United States: Biomanufacturing Technology Summit 2015 In Maryland: Bioanalytics Guiding Quality, Where Increased Collaboration Could Lead To Faster And Greater Discoveries

Last Updated: July 5 2015
Article by Brian J. Malkin

On June 25, 2015, the Institute for Bioscience and Biotechnology Research (IBBR), the National Institute of Standards and Technology (NIST), and the University of Maryland (UM) put on its second Biomanufacturing Technology Summit, "Manufacturing Science Analytics: Predictors of Biotherapeutic Product Quality", in Rockville, Maryland.  McGuireWoods LLP was a sponsor of this important Summit and had Brian Malkin and TaeSoo "Sean" Kim on hand to interact with speakers and attendees.

Thomas R. Fuerst, Ph.D., Director IBBR, and William Bentley, Ph.D., Distinguished Professor and Chair, Department of Bioengineering, UMD, set the stage for the Summit as a place to discuss new bioanalytical testing for predicting the quality attributes of biological products including biosimilar versions of those products.

Then FDA's Steven Kozlowski, M.D., Director, Office of Biotechnology Products, took center stage, where he said that in terms of analytics and biological products, there is always a need to strive for being better, challenging the current state of analytics that control quality as "not good enough." For the same sponsor, changes in biological product manufacturing are driven by the quality control of comparability; for a different sponsor, the quality control goal is biosimilarity. Traditionally, FDA has thought about quality as a set of specifications, with changes that may be made either simultaneous to agency notification (changes being effected – 30 days), following preapproval supplements, or in annual reports. FDA has been concerned, Koslowski explained, that industry was confused with what were the "established conditions" in an application or license that represents the core chemistry, manufacturing and controls for an approved application (new drug application (NDA) or abbreviated new drug application (ANDA)) or license (biologics license application (BLA)). So last month, FDA issued draft guidance on the agency's thoughts on "established conditions" in the guidance, " Established Conditions: Reportable CMC Changes for Approved Drug and Biological Products". Here, "established conditions" is defined as "the description of the product, manufacturing process, facilities and equipment, and elements of the associated control strategy, as defined in an application, that assure product performance and quality of the approved product."

Along these lines, Kozlowski described FDA's evolving thoughts about the established conditions for biological products. Because the landscape of analytics to choose from continues to change, initial process or release analytics may change over time, resulting in a reordering of the risk ranking of quality attributes. As a result, it is critical to retain useful samples for comparative studies in anticipation of life cycle changes to compare products made with older and newer processes in view of the changing analytic tools. And it is increasingly important for manufacturers to integrate analytics into manufacturing to watch for potential changes in biological characterization (biocreep), as well as developing biosimilar products, where the analytics drive the required animal and clinical studies.

Regarding biosimilars, Kozlowski said that FDA has received over 80 meeting requests for 15 proposed biosimilar products, which have resulted in several filed and publicly-disclosed biosimilar applications and one approved biosimilar product. Kozlowski said that in terms of analytics, he believes that there is a need for a consortium of biosimilar companies to work together to help develop common and current analytics to help all of the biological product companies meet their goals more quickly.

The morning session featured additional presentations on real-time predictive models: bio-sensors and bio-predictors. Govind Rao, Ph.D., Professor of Chemical and Biochemical Engineering, Director of the Center for Advanced Sensor Technology, UM. Rao explained that it is critical to monitor biological manufacturing from start to final product; if not, "it would be like having a child and not monitoring it until it went to college." Biosensors, such as oxygen levels, Rao observed, help to determine the window of optimal growth conditions for fermentation bioprocessing. Along these lines, Rao noted that there is a need to develop smaller-scale models that help to simulate ramp-up conditions for large-scale production for the final product.

