Friday, November 20, 2015

Join Think Tank, a knowledge community focused on the antibody engineering field


We are pleased to announce the launch of Think Tank, a free knowledge community focused on the antibody engineering field. Join us! IBC Life Sciences, producer of the annual Antibody Engineering & Therapeutics conference, hosts these conversations to enable efficient knowledge exchange amongst practitioners. Insight is within sight.

This easy-to-use Q&A platform will enable you to:
  • Ask experts for advice
  • Share your knowledge
  • Build your expertise
This community has been built for professionals in a mobile world, who need high-quality answers to difficult questions from people with experience and expertise. We invite you to join and start using it to get expert answers to your questions and to offer your own insights to others. Together we can transform the antibody-engineering field.

Please join Think Tank and start connecting with experts and exchanging knowledge.

We look forward to seeing you on Think Tank!

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Wednesday, November 18, 2015

Podcast: Using Antibodies to Treat Alzheimer’s a No-Brainer

By Marc Dresner, Senior Editor, IBC Life Sciences

While antibody therapies today are most commonly associated with oncology and inflammatory diseases, the next big breakthroughs may be on the neurology front.

Dr. Trudi Veldman, Senior Director of Biologics Generation at AbbVie Bioresearch Center, says deploying bispecifics as a “Trojan Horse” to enhance transport across the blood brain barrier could finally satisfy some extreme unmet needs.

“I see a lot of opportunities around Alzheimer’s, Multiple Sclerosis and Parkinson’s disease.”

“I see a lot of opportunities around neurological diseases, such as Alzheimer’s, Multiple Sclerosis and Parkinson’s disease,” said Veldman.

In this podcast interview for Inside Antibody Engineering, Dr. Veldman explains:

• Why she thinks antibody applications in neurology look so promising

• Where she sees impressive progress elsewhere in the field

• Why Fc receptor biology needs more attention and more!

Listen to the podcast or download a transcript here!

Editor’s note: Dr. Trudi Veldman will be chairing the Antibody Therapeutics for Non-Cancer Indications track at the Antibody Engineering and Therapeutics Conference taking place December 7-10 in San Diego.

Click here for an agenda. 

Or for more information visit:

Marc Dresner is sr. editor and special communication project lead with IBC Life Sciences. He is the former executive editor of Pharma Market Research Report, a publication for market research professionals specializing in pharmaceuticals and life sciences. He may be reached at Follow him @mdrezz.

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Tuesday, November 17, 2015

BPI is Paradise for an Old Technologist

By: Frank Corden

As I was driving in this morning to the Hynes Convention Center, I was thinking about how lucky we are to have an international meeting of this caliber in Boston.  I just love BPI. It’s such a great mix of presentations; the breadth of discussions from the applied science around cell engineering to the underlying business drivers that will carry us into the next decade is amazing.  The organizers successfully execute this daunting task with seeming ease, though I’m sure in the background their little duck feet are paddling away.

Those of you who know me have heard the story of how I became a scientist.  As a kid growing up in the sixties and early seventies, my interests in science and technology were birthed from watching Jacques Cousteau television specials and the race to the moon.  In the years since, I’ve had the pleasure of seeing first hand that those fish on the coral reef are really all those beautiful colors and that NASA used proven technology, kerosene and liquid oxygen (aka Rocket Propellant No. 1) to get our astronauts into space.  Fortunately, my interest in all cool things science hasn’t waned with age and that’s why I love BPI.

Yesterday afternoon, I was sitting in on the presentation “Raising the Bar: Advanced Analytics in Upstream Bioprocess Development.”  Much of the discussion focused on the use of Liquid Chromatography coupled with Tandem Mass Spectroscopy (LC-MS/MS) to identify and quantitate attributes of various cell culture processes.  Without getting overly technical, the technique can be used to map the amino acid sequence of a drug substance as well as the pattern of added sugars (glycosylation) that are bound to an intact monoclonal antibody molecule. 

LC-MS/MS works by very accurately measuring the mass of the peptide fragments created from the proteins in the sample during the sample preparation process.  By accurately measuring the mass, the LC-MS/MS can identify the amino acid composition of each fragment.  This composition and the mix of the fragments, especially unique fragments specific to the proteins of interest, enable the instrumentation to identify with a very high certainty the presence and relative concentration of different proteins in the sample.

In the data shown, the presenter, Chris Yu, demonstrated the practical power of the LC-MS/MS method to characterize drug substance.  Data showed that LC-MS/MS could identify and quantitate host cell proteins and, further, could give positive confirmation of glycosylation patterns.  But what was most interesting to me was a more basic discovery…

As part of the effort to characterize a particular drug substance, the team identified a low percentage of peptides which differed from the expected amino acid composition, often a swap between serine and asparagine.  Initially the thought was that the DNA sequence for a fraction of the cells was different, as a result of either spontaneous mutations or by misincorporation of the DNA sequence during cell engineering.  Surprising neither of these possible errors was the root cause.

