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Key Sessions

Tony D'Amore, PhD, MBA

Accelerating Development and Innovation: Advances & Challenges in Vaccine Development

Sanofi Pasteur

Christopher Crowell, PhD

Application of Frontier Science: Lessons from Implementation of Next Generation Manufacturing at Amgens Singapore Facility

Amgen Inc.

7:00am - 8:00am

Registration and Coffee

8:00am - 8:05am
Chairperson's Opening Remarks

Chairperson's Opening Remarks

Showing of Streams
9:15am - 9:55am

Networking Refreshment Break in the Poster and Exhibit Hall

Showing of Streams
Showing of Streams
Showing of Streams
Showing of Streams
Showing of Streams
Showing of Streams
3:20pm - 4:00pm

Networking Refreshment Break in the Poster and Exhibit Hall

Showing of Streams
5:30pm - 7:00pm

Opening Night Reception in the Poster and Exhibit Hall - co-sponsored by GE Healthcare

7:00am - 8:00am 60 mins
Registration and Coffee
8:00am - 8:05am 5 mins
Chairperson's Opening Remarks
8:05am - 8:40am 35 mins
Keynote Presentations
Accelerating Development and Innovation: Advances & Challenges in Vaccine Development
  • Keynote Presenter Tony D'Amore, PhD, MBA - Vice President, Product Research and Development, Sanofi Pasteur
more

This presentation will review the constraints and complexities of vaccine product development and manufacture.  With the increasing complexity, higher costs and competition; evolution in bioprocess and analytics technologies to accelerate and overcome these challenges are reviewed.  Strategies to leverage innovation and technology for rapid product development to shorten time to clinical trials and increasing productivity are discussed.  Specific examples of accelerating process and analytical development are provided as case studies.  In addition, this presentation will highlight some of the potential technologies that could play a role in accelerating product development in the future.

8:40am - 9:10am 30 mins
Keynote Presentations
Application of Frontier Science: Lessons from Implementation of Next Generation Manufacturing at Amgens Singapore Facility
  • Christopher Crowell, PhD - Executive Director, Global Operations, Amgen Inc.
more
9:15am - 9:55am 40 mins
Networking Refreshment Break in the Poster and Exhibit Hall
9:55am - 10:00am 5 mins
Flexible & Smart Facilities
Chairperson's Remarks
9:55am - 10:00am 5 mins
Early Stage Process Development: Molecule Selection and Manufacturability
Chairperson's Remarks
  • Arnie Horwitz, PhD - Consultant, formerly, XOMA
more
9:55am - 10:00am 5 mins
Late Stage Process Development: Optimizing Timelines
Chairperson's Remarks
9:55am - 10:00am 5 mins
Commercial Manufacturing: Continuous Production
Chairperson's Remarks
10:00am - 10:30am 30 mins
Flexible & Smart Facilities
Keynote Address: Future Facility Design Considerations with Single Use Based on Prior Experience
  • Ken Green, PhD - Head of Manufacturing Science and Technology, Shire
more
10:00am - 10:30am 30 mins
Early Stage Process Development: Molecule Selection and Manufacturability
Antibody Engineering to Improve Manufacturability
  • Sujeewa Wijesuriya, PhD - formerly Associate Director, XOMA
more

Antibody expression variation in CHO cells is well established.  While developing CHO-K1 cells expressing human antibodies against botulinum neurotoxin, we discovered that a lead antibody was expressed very poorly. Using expression analysis designed to assess manufacturability in CHO cells, we determined that the light chain variable region was responsible for poor expression since two other affinity matured antibodies sharing the same heavy chain but different light chains were highly expressed; these antibodies, however, had lower than acceptable affinities.  Comparison of the light chain V region sequence of the poorly expressed antibody with those of the two highly expressed antibodies containing the same heavy chain revealed three light chains sharing similar sequences.  To improve expression of the lead antibody, we swapped light chain frameworks 1, 2 and 3 separately or in combinations of the two highly expressed antibodies with those of the poorly expressed antibody.  Swapping all 3 frameworks from either alternate light chain significantly improved expression of the poorly expressed antibody; swapping framework 1 from the alternate light chains also improved expression, especially when coupled with V region codon optimization.  However, only the variants containing the framework1 swaps retained acceptable affinity.  This case study reveals that antibody manufacturability issues can be caused by light chain and demonstrates that light chain engineering through framework swaps can improve antibody expression while maintaining acceptable affinity.

