Cambridge Healthtech Institute’s Third Annual
Detection and Characterization of Particulates and Impurities
Rapid Tools and Strategies for Risk Assessment, Prediction and Characterization of Particles and Impurities
from Products, Excipients and Processes
January 10-11, 2017 | Hilton San Diego Bayfront | San Diego, CA
Particles and impurities can come from the products, any stage of bioprocessing, or the delivery devices and primary packaging, and they have potential to impact stability, safety, and efficacy of the biomolecules and biologic products. Therefore, early
understanding, detection and characterization of the impurities are critical to ensure safety and efficacy of the drug product for its intended duration of use. The Third Annual Detection and Characterization of Particulates and Impurities conference
provides a platform to explore novel tools and strategies to detect, characterize and carry out risk assessment of particles and impurities.
We invite you to present a poster and attend to join colleagues in this discussion of the key challenges and solutions for prediction, characterization, and risk assessment of particles and impurities from products and processes.
TUESDAY, JANUARY 10
1:00 pm Conference Registration
1:30 Refreshment Break in the Exhibit Hall with Poster Viewing
2:00 Chairperson’s Opening Remarks
Mehrshid Alai, Ph.D., Head, Global RA CMC (interim), Regulatory Affairs, Shire
Keynote Presentation
2:05 Regulatory Requirements and Guidance on Particles and Impurities for Late Stage Submissions
Mehrshid Alai, Ph.D., Head, Global RA CMC (interim), Regulatory Affairs, Shire
The regulatory concern on particles and impurities is an evolving topic. The expectations from regulatory agencies are increasing and it is important to ensure they are adequately addressed for a successful submission. In this presentation, we will examine
some key regulatory guidance documents, as well as compare and contrast expectations from some key regulatory agencies. Some strategies around dealing with regulatory requirements in late stages of development will be discussed.
2:45 Detection of Impurities: Use of Pharmacopeia Reference Standards
Kevin Carrick, Ph.D., Scientific Liaison,, Global Biologics, United States Pharmacopeia (USP)
This presentation will provide an overview of the type of reference standards (RSs) provided by the United States Pharmacopeia, specifically the RSs used to detect and measure impurities. Information on characterization of these materials as well as data
to support their suitability for use will be presented. Cases studies from simple peptide molecules to complex biological preparations will be discussed.
3:15 Sponsored
Presentation (Opportunity Available)
3:45 Refreshment Break in the Exhibit Hall with Poster Viewing
4:30 LCMS Detection of the Residual Peptides from Yeast Extract and Hypep in In-Process Samples of Biotherapeutical Drug Substance
Guifeng Jiang, Ph.D., Senior Manager, Analytical Science, Boehringer Ingelheim
Some peptides from yeast and soy proteins may be immunogenic, raising safety concerns. Health authorities expect data showing clearance of the components of yeast/Hypep hydrolysates during the downstream purification process to be included in the BLA.
A reverse phase liquid chromatography with high resolution mass spectrometry method was developed to separate and detect components of the Yeast extract/Hypep and to demonstrate the clearance of the components during the purification process.
5:00 Sources, Detections and Control Strategies of Beta-Glucan Impurity in Biopharmaceutical Manufacturing Processes
Jinshu Qiu, Ph.D., Principal Scientist, Process Development, Amgen
(1-> 3)-β-D-glucans (beta-glucans) are a process-related impurity arising from raw materials used in biopharmaceutical manufacturing processes. Beta-glucans can be an indicator of invasive fungal infection or modulate an innate immune response,
therefore their presence in drug products may pose a potential safety concern unless controlled below safety limits. Hence, it is critical to ensure their clearance during manufacturing. Beta-glucan sources, detections, and control strategies will
be discussed in the presentation.
5:30 Close of Day
WEDNESDAY, JANUARY 11
8:00 am Conference Registration and Morning Coffee
8:30 Chairperson’s Remarks
Qingchun Zhang, Ph.D., Senior Scientist, Attribute Sciences, Amgen
FEATURED PRESENTATIONS
8:35 What We Learned from MS-Based HCP Analysis
Qingchun Zhang, Ph.D., Senior Scientist, Attribute Sciences, Amgen
Host cell proteins are important process-related impurities for biologics. A mass spectroscopy based HCP analysis approach and its applications will be discussed.
9:05 Host Cell Protein (HCP) Control Strategy Reassessment for a CHO-Derived Protein Therapeutic
John Rolf, Ph.D., Director, Corporate Quality, Product Quality Leader, Amgen
Immunoassay tests are standard to establish HCP impurity specifications and monitor protein therapeutic lot-to-lot consistency. However, multi-analyte Immunoassay tests may over- or under-quantify. xhsngIn this case study, Mass Spectroscopy (MS) identified
and quantified individual HCPs from protein product drug substance, comparing results to the Immunoassay. The case study demonstrates how MS testing (and supplemental characterization data) was used to redefine the HCP control strategy –
without impacting product or patient safety.
