2016 Archived Content

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Cambridge Healthtech Institute’s 4th Annual
Extractables and Leachables
Protecting Quality of Biologics by Ensuring Safety and Compatibility
January 21-22, 2016

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 4th Annual Extractables and Leachables (E&L) conference brings together industry experts and thought leaders to share their insights on latest updates and guidelines, how to design analytical testing strategies for E&L, case studies on identification and risk assessment E&L in single-use system, container closure system and delivery devices, and impact of leachables on biologics safety.

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

Final Agenda

THURSDAY, JANUARY 21

7:45 am Conference Registration and Morning Coffee

8:15 Chairperson’s Opening Remarks

Ken Wong, Deputy Director, MTech/AP&T - Extractables & Leachables, Sanofi Pasteur

8:20 The PQRI Parenteral and Ophthalmic (PODP) Leachable and Extractable Working Group: Outcomes and Practical Applications

Diane_Paskiet Diane Paskiet, MS, Director of Scientific Affairs, West Pharmaceutical

The PODP recommendations for safety thresholds and best practices will be reviewed. Data from material characterization and simulation studies will be put into perspective based on biologics.

9:00 Featured Presentations: BPOG's Best Practice Guides

These presentations will discuss the BPOG’s standard extractable protocol along with regard to flexibilities, myths and misconceptions. Followed by the presentation of data from the completed proof of concept case studies data using bags and O-rings to demonstrate viability of the study design. Introduction of the new BPOG’s Best Practice Guide for SUS leachables testing, covering: risk assessment; leachable study design for SUS components; leachable test method(s). Wrapping up with end user perspective on how a member company adopts BPOG’s recommendations.

Part 1 - BPOG's Risk Assessment Tool/Process

Dhaval_Tapiawala Dhaval Tapiawala, Technical Project Leader, Fujifilm Diosynth Biotechnologies

Part 2 - BPOG’s Best Practice Guide for SUS Leachables Testing: Leachables Study Design for Single Use Components

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

Part 3 - BPOG’s Extractable & Leachable Best Practice Protocol for Single-Use Components

Ken_Wong Ken Wong, Deputy Director, MTech/AP&T - Extractables & Leachables, Sanofi Pasteur

10:00 Coffee Break in the Exhibit Hall with Poster Viewing

11:00 CMO Tech Transfer Material Control Strategies: A Case Study

Michael_DiFiore Michael DiFiore, Scientist I, Materials Science, Bristol-Myers Squibb

Chemical compatibility of a process stream with a disposable is a critical element of determining the suitability of the single use system. A case study is presented on the investigation and impact assessment of an incompatible filtration of a polyethersulfone (PES) membrane with 100% benzyl alcohol, resulting from a tech transfer to a CMO. The presentation will also discuss material control strategies related to CMO tech transfers.

11:30 De-Risking through Identifying the Unknowns in Controlled Extraction Studies for Halogenated Rubbers

Christiaens_Piet Piet Christiaens, Ph.D., Scientific Director, Extractables & Leachables Services, Toxikon Europe

Halogenated rubber oligomers – often seen in CES of halo-rubbers – are a group of compounds that are alkylating agents with a high reactivity for certain functional groups. Understanding this, would it be possible that a group of these reported unknowns could be linked to reaction products of these halo-oligomers with other rubber ingredients, such as curing agents, activators, accelerators?

12:00 pm Session Break

12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:15 Ice Cream Break in the Exhibit Hall with Poster Viewing

2:00 Chairperson’s Remarks

Diane Paskiet, MS, Director of Scientific Affairs, West Pharmaceutical

2:05 Experimental Design Considerations for Extractables Simulation Studies

Dennis_Jenke Dennis Jenke, Ph.D., Baxter Distinguished Scientist, Technology Resources, Baxter Healthcare Corp.

A simulation study produces an extractables profile that appropriately mirrors a test article’s leachables profile. This is accomplished via a controlled extraction study which uses an extraction solvent to mimic the “leaching power” of the contact solution (such as drug product) and accelerates the clinical conditions of contact (shorter duration at higher temperature). This presentation addresses those factors to consider in terms of simulating solvent selection and proper acceleration.

2:35 Qualitative Characterization and Visualization of Complex Mixtures of Extractables/Leachables and Other Pharmaceutically Relevant Compounds Using High Resolution LC-MS with 2-D and 3-D Mass Mapping

Douglas_Kiehl Douglas E. Kiehl, Principal Research Scientist, Spectroscopy & Raw Materials, Bioproduct Research & Development, Eli Lilly & Company

Extractables and leachables (E&L) associated with packaging and container systems, delivery devices and process equipment can pose risk to the safety and quality of drug products. E&L samples may represent complex mixtures of diverse organic molecules, presenting significant analytical challenges. This presentation discusses the application of 2-D/3-D mass mapping, mass difference correlation and visualization of high resolution exact mass LC-MS datasets to simplify interpretation of such complex mixtures.

3:05 Sponsored Presentation (Opportunity Available)

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

4:15 Extractables and Leachables Strategy for Parenteral Drug Products

Meera_Agarkhed Meera Agarkhed, Manager, Formulation Development, Eli Lilly and Company

This presentation will discuss extractables and leachables risk assessment strategy for manufacturing and fill finish operations and their impact on biotherapeutics safety, efficacy and stability.

