Extractables are compounds that can migrate from a container/delivery system under stressed laboratory conditions. Leachables are compounds that can migrate from a container/delivery system into a drug product under ordinary use conditions. Understanding the potential of both is essential to judge whether materials of construction of a system are compatible with a drug product. This section presents papers on experimental methods for identifying compounds, strategies for evaluating risks, and similar important topics.
Register below for access to our Online Technical Repository and for current customers, our Online Technical Customer Support Portal.
While many realize that regulatory agencies require extractable and leachable (E&L) information, many may not have knowledge of how to design an appropriate extractables study that will lead to proper selection of targets in leachables testing. This presentation will highlight different considerations of each phase of E&L testing. Since E&L studies encompass testing for both organic and inorganic species, an overview of elemental impurity testing, which is an area undergoing significant changes, will also be discussed.
Assessment of extractable data is a practical guide to support selection of components used in drug product container closure systems and to understand potential for leachables. According to the USP <1663> informational chapter on extractables assessment, the design of an extraction study is dictated by the purpose of the extractables assessment. This presentation will put into practice the overarching principles of USP <1663> for developing extractable study designs. Three case studies will be given representing risk of leachables across product lifecycle. Data will be shown related to the selection process, post approval changes, and considerations for biologic product quality.
This presentation discusses the results of a proof of concept study done to investigate the effect of these compounds on protein stability, the effect of aluminum, calcium, zinc, silicon, and magnesium on the accelerated stability of one model protein, Human Lysozyme. Protein samples were exposed to increasing levels of the elements in conjunction with elevated temperature stress. The resultant solutions were then analyzed by several analytical and biophysical assays as a function of concentration and stress condition to determine if the substances selected in this first tier of investigation have any impact on protein stability.
Regulations regarding elemental impurities in drug products have changed. Consistent with a focus on patient safety – West has remained ahead of these changes and developed the methods needed to help customers comply with them – whatever the stage of drug product development. Pharmacopoeia address certain requirements for the quality, safety and efficacy of marketed products which are country specific. This can be problematic because methods and specifications in compendia will be somewhat different and challenging to navigate depending on the requirements in both mature and emerging markets. Committed to the safest and most efficient delivery of drug products, West monitors these regulations continually to stay ahead of changes, and maintains the staff, expertise and facility to design, and perform, the studies needed to help Customers comply.
<p>This poster, comprising collaborative work between West Pharmaceutical Services, Inc. and Product Quality Research Institute, describes an approach to determining extractables from a bromobutyl-based elastomer formulation, including multiple solvents/conditions and multiple analytical methods.</p>
<p><em>D. Paskiet, et al. </em></p>
Five materials which represent commonly used elastomers/polymers are exposed to relevant extraction solvents and methods. Resultant extracts were characterized using spectroscopy and chromatography to determine extractable profiles. Conclusions discuss potential best practices going forward for packaging and devices.
<p><em>Jenke D1, Castner J, Egert T, Feinberg T, Hendricker A, Houston C, Hunt DG, Lynch M, Shaw A, Nicholas K, Norwood DL, Paskiet D, Ruberto M, Smith EJ, Holcomb F.</em></p>
This article gives the views of several industry experts on how to design studies to examine for extractables and leachables using a risk-based approach.
<p><em>A. Siew. Pharmaceutical Technology, 38 (5) (May 2014)</em></p>
This document is ICH (International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use) guidance on elemental impurities in drug products. In particular, document addresses toxicologically relevant permitted daily exposure (PDE) limits and risk-based assessment strategies.<br />
See also in this section Q3D Elemental Impurities Guidance for Industry which gives FDA position on this guideline.
<p>Discusses leachables and the safety assessment work strategy designed by the Parenteral and Opthalmic Drug Products Leachables and Extractables Working Group Chemistry and Toxicology teams. This working group was formed to make best practice recommendations for packaging/delivery systems, including safety thresholds for large-volume parenterals and special issues associated with biologics.</p>
<p><em>Paskiet D. Jenke D, Ball D, Houston C, Norwood DL, Markovic I.</em></p>
This FDA report considers ICH (International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use) guidance on elemental impurities in drug products. Specific areas considered are: (a) evaluation of the toxicity data for potential elemental impurities, (b) establishment of a permitted daily exposure (PDE) for each element of toxicological concern, and (c) application of a risk-based approach to control elemental impurities.<br />
See also in this section Guideline for Elemental Impurities - Q3D - the document on which this report is based
This article presents a simulated leaching study on a polymer/elastomer container system with model solvent systems. Data indicated that the leachate profile correlated qualitatively with container materials of construction; leachate profile was affected by solvent and direct contact with drug product was not required for leaching to occur.
<p><em>D. Jenke, et al. PDA Journal of Pharmaceutical Science and Technology, 71, 68-87 (2017)</em></p>
<p id="FullPage_65b4158c25fb41550591710821">By Fran DeGrazio and Diane Paskiet. Contract Pharma, Jan 23, 2012</p>
<p id="FullPage_8e111860efd7c1550591710821">This article considers the technical and legislative issues resultant from glass delamination.</p>
<p>This chapter presents a framework for the design, justification, and execution of an extractables assessment for pharmaceutical packaging and delivery systems. </p>
<p>User id and password required</p>
This chapter presents a framework for the design, justification, and implementation of assessments for drug product leachables derived from pharmaceutical packaging and delivery systems.
<p>User id and password required</p>