Cambridge Healthtech Institute’s Fifth Annual
Extractables and Leachables
Protecting Quality of Biologics by Ensuring Safety and Compatibility
January 10-11, 2017 | Hilton San Diego Bayfront | San Diego, CA

In biopharmaceutical development and manufacturing, containers, drug combination products, and even disposable equipment may leach chemicals into the product that can pose significant risks to product quality and potentially compromise the stability, safety and efficacy of the biotherapeutics. The Fifth Annual Extractables and Leachables (E&L) conference brings together industry experts and thought leaders to share their insights on the latest updates and guidelines, how to design analytical testing strategies for E&L, case studies on identification and risk assessment of E&L in single-use systems, container closure systems and delivery devices, and the impact of leachables on biocompatibility and safety.

We invite you to present a poster and attend to join colleagues from around the world in this discussion of the key challenges and solutions for E&L testing in biologics.

TUESDAY, JANUARY 10

1:00 pm Conference Registration

1:30 Refreshment Break in the Exhibit Hall with Poster Viewing

UPDATES FROM INDUSTRY AND WORKING GROUPS

2:00 Chairperson’s Opening Remarks

Kim Li, Ph.D., DABT, MPH, Senior Manager, Environment, Health, Safety and Sustainability Product Stewardship Toxicology, Amgen

Keynote Presentation

2:05 Extractables & Leachables Safety Information Exchange (ELSIE) Consortium – Update

Kim Li, Ph.D., DABT, MPH, Senior Manager, Environment, Health, Safety and Sustainability Product Stewardship Toxicology, Amgen

The ELSIE consortium, consisting of members from the pharmaceutical, biotechnology and medical device companies, advances the knowledge of chemical and toxicology assessment of extractables and leachables (E&L) through scientific and regulatory outreach. In October 2015, the consortium conducted a workshop in Basel Switzerland to understand the current practices of E&L risk assessment. This presentation will highlight the findings from the workshop and describe our collaborative efforts toward best practices.

2:45 USP GENERAL CHAPTER <661.3>: Plastic Components and Systems Used to Manufacture Pharmaceutical Drug Products

Desmond G. Hunt, Ph.D., Senior Scientific Liaison, Standards Development,

United States Pharmacopeia (USP)

USP General Chapter <661.3> contains tests, test methods and specifications for characterizing materials used to construct manufacturing components and for components used in manufacturing systems. The philosophy behind the development and contents of <661.3> will be discussed, specifically focusing on similarities and differences between packaging (addressed in <661.1> and <661.2>) and manufacturing. The essential aspects of <661.3>, including the Initial Assessment, the Risk Evaluation Matrix, and the Standard Extraction Protocol will be introduced.

3:15 Identification of Leachable from Single Use Component and Root Cause Analysis

Ben Jeyaretnam, Ph. D., MBA, Deputy Director, Unit Leader, E&L Analytical Lead, Analytical Process and Technology, Sanofi Pasteur

This presentation will showcase a well planned and executed study to characterize an observed leachable from single use bags that were used to ship drug product. Current industry practice is to use general screening methods to evaluate leachables. When a leachable is observed above the defined threshold, characterization and identification of the source is needed to evaluate the toxicological risk, product impact, and to support regulatory submission.

3:45 Refreshment Break in the Exhibit Hall with Poster Viewing

4:30 USP GENERAL CHAPTER <661.3>: Rationale for the Standard Extraction Protocol (SEP) Used in <661.3>

Dennis Jenke, Ph.D., Baxter Distinguished Scientist, Research & Development, Baxter Healthcare Corp.

The Standard Extraction Protocol (SEP) is applied in those high risk circumstances where extractables profiling of components is necessary. In this presentation the rationale behind the SEP is explained and the major features of the Protocol (extraction solvents, times and durations) are justified. Additionally, practical considerations in terms of generating extracts for different manufacturing components (e.g., bags, tubing, filters etc) are discussed. Lastly, the SEP will be compared to other proposed extraction protocols.

5:00 Redefine Extractable and Leachable (E&L) Terminologies for All Stakeholders

Ken Wong, Deputy Director, Process Technology, Sanofi Pasteur

The extractables and leachables terminologies have been used interchangeably by most stakeholders for over a decade. This has caused some confusion. In this talk, the speaker will propose a new definition for extractables and leachables which could help distinguish between the extractables and leachables regardless of who you are speaking to (suppliers, regulators, and drug manufacturers). Several examples will be examined from all stakeholder perspectives to demonstrate the confusion and clarity under the old and proposed definitions.

5:30 Close of Day

WEDNESDAY, JANUARY 11

8:00 am Conference Registration and Morning Coffee

ESTABLISHING DEVICES AND CONTAINER CLOSURE SAFETY: NEW TOOLS AND CASE STUDIES

8:30 Chairperson’s Remarks

Ping Wang, Ph.D., Principal Scientist, Material Sciences, Janssen R&D

8:35 Strategies for Managing the Impact of a Material Change in Components of Container Closure Systems

Michael A. Ruberto, Ph.D., President, Material Needs Consulting, LLC

The characterization and control of extractables and leachables from the plastic and elastomers used in container closure systems is a formidable task for the pharmaceutical industry. This presentation will provide a comprehensive review of the polymer supply chain for pharmaceutical packaging components as well as potential areas of concern. Case studies that illustrate the types of changes that can occur, both announced and unexpected, their chemical and regulatory impact, and strategies for managing the change will be discussed.

9:05 Updates on Guidelines on Establishing Delivery Device and Container Closure Safety

Diane Paskiet, MS, Senior Director, Global Scientific Affairs, West Pharmaceutical Services

This presentation will discuss PQRI safety and compatibility guidance based on chemistry of components used in delivery systems. It will also discuss regulatory expectations for chemical data on container closure systems, combination products and delivery devices. Lastly, it will also discuss how to use USP elemental impurity data for elastomers and correlating baseline data to finished systems for indented use.

