Extractables & Leachables（E&L）
Eurofins Analytical Science Laboratories, Inc. (E-ASL) can provide the total solutions to your needs.
- To perform Extractables & Leachables testing in advance and timely respond to the strengthening regulations.
- To perform Extractables & Leachables testing for commercial products according to ISO10993.
- To perform Extractables & Leachables testing to launch products in the US or Europe in conformance with the guidelines.
E-ASL can perform Extractables & Leachables testing by using analytical equipment under GMP management.
It is mandatory to perform Extractables & Leachables testing for filing in the US and Europe.
Extractables & Leachables testing is emerging as a high priority testing due to the rapid growth of the market of parenteral drugs in Japan.
There is a concern about the effects of extractables, as we have various container packages such as prefilled syringes and glass vials with rubber stoppers and several dosage forms such as liquid and freeze dried in accordance with the changes in treatment.
Leachable compounds will change structure of pharmaceuticals and affect the efficiency and safety, particularly for biopharmaceuticals.
It is considered that the importance of Extractables & Leachables testing will increase in Japan.
Overview of Extractables & Leachables testing
It is considered that pharmaceuticals may contact several components of manufacturing/packaging instruments and the final packaging materials in the process of manufacturing, packaging, storage, distribution, and administration, causing unexpected interactions.
Consequently, organic/inorganic compounds may leach from pharmaceuticals and affect the efficiency and safety of pharmaceuticals.
Extractables & Leachables testing is performed to determine what compounds in your products, that could raise the potential risk.
Differences between Extractables and Leachables are shown in the figure below.
Compounds extracted from contacted materials of pharmaceuticals under severe conditions (solvent, temperature, pH etc.).
Testing is for containers.
Leachables are compounds that migrate into the final formulations from contact materials of pharmaceuticals under actual process conditions (Manufacturing, Packaging, Storage, Distribution, Administration).
Testing is for drug products.
General workflow of E&L testing is as follows.
List all the components used in the process, confirm if those may contact with the intermediates and the final products, and determine if E&L testing is required. Evaluate risk based on the information such as location, temperature and time of contact, dosage form, and route of administration etc.
Extractables testing will performed based on the results of risk assessment. It is necessary to optimize the extraction method and conditions. The extraction method (in reflux, stirring, Soxhlet extraction etc.), extraction solvent, extraction time and temperature, pretreatment etc. are determined in consideration of the relevant guidelines.
Extractable compounds are analyzed by LC/MS、GC/MS、ICP/MS etc. corresponding to the characteristics of product. Extractable compounds are identified using commercial or proprietary spectral libraries.
Extractable compounds that exceed the Analytical Evaluation Threshold; AET will be assessed for toxicity. For institution of toxicity evaluation, you can choose our labs (Global Eurofins labs), the third party lab in Japan, or your laboratory, etc.
Leachable testing will be performed on extractable compounds that are recognized as risk elements as a result of toxicity evaluation. The most appropriate method is developed by using the toxicological data for the compound and the threshold set based on the dosing regimen.
The method developed is validated in accordance with the ICH guideline. The affects to product are monitored by performing long-term testing of leachables with validated method. The timing of the long-term testing is determined based on the term of validity of the product.
It is also recommended to perform screening in a standard method so as to ensure no compound which has not been detected in the extractable testing is to be generated in products.
Why choose Eurofins Analytical Science Laboratories for your Extractables & Leachables testing?
- Eurofins companies have over 15 years of experience performing Extractables & Leachables studies.
- Eurofins companies have our proprietary spectral database (LC/MS) that enables us to identify over 1,900 compounds.
- We have various analytical equipment under GMP control.
Eurofins companies have been focused on E&L testing for many years.
We have solid experience with E&L testing of the following products and components.
| Category | For examples |
| Product | Cell culture vessel, e-cigarettes, Catheter, Implant, Compress, Aspirator |
| Packaging | Blister package, Secondary packaging, Foil pouch, Labeling, Cap, Stopper |
| Syringes | Plunger, Barrel, Syringe tip cap, Needle |
| Containers | Bioprocess bag, Bottle/Vial, Pouch, Canister |
| Manufacturing equipment | Filter, Impeller, Connecter, Gasket, Tube, Graphite sealing |
| Others | Adhesives, Resin, Sealant |
Eurofins companies have solid knowledges and experiences of testing for regulatory filing in several countries. We can offer optimal testing proposal of E&L testing by utilizing these knowledges.
We utilize NIST and Wiley spectral libraries to identify extractable compounds. But we need to prepare specific libraries for LC/MS. The number of compounds in the library enables us to determine if it will be identified or not.
Eurofins companies identify extractable compounds by suing our library called Eurofins extractable Index that has over 1,900 compounds filed with years of experience.
We have an organization in compliance with GMP ordinances. We prepare proposal, perform testing, store samples, and manage facility/equipment/system.
Guideline of E&L testing
The US and Europe authority announces the following guideline of E&L testing. However, those guidelines do not include specific method of E&L testing.
This guideline provides you how to perform Extractables & Leachables testing and how to consider evaluation criteria.
- 21 CFR Part 211.94［FDA］
- Container Closure Systems for Packaging Human Drugs and Biologics Chemistry, Manufacturing and Controls Documentation [FDA]
- Guideline on Plastic Immediate Packaging Materials [EMEA]
The following guideline of the US PQRI (Product Quality Research Institute) is important for E&L testing.
- Safety Threshold and Best Practices for Extractables and Leachables in Orally Inhaled and Nasal Drug Products
The approach of this guideline is also reflected in USP 1663/1664.
In addition to the final packaging and containers, the plastic system (SUS: Single Use System) used in manufacturing of pharmaceuticals is also described in USP 665.
The industrial groups such as BPOG: BioPhorum Operations Group and BPSA: Bio-Process Systems Alliance have issued the guidelines, and it is necessary to consider the optimal guidelines depending what you evaluate.
Following the adaptation of ICH Q3E in June 2019, the conformity of the guidelines is expected.
Eurofins Analytical Science Laboratories, Inc. can select the optimum guidelines based on our abundant knowledges. We consider risks, develop evaluation and test methods, and design protocols. We provide total solutions to meet customer's needs.
We support your E&L testing. Please feel free to contact us if you have any questions and requests.