It turns out that there is a natural error rate for misincorporation of amino acids into the primary sequence of proteins.  The authors presented data that showed the error rate was in the same range for both mammalian cells and E. coli.  The error rate could also be influenced by the relative availability of the amino acids in the cell culture.  Restrict the availability of the intended amino acid relative to the incorrect amino acid and you get higher substitution.  Provide a plentiful source of the intended amino acid and the error rate decreases.

On reflection, it’s not surprising that some low level error rate should be expected.  After all, these biological processes are driven by chemistry.  You can have a preference for a given binding affinity or reaction path, but it’s just a preference even when it’s a very strong preference.  As an analogy, byproduct production in a chemical reaction is common and even if the reaction is very strongly directed for a particular outcome, in all but the simplest reactions, some byproducts are created.  So, you can view the amino acid substitutions as byproducts. 

Whether the protein with the substitution is functionally different than the desired product is unknown.  What we do know is that the LC-MS/MS can measure the error rate and that process conditions affect the error rate. So if the error rate turns out to be a critical quality attribute (CQA) of the protein that is the drug substance, we can monitor it and control it.  Neither the deeper insight gained about misincorporation nor the understanding of the ability to control the rate of amino acid substitution would have occurred without the applied research of Dr. Yu’s team and the advanced capabilities of the LC-MS/MS instruments. 

Gaining that insight into how biology really works is the 21st century equivalent of rocket science -  that’s why I love this meeting.

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Wednesday, November 11, 2015

Podcast: Genmab Scientific Director Looks Ahead, Highlights Need for More Potent Antibodies

In the red-hot world of antibodies, cancer specialist Genmab is one to watch.

Notably, Q3 2015 was a busy one for Genmab, with submissions for two antibodies fast-tracked in the US and one in Europe (the second pending), and a new DuoBody platform license deal with Novo Nordisk.

“The antibody field is without borders.”

“The antibody field is without borders,” says Genmab SVP and Scientific Director Dr. Paul Parren.
“These are very versatile molecules that are widely applicable in many disease areas and able to engage many different mechanisms.”

We caught up with Parren to discuss development trends in the space.

“The field is really moving away from naked antibodies or unmodified antibody drugs.”

“The antibody field is really moving away from naked antibodies or unmodified antibody drugs,” Parren noted.

“We see a lot of interest in new formats, mostly because we really think that we need to make more potent antibodies,” he added.

In this podcast interview for Inside Antibody Engineering, Dr. Parren discusses the future of antibody engineering and key trends including:

• Immunotherapeutics

• Combination treatments

• Personalized medicine and more…

Listen to the podcast or download a transcript here!

Editor’s note: Dr. Paul Parren will be chairing the “Antibody Effector Functions” track at the Antibody Engineering and Therapeutics Conference taking place December 7-10 in San Diego.

Click here for an agenda.

Or for more information visit:

(Ps. SAVE $100 when you register with code D15172BLOG!)

Marc Dresner is sr. editor and special communication project lead with IBC Life Sciences. He is the former executive editor of Pharma Market Research Report, a publication for market research professionals specializing in pharmaceuticals and life sciences. He may be reached at Follow him @mdrezz.

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Wednesday, November 4, 2015

Genome Editing Applications | Brussels, Belgium | 2-3 December 2015

Get updates on Therapeutic and Biomedical Applications of CRISPRs, ZFNs, TALENs and other Genome Engineering Technologies

Genome Editing Applications 
2-3 December 2015
Sheraton Airport Hotel
Brussels, Belgium

Biomedical researchers have long strived for a reliable and efficient method of making targeted changes to the genome of living cells. With the advent of CRISPR/Cas9 researchers are now able to explore gene function in a much more thorough and cost-effective way.

This year, Lorenz Mayer from Astrazenca will be giving a presentation on their genome wide target discovery and target validation studies. Ines Royaux from Janssen Phamaceutica will also be giving a presentation touching on the team’s first experience of using genome editing for ex vivo gene therapy. Read on to find out more about what you can expect to learn from the speakers at this year's conference.

Get a sneak peek into the new developments and data the speakers will be sharing during their presentations here.

Informa's Genome Editing Applications 2015 conference, taking place on 2-3 December 2015 in Brussels, will showcase the most up-to-date therapeutic and biomedical applications emerging using CRISPRs, ZFNs, TALENs, AAVs and other genome engineering technologies. From improving lead discovery, validation of targeted cell lines and development of transgenic animal models to therapeutic uses in cell therapy & gene therapy.

