“We'll have both small biotech CEOs and large pharma representation,” Lau told BPI's contributing editor, Lorna McLeod. “Malcolm MacCoss is head of chemistry for what was Schering-Plough but now Merck. He's moderating and will be asking all the panel questions.” Discussion will cover not only discovery, but also preclinical development, and early drug development (phase 1, phase 2).

“In many ways,” Lau went on, “it's very important for small companies to do the homework of large pharma. They have a lot of complex issues facing them. I would think that there's a wide range of understanding from small pharma. Some truly understand, and some may not as well.”

Among discovery collaborations, Lau's own company is involved in a few. “We have an ongoing collaboration with Novartis,” she told Lorna. “And we also have a collaboration ongoing with Ono pharmaceuticals from Japan. Scynexis and Chromocell also have collaborations, and those two CEOs will also be on the panel.”

DELIVERY AND MANUFACTURING OF BIOLOGICS AND DRUGS SESSIONS AT THE CONVENTION
Sponsored by Novozymes

Monday, 3 May 2010
2:00–3:30 PM
New Methods for Bioprocess Modeling and Monitoring: A Multidisciplinary Approach
4:00–5:30 PM
Personalized Medicine: Solutions for GMP Manufacturing of Autologous Cell Products

Tuesday, 4 May 2010
8:00–9:00 AM
Sustainability and Energy Efficiency in Biotech Facilities
9:30–10:30 AM
Quality-by-Design for Biologicals: What's Next?
2:00–3:30 PM
Build or Buy? Strategic Choices in Biomanufacturing
4:00–5:30 PM
Expression Systems for the Manufacture of Recombinant Proteins

Wednesday, 5 May 2010
8:00–9:30 AM
Handle with Care: Solving the Delivery Challenges of siRNA Therapeutics
2:00–3:30 PM
Biologic Drug Product and Combination Device Manufacturing Considerations
4:00–5:30 PM
Is Your Supply Chain a Blind Spot? Avoiding Common Post-Commercialization Issues

Product Innovations, Delivery and Manufacturing

Biomanufacturing has seen real growth over the past decade, especially due to the success of MAbs as therapeutic agents. Production of these products for a global market presents many unique challenges in processing, packaging, and combining drug products with delivery devices. For controlling quality and providing QbD as required by the FDA's process analytical technology (PAT) initiative, knowledge and understanding of complex and highly interactive bioprocesses needs to improve. QbD approaches are already maturing in the industry, and initial global regulatory submissions using QbD development will soon enter review stages. Process optimization through online monitoring, prediction of meaningful parameters, and modeling is subsequently coming into focus. Meanwhile, at least a few autologous cell therapies are moving closer to commercialization, and they face the challenge of ensuring appropriate GMP manufacturing and scale-out (rather than scale-up).

Drugs based on RNAi hold significant promise in treating an array of diseases. Unlike earlier technologies, RNA interference (RNAi) is a catalytic mechanism, so only a few molecules are needed to suppress gene expression. The technology presents its own challenges, of course, and solutions under exploration include synthetic oligonucleotides with functional conjugates or transfection carriers and inverse complementary molecules expressed from plasmid or viral vectors. Those are used in target discovery and validation, but they could also be developed into therapeutics themselves — although systemic delivery of RNAi therapies to target tissues remains a major challenge.

Several companies are developing unique delivery technologies, ranging from lipid-based formulations to polymer engineering and novel nanofabrication techniques. Nanotechnology, imaging, and other technologies are also expected to play a key role in the future of health care delivery and management. Rapid and multiplexed detection modalities for clinics, hospital bedsides, laboratory settings, and even homes could be pivotal in rapid monitoring of genomic, proteomic, metabolic, and other types of markers and indicators. Novel therapeutic delivery technologies (e.g., nanoparticles) are poised to significantly change the treatment of disease. But discovery, identification, and development of new receptors will be critical to the successful use and deployment of nanotech-based sensor systems.

Some companies are researching multifunctional nanoparticles for additive or synergistic effects in addition to useful first-generation nanoparticles that offer prolonged circulation in blood, passive or active target specificity, and increased cell penetration. For instance, certain nanomaterials respond to physiological stimuli such as pH, temperature, or dissolved oxygen and can increase selectivity in drug delivery to target tissues. Multifunctional nanosystems offer a single carrier platform to incorporate multiple therapeutic agents for simultaneous or sequential delivery, using energy (e.g., heat, light, or sound) to enhance therapeutic effects, and combining drug(s) with imaging agents for real-time monitoring of therapeutic efficacy.

