Cambridge Healthtech Institute’s Inaugural
Bioprocess Quality and Regulatory Compliance
A best practices forum for process characterization, control strategies and maintaining quality throughout the product lifecycle
August 3-4, 2015
Part of CHI's 7th Annual The Bioprocessing Summit

August 3-7, 2015 | Westin Copley Place Hotel | Boston, Massachusetts

For biologic drugs, regulatory agencies expect that manufacturers will demonstrate a complete understanding of product and process based sources of variability and have in place control strategies that manage production processes within an established design space. CHI’s Inaugural Bioprocess Quality and Regulatory Compliance offers best practices from across the industry of experiences with the essential steps of identifying critical quality attributes and process parameters, implementing appropriate control strategies and managing the quality and variability of raw materials and consumables. Speakers will also offer insights into their approaches to risk assessment and resource allocation for these complex steps.

Monday, August 3

8:00 am Pre-Conference Registration and Morning Coffee

9:00-11:30 Recommended Short Course*
Optimizing Media – Achieving Super Soup

* Separate registration required

11:30 Main Conference Registration

1:00 pm Chairperson’s Opening Remarks

Bob Kozak, Ph.D., Senior Regulatory Science Advisor, Bayer HealthCare Pharmaceuticals

1:10 KEYNOTE PRESENTATION: Analytical Methods and Specification Revisions during the Product Lifecycle

Stephan Krause
Stephan O. Krause, Ph.D., Director, QA Technical Support, AstraZeneca Biologics

This presentation provides best practices for specifications setting for clinical biological products within the framework of ICH guidelines on pharmaceutical development (Q8(R2) and Q11), quality risk management (Q9) and quality systems (Q10). The need to link the life cycles of test method(s) and specifications is illustrated. A case study illustrates how the IMP specification revision process can be managed and how specifications can be set and justified for early and late development stages.



1:45 Strategies for Immunogenicity Risk Assessment and Regulatory Compliance

Bob Kozak Bob Kozak, Ph.D., Senior Regulatory Science Advisor, Bayer HealthCare Pharmaceuticals

Many biotherapeutic products are immunogenic with minimal tools for predicting clinical outcome, therefore immunogenicity risk identification, analysis, evaluation, mitigation and management need to be incorporated into your programs as an iterative process. Immunogenicity risk assessment strategy, process and regulatory expectations will be discussed.


2:15 Implementation of QbD Principles into Commercial Process Development and Process Characterization for mAbs and Fc-fusion Proteins

Angela Lewandowski
Angela Lewandowski, Ph.D., Manager, Biologics Process Development, Bristol-Myers Squibb

Risk assessments are a useful tool during commercial process development and process characterization to drive process control strategies, thereby ensuring consistent process performance and product quality. This talk will focus on the implementation of QbD principles (via risk assessment and management) during upstream and downstream commercial process development and characterization. Case studies for both mAbs and Fc-fusion proteins will be discussed.


2:45 Refreshment Break

3:15 Risk Management of Regulatory Submissions

James Stonecypher James Stonecypher, Regulatory Affairs Executive

Identifying and managing risks is an essential and continuous activity in the development of (bio)pharmaceutical products. ICH Guideline Q9 outlines the principles, process, and tools for utilizing quality risk management in the pharmaceutical industry. Risk management activities are often overlooked or underutilized in the regulatory submissions process. This presentation will discuss the benefits and applications of risk management for regulatory submissions and practical examples of how it can be implemented.


3:45 Regulatory Issues in the Development of a Biosimilar Rituximab

Mauricio SeigelchiferMauricio Seigelchifer, Ph.D., Director, Tech Transfer, Mabxience, Argentina

The development pathway for biosimilar medicines is established in guidelines from WHO, EMA and more recently FDA and different Latin American countries. The process, from the cloning, passing through upstream and downstream, has to be driven to obtain a highly similar molecule to the reference product. Here we present a case study of a biosimilar Rituximab developed and produced to fulfill these biosimilar requirements. We also present the comparison with the market reference.


4:15 Breakout Discussions

This session provides the opportunity to discuss a focused topic with peers from around the world in an open, collegial setting. Select from the list of topics available and join the moderated discussion to share ideas, gain insights, establish collaborations or commiserate about persistent challenges. Then continue the discussion as you head into the lively exhibit hall for information about the latest technologies.

Best Practices for Analytical Support of Product Quality  

Moderator: Stephan O. Krause, Ph.D., Director, QA Technical Support, AstraZeneca Biologics  

  • Specification setting
  • Method life cycle (AMQ, AMV, AMT)
  • Accelerated program considerations: specifications, AMV, etc.
  • USP <129>
  • ICH Q3D
  • Analytical similarity (biosimilars): acceptance criteria, sample size, comparison model(s) etc.

How to Build a QbD Infrastructure in CMC from Early Phase Drug Development Without Impacting Timelines and Resources  

Moderator: Zhimei Du, Ph.D., Principal Scientist, Teva Pharmaceuticals  

  • What is the right time to define quality target product profile (QTPP)?
  • How much effort is appropriate to determine critical quality attributes for early phase drug development?
  • How to define critical process parameters?
  • What is the right design space for early phase drug development?

Process Characterization Studies

Moderator: Angela Lewandowski, Ph.D., Manager, Biologics Process Development, Bristol-Myers Squibb  

  • What is your strategy for the risk assessment in determining CQAs prior to process characterization studies? What data/studies is your risk assessment based on? What type of risk assessment is performed?
  • What is your strategy for determining the ranges evaluated in process characterization studies? Do you focus on bracketed ranges around the expected normal operating range (NOR)? If so, how do you determine the bracketed range? Or, do you probe the “edge of failure”?
  • What is your strategy for determining which impurities to evaluate in spiking/clearance studies during process characterization?
  • What is your strategy for determining Critical Process Parameters (CPPs) versus non-CPPs? Do you have a systematic and quantitative system? Or is this based on subject matter expertise? What type of risk assessment is performed?
  • What is your strategy for determining which non-CPPs, if any, to include in the marketing application? Is there a systematic methodology? Have you received health authority feedback on number of CPPs versus non-CPPs or on your methodology?


5:15 Discussion Report-Outs

5:30 Grand Opening Reception in the Exhibit Hall with Poster Viewing

7:00 End of Day

Tuesday, August 4

7:30 am Registration and Morning Coffee


7:55 Chairperson’s Remarks

Karthik P. Jayapal, Ph.D., Deputy Director, Manufacturing Technologies, Sanofi-Pasteur

8:00 Challenges and Learnings Applying Retrospective QbD for Marketed Biologics

Kenneth Green Kenneth Green, Ph.D., Head, Manufacturing Science and Technology, Shire

For clinical candidates, QbD is generally applied during development and commercialization phases as a standardized business process. However, this is not typically the case for marketed products where retrospective QbD requires consideration of established controls and regulatory commitments. This talk discusses Shire’s approach for retrospective QbD for marketed products including establishing a business process, associated criticality and change control strategy via application of risk assessments, and the behavioral changes required for successful implementation.


8:30 Product Characterization Methods and Strategies for Process Development

case studyChristine P. Chan, Ph.D., Principal Scientist and Technical Lead, Manufacturing Science & Technology, Genzyme - a SANOFI company

Development of complex glycoproteins requires an array of analytical techniques to adequately understand and control product quality during the manufacturing process. This presentation will discuss strategies in product testing and review case studies on characterization of different proteins in support of process development.

9:00 Troubleshooting Bacterial Vaccine Production

Karthik Jayapal
Karthik P. Jayapal, Ph.D., Deputy Director, Manufacturing Technologies, Sanofi-Pasteur

The use of complex raw materials like casamino acids or soy hydrolysates in bacterial fermentation can contribute to process and ultimately product variability. This case study will focus on our approach to mitigating such risks for a bacterial vaccine production process by exploring opportunities for better raw material characterization, improved process robustness and simplifying, and/or modernizing the current manufacturing process.


9:30 Late-Breaking Presentation

9:45 Coffee Break in the Exhibit Hall with Poster Viewing

10:30 Using New Analytical Technologies for Process Characterization

Nadine Ritter Nadine M. Ritter, Ph.D., President and Analytical Advisor, Global Biotech Experts, LLC

Initiatives such as PAT and QbD, plus the desire to continuously improve production by leveraging process comparability paradigms, have enhanced the need to utilize both classic and state-of-the-art analytics for upstream and downstream characterization and comparability exercises. This talk will provide an overview of current applications of analytics in process development, and highlight practical issues to be considered in selecting and applying a wide array of analytical technologies to biotechnology processes.


11:00 Analytical Characterization to Support Development of Antibody Biopharmaceuticals: Identity, Purity, Potency and Safety

Xuan Gao
Xuan Gao, Ph.D., Scientist, Sutro Biopharma, Inc.

During our early development of an IgG1 molecule, LC/MS/MS was used to identify sequence variants and post translational modifications; Biacore and other assays were used to determine consequences of such variants and modifications on potency and safety. We correlated characterization results with process procedures to identify the root cause of sequence variants and modifications. Furthermore, rapid analytical methods were developed to support screening and production of desired molecule during development.


11:30 Bioprocess Characterization Approach for a Marketed Biosimilar

case studyDaliborka Dušanić Ph.D., Validation Lead, MS&T, Lek Pharmaceuticals, Slovenia

For the registration of legacy products marketed outside the US, FDA regulations demanding in depth understanding of sources of variability in the production of a biosimilar can be challenging. The knowledge gained during process characterization can be beneficial from the manufacturing and QA perspective; however, it can also pose business risks such as the need for re-validation and changes in filings in other countries. This case study reviews the approach for PC of a legacy biosimilar product.

12:00 pm Late-Breaking Presentation

12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:15 Session Break


1:55 Chairperson’s Remarks

Zhimei Du, Ph.D., Principal Scientist, Teva Pharmaceuticals

2:00 Utilization of Advanced Process Control to Drive Consistent Processes in Mammalian Cell Culture

Vijay Janakiraman, Ph.D., Senior Engineer, Biogen Idec

Advances in online process monitoring have paved the way for the next generation of control strategies for achieving advanced process control. The end result will be more consistent process performance and product quality control. This talk will provide insight into new process analytical technologies (PAT), such as spectroscopy and biocapacitance, to assist in the implementation of online process monitoring.

2:30 Control Strategy Approach for a Well-Characterized Vaccine

Parag Kolhe
Parag Kolhe, Ph.D., Senior Principal Scientist, Pfizer

Robust control strategy as proposed in ICH Q10 is the foundation for ensuring consistent process performance and product quality. This presentation will describe approach towards developing control strategy during development lifecycle. Case study will be presented for well-characterized vaccine product that illustrates the approach and its utility during process performance qualification (PPQ) and commercial manufacturing.


3:00 Practical Considerations of Using Real-Time Multivariate Statistical Process Monitoring to Ensure Batch Consistency

Eric Kwei
Eric Kwei, Process Engineer, Amgen

Commercial bioprocess manufacturing facilities generate significant amounts of continuous data that can be challenging to analyze effectively. Presenting meaningful, accessible, and timely conclusions about this data requires a broad understanding of statistical methodology, process design, process automation, and human factors. The intersection of these elements will be discussed in the context of a real-time multivariate process monitoring program implementation.


3:30 Refreshment Break in the Exhibit Hall with Poster Viewing

4:15 Deciphering Factors that Have Impacts on Glycosylation of mAb and its Biophysical Properties

Zhimei Du Zhimei Du, Ph.D., Principal Scientist, Teva Pharmaceuticals

Consistent and reproducible generation of mAb glycoform profiles still remains a considerable challenge in biopharmaceutical industry. To assess the mechanism of immature glycan process, and to minimize the environment-mediated lot-to-lot variations, we identified a broad range of factors that impact on the glycosylation maturation of mAbs. Our results indicate that high mannose may lead to changes in biophysical properties including protein conformation, thermal stability, colloidal stability, and aggregation propensity.


4:45 Core Components for Contamination Prevention and Control in Biopharmaceutical Manufacturing Operations

Gary du Moulin Gary C. du Moulin, Ph.D., M.P.H, RAC, Adjunct Associate Professor of Drug Regulatory Affairs, Massachusetts College of Pharmacy and Health Sciences University

Microbial contamination in bioprocessing operations remains a key concern in plant operations. Microorganisms, such as Acinetobacter baumanii, find areas in our manufacturing facilities to reside and constitute a potential risk to bioreactor operations. Contamination events result in costly delays and restarts but most importantly, threaten the supply of lifesaving products to our patients. This presentation identifies those core components of contamination prevention which if implemented can provide the greatest impact in minimizing the microbiological risks in our manufacturing sites.


5:15 Close of Conference

6:00-8:30 Recommended Dinner Short Course*
Patent Strategies for Bioprocess Scientists

* Separate registration required

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