10:00am - 10:30am 30 mins
Late Stage Process Development: Optimizing Timelines
The Evolution of the Global Technology Roadmap: Latest developments from BPOG
  • Reed Harris - Senior Staff Scientist, Technical Development, Genentech, a member of the Roche group
more
10:00am - 10:30am 30 mins
Commercial Manufacturing: Continuous Production
Commercial Capacity Planning and Forecasting for Low-cost bnAb Manufacturing for Sub-Saharan Africa Using Flexible Facilities
  • Fernando Garcia, PhD - Process Engineer III / Data Scientist, Just Biotherapeutics
more

Recently, Broadly Neutralizing Antibodies (bnAbs) have gained prominence due to their potential as an alternative to HIV prevention programs such as PRe-Exposure Prophylaxis (PREP). In order to be a viable option to PREP and other treatments, bnAbs must be competitive on cost, which is directly linked to manufacturing and product demand. In this presentation, a “real options” based analysis will be introduced with the goal of estimating the financial value of flexible manufacturing when performing commercial capacity planning for the manufacturing of bnAbs with demand uncertainty. Through this approach, it is possible to understand the effect that facility and process design have on capital investment allocations, supply chain and other operational considerations. Moreover, financial risk metrics will be employed to quantify the extent and likelihood of unfavorable cost scenarios.

10:30am - 11:00am 30 mins
Flexible & Smart Facilities
Innovation in bio-manufacturing: disposables, ballroom plants and continuous processing
  • Berthold Boedeker, PhD - Chief Scientist, Bayer Healthcare
more

Recent developments in processing, equipment and plant design have substantially changed the way of biopharmaceutical production. By using disposable technologies, closed systems operation and continuous processing, small and flexible production plants are nowadays an attractive alternative the established large scale , hard piped facilities. Different aspects for such ball room plant based flexible set-ups will be discussed in combination with the benefits and limitations of using disposables and continuous processing.

10:30am - 11:00am 30 mins
Early Stage Process Development: Molecule Selection and Manufacturability
Structure vs. Function: In-Vivo and In-Vitro Modification of N-Linked Glycosylation on Monoclonal Antibody Based Therapeutics
  • Yekaterina Lin, PhD - Senior Scientist II, Abbvie
more

Glycosylation patterns of N-linked glycans on therapeutic monoclonal antibodies and monoclonal antibody-like molecules are known to affect product quality attributes including antibody dependent cell-mediated cytotoxicity (ADCC), complement dependent cytotoxicity (CDC), pharmacokinetics (PK) and may contribute to immunogicity. Thus, the abundance of N-linked glycan type can be linked to product efficacy. Glycosylation patterns can be modified in-vivo by supplemental additions to cell culture or in-vitro by enzymatic glycoengineering. Selectively generating these modified molecules to specifically enhance the mechanism of action may help further improve clinical efficacy. Here we present the specific methods and results for in-vivo and in-vitro modifications of monoclonal antibodies including a simple and effective afucosylation methodology. The effect of glyco-modification on biological activities will also be presented.

10:30am - 11:00am 30 mins
Late Stage Process Development: Optimizing Timelines
From Here to There: Technology Transfer and Improving Timelines
  • Javier Femenia, PhD - Principal Scientist, Cell Culture Process Development, BioMarin Pharmaceuticals, Inc.
more

Advancing a process from the lab to GMP manufacturing and then to treating patients is always challenging, and not only technically. Further complications arise when working with international partners. This presentation will discuss strategies we’ve taken to keep up with aggressive timelines while mitigating risk.

10:30am - 11:00am 30 mins
Commercial Manufacturing: Continuous Production
Commercialization of an Integrated Continuous Biomanufacturing Process
  • Franqui Jimenez, PhD - Senior Director of Manufacturing Science and Technology, Sanofi Genzyme
more
11:00am - 11:30am 30 mins
Flexible & Smart Facilities
Producing More with Less - A Look at Total Cost of Ownership Using a Standardized Approach to Single-Use Technology Implementation
  • Sara Bell - Senior Marketing Manager, Single-Use Technologies, MilliporeSigma
more

There are many dynamics impacting the biotech industry, causing drug manufacturers to take a hard look at how to reduce costs, while increasing their flexibility and productivity. They’re asking themselves, “how can we produce more with less?”. Biosimiliars, emerging markets, novel therapies and next generation processing are just a few of the variables affecting the industry and driving the adoption of single-use technologies. This presentation will include a review of the single-use total cost of ownership, as compared to multi-use processing, as well as a playbook of how to successfully implement a single-use strategy that allows design flexibility, while supporting standardization and harmonization across your network to minimize raw material qualification and extractables testing, and ensure security of supply.

