Authored by Dean Marbury, Microbac Laboratories Southern Testing & Research Division

GMP Extractables and Leachables (E&L) testing is required by FDA and other regulatory agencies for many pharmaceutical packaging materials and drug delivery devices, along with their associated drug formulations, to determine the potential of patient exposure to undesirable compounds arising from the packaging or device.   The typical types of devices and materials to be evaluated for E&L, in approximate descending order of concern, include inhalation products (metered dose and dry powder inhaler products), nasal delivery systems, parenterals, materials placed in-situ in patients, ocular drugs, transdermal delivery systems, and other packaging and closure systems.

Extractables testing (characterization) is performed on the actual materials in the drug product that may contact the drug formulation to be delivered to the patient.  Characterization involves rigorous chemical extraction and analysis of the packaging and device materials (e.g. polymers, adhesives, labels, closures, device components, primary and secondary packaging of drug product), typically using a range of extraction solvents such as water, isopropanol, and methylene chloride.  The extracts are subsequently analyzed using gas chromatography/mass spectrometry (GC/MS) and high-performance liquid chromatography/mass spectrometry (LC/MS) to provide identification of potential compounds of concern and to provide semi-quantitative assessment of the identified compounds. A wide range of compound classes may be identified in characterization studies, including polymer additives, degradants, colorants, adhesives, lubricants, silicones, polymers and monomers, metals, nitrosamines, and polynuclear hydrocarbons.

Compounds identified in characterization studies are assessed for toxicological and safety parameters and, based on this assessment, a list is created of a subset of these compounds suitable for further development of appropriate manufacturing controls in the device/packaging manufacturing process.  Microbac Laboratories conducts a full range of extractables testing, including analytical method development and validation for use in control of the compounds of interest.  The validated methods are then used for routine sample analysis for specifications setting, product refinement, and product release testing.

Leachables testing involves analysis for the presence of compounds of interest in the drug product itself, and involves analytical method development and validation, stability studies, and product leachables testing for release.  The potential for patient exposure is calculated based on regulatory and consortium guidelines, and the results are then compared against regulatory guidelines for such exposure.  Limits of the amounts of compounds of interest that may be present in the product are established and analytical methods are developed and validated to verify that these limits are met before release of the product. 

Microbac Laboratories Capabilities for Extractables and Leachables Testing

Microbac has the staff, facilities, instrumentation, and quality systems to perform all aspects of cGMP E&L project development and execution.  We maintain the strictest control of confidentiality to protect intellectual property, and have a highly experienced quality assurance program to execute fully compliant cGMP projects. Microbac’s site in Wilson, NC is an FDA-inspected GMP facility containing over 30,000 square feet of laboratory and administrative space.

Microbac’s staff is highly experienced in the execution of MD/MV projects for E&L, and each project is performed under the direct supervision of Ph.D.-level scientists.  Microbac has state-of-the-art instrumentation for E&L development, including API-3000 through API-5000 LC/MS/MS instruments; numerous GC and GC/MS instruments with all the needed detection modalities; over 25 HPLC instruments possessing all requisite detection modes; AA, GFAA, and ICP instruments for inorganics analysis, and extensive sample preparation and storage facilities, including ICH and custom stability storage chambers.

In addition, our family of laboratories located nationwide can bring specialized expertise and instrumentation to bear upon unusual project requirements, such as polymer characterization, material formulation analysis, and component failure analysis.

For more information, please contact: microbac_info@microbac.com.