Bioprocessing Decisions: A major hurdle in taking vaccines and other biologics to market is developing an economically viable process to make them at industrial scale. Some advances have provided manufacturers with more choices among production systems than were available even five years ago. They span the range of prokaryotic and eukaryotic organisms and include bacterial, yeast, fungal, plant, and insect- or mammalian-cell systems. Many systems are based on cell lines that have been specifically engineered for improved production characteristics, such as defined post-translational modifications or localization/secretion of expressed proteins. Several products made using nontraditional systems are now in mid- to late-stage development, and some have even made it to market.

Biologics and vaccines are facing global competition and political cost pressures, so biomanufacturing has become a critical component in development and commercial strategy. Issues such as geographic manufacturing capacity imbalances, potentially game-changing technologies, biosecurity and supply-chain worries, and emerging countries' desire to serve their own markets, are driving interest in smaller, more widely distributed production approaches. Drug developers both large and small face hard choices (with trade-offs on costs, timing, location, and control) in deciding whether to build (or reengineer) in-house facilities or outsource their drug production.

Robert Gottlieb (principal of RMG Associates) and Ellen M. Martin (a partner in Kureczka∣Martin Associates) organized a session for the 2010 BIO International Convention's delivery and manufacturing track called “Build or Buy? Strategic Choices in Biomanufacturing” as well as a second panel for the exciting science track called “Is Biomanufacturing the Next Disruptive Technology Frontier?” Martin described them this way: “Build-or-Buy is about faster, cheaper, better, and safer, where you put it, and who's in control. And Disruptive Tech is about what's new, exciting, and different.”

She went on: “When genetic engineering started 30-some years ago, it was a totally hot technology, and it still is a miracle. But I think people have gotten used to it, and it's lost some of that miraculous charm. It's still an extremely cool technology to take living organisms or pieces of them and harness those to do much more exotic things than make beer or wine or bread, which is how biotech got started. There's a rule of thumb in engineering that 20–30 years is about the time it takes for a technology to mature. Transistors are a great example. The time between Bardeen's Nobel prize and the personal computer was about that. So what we're seeing here is an industry that has really matured. From the build-or-buy perspective, with consolidation and big pharma buying biotech capacity, it's ended up very much concentrated worldwide. Howard Levine (of BioProcess Technology Consultants, chair of the ‘Disruptive’ panel) used a figure in a panel last year showing that some 80–90% of the capacity is controlled by the top 10 companies. That's very concentrated geographically in North America and Europe.”

But China and India are working hard to come up to speed. Martin said they're motivated “not only to establish their own industries but also to establish their own markets. Who's going to sell to emerging markets is becoming a big creative decision issue for many companies, from big ones to start-ups.” And not just China and India. A-Bio Pharma, a pioneering biologics contract manufacturer in Singapore, will be represented by a speaker on the Build-or-Buy panel.

How have the economics of biomanufacturing changed over the past couple of decades? Martin says there's probably overcapacity now, “but it's not in optimal locations for growing markets or for small companies. Big companies control it, and it's not always easy to get access to that — especially since most of those companies don't think of themselves as being in the contract manufacturing business.”

Gottlieb pointed out that building manufacturing capacity is “an enormous capital investment, certainly for emerging companies. It's investment that often has to take place early on, before you even know you have a viable product — and that has not changed, although potentially it's starting to with some of the newer technologies such as disposables and flexible facilities. They take much less time to construct and scale, so companies can delay a major investment decision until they're hopefully a little more ‘derisked’ on the development side.”

So disposables and outsourcing provide some means for companies to advance until they can afford to build a facility. Gottlieb said the Build-or-Buy panel includes case studies involving two companies, Itero Biopharmaceuticals and Crucell, who are partnering with Xcellerex. “For clinical-scale material, Crucell is acquiring a complete manufacturing train from Xcellerex. If you look at improvements that have been made in process development and culture/yield,” Gottlieb said, “fewer facilities will need 20,000-L fermentors. Instead, they're looking at much smaller scales.”