Pharmaceutical and biotechnology companies are responsible for qualifying various materials used in the manufacturing process of a drug product, including, if necessary, conducting an Extractables and Leachables risk assessment. The purpose is to ensure that materials are appropriate and meet defined specifications for:

• product quality: impact on final drug product quality, e.g., stability, activity, assay, etc.
• toxicological risk: final drug product safety, potential adverse effects
• process performance: impact on process performance, e.g., cell growth, holding times etc.

When polymer-based contact materials are used in a production process, there is a risk of compounds leaching from the polymeric component(s). These compounds can enter the process stream with potential negative impact on product quality, safety, and/or process performance. There are two distinct types of components:

• Extractables: components which will arise from polymer-based materials under extreme contact conditions
• Leachables: components which will arise from polymer-based materials during normal contact conditions

Current regulations and guidelines (ICH Q3E Guideline for Extractables and Leachables) provide limited insight into how testing plans should be designed, how analyses should be performed and how Extractables and Leachables (E/L) profiles should be interpreted. (Bio-)Pharmaceutical companies are forced to define this in detail for their products. This, because each final drug product is different with respect to formulation, active dose, intended use, administration route etc. Basic principles of risk management/assessment should be applied to identify, evaluate, communicate, and mitigate the potential impact of (E/L) on product quality and patient safety. Effective risk mitigation will ensure product quality and safety and minimize potential delays during product filing.

The presence of potential toxic compounds can be defined by the composition of materials (i.e., tubing, filters, bio containers) provided by the supplier. Information about the qualitative/(semi-)quantitative composition of the material, including additives such as antioxidants, stabilizers, plasticizers, lubricants, metals, solvents, and/or dyes should be available. Based on this information and the administration regime of the drug product a toxicological assessment can be performed to evaluate potential risk due to the nature of the extractables.

Case study: implementation of a single-use storage system

A drug product manufacturer needed a custom-made single-use system (SUS) as back-up for the storage of an intermediate product which is routinely stored in stainless steel containers. Moreover, the SUS needed to be suitable for shipment of the intermediate product to a CMO for additional production steps, therefore limiting the container size. In addition to the bio container assembly, a single use manifold system was designed to connect a flexible number of bags based on the required batch volume.

In cooperation with the manufacturer of the bio container, the system was designed and produced. The manufacturer of the SUS could provide all required extractable study reports of the individual bio container components (i.e., tubing, container film material and inlet/outlet ports). Therefore, without primary studies, calculations were performed to assess the toxicological impact. The result was that all potential leachable components were within acceptable limits. For that reason, the change for introduction of the SUS was accepted by the authorities without the request for additional studies.

How can we serve you regarding Extractables and Leachables challenges?

We can provide project management professionals and specialists to help you tackle your extractables and leachables (E/L) challenges effectively. Progress can perform assessments of a single new material introduction (e.g., a filter change) to adopt in your production process safely. Progress can take care of the complete implementation of single use system within your production process. Depending on the availability and quality of extractables study data from the suppliers, expensive studies might not always be required resulting in cost reduction. Our consultants can initiate, lead and/or facilitate risk assessment sessions to identify the size of the study program, the need for (E/L) studies for meeting regulatory guidelines and minimizing the risk for impact on product quality and patient safety. When specialized (E/L) studies are required, Progress can perform the project management of such studies based on the needs and wishes of the client.

Our approach

Project management

Progress is specialized in project management for pharmaceutical and biotechnology companies. Each project demands a different kind of approach and strategy. Our experienced project managers are Prince2®certified, pragmatic and client driven. Projects are executed with the support of extractables or leachables (E/L) trained consultants and if needed with other specialists from Progress.

In consultation we determine together a tailormade approach for the topic and scope of your project:

• Structure your project team
• Define deliverables
• Identify risks and opportunities

We monitor the progress continuously and adjust where necessary, to ensure we deliver what you need. Expect excellent communication and organizational skills!

Quick Scan

Progress has developed a Quick Scan to identify gaps, such as the availability of required information and quality standards. The scan consists of an assessment of your proposed change, production process and related contact materials:

• Overview of the applied and suggested contact materials
• Overview of all contact conditions at intended use
• Identification of process steps to eliminate or remove PERL’s (Process Equipment Related Leachables)
• Availability and quality of extractable data by the supplier
• Availability of additional toxicological assessments

By conducting this scan of your activities and proposed changes, an overview will be created of the current situation, visualizing the gaps and opportunities. Subsequently, a risk assessment can be prepared to support your change, or a project plan can be prepared to facilitate an extractables or leachables (E/L) study.