Later, Patrick Swann, Ph.D. Senior Director, Technical Development, Biogen, discussed how different bioanalytics are utilized at various processing stages, including intermediate products or process-related impurities monitored, such as acidic isoforms that can limit shelf life, as part of quality-by-design. Alexion's Kyle Zingaro, Ph.D., Development Scientist I, Upstream Development, then discussed how improved bioanalytic characterizations lead to accelerated process development and platform development with the goals of quality, robustness, raw material supply chain, scalability, productivity, and cost effectiveness. Zingaro described how the need for a better connection between biophysical quality and clinical safety and efficacy drives to a consensus development of a biological fingerprint, which will be increasingly important.

FDA's Lieutenant Commander Cyrus Agarabi, Ph.D., Senior Regulatory Researcher, Center for Drug Evaluation and Research, rounded out the morning's program. Agarabi described how FDA's internal regulatory research, including biological product analytical testing, helps to support policy development and biotechnology review decisions. Agarabi encouraged industry to collaborate more with less compartmentalization of knowledge by sharing information about equipment and use for integrated bioprocessing systems to drive product quality in-line, on-line, and at-line with continuous manufacturing. As an example, nutrient analysis is often critical to affect cell viability and reliability, which can be integrated into bioreactors and autosamplers, including continuous sampling of media and cell membrane charges (indicating a cell is alive) to maximize cell harvest.

The afternoon focused on computational and analytical methods for predictive final product characterization. Michael Tarlov, Ph.D., Division Chief, Biomolecular Measurement Division, Material Measurement Laboratory, NIST, said that NIST is looking for more collaboration in the development of bioanalytical predictors for biological product quality. Steven Rose, Associate Director, Upstream BioProcess Engineering, MedImmune, described how MedImmune has been linking certain predictive cell culture scaling methods, e.g., pH and the carbon dioxide equilibrium to optimize inputs. Then Elizabeth M. Topp, Ph.D., Head, Department of Industrial and Physical Pharmacy, Purdue University, described how mass spectroscopy and other analytical methods may be used to test lyophilized biological products to obtain test and accelerated stability data, which has been conducted as part of a NIST consortium. Merck's Marina Goldfeld, Associate Principal Scientist, described an innovative real-time measurement tool for glycerol, methanol, and biomass in a particular fermentation culture. And then Florian M. Wurm, Ph.D., Honorary Professor, Swiss Federal Institute of Technology and Founder and CEO, ExcellGene, described how Chinese hamster ovary (CHO) cells have been used for over 30 years for production of proteins in high quantities by making a selected cell with a desired gene "happy" through positive growth factors.

The Summit concluded with a robust panel discussion from the day where there was considerable discussion about how long it takes for an analytic method to become a standard and how there is room for collaboration for next generation analytics. Given the 12-year exclusivity for new biologics, even if there were sharing of manufacturing information now, Kozlowski speculated, it will only help the originator industry grow better. For instance, Kozlowski thought there could be a social-network-type way to share information without any one group feeling left out or some singularity. Zingaro thought that there were few new manufacturing processes to share but that there was some sharing going on with analytics with room to grow. As a "stretch goal", Kozlowski thought that while the Agency is not at a point of saying clinical studies would not be required for market approval, in theory physical attributes could be linked to clinical outcomes. On a last point, it was agreed that better analytics at predicting quality would be a productive next step.

The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.

To print this article, all you need is to be registered on Mondaq.com.

Click to Login as an existing user or Register so you can print this article.

In association with
Related Video
Up-coming Events Search
Font Size:
Mondaq on Twitter
Register for Access and our Free Biweekly Alert for
This service is completely free. Access 250,000 archived articles from 100+ countries and get a personalised email twice a week covering developments (and yes, our lawyers like to think you’ve read our Disclaimer).
Email Address
Company Name
Confirm Password
Mondaq Topics -- Select your Interests
 Law Performance
 Law Practice
 Media & IT
 Real Estate
 Wealth Mgt
Asia Pacific
European Union
Latin America
Middle East
United States
Worldwide Updates
Mondaq Ltd requires you to register and provide information that personally identifies you, including what sort of information you are interested in, for three primary purposes:
  • To allow you to personalize the Mondaq websites you are visiting.
  • To enable features such as password reminder, newsletter alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
  • To produce demographic feedback for our information providers who provide information free for your use.
  • Mondaq (and its affiliate sites) do not sell or provide your details to third parties other than information providers. The reason we provide our information providers with this information is so that they can measure the response their articles are receiving and provide you with information about their products and services.
    If you do not want us to provide your name and email address you may opt out by clicking here
    If you do not wish to receive any future announcements of products and services offered by Mondaq you may opt out by clicking here