This inaugural event in Europe follows the enormous success of Genome Editing Applications in March 2015 in the US from our sister company, IBC Life Sciences.

*Genome Editing Applications is co-located with Cell Therapy Manufacturing and Gene Therapy conferences with a shared exhibition area

So far, across the three conferences, over 120 have confirmed to attend with representation from biopharm, pharma and biotech companies - including Novartis Pharma AG, Glaxosmithkline, CRISPR Therapeutics, Astrazeneca, F Hoffmann-La Roche AG, GSK Pharma, Hitachi LTD, Bluebird BIO, Sanofi Pasteur, Janssen Pharmaceutica NV, Merck & CO., INC., Precision Biosciences, INC.

Hear from influential industry experts such as:

Genome Editing Applications conference in Brussels


*Based on standard industry rate Biopharm/Pharma/Biotech 2 day conference pass for one attendee. Not including suppliers/vendors.

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Monday, November 2, 2015

Cell Therapy Manufacturing Best Practices from PCT

This article is the second in a series of weekly posts featuring cell therapy news and articles as reported by BioProcess International Magazine. 

By: Leah Kinthaert

In the October 15 issue of BioProcess International, a group of industry thought leaders consisting of Bob Preti, Ann Daus, Cenk Sumen and Brian Hampson from PCT - Caladrius were asked to give their opinions on the most successful strategies for manufacturing in the cell therapy industry.

Best practices for commercial cell therapy manufacturing
The team states that implementing DbD or Development by Design, consisting of these facets: quality, cost of goods, scalability and sustainability (picture above), will "provide significant cost and time advantages as a cell therapy moves along in its clinical process".

Compliance at cell therapy manufacturing facilities
A foundational state of compliance entails that people, facilities, systems and processes are unified in compliance, and that a QTF or quality task force is created  which includes "representatives from manufacturing, operations, and quality groups, with different areas of industry experience." They caution cell therapy developers not to wait to worry about quality until something has gone wrong - such as delays or regulatory actions - but to have the QTF in place from the beginning.

Develop QTPP early
The team gives another strong message about preparation when it comes to QTPP or quality target product profile. As with QTF, waiting to develop a QTPP can lead to problems.

Strategic Commercial Manufacturing Plan
One last acronym they recommend is a SCMP or strategic commercial manufacturing plan. Keeping with the theme of planning the future to avoid potential problems, a SCMP needs to include: "an evaluation of a developer’s current manufacturing processes; an analysis of those processes for areas of potential optimization and improvement; and a practical, implementable strategy to take a process from its current state to a future, commercial-ready state while reducing risks." You can read the entire article here.

PCT - Caladrius in the News: 
In his opening remarks at the BioProcess International Conference Cell Therapy Pre-Conference Symposia, Chairperson Kurt Tisler showed a map of the US with a handful of companies on it. The map included "Cell Therapy CMO Options in the US" and PCT was one of only 3 private companies and another handful of institutions that were options for Phase III in cell therapy. The map gave a striking picture of just how much those companies are in the forefront of cell therapy manufacturing. The past two months have been eventful for this industry leader, with news on multiple fronts. What follows is a brief run-down of noteworthy news about this organization.

PCT supporting IRX's development of IRX-2
PCT is providing IRX "with personnel and dedicated clean room capacity within its current cGMP infrastructure and pursuant to EU cell therapy manufacturing standards.” Caladrius is the only cGMP-compliant cell therapy manufacturing provider that has facilities on both the East and the West Coasts. Additionally they are the only one to see a client's cell therapy product receive approval from the FDA for commercial sale.

PCT has entered into a collaboration agreement with Sanford Research to develop CLBS03
The initial focus will be the execution of a clinical trial to evaluate the safety and efficacy of CLBS03 in adolescents. The Phase 2 study has an open and active IND; subject enrollment is expected to commence the first quarter of 2016.

NIH's National Cancer Institute gives $300K in funding, with a potential $2 million to follow
This will fund the first phase process optimization of Caladrius' therapeutic agent targeting tumor-initiating cells. The $2 million in funding is to be expected in June 2016 if both the government and Caladrius agree to proceed at the conclusion of the first phase.

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Thursday, October 29, 2015

BPI 2015: Day Two Recap


Day two of the 12th annual Bioprocess International (BPI) Conference & Exposition featured a full day of exhibitions and continued high-level technical discussions and presentations that attendees have come to expect from the show. The day began on a high note with keynote speakers giving insight into the next generation of manufacturing. Valuable conversations continued during exhibit hours with the curtain rising on the BPI Theater. Of course, there were technical sessions throughout the day, as well. Some of the highlights from the second day of BPI 2015 are below.

