn all the details of our innovative approach. 

Whitepaper: Development of a new approach to assess the interaction between Extractables & Leachables and active substance of biological finished products