    Terms & Conditions and Privacy Statement

    Mondaq.com (the Website) is owned and managed by Mondaq Ltd and as a user you are granted a non-exclusive, revocable license to access the Website under its terms and conditions of use. Your use of the Website constitutes your agreement to the following terms and conditions of use. Mondaq Ltd may terminate your use of the Website if you are in breach of these terms and conditions or if Mondaq Ltd decides to terminate your license of use for whatever reason.

    Use of www.mondaq.com

    You may use the Website but are required to register as a user if you wish to read the full text of the content and articles available (the Content). You may not modify, publish, transmit, transfer or sell, reproduce, create derivative works from, distribute, perform, link, display, or in any way exploit any of the Content, in whole or in part, except as expressly permitted in these terms & conditions or with the prior written consent of Mondaq Ltd. You may not use electronic or other means to extract details or information about Mondaq.com’s content, users or contributors in order to offer them any services or products which compete directly or indirectly with Mondaq Ltd’s services and products.


    Mondaq Ltd and/or its respective suppliers make no representations about the suitability of the information contained in the documents and related graphics published on this server for any purpose. All such documents and related graphics are provided "as is" without warranty of any kind. Mondaq Ltd and/or its respective suppliers hereby disclaim all warranties and conditions with regard to this information, including all implied warranties and conditions of merchantability, fitness for a particular purpose, title and non-infringement. In no event shall Mondaq Ltd and/or its respective suppliers be liable for any special, indirect or consequential damages or any damages whatsoever resulting from loss of use, data or profits, whether in an action of contract, negligence or other tortious action, arising out of or in connection with the use or performance of information available from this server.

    The documents and related graphics published on this server could include technical inaccuracies or typographical errors. Changes are periodically added to the information herein. Mondaq Ltd and/or its respective suppliers may make improvements and/or changes in the product(s) and/or the program(s) described herein at any time.


    Mondaq Ltd requires you to register and provide information that personally identifies you, including what sort of information you are interested in, for three primary purposes:

    • To allow you to personalize the Mondaq websites you are visiting.
    • To enable features such as password reminder, newsletter alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
    • To produce demographic feedback for our information providers who provide information free for your use.

    Mondaq (and its affiliate sites) do not sell or provide your details to third parties other than information providers. The reason we provide our information providers with this information is so that they can measure the response their articles are receiving and provide you with information about their products and services.

    Information Collection and Use

    We require site users to register with Mondaq (and its affiliate sites) to view the free information on the site. We also collect information from our users at several different points on the websites: this is so that we can customise the sites according to individual usage, provide 'session-aware' functionality, and ensure that content is acquired and developed appropriately. This gives us an overall picture of our user profiles, which in turn shows to our Editorial Contributors the type of person they are reaching by posting articles on Mondaq (and its affiliate sites) – meaning more free content for registered users.

    We are only able to provide the material on the Mondaq (and its affiliate sites) site free to site visitors because we can pass on information about the pages that users are viewing and the personal information users provide to us (e.g. email addresses) to reputable contributing firms such as law firms who author those pages. We do not sell or rent information to anyone else other than the authors of those pages, who may change from time to time. Should you wish us not to disclose your details to any of these parties, please tick the box above or tick the box marked "Opt out of Registration Information Disclosure" on the Your Profile page. We and our author organisations may only contact you via email or other means if you allow us to do so. Users can opt out of contact when they register on the site, or send an email to unsubscribe@mondaq.com with “no disclosure” in the subject heading

    Mondaq News Alerts

    In order to receive Mondaq News Alerts, users have to complete a separate registration form. This is a personalised service where users choose regions and topics of interest and we send it only to those users who have requested it. Users can stop receiving these Alerts by going to the Mondaq News Alerts page and deselecting all interest areas. In the same way users can amend their personal preferences to add or remove subject areas.