11:00am - 11:30am 30 mins
Early Stage Process Development
Presentation Title Coming Soon - Maxcyte
11:00am - 11:30am 30 mins
Late Stage Process Development
Expertise in Vaccine Process Development Leads to Successful Clinical Trials
  • David Clements, MD - Director of Vaccine Research, Hawaii Biotech
more
11:00am - 11:30am 30 mins
Commercial Manufacturing
Presentation Title Coming Soon
11:30am - 12:00pm 30 mins
Flexible & Smart Facilities
Next Gen Biomanufacturing
  • Derek Ung - Senior Process Engineer, CRB
  • Peter Walters - Process Engineer, CRB
more

This presentation will discuss next generation biomanufacturing which can significantly reduce a facility's footprint, capital investment, manufacturing cost of goods and improve utilization of assets when compared to conventional batch processing. In response to the uncertainty of ever-changing product pipelines, the biotech industry has recently been evolving to develop flexible manufacturing solutions that can be quickly mobilized to provide a nimble response to changes in production demands. The industry has concurrently improved its ability to assess and control the risk to the manufacturing process by engineering solutions to improve the closure of the process. However, these flexible manufacturing solutions come with capacity limitations that can inhibit their applicability for certain larger scale applications. The advent of continuous processing technologies opens the door to coupling upstream and downstream unit operations to achieve a viable solution for end to end continuous manufacturing of bulk drug substances. Compounding the benefits of other enabling technologies – continuous closed processing and implementation of single-use systems, where appropriate – results in a next generation biopharmaceutical manufacturing facility that significantly reduces the facility footprint, capital investment, manufacturing cost of goods, and improves utilization of assets when compared to conventional batch processing.

11:30am - 12:00pm 30 mins
Early Stage Process Development: Speed to IND
Gene to GMP in 9 Months Through Use of High Throughput Technologies
  • Sigma Mostafa, PhD - Vice President, Upstream & Downstream Process Development, KBI Biopharma
more

Employing the fastest CMC pathway to IND is a priority for all biotech organizations. Often the cost of the swift speed is a non-optimized, non-robust process and a non-commercializable cell line. This presentation will describe the Selexis-KBI integrated (SKI) approach that delivers a commercial cell line & a robust process while achieving Gene to GMP in 9 months. This feat is possible through the use of the high productivity Selexis cell line platform in conjunction with KBI's robust process development approach utilizing high throughput technologies across all development functions.

11:30am - 12:00pm 30 mins
Late Stage Process Development: Process Characterization Case Studies (Upstream and Downstream)
At-Line In-Process Titer Determination Using Variable Pathlength Spectrophotometry to Eliminate HPLC Hold Step
  • Joe Sexton - Senior Technical Specialist, Genentech
more

We have developed and implemented a novel method of determining HCCF Titer that eliminates the hold step of an offline HPLC. This method takes advantage of variable pathlength spectrophotometry which is already utilized in many downstream manufacturing facilities within industry. Through this technique, the HCCF is loaded onto the capture affinity chromatography and titer is determined concurrent with the load of first cycle. Within our Process Development Pilot Plant we have been utilizing this method for all CHO runs on affinity chromatography for over a year with no adverse impact. This method has strong potential to drive efficiency in manufacturing facilities as well as simplifying and migrating assays from an off-line QC environment to at-line on the manufacturing floor.

11:30am - 12:00pm 30 mins
Commercial Manufacturing: Formulation
Evaluation of the Technology Landscape for Development of a High Concentrated mAb Formulation
  • Radhakrishna Maroju, PhD - Senior Scientist, DP Development, Biologics CMC, TEVA
more

Definition of a ‘high concentration’ protein formulation is changing with multiple approved drug products available at above 100 mg/mL. It is not exaggerating to realize that efforts have been made to reach concentrations as high as 200-600 mg/mL. Technologies from different disciplines are being explored for this purpose. The presentation will discuss the current state of the art in developing a high concentration protein formulation and focus on an evaluation process of the technology landscape for a monoclonal antibody.

12:00pm - 12:30pm 30 mins
Flexible & Smart Facilities
Evolving Role of the Process Architect: Case Studies Using a Modular Delivery Approach
  • Peter Cramer, AIA NCARB - Vice President, Life Sciences Facility Design, M+W Group
more

The “Evolving Role of the Process Architect” presentation will cover how Process Architect are now working a systems integrators to define and leverage modular delivery platforms aimed at meeting clients fast-track project delivery requirements.. Case studies will be presented to demonstrate the value of designing a facility that can take full advantage of pre-engineered, modular and kit-of-parts solutions that are becoming increasing available in today’s market.

12:00pm - 12:30pm 30 mins
Early Stage Process Development: Speed to IND
Development of a Scalable Platform for Protease Triggered Immuno-oncologic Activators
  • Ulrich Ernst, PhD - Chief Operating Officer and Senior Vice President, Technical Operations, Amunix
more

Advances to overcome the inherent functional limitations of current immuno-oncology therapies are being developed at Amunix. The melding of Amunix’ established XTEN® half-life extension technology with bispecific T cell engagers has yielded a novel class of long-acting, pro-drug, immuno-oncologics under Amunix’ recently unveiled ProTIA technology platform. The design of ProTIA molecules represents a technical enhancement of bispecific scFv therapeutic formats, with the benefits of significantly improved circulatory half-life, enhanced tumor-targeting and safety profiles. To enable clinical application of its pipeline of ProTIA therapeutics, Amunix has applied its extensive experience with XTENylation of proteins, thus, yielding a scalable, platform process for efficient production of these new therapeutic compounds.