Keynote Addresses
Bioprocessing manufacturing facilities were the topic of the day during the keynote addresses, as representatives from Amgen and Genzyme, a Sanofi company, built on the keynotes presented on day one. Both day two speakers opened the door on technologies and trends to provide a peak on what the future may hold for the industry.

The future is now was the theme of the first presentation, given by Kimball Hall, Vice President Manufacturing, Amgen Singapore Manufacturing Pte. Ltd. Her address was on Amgen’s Next-generation Biomanufacturing Facility, which was four years in the making and is scheduled to open its doors in 2017. In changing the manner in which Amgen conducts bioprocessing manufacturing, the company is also re-shaping the entire industry, according to Hall.

“Whereas in the past, the focus was on high margins and capacity, today biomanufacturing is centered on cost, speed, and operation flexibility,” she explained.

Hall shared the thoughts of one of Tuesday’s keynote speakers, David J. Pollard, PhD, Executive Director, BioProcess Development, Merck & Co., Inc., when she spoke of a modular method for facility design.

“In a conventional facility design, capacity becomes a consideration in Phase II. That is not the case with a modular design as it allows facilities to expand or contract as the market demands. Additionally, the modular format is agnostic to a country or location,” she explained.

In addition to a modular format, the Amgen Singapore facility incorporates other design elements that have proven to create benefits in construction time, operations, and environmental footprint. Among those elements mentioned by Hall were integration of single-use technologies (95% of the equipment is single use), incorporating connected processing, and real-time and remote monitoring.

Hall explained that the disruptive approach taken by Amgen has cut the construction time of the Singapore facility in half and capital costs are one quarter that of a conventional facility. Operating expenses will be lowered by a third, as well, according to Hall. The end result will be an approximately 60% reduction in protein development cost.

“One of the first questions I’m asked about is the environmental impact of the facility. I am happy to say that it will use less water for heating, cooling, and cleaning. Because it is a smaller facility, it will have a lower air quality classification, and emissions will be lower due to reduced energy usage and Singapore’s cleaner energy,” explained Hall.

All told, the new facility in Singapore is expected to have an 80% reduction in energy and water use. 

In the second keynote, Konstantin Konstantinov, PhD, Vice President, Technology Development for Genzyme asked What is the Future of Continuous Processing – What is the Time Frame for Implementing Fully Continuous Processing in Commercial Production? He spoke of changes in upstream and downstream processes that will help create a “dominant design” in the next 5-10 years that will help shape bioprocessing.

“The commercialization of innovation will lead to a dominant design where almost any protein can be developed using a universal platform. It will take a lot of courage and focus to accomplish this dominant design,” offered Dr. Konstantinov.

The dominant design outlined by Dr. Konstantinov is an end-to-end continuous integrated upstream and downstream principle. While there has been promising results in a pilot facility, Dr. Konstantinov noted, “Success is impossible without a high-performance cell line.”

Thankfully, Dr. Konstantinov believes there is tremendous opportunity to improve cell lines. Success will be determined by three factors – stable productivity over a long period of time, stable quality over a long period of time, and low cell specific perfusion rate.

While upstream processing improvements are one step, Dr. Konstantinov expects “a lot of changes” in the downstream. He noted developments in equipment, and spoke of a large scale continuous purification system with a very broad capacity range currently in a laboratory at Genzyme’s Framingham, Massachusetts, campus.

Despite all the progress, Dr. Konstantinov noted that the industry is entering a “very interesting stage.” New technologies still need to be developed to fill a few gaps, including cell retention devices and viral inactivation.

He also suggested the industry broaden its approach to the integration of continuous processing. “Why stop at drug substance? We should also look at drug product because continuous manufacturing can bring advantages there, as well.”

Technical Session Highlights
In his session entitled High-throughput Process Development to Accelerate Speed to the Clinic for Antibodies, Gregory A. Barker, Ph.D., Sr. Engineer, Biologics Process Development, Bristol-Myers Squibb spoke of High-throughput Process Development (HTPD) and how it allows scientists to examine 300,000 compounds per day so it only takes a few weeks to screen millions of substances. Before HTPD, Bayer researchers could take several months to develop special activity assays.

The goal of using HTPD, a computer-based serial-testing method that incorporates robotic systems, is to determine whether a substance reacts biochemically with the target, according to Dr. Barker. During the HTPD process, robots fill millions of reaction vessels with the assays.