    A cookie is a small text file written to a user’s hard drive that contains an identifying user number. The cookies do not contain any personal information about users. We use the cookie so users do not have to log in every time they use the service and the cookie will automatically expire if you do not visit the Mondaq website (or its affiliate sites) for 12 months. We also use the cookie to personalise a user's experience of the site (for example to show information specific to a user's region). As the Mondaq sites are fully personalised and cookies are essential to its core technology the site will function unpredictably with browsers that do not support cookies - or where cookies are disabled (in these circumstances we advise you to attempt to locate the information you require elsewhere on the web). However if you are concerned about the presence of a Mondaq cookie on your machine you can also choose to expire the cookie immediately (remove it) by selecting the 'Log Off' menu option as the last thing you do when you use the site.

    Some of our business partners may use cookies on our site (for example, advertisers). However, we have no access to or control over these cookies and we are not aware of any at present that do so.

    Log Files

    We use IP addresses to analyse trends, administer the site, track movement, and gather broad demographic information for aggregate use. IP addresses are not linked to personally identifiable information.


    This web site contains links to other sites. Please be aware that Mondaq (or its affiliate sites) are not responsible for the privacy practices of such other sites. We encourage our users to be aware when they leave our site and to read the privacy statements of these third party sites. This privacy statement applies solely to information collected by this Web site.

    Surveys & Contests

    From time-to-time our site requests information from users via surveys or contests. Participation in these surveys or contests is completely voluntary and the user therefore has a choice whether or not to disclose any information requested. Information requested may include contact information (such as name and delivery address), and demographic information (such as postcode, age level). Contact information will be used to notify the winners and award prizes. Survey information will be used for purposes of monitoring or improving the functionality of the site.


    If a user elects to use our referral service for informing a friend about our site, we ask them for the friend’s name and email address. Mondaq stores this information and may contact the friend to invite them to register with Mondaq, but they will not be contacted more than once. The friend may contact Mondaq to request the removal of this information from our database.


    From time to time Mondaq may send you emails promoting Mondaq services including new services. You may opt out of receiving such emails by clicking below.

    *** If you do not wish to receive any future announcements of services offered by Mondaq you may opt out by clicking here .


    This website takes every reasonable precaution to protect our users’ information. When users submit sensitive information via the website, your information is protected using firewalls and other security technology. If you have any questions about the security at our website, you can send an email to webmaster@mondaq.com.

    Correcting/Updating Personal Information

    If a user’s personally identifiable information changes (such as postcode), or if a user no longer desires our service, we will endeavour to provide a way to correct, update or remove that user’s personal data provided to us. This can usually be done at the “Your Profile” page or by sending an email to EditorialAdvisor@mondaq.com.

    Notification of Changes

    If we decide to change our Terms & Conditions or Privacy Policy, we will post those changes on our site so our users are always aware of what information we collect, how we use it, and under what circumstances, if any, we disclose it. If at any point we decide to use personally identifiable information in a manner different from that stated at the time it was collected, we will notify users by way of an email. Users will have a choice as to whether or not we use their information in this different manner. We will use information in accordance with the privacy policy under which the information was collected.

    How to contact Mondaq

    You can contact us with comments or queries at enquiries@mondaq.com.

    If for some reason you believe Mondaq Ltd. has not adhered to these principles, please notify us by e-mail at problems@mondaq.com and we will use commercially reasonable efforts to determine and correct the problem promptly.

    By clicking Register you state you have read and agree to our Terms and Conditions