Introduction

While attending this year’s BioProcess International Conference (BPI) in Boston last month, I was excited because it seemed to be a larger turnout then I’d remembered from previous years. BPI recently confirmed that it was in fact the largest attendance in BPI’s twelve-year history. In addition to the larger turnout, the content felt fresher and very relevant to the current challenges and potential solutions facing the industry. BPI provides talks focused on improving the manufacturing process for biopharmaceuticals, enables industry networking opportunities, and the chance to see the latest products and technologies.

Conference Highlights

For me one of the biggest highlights of the conference was the keynote, “Amgen’s Next-Generation Biomanufacturing Facility by Kimball Hall, Vice President Manufacturing, Amgen Singapore Manufacturing Pte. Ltd. In the talk Ms. Hall describes the 200 million dollar next generation manufacturing facility Amgen built in Singapore. The facility was built in less than two years, half the time of a more traditional facility, and is state of the art in terms of innovative technologies. One of the enabling technologies used in the facility is single-use technology. The facility is over 90% single-use, in fact they only need one autoclave. The facility also incorporates continuous processes and relies on the concept of closed system manufacturing.

Ms. Hall describes how they have implemented a closed system approach to allow for a central manufacturing suite where upstream and downstream can be conducted in the same room. They are using smaller, single-use bioreactors coupled with continuous processes in downstream and real time quality analysis to ensure both an efficient process and a closed system. Ms. Hall states that using this manufacturing approach, they have been able to achieve improvements in yield and reduction in cost per gram.

In addition this closed system approach also permits their solution prep area to operate for both media and buffer prep with closed raw material bags, anti-static powder transfer sleeves and connections to 5,000 L single-use mixing vessels ensuring material stays closed within its equipment. To move solutions from the prep room to manufacturing, they have built openings in the walls, which allow solutions to be pumped through this opening into the other room. Material can also be pumped from the central manufacturing suite through an opening in the wall into the final purification room.

Ms. Hall addresses possible environmental impact concerns about the amount of single-use materials by walking through the environmental impact. First, they use less water for heating, cooling and cleaning. The facility overall has a smaller footprint with lower air quality classifications, thus reducing energy consumption and lowering emissions. They have can achieve solid waste reduction due to the smaller reactor size and they are working on recycling the bags and are with a group developing a way to incinerate them for biofuel.

Responding to a question about perceived regulatory risk for this next generation facility, Ms. Hall said that they have met with regulatory bodies along the way, who have been positive but have always said “we’ll have to see on inspection”. They would like it to be licensed as is but have risk mitigation plans in place for how to accommodate any required changes.

One thing that Ms. Hall also makes clear is that the relationships with suppliers have been critical. The suppliers are deeply embedded in this process and she even remarked that there were employees from the supplier companies sitting in her cafeteria during performance lot runs, waiting to help solve any problems that might arise. With the increasing complexity of these technologies, it is key that the relationships with suppliers be strong and that there is trust. Specifications and product details must be shared back and forth so that the best process can be developed and if any problems arise they can be addressed quickly.

As the question and answer session began, one person stood up to ask a question, I’m sorry I didn’t catch her name, but she called the building of this facility “Brave.” Initially it struck me that she used that that term to describe the building of this facility, but upon further reflection I understand why. In building this facility, Amgen has really committed to changing the biomanufacturing paradigm. They have invested incredible amounts of time and resources into a project that has no absolute assurance of regulatory licensing and have shared these details publically as a guide for others. For the industry to evolve it takes a company to embrace new technology and to “go first” to prove that it is feasible and that it can receive approval from the regulatory bodies. The first or firsts must pave the way before others feel comfortable to do it as well. To some in the industry who have been considering this kind of manufacturing platform, but have been waiting to see what will happen, I can see how this move may be considered brave. For a person who has been covering these innovative technologies and was able through Ms. Hall’s talk to see it all put together into one facility, for me it was inspiring.

Another really interesting talk was the keynote on “What is the Future of Continuous Processing – What is the Time Frame for Implementing Fully Continuous Processing in Commercial Production?” by Konstantin Kostantinov, Ph.D., Vice President, Technology Development, Genzyme. Genzyme has long been a proponent and pioneer for continuous processes in biomanufacturing. At the BDP conference earlier this year, there was a wonderful talk given by Dr. Veena Warikoo, Director, Purification Development, Genzyme on their concept of the bioprocessing facility of the future. Please see, “Continuous Bioprocessing – The Biomanufacturing Model of the Future?” for more details.

Other conference highlights this year included:

• Keynote presentations from Merck, Novartis, and the Duke Human Vaccine Institute
• A pre-conference symposium that had an entire track dedicated to Cell Therapy
• Ask the Regulators Open Forum
• Bioprocessing Problem-Solving Moderated Discussions
• Town Hall Forums
• BPI Theater Panel discussions on “Accelerating Biopharmaceutical Development and Manufacturing” and “CMO Panel Discussion on Perspectives and Lessons Learned on Overcoming Challenges with Tech Transfers and Biomanufacturing,”

Different Discussions by Conference Track

There were some overall themes this year that I felt were a continuation of many great discussions that were presented at the BDP Conference earlier this year including continuous processing in both upstream and downstream and implementation of closed systems. This is by no means an exhaustive list, but some highlights of the talks I attended by track include:

Cell Culture

• Perfusion and continuous processes continue to be a hot topic
• Several talks on novel approaches to cell line development including talks on CRISPR/Cas9 technology and how this can be applied to cell line development and production.
• Good discussion surrounding glycolsylation and how to achieve consistentcy. This included discussions around how media is involved in that process and predicting glycosylation profiles using metabolic data.
• Media improvements and using high throughput approaches to process development and media screening.

Recovery and purification

• In downstream, just as in upstream, implementation of continuous processes was a hot topic.
• Several discussions around using new recovery and purification technologies to improve overall efficiency and purification
• Looking at non-chromatographic purification of proteins
• High throughput process development strategies.

Manufacturing strategy

• Facility design incorporating the ballroom suite or central manufacturing suite approach.
• Closed systems as a way to enable more flexible facilities, see “Closed Systems in Biomanufacturing Offer A Variety of Benefits,” for more information.
• Continued process verification (CPV) strategies
• How to utilize facility design, single-use technologies and bioprocess automation in BRIC countries.
• Data collection, data management and bioprocess automation.

Drug Product Manufacturing and Fill-Finish Processing

• Implementing PAT tools and applying QbD
• Streamlining and integrating drug substance and final drug product manufacturing
• New strategies for aseptic filling
• Several talks on particulates and appropriate approaches

Analytical, Formulation and Quality

• Talks on integrating critical quality attribute monitoring and multi-attribute monitoring and control.
• High throughput analytical assays for process development support and quality control
• Many talks on biosimilars and product quality, characterization and comparability.
• Good discussion on supplier relationships and ensuring raw material tracking and control.

I will cover several of these areas in more detail in the coming weeks – stay tuned.