12:00pm - 12:30pm 30 mins
Late Stage Process Development: Process Characterization Case Studies (Upstream and Downstream)
Mechanisms of Monoclonal Antibody Low Molecular Weight (LMW) Formation and Strategies of Mitigation in Bioprocessing
  • Yuanli Song, PhD - Scientist II, Bristol-Myers Squibb
more

Monoclonal antibodies, accounting for a big sector in therapeutic protein market, are comprising of two light (L) chains and two heavy (H) chains linked through inter-H-H and inter-H-L disulfide bonds. During the bioprocessing, the breakage or reduction of these inter-chain disulfide bonds leads to undesirable LMW formation. It is essential to understand the frangibility of these inter-chain disulfide bonds to avoid undesirable LMW. We studied mechanisms of IgG1 and IgG4 LMW formation using micro-chip based capillary electrophoresis and computer modeling. Our data suggest that IgG1 and IgG4 follow different pathways to form LMW. At the end of the presentation, strategies in upstream processing to avoid disulfide bond reduction and strategies in downstream processing to remove different are suggested and discussed.

12:00pm - 12:30pm 30 mins
Commercial Manufacturing: Formulation
Case Study: Challenges in Development of a High Concentration Liquid Formulation for mAb Process
  • Daniel Chen - Scientist, Protein Science, Boehringer Ingelheim
more

Daniel Chen, Lin Wang, Alpana Naresh and Min Zhu

A HCLF process with mAb concentrations, up to 250 mg/mL, was developed successfully and transferred to a commercial facility. Issues encountered in HCLF development included high operating pressures, unstable pressure fluctuation up to 20 psi and 90% cross-flowrate reduction. This was mitigated during development with the use of open-screen membranes, select buffers and optimization of operating conditions, resulting in pressure fluctuation up to 5 psi and 50-65% cross-flowrate reduction. Gibbs-Donnan effect resulted in 0.3 pH shift and 2-fold increase of anions, with data applied to a predictive model.

12:30pm - 1:40pm 70 mins
Networking Lunch in the Poster and Exhibit Hall
Networking Lunch in the Poster and Exhibit Hall
12:30pm - 1:40pm 70 mins
Luncheon Presentation and Panel Discussion
Implementing Process Intensification in Commercial Manufacturing: Drivers & Challenges (seating is limited)
  • Presenter Detlef Eisenkraetzer - Director, Fermentation Development Pharma, Roche Diagnostics GmbH
  • Presenter Gerben Zijlstra - Continuous BioManufacturing Platform Marketing Manager, Sartorius Stedim Biotech
  • Moderator Miriam Monge - Director of Marketing Integrated Solutions, Sartorius Stedim FMT SAS
  • Panelist Raquel Orozco, PhD - Senior Bioprocess Engineer, Boehringer-Ingelheim
  • Panelist Mandar Dixit - Director of Marketing- Filtration technologies, Sartorius Stedium Biotech
  • Panelist Fritjof Linz - VP Purification, Sartorius Stedium Biotech
  • Panelist Anna Persson - Senior Principal Data Scientist, Sartorius Stedium Biotech
more

Introduction to seminar: Drivers for process intensification : Dr Detlef Eisenkraetzer & Jon Coffmann ( to be confirmed) 10 minutes

Presentation: Gerben Zijlstra, Platform manager intensified/continuous processing: Sartorius platform for process intensification ( 25 mins)

Continuous and intensified bioprocessing is attracting much attention amongst companies seeking to maximize the efficiency of their manufacturing assets. It promises smaller facilities, reduced scale-up risk, more consistent product quality and higher throughputs, however there are still many challenges for practical implementation. In USP tools for high throughput intensified and continuous cell culture development are limited, furthermore many single use bioreactors may not be suitable to support the high cell densities required for intensified processing at scale and current cell retention systems suffer from product sieving and long term blocking effects. In addition clarification of extremely high cell density cell cultures is challenging.

In DSP MCC product capture is finding its way into manufacturing, but continuous DSP processing challenges include sterility over longer periods, robustness over longer times, continuous low pH viral inactivation, continuous virus filtration and continuous diafiltration. Furthermore, the balancing of flows and feedback control using PAT tools and advance process control across the entire process chain is a key challenge. Here we will discuss some of the latest solutions to address these issues, showing real life examples and added value with cost modeling data.