9:35 Selected Poster Presentation: Analysis of Stir Bar Sorptive Extraction Recovery: Influence of Pharmaceutical Matrix Solutions and Mitigation of Inhibitory Effects

Nicole Scherer, Graduate Student, Pharmaceutical Technology & Biopharmaceutics, Ludwig Maximilians University

Stir bar sorptive extraction in combination with thermal desorption and GC-MS was used to detect trace amounts of leachables in protein based drug products. The influence of several drug matrices on the method’s recovery was tested with differently coated stir bars. Optimal sensitivity was obtained using polydimethylsiloxane stir bars, in the presence of solutions containing salts, surfactants or proteins. Simple stir bar preparations were found to facilitate increased detection sensitivity.

10:05 Coffee Break in the Exhibit Hall with Poster Viewing

10:50 Generic Approaches of Extractable Assessment of Ancillary Devices for Parenteral Dosing

Ping Wang, Ph.D., Principal Scientist, Material Sciences, Janssen R&D

Ancillary devices are usually needed for the delivery of biologics to patients. Those devices include iv bags, iv admin sets and/or extension sets, etc. The extractable/leachable risks of those devices are not widely studied comparing to manufacturing materials and container closure systems, even though the ancillary devices are closer to patient and therefore have higher safety risks. A generic approach has been developed to assess the E&L risks of the commonly used iv bags (8), iv sets (9) and extension sets (8). Results will be reported.

11:20 Forensic Features and Mitigations of Glass-Related Particles in Parenteral Glass Vials

“Gary” Guiyang Li, Ph.D., Senior Scientist, Attribute Science, Amgen

Proper classification and investigation of the glass-related particles (GRP) occurring in product will help to understand GRP formation mechanism, improve process control, reduce GRP occurrence rate, and deliver safer parenteral drugs to patients. In this talk, we introduce a classification scheme and characterization tools for GRP. We propose to classify GRP as glass chip, glass lamella/flake, and silica gel particles. This study summarized their forensic differentiations based on SEM and FTIR and mitigation methods for each type of particles.

11:50 PANEL DISCUSSION: Interaction between E&L and Proteins and Its Impact on Stability, Potency and Immunogenicity of Drug Substance and Drug Product

Moderator:

Diane Paskiet, MS, Senior Director, Global Scientific Affairs, West Pharmaceuticals

Panelists:

Michael A. Ruberto, Ph.D., President, Material Needs Consulting, LLC

Ping Wang, Ph.D., Principal Scientist, Material Sciences, Janssen R&D

Gary Li, Ph.D., Senior Scientist, Forensic Lab, Systems Analytics, Amgen

12:20 pm Sponsored Presentation (Opportunity Available)

12:50 Session Break

1:00 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

E&L CHALLENGES IN SINGLE-USE SYSTEMS AND PROCESSES

2:00 Chairperson’s Remarks

Diane Paskiet, MS, Senior Director, Global Scientific Affairs, West Pharmaceuticals

2:05 New Studies on Leachables in Protein Production Lines

Gerhard Winter, Ph.D., Professor, Chair, Pharmaceutical Technology and Biopharmaceutics, LMU Munchen

Leachable studies on production lines under commercial scale conditions using four marketed protein drug products are presented. The lines combine disposable container systems, steel vessels, silicone tubings, filters and gaskets. GC –MS was used as the main analytical method. The use of fluor-polymer coated extraction twisters followed by heat desorption allowed excellent leachable detection and quantification in the presence of the protein drugs. Leachables were found in extremely low concentrations.

2:35 Creating a Holistic Extractables and Leachables Program for Biotechnology Products

Yasser Nashed-Samuel, Ph.D., Principal Scientist, Process and Product Development, Amgen

The risk mitigation of extractables and leachables (E&L) presents significant challenges to regulators and drug manufacturers with respect to the development, as well as the lifecycle management of drug products. A holistic program should include a science- and risk-based strategy for testing E&L for primary containers, drug delivery devices and single-use systems for the manufacture of biotechnology products. The strategy should be designed to ensure patient safety and product quality.

3:05 Impact of Single-Use Systems on the Risk for Product Quality During Pharmaceutical Processing

Nina Xiao, Senior Research Associate, Late Stage Pharmaceutical Development, Genentech

Application of single-use systems for the manufacturing of biologics has increased significantly over the years and poses challenges for pharmaceutical processing in terms of leachables and their potential impact on product quality. There is a potential risk for protein particle formation with prolonged liquid storage in bioprocess containers and from silicone tubing originating from gamma irradiated single-use assemblies. Extractable analysis on localized silicone tubing discoloration will be examined and discussed.

3:35 Refreshment Break in the Exhibit Hall with Poster Viewing

4:30 SUS Leachables Testing: Leachables Study Design for Single-Use Components

Kathryn A. McGohan, MS, Associate Scientist II, Manufacturing Sciences and Technology: Materials Science, Bristol-Myers Squibb Co.

5:00 Improving Imaging-based Subvisible Particle Classification through Deep Learning

Neelima Chavali, MS, Engineer, Technology and Automation in Operations, Amgen

Imaging based systems are routinely used to characterize sub-visible particles like silicone oil and protein like particles. These systems distinguish between particle types primarily by analyzing particle image aspect ratio which is not always an accurate measure of particle type. We show how deep learning can be used instead, to determine particle type and demonstrate a big improvement in particle classification accuracy.

6:20 - 7:20 Reception in the Exhibit Hall with Poster Viewing

7:20 Close of Conference