9:35 SELECTED POSTER PRESENTATION: Characterization of Commercial Drug Products and Comparison with In-House Produced Biosimilars
Anne Trappe, Graduate Student, Characterisation & Comparability Laboratory, National Institute for Bioprocessing Research & Training
Biosimilars are a hot topic. The purpose of this project is to populate a model to de-risk the biotherapeutic development process. A Trastuzumab biosimilar was transiently produced in HEK and CHO cells. The charge variant and glycan profiles of these
mAbs were characterised using LC-MS techniques and compared with the profiles of a commercially available drug product. Our findings showed significant difference in the profiles prior to media optimisation.
10:05 Coffee Break in the Exhibit Hall with Poster Viewing
10:50 Specific Immune Response to a Host Cell Protein Impurity
Sally Fischer, Ph.D., Principal Scientist, BioAnalytical Sciences, Assay Development and Technology, Department of Development Sciences, Genentech
A product related impurity was identified in the material used in clinical study. To assess the potential ability of patients to develop an immune response to the impurity and impact on immunogenicity of the therapeutic two bridging ELISA were developed
and validated. Samples from treated subjects were evaluated in both assays. This presentation will discuss the results of the immunogenicity assessment to the impurity and observed immunogenicity rate of the therapeutic.
11:20 Assessing Immunogenicity Risk in Biotherapeutic Product and Process Development
Valerie Quarmby, Ph.D., Staff Scientist and Director, BioAnalytical Sciences, Genentech
Every biotherapeutic has the potential to elicit unwanted immune responses, and these may compromise safety and efficacy. Several approaches can be used during lead selection and optimization to assess the likelihood that a biotherapeutic may be immunogenic.
Some of these may also be used to assess immunogenicity risk from product variants or process related impurities. This talk will review immunogenicity risk assessment systems in the context of process development.
11:50 PANEL DISCUSSION: Establishing Relationship of Impurity to Potency and Activity and How They Affect Patients, Storage and Shelf Life
Moderator:
Sally Fischer, Ph.D., Principal Scientist, BioAnalytical Sciences, Assay Development and Technology, Department of Development Sciences, Genentech
Panelists:
Valerie Quarmby, Ph.D., Staff Scientist and Director, BioAnalytical Sciences, Genentech
Qingchun Zhang, Ph.D., Senior Scientist, Attribute Sciences, Amgen
John Rolf, Ph.D., Director, Corporate Quality, Product Quality Leader, 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
2:00 Chairperson’s Remarks
Wendy Saffell-Clemmer, MS, Director, Research, Pharmaceutical Development, Baxter Healthcare
2:05 Selection of Pre-Filled Syringe for Biologic Products on Particulate Matter and Product Stability – A Case Study
Wendy Saffell-Clemmer, MS, Director, Research, Pharmaceutical Development, Baxter Healthcare
Pre-filled syringes provide significant advantages to the clinician and the patient. However, the pre-filled syringe and syringe filling process can have a significant impact on particulate formation and product stability. Methodical laboratory studies
on the formulation are needed to understand potential causes of particle formation. A case study describing development of a liquid monoclonal antibody pre-filled syringe product will be presented along with a discussion of manufacturing scale-up
challenges.
2:35 Developing a Multi-Pronged Approach to the Identification of PS20 Degradation Mechanism
Anthony Tomlinson, Senior Research Associate, Late Stage Pharmaceutical Development, Genentech
Polysorbates are commonly used non-ionic surfactants in protein pharmaceuticals. In recent years, there has been increasing concern in the degradation of these materials on long-term stability and the subsequent increase of insoluble degradation
products. In this talk, we will discuss the detection of PS20 degradation products and the identification the mechanism of degradation for root cause analysis.
3:05 Subvisible Particles: Rapid and High-Throughput Tools for Prediction, Detection and Characterization of Subvisible Particles and Other Aggregates
Andrea Hawe, Ph.D., CSO, Coriolis Pharma
Aggregates and subvisible particles (SVP) are considered cQA for biologics, and it is crucial to include a comprehensive characterization early during drug product development. Especially, for early development a reduction of required time, material
and resources is essential. Within the talk an overview of methods and strategies for SVP and aggregate analysis is given, with special focus on minimization of material requirements, increase in throughput and possibilities for prediction
of stability.
3:35 Refreshment Break in the Exhibit Hall with Poster Viewing
4:30 Prediction of Antibody Stability in Lyophilized Solids by Hydrogen Deuterium Exchange with Mass Spectrometric Analysis (HX-MS)
Kathleen Abadie, Engineer I, Late Stage Pharmaceutical Development, Genentech
We explore HX-MS to study protein structure in lyophilized solids for deeper understanding of solid state stability and to save time and resources in pharmaceutical development. HX probes structure by measuring the frequency of stabilizing amide
H-bonds. Indeed, we show that reduced stability as indicated by increased deuterium uptake versus time correlates with increased aggregation propensity. Stability effects of lyoprotectant concentration and processing conditions are assessed
by HX-MS.
5:00 Scaled Down Containers for Protein Stability Studies
Eric Meinke, Ph.D., Senior Scientist, AstraZeneca Supply Biologics
Real-time, real-condition stability study is essential to establish the expiry of biological therapeutics. For drug substance, stability study is typically performed in small scale containers that mimic the actual storage container/condition at
scale. A case study will be presented to highlight the criticality of understanding and controlling of the scaled down container for stability studies.
6:20 - 7:20 Reception in the Exhibit Hall with Poster Viewing
7:20 Close of Conference