Panel discussion: 25 mins

Panel discussion chair: Miriam Monge, Director of Marketing Integrated Solutions

Building the business case for intensified processing at commercial scale

  • when does a fully automated stainless steel facility make sense
  • when do SU facilities based on concentrated fed batch and /or perfusion make sense?
  • Building a risk mitigation strategy

Panelists: Detlef Eisenkraetzer (Roche), Raquel Orozco (Boehringer Ingelheim), Gerben Zijlstra ( continuous processing platform manager), Mandar Dixit (Sartorius), Fritjof Linz ( Sartorius), Anna Persson (Sartorius Stedim Data Analytics)

1:40pm - 1:45pm 5 mins
Flexible & Smart Facilities
Chairperson's Remarks
1:40pm - 1:45pm 5 mins
Early Stage Process Development: Case Studies in Cell Line Development
Chairperson's Remarks
  • Camilla Oxley, PhD - Scientist, Process Development and Manufacturing Sciences, API-LM, Janssen
more
1:40pm - 1:45pm 5 mins
Late Stage Process Development: Process Characterization Case Studies (Upstream and Downstream)
Chairperson's Remarks
1:40pm - 1:45pm 5 mins
Commercial Manufacturing: Process Validation
Chairperson's Remarks
1:45pm - 2:15pm 30 mins
Flexible & Smart Facilities
Evolution of a Flexible Development Facility to Accommodate the Increasingly Fast-Paced Pharmaceutical Landscape
  • Paul Ko, PhD - Senior Scientist, Cell Technologies, API Large Molecule, Janssen Research & Development
more
1:45pm - 2:15pm 30 mins
Early Stage Process Development: Case Studies in Cell Line Development
Industry Perspectives and Case Studies Towards Demonstration of Monoclonality for Biologics Manufacture Development
  • Amie Lundquist - Senior Development Specialist II, Shire & BPOG
more

Clonality of mammalian cell lines used for production of biologics is a regulatory expectation and one of the mechanisms applied to ensure quality consistency of the biologic. Historically clonality has been demonstrated through statistics generated from limiting dilution cloning or through verified FACS. A variety of new technology platforms have been developed and enabled potentially more efficient and more robust approaches to generating a clonal cell line. Here we present an industry perspective providing alternative approaches to composition of a regulatory submission to support a monoclonality claim. These approaches represent the views of a consortium of companies within the BioPhorum Development Group and include case studies utilising imaging technology including scientifically sound approaches and efforts in demonstrating monoclonality. By highlighting both the utility of these alternative approaches and the advantages they bring over the traditional methods and their adaptation by industry leaders we hope to gain wider acceptance of their within the biologics cell line development space.

1:45pm - 2:15pm 30 mins
Late Stage Process Development: Process Characterization Case Studies (Upstream and Downstream)
In-Process Pool Mixing: Impact on Product Quality and Process Performance
  • Jim Keba - Engineer II, Purification Development, Genentech
more

Protein product mixing in the biotechnology industry is used to perform pool additions and adjustments, for temperature control and to ensure homogeneity prior to sampling or performing a subsequent unit operation. Product pool mixing is typically validated to demonstrate that solution homogeneity can be reached within an established amount of time. However, after several process-impacting events observed in manufacturing it was also necessary to evaluate the impact of over-mixing on product quality and process performance. A small-scale mixing model was developed utilizing various mixer types (top and bottom-mounted agitators). Test conditions were scaled to generate a worst-case power per unit volume or circulation time and mixing times were set well beyond typical manufacturing experience. Experiments at these worst-case mixing conditions were conducted on a variety of in-process product pool types covering a range of pH, protein concentrations, temperatures and molecule formats. Worst-case mixing results for product quality, summarized from 12 different validation studies, indicate that across a wide range of molecules and pool parameters there is no practically meaningful impact as tested by a variety of product quality assays. This could reduce the need for process validation work on future projects. For process performance, as measured by filterability after mixing, an impact was only observed when using bottom mounted magnetically driven agitators.

1:45pm - 2:15pm 30 mins
Commercial Manufacturing: Process Validation
Relevance of a Risk-Based Approach in the Successful Commercialization of a Monoclonal Antibody
  • Marlene Castro-Melchor, PhD - Senior Engineer, Genentech
more

Process validation is an integral element of the product and process lifecycle. Process validation programs follow a scientifically sound and risk-based approach to provide a high degree of assurance that a specific manufacturing process performs as intended and will consistently produce a result or product meeting pre-determined acceptance criteria. Process validation consists of three stages: process design, process performance qualification (PPQ), and continued process verification. These stages however are not necessarily sequential. They may overlap depending on variables such as clinical outcomes, regulatory program designation, evolving regulatory expectations, and availability of manufacturing facilities. This presentation will focus on the case of a monoclonal antibody commercialization for which process validation stages overlapped per some of the variables above, and the lessons learned from this program. The successful commercialization of this product showcase the relevance of a risk-based approach and its evolution.

