4031 Ready Methods Reduce E&L Timelines as Part of the AccelTRA® Component Program

The FDA states: Drug product containers and closures shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality or purity of the drug beyond the official or established requirements.*  While they make this statement, there is no prescription offered in actually how to execute an extractables and leachables evaluation, which is, of course, an essential aspect of demonstrating suitability of containers and closures.

Working groups like Product Quality Research Institute (PQRI) and guidance chapters like USP <1663> Assessment of Extractables Associated with Pharmaceutical Packaging/Delivery Systems and <1664> Assessment of Drug Product Leachables Associated with Pharmaceutical Packaging/Delivery Systems provide direction. For small molecule drug products, manufacturers must understand these guidances and determine how to apply them for extractables and leachables evaluations of individual drug products.

With expertise in both materials science, and extractables and leachables evaluations for pharmaceutical packaging components and delivery devices, West Analytical Services has an established approach for executing extractables and leachables evaluations for individual drug products. This approach comprises understanding risks, developing and validating targeted leachables studies, and supporting drug products through stability testing. Through knowledge and experience, West subject matter experts partner with customers to reduce the risk to their drug product by designing and performing the studies that identify leachables from the primary packaging components.

Industry best practices ask drug product manufacturers to gain data on extractables first, then evaluate those extractables via a risk assessment to identify target leachables, and lastly develop and validate methods at appropriate levels to quantitate leachables levels in the drug product. The process of performing these studies can be time intensive. This is a challenge given the nature of market demands for drug product manufacturers, who need to move quickly to help ensure that drugs reach the market safely and efficiently. To meet this need, West’s AccelTRA^® component program is designed to deliver stoppers and plungers to generics manufacturers with quality, speed, and simplicity. As part of this program, West customers have access to the AccelTRA Extractables Profile, which allows them to perform an assessment of extractables from the 4031 component..

In addition to understanding the guidances mentioned above, the industry faces challenges of quickly getting a therapeutic or life-saving drugs to market, and the potential lack of knowledge and resources needed to meet regulatory expectations. To enhance the AccelTRA component program further to address these challenges, West Analytical Services has developed 4031 Ready Methods. The 4031 Ready Methods are partially validated leachables methods for extractable compounds. These methods were developed using drug product solutions such as water-based solutions, common solvent solutions such as buffer solutions, and benzyl alcohol. These drug product solutions were used as models based on an understanding of their typical use in small molecule injectable drug products. Customers can perform a gap assessment with the 4031 Extractables Profile. If additional extractables testing is not needed, they can move directly to next steps: (a) risk assessment for the toxicological evaluation; (b) identification of target extractables for leachables and the minimum quantitation limit (MQL); and (c) determination of feasibility of the chosen extractables in their small molecule drug product and drug specific validation. This can help reduce the overall testing time. After the completed validation work, the end result is specific customer-based leachables methods that then can be used for stability testing.

West Analytical Services is also able support customers with two additional services:

• E2L™ Service. : This service provides a paper-based risk assessment on the extractables data in the 4031 extractables profiles. This risk assessment uses nine different categories to rank the extractable compounds that take into consideration aspects of the intended drug product. The purpose is to assist in the customer's assessment of the extractables package, as well as their selection of compounds to target during a leachables study. It does not specify specific compounds to target; the E2L service does not take the place of the need to perform a risk assessment for leachables specific to their drug product.
• Simulation Study. This study generates data based on the targeted storage conditions, in order to provide customers a first glimpse as to what extractable compounds could truly migrate into their drug product. Actual drug product, or placebo, is aged (by high temperature accelerated aging conditions) and evaluated using screening methods to determine what, if any, extractable compounds might be observed using “actual-use extraction conditions”. A detection threshold is determined (analytical evaluation threshold, i.e., AET) based on the intended use of the product and used to ensure that the necessary sensitivity of the methods are achieved.

The goal of both is to aid in the customer’s assessment of the extractables data in order to, ultimately, pick the appropriate 4031 Ready methods as well as target levels.

West Analytical Services has been performing extractables and leachables evaluations for over 20 years, providing a holistic approach for customers’ container closure system, device, or combination product. We deliver tailored extractables and leachables solutions based on the stage of development of the product to address the challenges faced by the customer and the industry. By integrating our knowledge and expertise of materials, components, packaging, and analytical testing, West is able to offer a more comprehensive approach and timely delivery of generics manufacturers' packaging and regulatory needs through the AccelTRA component program with the 4031 Ready Methods. Contact us for more information.

AccelTRA and E2L are trademarks and registered trademarks of West Pharmaceutical Services, Inc., in the United States and other jurisdictions.

* Code of Federal Regulations Title 21. Section 211.94. Drug product containers and closures (a) https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=211.94