“For example, a specific vessel may hold only 50 nanoliters of fluid with the vessels aligned on a plate that holds 1,536 wells. This would allow for 1,536 biochemical or cell-based assays to be performed simultaneously on a single microliter plate. In fact, thousands of these are often used in a single HTPD run,” said Dr. Barker.

As Dr. Barker explained, key benefits of HTPD for chromatography unit operations include:
-          A platform for rapid execution of experiments using sparingly small amounts of material to enable investigation of a broad range of process conditions
-          Fundamental data that may be used for scale-up via statistical modeling and process simulate
-          Systematic and highly reproducible execution of complex DOEs to survey the knowledge space and enable multivariate understanding

Specific methods of HTPD for chromatography were detailed, such as:
1. Isotherms
2. Batch uptake curves
3.  Batch chromatography

Dr. Barker described several HTPD methods that are used to augment FIH process development packages, including protein solubility, Protein A optimization and Sartobind Q membrane optimization. The comparison between common data sets enables adaptation of the platform and modification to process ranges.

In summarizing his remarks, Dr. Barker said that HTPD methods are well-defined and are producing data aligned with literature values. The data alone enables a broader PD knowledge space. Empirical models built directly from batch chromatography data enable a first level of prediction for large scale chromatography and rapid FIH timelines. One thing he noted was that a comparison of HTPD campaigns across different proteins reflected both commonalities and differences. As a result, the next steps will be to explore the drivers of commonalities and differences based on structural motifs.

Poster Highlight
One of the more distinguished posters at BPI 2015 was presented by MedImmune and was entitled The Final Push? Expelling mAb Drug Product from Pre-Filled Syringe Configurations for Sub-Visible-Particle Testing. The poster proposed that a partial expulsion of drug products in pre-filled syringe (PFS) configurations would more accurately reflect protein behavior.

The poster showed that completely expelling a PFS generates a significant surge of sub-visible particle (SVP) counts, stemming from the silicone oil (SiO) scraped from the syringe barrel and forced through the needle. Conclusions drawn from the experiment and published were that completely expelling a PFS results in SVP counts as much as 50x greater than if PFS was partially expelled. Particles in the surge are SiO droplets scraped off the barrel during the expulsion process and introduced into the liquid upon complete expel. Other conclusions drawn are that partially expelling a PFS is robust with respect to expel volume. Removing the product through the stopper is an orthogonal method of sampling without introducing the high artificial SiO background. The final conclusion was that product stability should be monitored by partial expel during the drug development process, as it best isolates the protein behavior.

Product Highlight 
Roche Custom Biotech made three announcements, two on products and a third on partnership, at BPI 2015.

The two new production introductions were:
Cedex Bio HT, a highly reliable metabolite and substrate analyzer for cell culture analysis. It offers unique photometric technology that delivers high data accuracy, as well as a cost-saving expandable menu. 

Tools for In Vitro Glycoengineering that can be used after proteins have been harvested. The tools increase productivity and can be used in early stage development.

Roche also announced a partnership with Flownamics that features auto sampling technology. Through the technology, multiple bioreactors can be sampled simultaneously to streamline testing and reduce down time to enhance manufacturing efficiencies

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Wednesday, October 28, 2015

BPI 2015: Data Rules

By: Frank Corden

The explosion of readily available data is everywhere around us.  Silicon Valley is bombarding us and those who would like to sell to us with data to purportedly make our lives easier. Whether it be the articles you see on your news feed or the research you do before buying the next gadget, it seems like the current strategy is to conceive of a potential use for the data and throw it at us to see what sticks.  However, often the data isn’t timely or even useful. 

Take my commute in this morning to Boston. The warning of the traffic congestion came about 5 minutes before I hit the slow down.  Since several of the exits are more than 5 miles apart, there wasn’t time to get off Mass Pike.  But even if the data was timely, it wasn’t actionable.  Once you get to I-90 to head into town, there really isn’t an alternative route to get there.

A major theme of this year’s BioProcessing International Conference (#BPIConf) revolves around making informed decisions with data.  Whether it be on-line monitoring data, laboratory data, or process analytical technology (PAT) based data, data rules.  But what are the rules around data and how do we make it useful? What are the “rules” around using process data in bioprocessing?

I was sitting in the 8:15am presentation Evaluation of Continuous Manufacturing in a Downstream Process.  I guess I wasn’t the only one who headed into town early, the room is pretty full.  It’s great to feel the energy and enthusiasm of the group first thing in the morning.

The introduction to the Recovery and Purification track delivered by Marc Bisschops of Pall Life Sciences was provocative.  He challenged us to move from batch manufacturing to continuous manufacturing.  The benefits are clearly dependent on our ability to balance throughput of the various unit operations as you move through the process. 

