Extractables and Leachables are organic or inorganic impurities originating from primary packaging material (plugs, blisters, vials, etc.) or production tools. Pharmaceutical companies and medical device manufacturers must analyze extractables and leachables (E&L studies) for new pharmaceutical products. This also includes the toxicological assessment of extractables.
SYNLAB Analytics & Services Germany GmbH divides E & L studies into 4 essential production steps:
1. Extractables Study:
Extractables are chemical compounds extracted from primary packaging materials under extreme conditions (high temperatures, different solvents, pH and periods of stress).
Then, the extractables are analyzed using highly sensitive analytical methods, such as LC Q-ToF MS, LC-MS / MS, GC-MS, Headspace-GC-MS, and SPME-GC-MS.
In close consultation with our customers, Analytical Services defines the AET value (analytical estimated threshold).
2. Simulations Study:
The simulation study is an intermediate step to more reliably represent extractables as probable leachables in placebo and drug products stored under extreme conditions. The analysis of extractables from the simulation study is performed similarly to the extractables study using highly sensitive analytical methods.
3. Toxikological Assesment:
All extracts obtained from the extractable study are evaluated from a toxicology perspective. A detailed extractables report estimating the toxicological and genotoxicological characteristics of the extractables is then forwarded to our client. Only the extractables above the AET value are considered for such a toxicological assessment.
4. Leachables Study:
Leachables are chemical compounds that are released from packaging materials, coatings and locking mechanisms under normal environmental conditions. Please note that not all leachables in the previous extractables study were necessarily found, because some pharmaceutical formulations can cause a reorganization of known, extractable chemical compounds. Therefore, the correlation of extractables results with potential leachables requires experience and a special circumspection .
Synlab Analytics & Services Germany GmbH performs all E & L testing in our in-house GMP analysis laboratories according to the latest official guidelines. Our state-of-the-art equipment enables the detection of extractables & leachables at ultra trace Levels.
Extractables & Leachables Summary:
- E&L studies are divided into 4 steps: the extractables study, the simulation study, the toxicological evaluation and the leachables study
- extractables & leachables studies are carried out in our GMP laboratory according to the most recent guidelines
- stress and compatibility studies of packaging materials are included
The leachables and extractables studies are realized according to the following guidelines:
- ISO 10993: Biologial evaluation of medical devices
- FDA Guidances for Industry on inhalation drug products
- EMA/Health Canada guideline on the pharmaceutical quality of inhalation and nasal products, October 2006
- Recommendations of the Product Quality Research Institute (PQRI) Leachables and Extractables Working Group “Safety Thresholds and Best Practices for Extractables and Leachables in
- Orally Inhaled and Nasal Drug Products (OINDP)”, September 2006
- Product Quality Research Institute (PQRI) Leachables and Extractables Working Group Initiatives for Parenteral and Ophthalmic Drug Products (PODP), Paskiet, D. et al., PDA J Pharm Sci and Tech 2013, 67
- SFDA: Draft Technical Guideline for Compatibility Studies between Chemical Drug Injections and Plastic Packaging Materials
- EMA Guideline on Plastic Immediate Packaging Materials (CPMP/QWP/4359/03)