2:15pm - 2:45pm 30 mins
Flexible & Smart Facilities
Using an Integrated Design Approach to Upgrade an End-to-End Single Use Drug Substance Facility to be Commercial Manufacturing Ready
2:15pm - 2:45pm 30 mins
Early Stage Process Development: Case Studies in Cell Line Development
Methods to Verify a Clonal Cell Origin
  • Amritha Menon, MS - Associate Scientist II, Gilead Sciences
more

Demonstrating a single cell origin of cell lines used for clinical & commercial production of therapeutic proteins is a key regulatory expectation.  Use of fluorescence-activated single cell sorting (FACS) in combination with high resolution imaging enables generation of cell lines with demonstrable single cell origin in a single round of cloning.

2:15pm - 2:45pm 30 mins
Late Stage Process Development: Process Characterization Case Studies (Upstream and Downstream)
Case Study: Determine CQAs for a Late Stage Complex Fusion Protein
  • Johnson Varghese, PhD - Biologics Process Development, Celgene
more

Developing a robust control strategy for the commercial manufacturing process of biologic products is a multistep/staged approach. Successful commercialization requires a keen understanding of the molecule, cell line, manufacturing processes and analytics that often builds upon prior development and manufacturing experience. When in-licensing complex molecules, where there is little or no prior knowledge regarding the impact of product quality attributes and process performance on product safety or efficacy, platform development approaches may not be sufficient to establish a robust control strategy.

More established companies with a large portfolio of biologic products typically have well defined business processes that use a systematic approach to product and process development, “from cradle to grave”, that ensure consistent delivery of a high quality product. Identifying the Critical Quality Attributes (CQA) of a biotherapeutic is an important starting point in developing a control strategy.

The case study presented here discusses the approaches taken by Celgene’s Biologics team to develop the control strategy for an in-licensed complex Fc-Fusion molecule to support commercialization. The presentation will describe the strategies taken to rapidly increase our knowledge of the molecule to define a BLA enabling process and analytical control strategies.

2:15pm - 2:45pm 30 mins
Commercial Manufacturing: Process Validation
Analytical Approach for Implementation of Visual Inspection
  • Mariann Neverovitch, MS - Research Scientist, Bristol-Myers Squibb
more

Visual inspection following equipment cleaning is a mandatory step in the cleaning verification workflow for pharmaceutical equipment. Equipment must pass visual inspection before swab sampling for analysis can be performed. However, since a significant number of low risk compounds are visible well below established safety levels, it is possible to justify equipment as “visually clean” without performing swabbing analysis.  Internal studies performed at BMS showed that over 90% of participants could identify residual product at a level of ~2 ppm without preliminary training.  The implementation of a robust visual inspection qualification program and clear “Visually Clean” inspection parameters can enable visual inspection to be used to qualify equipment in lieu of swab analysis for low risk products.

2:50pm - 3:20pm 30 mins
Technology Workshop 1
Process Characterization - A Road Map to Enhance Process Understanding
  • Eliza Yeung, PhD - Strategic Projects Manager/PC Study Director, R&D, Cytovance Biologics
more
2:50pm - 3:20pm 30 mins
Technology Workshop 2
Start with the End in Mind: new Solutions for High Capacity mAb Capture and Efficient Transition to GMP Environment
  • Avril Vermunt - Bioprocess Hardware Specialist, GE Healthcare
more
2:50pm - 3:20pm 30 mins
Technology Workshop 3
Process Development: The Key to a Successful Biomanufacturing Strategy
  • Brad Johnson, PhD - Manager, Purification Development, Patheon
more
2:50pm - 3:20pm 30 mins
Technology Workshop 4
Laboratory Data to Machine Learning in 30 seconds
  • Tim Gardner, PhD - Founder and CEO, Riffyn
more
2:50pm - 3:20pm 30 mins
Technology Workshop 5
High Throughput BLI Potency Assay for Screening of Product Degradation by Industrial Cleaning Solutions
  • Jonathan Crane, PhD - Senior Development Scientist, AGC Biologics
more

AGC Biologics is a CDMO offering services for the scale-up and cGMP manufacture of protein therapeutics, from pre-clinical to commercial production. One challenge when operating a multi-product manufacturing facility is sufficiently demonstrating cleaning between batches to prevent cross-contamination of products. In addition to total organic carbon testing of cleaned manufacturing equipment, we designed a high-throughput potency assay using the ForteBio Octet HTX to screen for product degradation upon exposure to industrial cleaning solutions. Here we present results from four different types of biologics (monoclonal antibody, bispecific scFv fusion, receptor-Fc fusion, ligand-Fc fusion), showing degradation of binding potency upon exposure to cleaning reagents of various types, and over varying times and temperatures. Our results indicate that a variety of cleaning conditions are required for degrading different types of biological products.