Kudo’s to the first presentation, Data Based Comparison of Capture and Polishing Steps in a Continuous Mab Process.  The authors, from the chromatography company ChromaCon compared continuous versus batch approaches with hard data analysis.  By evaluating throughput, cost, and resource requirements, the analysis demonstrated that a change in the manufacturing paradigm from batch to continuous chromatography can have some impressive benefits. 

With a better quality outcome (increase in purity from mid 70% to mid 80%), you can cut chromatography resin usage by one-third.  For the resin selected, the reduction in resin usage translated into $190,000/year.  In the pilot facility studied, the breakeven for the investment in continuous chromatography occurred after the transfer of only two molecules.  Clearly, the dollar savings in a full production facility would be significantly greater. 

The decision to shift from the tried and true manufacturing approaches we use today is a difficult one.  We all realize the risk of getting it wrong is what keeps us up at night.  A delay in the release of a product not only affects our companies but also the patients who depend on these products to keep them healthy, or in some cases alive. 

Hard data to help make a difficult decision; now that’s data that rules.

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BPI 2015: Day One Recap

The 12th annual Bioprocess International (BPI) Conference & Exposition began with a series of technical sessions, many of which broke new ground. BPI 2015 also proved to be an invaluable forum for scientists and engineers with its poster presentations and product announcements, as well as keynote talks from industry leaders. Here are some highlights of Day 1.

Keynote Addresses
Market leaders from Merck & Co., Novartis Pharma, and the Duke School of Medicine gave compelling and insightful keynote presentations on Tuesday at BPI 2015. And it is fitting that in Boston, one of the keynote speakers noted that there is a “revolution” underway in fighting cancer.


Innovating mAb Production to Support the Immunotherapy Revolution was given by David J. Pollard, PhD, Executive Director, BioProcess Development, Merck & Co., Inc.  Dr. Pollard began the keynote session by stating it was an “exciting time in immunotherapy” and that a revolution is now underway in cancer treatment. To be successful in this revolution, the industry needs to be agile and flexible so it can quickly adapt to change.

To that point, Dr. Pollard emphasized the importance of there being a “collaboration between suppliers and end users” to help lower costs and increase throughput. “Working as a community we can help create a facility of the future,” he stated.

Such a “facility of the future” will create a tremendous opportunity to lower the cost of manufacturing while also being able to handle increased capacities, according to Dr. Pollard. He explained that a modular approach will be taken to develop these facilities so they can easily be built out as needed.

Dr. Pollard stated this next-generation manufacturing approach will improve acceleration to clinical trials and that technology will be used to de-bottleneck activities. This will create high-throughput workflows using enabled formulations from cell line development, process development (both upstream and downstream), and formulation.

Another challenge during this revolution is to create a bridge from IV to subcutaneous. The goal is to achieve the necessary high concentration of >150 mg/mL while also addressing viscosity issues. Dr. Pollard stated that, while it is early proof of concept, Merck has done research in which novel excipients have been added to meet this challenge. 

Next to speak was Spencer Fisk, Global Head, Biologics Process, R&D, Novartis Pharma, AG who spoke of Innovative Process Development Strategies to Drive the Rapid Clinical Introduction of Emerging Biologics. Fisk challenged the industry go beyond the “heavily walked path” and push boundaries to speed drug development and improve efficacy.

Fisk’s approach to accelerating drug development was for his colleagues to not avoid taking risks. He suggested to “use data to guide us” so scientists and engineers can approach the “edge of the cliff.” Using data, risk levels can be determined and comfort levels established with the end result of more quickly selecting the proper candidate for development.  

Choosing the best candidate requires evaluating all the variables such as the biology and the ability to develop the candidate. Each variable has its own elements. For example, in the case of biology, binding, potency and efficacy need to be assessed. In terms of development there are a number of aspects, including stability, that need to be determined.

Risk factors not only need to be established, they should be classified as critical (red), moderate (yellow), and low (green), suggested Fisk. If the risks are predominantly low, then the candidate should be moved ahead. “Green means go,” stated Fisk. The results will be favorable the majority of the time.

“If we get it right >80% of the time, we have significant time savings. In many cases, the 20% that does not work is simply due to the fact that more time is needed,” said Fisk.

Taking this approach will create a cycle that will benefit the market, as well as society. Once scientists have “walked to the edge” and realized it was not as close as they originally believed they will push the boundaries further, creating a continuum of accelerating drug development, according to Fisk.

