Extractables are compounds that can be extracted from the Container Closure System (CCS) in the presence of a solvent. Leachables are compounds that leach into the drug product from the CCS as a result of direct contact with the formulation.

Sources of E&L can be plastic components, rubber, inks and adhesives, stainless steel components and other material used in the various types of drug packaging. Control of extractables and leachables in drug products is very important for ensuring safety, efficacy, quality and stability of drug products.

E&L – A growing concern

Extractables and leachables are a growing concern for pharmaceutical manufacturers and regulatory bodies.

• The development of unique packaging, novel formulations, delivery systems and drug-coated medical devices has exacerbated this issue.
• The increasing popularity of single-use disposables such as filters, tubing and bags for biopharmaceuticals can induce unwanted extractables.
• US FDA demands detailed information about every packaging component.

Assessment of Extractables and Leachables

FDA provides guidance for protection against extractables and leachables in various documents. Therefore, the qualification and quality control of all components coming into contact with the drug formulation is an integral part of any FDA application process. The development, validation, and testing of these components must be carried out under ICH and USP guidelines in a cGMP compliant laboratory.
Since there are limited guidelines on E&L for final dosage forms, PQRI (Product Quality Research Institute) gives regulatory guidance for E&L analysis which is recognized by the FDA.

Risk Analysis:

Detecting Extractable and Leachable

Piramal Capabilities

Integrated Solution for Extractable and Leachable – Ensuring Quality on Time

Development Strategies: We understand the latest trends, requirements and pitfalls that potentially occur during development of E&L which includes:

• Packaging material COA evaluation
• Solvent extraction studies (varying polarity)
• Screening and identification with LCMS/MS and GCMS/MS
• Qualifying extractable as per vendor COA, PQRI, PODP, and USP guidelines
• Validation/verification of analytical methods
• Toxicity evaluation as per Derek Nexus updated software
• Conducting leachable studies

Research capabilities: Piramal Pharma Solutions has developed analytical methods for quantification of the below potential extractable by various techniques.

• Phthalates
• Nitrosamines
• Elements
• Volatile /Semi-volatile organic compounds
• Polynuclear aromatic hydrocarbons
• Antioxidants and elastomer additives
  • Fatty acids   Piramal Pharma Solutions has developed analytical methods