3:20pm - 4:00pm 40 mins
Networking Refreshment Break in the Poster and Exhibit Hall
4:00pm - 4:30pm 30 mins
Flexible & Smart Facilities: Design and Challenges
Modular Doesn't Necessarily Mean Flexible
  • Dennis Powers - Director of Sales Engineering, G-CON Manufacturing Inc.
more

Demand is growing in our industry for flexible facility designs that can meet the evolving drug manufacturing strategies.  Modular facility platforms today being considered more frequently over traditional construction to meet this demand. This presentation will discuss the various facility designs available with regard to modularity and flexibility.

4:00pm - 4:30pm 30 mins
Early Stage Process Development: Technology and Innovation
Integration of Automation Technologies for Efficient Stable Cell Line Generations from Transfection to GMP Clone for Viral Antigens
  • Naga Chalamalasetty - Scientist, Vaccine Production Program, NIAID, NIH, Vaccine Research Center
more

At the vaccine research center, aggressive timelines are set for development of a diverse portfolio of therapeutic antigens and monoclonal antibodies. An efficient CHO-DG44 based expression platform with a development timeline of 3 months from transfection to final clone selection was developed with titers ranging between 0.5 to 2 g/L for viral antigens and 5 to 7 g/L for monoclonal antibodies. Process efficiencies were achieved by integrating emerging automation technologies such as ClonepixII, for colony picking, Hamilton cell culture automation station and Meso Scale Diagnostic multiplex Elisa plate reader for down-selection and clone expansion from 96 well plate stage to shake flask stage. Clones from shake flask stage were evaluated using a 14-day standard fed batch process using AMBR15 and Tecan High-throughput purification stations for further down-selection of top 5 clones based on process and quality attributes. Further process optimization studies on the top 5 clones were performed in AMBR250 to select and define the manufacturing process for the top clone for GMP master cell banking and clinical material manufacturing. Integration of automation stations enabled data integrity of the final clone at each stage of the process by using bar code stamping and data archiving in a PAT II compliant system. A case study will be presented on viral antigen production showing all the steps and associated data.

4:00pm - 4:30pm 30 mins
Late Stage Process Development: Technology and Innovation
Manufacturing Incytes: Leveraging Online Biomass Probes for Robust Seed Train Performance
  • C. Eric Hodgman, PhD - Engineer II, Manufacturing Science & Technology, Bristol-Myers Squibb
more

Lessons learned from commercial manufacturing of legacy processes can be helpful in guiding late stage process development. I will discuss how online biomass monitoring can be leveraged for robust seed train execution to boost overall yield as well as streamline tech transfer and scale-down model qualification by minimizing instrument variation.

4:00pm - 4:30pm 30 mins
Commercial Manufacturing: Process Validation
Challenges in developing a representative scale-down model
  • Shyamsundar Subramanian, PhD - Director, Biologics R&D, Teva Pharmaceuticals
more

Scale-down bioreactor models are essential for process characterization prior to process validation. Deliberate choices have to be made on what aspects of manufacturing scale operation and performance are important for a representative scale-down model. In this talk, I will highlight the challenges in developing a representative scale-down model for a CHO based antibody process and how we addressed them.

4:30pm - 5:00pm 30 mins
Flexible & Smart Facilities: Design and Challenges
A Suite-Focused Flexible Facility Design for Biologics Production
  • Sue Behrens, PhD - Senior Director, Process Design, IPS-Integrated Project Services, LLC
more

This presentation will describe a suite-focused facility that provides for multiproduct operation and discuss tools and capabilities used in development of the project.  This design leverages single-use technology and closed system processing with an integrated personnel/material flow to ensure proper containment.  Equipment can be rapidly exchanged to reconfigure the facility for a variety of different production modes.  The flexibility functions to support both known platform processing and to accommodate the unknown manufacturing needs of the future.  Key deliverables for the facility include reduced initial capital, minimization of the required footprint/cleanroom area, ability for continued process optimization and integration of validation into the full project life cycle. 

4:30pm - 5:00pm 30 mins
Early Stage Process Development: Technology and Innovation
Technology Toolboxes and Modeling Approaches to Expedite Process Development
  • Natraj Ram, Ph.D. - Associate Director, Purifiaction, Manufacturing Sciences, AbbVie Inc.
more
4:30pm - 5:00pm 30 mins
Late Stage Process Development: Technology and Innovation
Hydrogen Deuterium Exchange Mass Spectrometry (HDX-MS) for Formulation and Process Optimization
  • Lokesh Kumar, PhD - Associate Scientist, Pharmaceutical Processing and Technology Development, Genentech
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This presentation will discuss the use of HDX-MS for formulation/process optimization of lyophilized protein formulations. Applicability to wide variety of protein formats (mab, fab, bispecifics, enzyme) will be demonstrated. Furthermore, applicability to lyophilization processing (eg. controlled ice nucleation vs uncontrolled ice nucleation) will be shown. Finally, experiments to mechanistically understand the basics of the technique will be discussed.