The final keynote, Novel Approach to Developing and Producing Human Experimental Vaccines for HIV, was given by Michael Anthony, M.D., Chief Medical Officer, Associate Professor of Pediatrics, Duke Human Vaccine Institute, Duke School of Medicine. Dr. Moody emphasized that because HIV is a unique and challenging virus it poses many challenges. Vaccines that are developed and aim to be effective must deal with an incredible diversity of circulating strains.

“By locating and neutralizing antibodies we can prevent disease but this is not an easy task. Antibodies at a sufficient level can target many strains of HIV1,” said Dr. Moody.

One question posed by Dr. Moody during his session was if information gathered from those patients who are infected can be used to make antibodies. “But it’s not that simple. There are many changes to the immunosystem that we may need to mimic with adjuvants to be successful,” he explained.

Novel adjuvants will need to be developed, according to Dr. Moody. Human trials are in the planning stages but there is no guarantee that the answers will be found. There is a paradox in the bnAb development – mutations develop. As a result, Phase I human testing is required. Within that context, two important elements are needed:
·         Targeting of multiple lineages
·         Multiple immunogens, likely in sequence

“Industry, academia and government will need to come together, as one of these alone cannot muster the resources needed to be successful,” emphasized Dr. Moody.

Technical Session Highlights
New Data on Continuous Manufacture in Downstream Process: In the Recovery and Purification technical track, Michael Bavand, PhD, Chairman and CEO of ChromaCon AG, released new data during his presentation entitled Data Based Comparison of Capture and Polishing Steps in a Continuous Mab Process.

Dr. Bavand spoke of a study conducted in which four resins were compared using batch mode, dynamic flow load, and continuous chromatography. The experiment evaluated five outputs – recovery percentage, high molecular rate (HMW%), productivity, host cell protein, and 0.1M NaOH tolerance. The results revealed:
·         Very little difference in recovery percentage, as all the conditions were > 90%
·         Slight reduction in HMW% in the continuous condition
·         Host cell protein (ng/mg) was equivalent or better in continuous condition
·         All DBC levels were > 90% initially after 100 cycles; resin 4 showed reduction in DBC after first measurement

A model was generated with all the productivity data. Validation cost estimates, lab scale system purchase, GMP system purchase, FTE estimates, and the number of new molecules arriving in a plant annually were all accounted for by the model. The model was used to estimate return on investment across the number of new molecules to come into a pilot plant every 12 months. Using a baseline of two new molecules per year, the initial estimates were that cost savings would be realized after three years.

Dr. Bavand also discussed a second part of the experiment that studied a process using MCSGP with a membrane adsorber to determine if it would have equivalent or better outputs than a cation exchange (CEX) resin step in terms of recovery, productivity, and impurity levels. Through the experiment, a Flow Through MCSGP was demonstrated to have equivalent purity and recovery with significant higher productivity levels than batch mode.

As revealed by the results, higher productivity and large cost savings are possible using a continuous chromatography system for both capture and polishing steps. Additional verification of these processes is needed before they can be implemented into a pilot plant concluded Dr. Bavand.

Poster Highlight
Essential Pharmaceuticals’ poster entitled Novel Lipid Based Supplement Increases Protein Yield in Single Use Bioreactor presented the use of a lipid supplement using various strategies to improve protein yield.

The poster stated that by adding the lipid supplements at the beginning of the culture, the yield in titer antibody protein production increased 30% from CHO cells without increasing proliferation. Further, when the metabolic profile was examined, it was discovered that there were no differences in any of the metabolites.

The poster also stated that the supplement was used as a feed and there were two notable effects: 1) increasing the titer yield by 25% and 2) extending the window for peak protein production from one day to two. These results show that there are windows for further optimization of protein production using lipids. It is possible the use of lipids reduces the energy requirement for new cell formation and, therefore, can be used for protein production. 

Product Highlight 
Pall Life Sciences is showcasing key components of its biopharmaceutical portfolio in its booth (#309). A host of updated and new portfolio products will be on display, with particular emphasis on continuous solutions Pall has available for downstream processing support.

Included in the BPI 2015 booth will be:
  • The disruptive Acoustic Wave Separation technology for cell-culture clarification in either fed-batch or perfusion applications
  • A preview of Pall’s latest advance in depth filtration: Stax™ Depth Filters with Hyperion Flow technology, for direct mammalian cell harvest with a new filter to remove cells and cellular debris effectively and efficiently
  • The award-winning Cadence™ Inline Concentrator single-pass tangential flow filtration system for direct flow-through and in-process volume reduction in an integrated or stand-alone format
  • The recently introduced BioSMB® System for single-use or multicolumn continuous chromatography featuring a disposable flow path with a proprietary integrated valve cassette to service up to 16 columns or devices.

