Extractable and Leachable analysis is an area of growing regulatory significance, and provides many challenges in the development of pharmaceutical and biopharmaceutical products and their container systems as well as components used in single use pharmaceutical devices as well as food manufacture and packaging.
It is concerned with the potential for compounds to migrate into the drug product from processing equipment, closed container system drug delivery devices or single use medical devices.
- pre-filled parenterals
- elastomer and plastic ancillary components of the primary packaging
- single use medical devices (IV bags, syringes etc.)
- plastic and coated materials used in pharmaceutical and food manufacture and packaging
Our vast experience with different materials used in container/closure and packaging systems allows us to understand your requirements and in many cases we are able to offer assistance in these areas.
By performing a detailed extractable study, using a variety of appropriate methods, we can characterise and quantitate the components observed. Using a combination of gas and liquid chromatography combined with mass spectrometry we are able to provide structural information on a wide range of extractable materials. Our own, extensive, in-house library assists in identifying “unknown” components.
Typical migratory compounds include:
- Monomers and polymers i.e. elastomers, lubricants and thermoplastics
- Additives i.e. plasticisers, antioxidants, initiators and metal catalysts
- Adhesives, inks, lacquers and laminate films
- Rubber constituents
Employing the published best practice recommendations of the PQRI Leachables and Extractables Working Group (2006), we have gained an international reputation for the development of highly cost effective and efficient strategies which deliver results that are fully compliant with these recommendations. Our approach will typically include:
- Collaborative information gathering and existing data analysis
- Test protocol development for extractables and leachables studies
- Investigation of sequential extraction or alternative extraction methodologies where required according to our extensive experience
- Organic and inorganic extractables profile production
- Unknown extractable characteristaion using mass spectrometric and spectroscopic techniques
- Determination of the Analytical Estimation Threshold (AET) and qualification based on the Safety Concern Threshold (SCT) using dose scaling to evaluate risk where appropriate
- Method development and validation of method(s) for the Leachables Study
- Reporting Leachable Study results within the current guideline recommendations
Analytical methods, including specific screens for compounds of particular toxicological interest i.e. nitrosamines, PAHs, 2-mercaptobenzothiazol etc., provide quantitative determination of leachable compounds which enables accurate and efficient measurements of the accumulated level of migratory species throughout the shelf life of the product.
Such data has been used to successfully support FDA and other licensing regulatory submissions.
Equipment and technology available for Extractables and Leachables testing includes:
- Soxhlet, Ultrasonic and Accelerated Solvent Extraction (ASE)
- HPLC – MS/MS, HPLC Q-TOF, HPLC-Diode Array
- Headspace GC, GC-MS, GC-HRMS
- GC-FID, GC-ECD
Extractables and Leachables testing is also available for food and beverage, packaging and a host of other industries. Our extensive experience in this field of testing allows us to advise you on the most appropriate and cost effective analytical approach to meet your business and regulatory requirements.