4:30pm - 5:00pm 30 mins
Commercial Manufacturing: Process Validation
Pharma Quality System and Validation Best Practices
  • Hamid Mollah, PhD - Principal Engineer, Genentech
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Pharma quality systems (PQS), the basis of cGMP manufacturing and regulatory compliance, universally aim to ensure patient safety. Evolving regulatory expectations, company quality culture, and even company size, all contribute to the wide variations in PQS throughout the industry. This presentation will discuss critical factors to consider and best practices when designing a PQS that meets the demand for continuous improvement and innovation.

5:00pm - 5:30pm 30 mins
Flexible & Smart Facilities: Design and Challenges
Lessons Learned from a Retrofit Facility
5:00pm - 5:30pm 30 mins
Early Stage Process Development: Technology and Innovation
Developing a better understanding of the interactions between new ADC payloads and antibody post conjugation
  • Scott Hilderbrand, PhD - Senior Scientist, ImmunoGen, Inc.
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The development of new Antibody Drug Conjugates (ADCs) incorporating novel small-molecule payloads is challenging and often involves unexpected observations.  During the conjugation development process a photo-sensitivity of our benzodiazepine containing ADCs was discovered resulting in elevated protein methionine oxidation.  Here we report on the identification and investigation of these interactions as well as the implementation of appropriate control measures.

5:00pm - 5:30pm 30 mins
Late Stage Process Development: Technology and Innovation
Progress Towards Continuous Upstream Process Monitoring Using Raman Spectroscopy
  • Nobel Vale - Research Scientist II, Bristol-Myers Squibb
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Various methods have been developed to monitor cell metabolism in CHO bioprocesses. We are currently evaluating the potential for these techniques to routinely support upstream process development. The evolution of various process analytical technologies (PAT) and real-time analytical (RTA) has allowed for creative ways to optimize bioprocesses. One spectroscopic technology that has been used is Raman spectroscopy. Potential benefits from these techniques are the ability to have optimized feeding strategies, automated sampling procedures, improved temporal resolution of cell metabolism, and highly precise measurements.The ability for spectroscopic methods to resolve and predict different analytes online and offline will be described. One unique aspect of this work is the development of preliminary models for prediction using standards developed offline. Calibrations developed using standards can accelerate the calibration process and potentially eliminate spurious correlations from the model that would otherwise occur during multiple bioreactor runs.With the proper development of methods, Raman can accurately measure bioprocess data in real-time allow for further bioprocess optimization and manipulation that would not have been possible through taking daily off-line samples for analysis. We can then characterize a bioprocess in greater detail, such as looking into glucose consumption based on viable cell density. Concentrations of nutrients in bioprocesses such as glucose can also be tightly controlled to optimize protein production. This is essential especially perfusion bioprocesses. Another application is to utilize Raman in a feedback control system to maintain glucose at a consistent level.

5:00pm - 5:30pm 30 mins
Commercial Manufacturing: Process Validation
Process Validation & Regulatory Approval Strategies Required for Drugs that Have Been Designated Fast-track & Breakthrough Therapies
  • Tracy TreDenick - Head of Regulatory and Quality Assurance and Founding Partner, BioTechLogic
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The Fast Track designation was brought into effect in 1997 with the FDA’s Modernization Act (FDAMA). The Breakthrough Therapy provision was brought into effect in 2012 through the FDA’s Safety and Innovation Act. Based on FDA’s 2016 Novel Drug Summary report, “Fast Track drugs have the potential to address unmet medical needs. Eight of the 2016 novel drugs (36%) were designated by CDER as Fast Track. Breakthrough therapies are drugs with preliminary clinical evidence demonstrating that the drug may result in substantial improvement on at least one clinically significant endpoint (e.g., study result) over other available therapies. CDER designated seven of the 2016 novel drugs (32%) as Breakthrough therapies.” Both designations permit rolling reviews of the regulatory submission documentation, but Breakthrough Therapy also comes with “organization commitment and intensive guidance of efficient drug development.” These percentages and review benefits seem to show FDA’s concerted effort to make important drug therapies available to patients as quickly as possible. To understand the importance of these designations we can reflect back to 2006 and 2007. At this time the President enacted an Emergency Plan for Aids Relief. In these two years FDA designated 11 new drugs for the treatment of HIV as Fast Track. This presentation will provide process validation and regulatory strategies for Fast track and Breakthrough therapy designated products. We will explore approaches to accelerating process validation and regulatory activities.

5:30pm - 7:00pm 90 mins
Opening Night Reception in the Poster and Exhibit Hall - co-sponsored by GE Healthcare