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Podcast: Genentech Antibody Engineering Director Talks Bispecifics

With two approved and about 30 in clinical development, bispecific antibodies are at last moving into the therapeutic mainstream.

We sat down with Genetech Senior Director of Antibody Engineering Dr. Paul Carter for a brief look at where the field is going.

Paul Carter

In this podcast interview for Inside Antibody Engineering, Dr. Carter discusses:

• Choosing a format

• New applications

• Emerging routes of administration and more...   

Listen to the podcast or download a transcript here!

Editor’s note: Dr. Paul Carter will co-chair a track on new technologies and applications for bispecific antibodies at the Antibody Engineering and Therapeutics Conference taking place December 7-10 in San Diego.

Click here for an agenda

Or for more information visit:

(Ps. SAVE $100 when you register with code D15172BLOG!)

Marc Dresner is sr. editor and special communication project lead with IBC Life Sciences. He is the former executive editor of Pharma Market Research Report, a publication for market research professionals specializing in pharmaceuticals and life sciences. He may be reached at Follow him @mdrezz.

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Start-Up of the Week: Semma Therapeutics

This article is the first in a series of weekly posts that will look at cell therapy start-ups that are making headlines. 

By: Leah Kinthaert

At the Cell Therapy BioProcessing Pre-Conference Symposia for the BioProcess International Conference and Exposition, Chris Gemmiti of Wyss Institute, in his "State of the Industry" talk brought up six companies who have received funding this year. His list included Semma Therapeutics, a company who was all over the news back in March when they closed a $44 million series A funding round.

What has Semma Therapeutics been up to since March?
Semma Co-Founder and CEO Robert Millman recently spoke at BioPharm America where he gave some incredible insight on the choices he and his organization have made in regards to partners, manufacturing and other strategic goals.

Millman discusses the two hats he wore, in acquiring funding for Semma.  As CEO... "I want non-diluted financing, I want a strategic partner...I don't want to be in a situation where I need data and have to go out to reraise capital. I need a partner who's committed."

Millman continued: As VC... "I want to reduce risk, reduce cost basis of my investment, pre money evaluation”. Millman explains: "The intersection of a wants of a biotech company, and the wants of a venture partner came together the funding of Semma.”

Semma Therapeutics has partnered with Novartis and Medtronics, a company which has a multimillion dollar business in diabetic pumps. Why a company that makes pumps is suddenly interested in cell therapy says a lot about how cell therapies are shaking up the healthcare industry. Millman explains: "If cells work better than pumps that industry goes away."

How Semma came to be: 
"Semma Came together very quickly once Doug Melton (scientific founder of Semma) committed that he wanted to do this not through a strategic relationship with a single pharmaceutical but wanted to incubate it with a biotech, because a biotech company can really progress things faster and it also leaves a lot of incentive on the table for the founding and the founding institution where a direct license to a pharmaceutical company may not. The goal of Semma was to raise enough capital to move it to a point of strategic advancement, but remain enough leverage on the table so when you got to that next point of value creation and had a need for another raise it would be at a high incremental value."

Millman has had several years of experience in biotech, and has some specific theories as to why some cell therapy companies have failed: “In my career I watched a lot of biotech companies fail because the CEO at the time said ‘Look I’m smarter than pharm, I am going to keep this agent and move it farther down the stream' and that’s where the problems typically happen.“

Explaining why Semma opted to choose Novartis as a partner: 
“When a pharmaceutical company wants something it will put more resources than any biotech company can put on something to move it over the hump. It’s an amazing relationship when pharma really wants what you’re working on.” Millman does, however, seem to understand why some start-ups are hesitant: “The downside of bringing in a strategic partner in the beginning is that you’re almost like captured bait”...“Some VCs will say that’s a bad model because I want to go out and hit the free market later.”

On Semma's decision to not build their own plant:
"What happens is you spend $100 million on facility infrastructure and maintenance cost for a product that you don’t even know is there. You control the process, but that is not always the best way to go forward. The investment in time to get a plant up, get ready for manufacturing...adds about a year and a half to a minimum of two years on my timeline. Renting that will triple my costs on the front end for that single per gram basis, but over the long run I think it's a better investment for us.”

Semma's biggest hurdle: 
“Our cells need to come together for the general population with a device... a delivery technology. The goal here is treating patients, how do I get what I have for patients. In my in my case I need delivery and delivery technology to access a very large patient population.”

A lot is at stake for Semma right now. As Chris Gemmiti, speaking this week at BioProcess International commented: (They got) "$44 billion in funding and they're not even at the IND stage." All eyes are on Semma as they attempt to bring their technology to the clinical stage.

Click here to watch the full panel discussion with Robert Millman of Semma at BioPharm America last month.

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