4:45 The Value of the “Simulated Study” as a Tool to Predict Actual Leachables in Parenteral Drug Products

Carsten_Worsøe Carsten Worsøe, Principal Scientist, CMC Analytical Support, Novo Nordisk

This presentation will describe the simulated study as the optimal study to predict actual leachables in different parenteral drug products including cartridges, vials and prefilled syringes and how it can be used to reduce the risk for having critical leachables and reactions between leachables and formulation components or the active ingredient at a late drug development phase. The presentation will also describe a number of different opportunities on how to perform simulated studies and finally a number of cases will be presented showing the value.

5:15 A Vision of Understanding Extractables and Leachables; Impact on Drug and Device Manufacturing Processes

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

Extractables and leachables are critical product contact assessments throughout the product life cycle due to their possible impact on product quality and patient safety. A thorough evaluation of the extractables from product contact surfaces during product development will ensure successful long term leachables testing, process robustness, product quality, device functionality and patient safety. Selected case studies presented will reflect the importance of extractables evaluation to product development.

5:45 Close of Day

6:00-7:00 Reception in the Tiki Pavilion

FRIDAY, JANUARY 22

8:00 am Conference Registration and Morning Coffee

8:30 Chairperson’s Remarks

Joël Richard, Ph.D., Vice President, Peptides, CMC & Engineering, Ipsen

8:35 Predicting the Risk of Extractables and Leachables (E&L) Interacting with Therapeutic Proteins

Kim_Li Kim Li, Ph.D., DABT, MPH, Senior Manager, Environment, Health, Safety and Sustainability, Amgen, Inc.

Therapeutic proteins can be subject to chemical modifications which may lead to product quality and safety concerns. Extractables and leachables (E&L) arising from process- and product-contact surfaces present the risk of interacting with the protein products. This presentation will describe the mechanisms of such interactions and the use of an in silico software that classifies E&L structures into reactive functional groups for risk prediction.

9:05 Extractables & Leachables in Liquid Formulations of Proteins: Impact on Stability, Aggregation, Potency and Immunogenicity of Drug Product

Joel_Richard Joël Richard, Ph.D., Vice President, Peptides, CMC & Engineering, Ipsen

Extractables and leachables are impurities that can contaminate liquid formulations of biologics, leaching from the surface of glass walls or being extracted from the rubber stoppers and plungers. They can interact with and degrade proteins, modifying their higher order structure, forming mixed micelles, or composite protein aggregates. These impurities may have a strong impact on stability, quality attributes and immunogenicity profile of the protein drug products.

9:35 Oxidation of Methionine in Aggregated Antibodies does not Increase the Potential Risk of Immunogenicity

Marisa_Joubert Marisa K. Joubert, Ph.D., Senior Scientist, Process Development, Amgen, Inc.

This talk will give an update on the aggregate attributes of monoclonal antibodies (mAbs) that may cause an immune response. The potential impact of Met oxidation of both aggregated and monomeric antibodies was investigated in a population of human peripheral blood mononuclear cells (PBMC) from healthy and disease state individuals (50+ donors tested) in vitro. Met oxidation was found not to increase the potential risk of immunogenicity of both aggregated and monomeric antibodies.

10:05 Coffee Break with a Poster Pavilion

PepTalk is proud to support and recognize the protein scientists of tomorrow during the Poster Pavilion. This time has been set aside to view the Student Fellowship posters and interact with presenters one on one. This opportunity gives job seekers the chance to share their expertise with future/potential employers or develop contacts to further their research.

11:00 Investigation of Reversible Self-Association during Early Stage Development of a Low Concentration Antibody-Drug Conjugate

Elizabeth Bartlett, Scientist II, Analytical & Pharmaceutical Sciences, ImmunoGen, Inc.

Reversible self-association is often present in high concentration antibody products, but may also occur in lower concentration preparations. In the case of antibody-drug conjugates (ADCs), a novel class of molecules for the treatment of cancers, this property can present substantial challenges to successful formulations. In this study, a multi-technique approach was used to identify and investigate the effects of various excipients on reversible self-association in a low concentration ADC.

11:30 Characterizing Changes in Protein Quality Attributes to Assess Leachable Risks from Single-Use Bioprocess Containers

Nina_Xiao Nina Xiao, Senior Research Associate, Late Stage Pharmaceutical Development, Genentech, Inc.

Application of single-use bioprocess containers for the manufacturing of biologics have increased significantly over the years. This study examines two monoclonal antibodies in a small-scale stressed model to detect and assess the presence of leachables by monitoring protein quality attributes. The results from this study demonstrate that the stress model can inform a risk assessment of leachables on protein quality attributes during routine manufacturing. Leachable characterization will also be discussed.

IT’S A WRAP:
PEPTALK 2016 CLOSING PLENARY PANEL DISCUSSION
Friday, January 22, 12:00 pm

Protein therapeutics is one of the fastest-growing global markets, driven by increasing adoption of protein- over non-protein drugs, growing funding for protein engineering and reduced drug discovery timelines and costs. As the science improves, so does the complexity of the R&D organization: it really does “take a village” to bring nextgeneration therapies to market and patients who need them. Ensuring product quality plus speed to market requires collective insights from experts working across the stages of protein science R&D – as embodied by panelists representing each PepTalk Pipeline topic.

They discuss: