Cambridge Healthtech Institute’s 2nd Annual
Process Characterization, Qualification and Control
A best practices forum for process characterization, control strategies and maintaining quality throughout the product lifecycle
Part of CHI's 8th Annual The Bioprocessing Summit

August 18-19, 2016 | Westin Boston Waterfront | Boston, Massachusetts

With the recent publication of process validation guidances from both US and European regulators, the demonstration of process understanding, identification of critical quality attributes and the implementation of well-validated control strategies must now become a routine part of biologics manufacturing operations. But significant ambiguities remain in the specific steps that must be taken in the production of legacy and new products, by companies of different scale and resources and for specific product formats. Process Characterization, Qualification and Control offers a forum for the sharing of strategies and best practices from a wide range of industry companies working to implement these complex new standards.

Thursday, August 18

11:30 am Registration Opens

12:15 pm Lunch Available for Purchase in the Exhibit Hall

1:15 Dessert Refreshment Break in the Exhibit Hall with Poster Viewing

1:55 Chairperson’s Opening Remarks

Paul Bigwarfe, Ph.D., Director, Analytical Sciences, Regeneron Pharmaceutical.

Line of Sight to the Process Control Strategy: A Plan for Commercial Success

Tim_SchofieldTimothy Schofield, ‪Senior Advisor, GlaxoSmithKline‬

The biopharmaceutical control strategy is a covenant between the manufacturer and the customer. Early consideration of manufacturing conditions and constraints, coupled with process and analytical knowledge, inform process and analytical development. The control strategy represents the translation of development experiences and supporting plans to ensure product quality and supply. This presentation highlights a proactive approach to development of a robust control strategy that meets the requirements of both patients and manufacturers.


2:45 DOE Studies in Support of Early Stage Process Characterization

Paul_BigwarfePaul Bigwarfe, Ph.D., Director, Analytical Sciences, Industrial Operations and Product Supply, Regeneron Pharmaceuticals

A DOE is becoming an essential part of the method development life cycle to better understand the acceptable ranges for the method. However, for methods at preclinical and Phase I stages, resources may not exist to evaluate every parameter. A rational strategy has been designed to analyze the most critical parameters for release assays for each new molecule, saving a more comprehensive robustness study for later in development.

3:15 Efficient High-Throughput Biological Process Characterization

Mithell_TaiMitchell Tai, Ph.D., Scientist, Biologics Process Development, Bristol-Myers Squibb

Systems for high-throughput process characterization are poised to greatly improve development timelines. Here we combine the Sartorius ambr250 system with definitive screening design experiments to perform rapid process characterization for a microbial process for recombinant protein production. Main effects screening and process modeling can be generated within a single round of experimentation. The results demonstrate a quality-by-design (QbD) approach for both early-stage process development and late-stage process characterization.

3:45 Considerations for Material Qualification During Process Development

Doherty_StephenStephen Doherty, Ph.D., Department Head, Analytical Chemistry, Toxikon Corporation

This presentation will outline key considerations when selecting material and components for single use systems. Thought processes and evaluation strategies related to the selection of these materials and components will be discussed. This presentation will benefit scientists and engineers engaged in the development, production and implementation of single use systems in understanding in the selection of these materials.

4:00 Refreshment Break

4:15 Multi-Attribute LC/MS Methods for Process Characterization and Design Space Development

Kristin_KrukenbergKristin Krukenberg, Ph.D., Analytical Scientist, Process Development, Shire

Complex biologics provide a unique analytical challenge for characterizing and monitoring multiple CQAs. We developed an LC/MS based approach that provides more detailed information than six “standard” analytical methods reducing analytical testing time and allowing for more comprehensive and timely support of process characterization and development.


Analytical Considerations for QbD and PAT of Biotechnology/Biosimilar Process Development

Nadine_RitterNadine M. Ritter, Ph.D., President & Principal Advisor, Global Biotech Experts LLC

The value derived from QbD studies and PAT measurements is only as good as the analytical methods they employ. If analytical data are inaccurate or inconsistent due to method performance capabilities, the observations and conclusions could be erroneous. This presentation will highlight some of the most challenging analytical aspects of process characterization, illustrate examples of common mistakes made, and provide recommendations on how to minimize the analytical risks to process design and process control.

5:15 End of Day

5:15 Registration for Dinner Short Course

Friday, August 19

8:00 am Registration Opens and Morning Coffee


8:25 Chairperson’s Remarks

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

8:30 Continuous Process Validation

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

9:00 Extraction Study of a Cartridge Filter Based upon the BioPhorum Operations Group (BPOG) Recommendation

Kurt_MoyerKurt Moyer, Ph.D., Director, Research, NSF Health Sciences

In this study the extractables from a process filter were evaluated based upon the protocol developed by BPOG. The sample was extracted in six extraction solvents at 40°C with orbital rotation for 7 days. Sample extracts were analyzed for organic and inorganic extractables. For the organic extractables, a total of 9 were observed with 6 being identified. For the inorganic extractables, a total of 7 were observed and identified.

9:30 Whole Molecule LC-MS Analysis for HT Monitoring of Asn-Ser Substitution in an Antibody: Challenges in Method Performance Assessment

Celine_DuhotCéline Duhot, Assistant Manager, Biotech Process Sciences, Merck KGaA, Germany

Product quality testing along process development and characterization requires HT tools as well as deep method understanding. This presentation discusses the case study of Asn-Ser substitution analysis of an IgG by whole molecule LC-MS. Method performances were evaluated using a genomically designed fully substituted antibody. Talk addresses challenges in assessing semi-quantitative performances of MaxEntropy deconvoluted data for the monitoring of small Dmass, not fully resolved even on a state-of-the-art Q-Tof.

10:00 Networking Coffee Break


10:30 Technology Update: Process Analytical Technologies for Biologics Manufacturing

Sheila G. Magil, Ph.D., Senior Consultant, BioProcess Technology Consultants, Inc.

11:00 Plant-Wide Process Control Model for Biologics Manufacturing

Richard_BraatzRichard Braatz, Ph.D., Edwin R. Gilliland Professor of Chemical Engineering, Massachusetts Institute of Technology`

A case study is presented in which mechanistic models are constructed for all unit operations in an integrated biopharmaceutical manufacturing pilot plant. The individual models are interconnected to form a dynamic operations model of the entire plant. The mechanistic models are used in the design of control systems for individual unit operations, and a strategy is described in which the overall plantwide control strategy is designed to suppress the effects of disturbances and uncertainties on the critical quality attributes.

11:30 Production Process Optimization and the Development of In-Process Controls Utilizing In-Line Spectroscopic Measurements

Terrence_DobrowskyTerrence Dobrowsky, Ph.D., Senior Engineer, Biogen

Second generation process development offers an opportunity to increase productivity and process robustness by implementing process changes and new control schemes. DOE practices were used to optimize parameters and increase productivity for an IgG producing CHO culture. Additionally, Raman spectroscopy enabled online glucose control to reduce glycated product. This work increased productivity, decreased scale up and raw material risk, and demonstrated the relative ease of implementing advanced process analytics.

12:00 pm Application of a QbD Approach to Control System Design for a Late Stage Monoclonal Antibody

John Eschelbach, Ph.D., Scientist, Genentech

12:30 Luncheon Presentation: Extractables Leachables for Single Use Systems in Bio Manufacturing

Schaible_SandiSandi Schaible, Director, Analytical Chemistry, WuXi AppTec

Extractables Leachables for Single Use Systems in Bio Manufacturing : Regulatory, industry and risk considerations for designing a successful extractables leachables program. A review of current regulatory environment, a summary of recognized industry schools of thought and risk to be considered in development of a customized approach that works for your system and product application.

1:15 Session Break

1:25 Chairperson’s Remarks

Vincent Lau, Manager, Cell Culture Development, Biogen

1:30 A Two-Tiered Approach to Process Characterization for Late Stage Monoclonal Antibody Programs

Mike_ClarkMichael Clark, Ph.D., Senior Scientist, Process Sciences, AbbVie

For efficiency of downstream process characterization, first tier DOE studies utilized Definitive Screening Design (DSD) to identify the process parameters with the highest impact on product quality attributes. This allowed minimalized second tier DOE studies using Response Surface Design (RSD) to thoroughly investigate these high impact parameters. This presentation describes the statistical design and model selection of the studies, and provides a comparative analysis of the DSD and RSD results.

2:00 Vaccine Control Strategy Evolution during Late-Stage Development and Commercialization

Jennifer_DashnauJennifer Dashnau, Ph.D., Director, Global Vaccines and Biologics Commercialization, Merck & Co., Inc.

Modern vaccines are amenable to characterization through a wide range of analytical techniques and robust control strategies may be developed. GARDASIL®9 provides an opportunity to understand analytical control strategy evolution for a well-characterized, recombinant vaccine product from late-stage development to commercialization. Examples of the impact of 1) process modifications made during development and 2) increased process and product performance understanding gained during commercialization on control strategy will be provided.

2:30 Application of Monte Carlo Simulations in the Development of Advanced Control Strategies and Manufacturing Facility Fit

Vincent_LauVincent Lau, Manager, Cell Culture Development, Biogen

Real time control strategies introduce additional complexity to the task of setting process controls on bioprocesses. Stochastic cell growth modeling and Monte Carlo simulation methods were evaluated for use in dealing with the relative complexity of setting appropriate control limits for these types of processes, as well as other common facility fit or scale-up concerns. Use of these new methods allows for controls that ensure process consistency and reliable performance.

3:00 Real-Time Product Attribute Control of N-Linked Glycan Levels

Jeff_UnderhillJeff Underhill, Senior Associate, Pivotal Cell Sciences & Technology, Amgen

The active control of product quality in biologic manufacturing processes is challenging due to measurement lags, system nonlinearities, and a lack of robust control levers. A product attribute control method utilizing nonlinear model predictive control coupled with a rapid PAT system will be presented along with data from a pilot scale bioreactor run where this method successfully maintained a critical product quality attribute, percent high mannose, at a predetermined level.

3:30 Close of Conference