Aside from the keynote speakers, there was also a poster session bringing together some 30 sets of research from British universities. Topics ran from small-scale chromatography resin development for the purification of Japanese encephalitis virus to a biotechnology-based platform to optimise the expression of monoclonal antibody (MAb) sequence variants in CHO cells. University College London was extremely well represented, contributing almost a third of all posters. There was a competition for best poster and the winner was Rhian Grainger from the University of Sheffield with the title “Cell line specific control of recombinant antibody N-glycosylation.”

Howard Levine, president of BioProcess Technology Consultants, discussed the changing landscape of mammalian cell culture manufacturing capability and presented some very interesting data. He noted that MAbs are driving biopharmaceutical revenue and predicted that commercial antibody demand could double by 2016. But what about manufacturing capacity to cope with increasing biopharm demand? The main take away point was that while utilisation currently stands at 43%, this figure is expected to increase to 64% in five years and because much of the capacity (around 75%) is controlled by only 10 companies, access to manufacturing could become difficult. Are CMOs readying themselves?

Research Centre Jülich’s Peter Rohe stepped up the technical detail with his research into boosting bioprocess optimisation through the use of an automated micro-titer plate cultivation system. The system aims to hit the middle ground between controlled conditions and high throughput.

Aidan Courtney from Roslin Cells gave a thought provoking talk on scaling up cell manufacture from the point of view of translating research protocols into GMP processes. He noted that “the destination defines the journey” meaning that, depending on the application of a particular cell therapy, the quantity of cells required for treatment becomes a crucial parameter. Courtney went on to provide numbers for a couple of example scale-up scenarios; ischemia therapy would probably require 100000000 cells per treatment, so estimating perhaps 10,000 treatments per year, the numbers start multiplying faster than the cells… He concluded that GMP translation and scale-up are challenges best addressed in tandem.
There were several more presentations during the first day including an introduction to the “Kymouse” from Kymab’s Tom Shepherd. Watch this space. The final lecture was given by this year’s recipient of the Peter Dunnill Award, Professor Mike Hoare from University College London. It was an inspiring presentation and almost a supplication for companies, funding organisations and academic institutions to continue working together to facilitate breakthroughs in bioprocessing. Focusing on ultra scale-down for enhanced bioprocess discovery, Hoare concluded “Design for manufacture; design for lower cost.”

Regrettably, I couldn’t make the second day of the conference, but I hope that PharmTech will be able to deliver some of that content through contributions from some of the speakers in 2012. You can find more information about BioProcess UK conference here.

Topical formulations can be used to treat local and systematic indications, offer ease of delivery, facilitate patient compliance, and avoid the problem of first-pass metabolism. Successfully developing a topical formulation requires an understanding of the physiochemical properties, such as release characteristics, composition of the drug-delivery system, and the nature of the drug-delivery vehicle. Manufacturing a semisolid dosage requires implementing a CMC (chemistry, manufacturing, and controls) strategy to ensure stability, photosafety, avoidance of product degradation, and minimization of process impurities. The Pharmaceutical Technology webcast, “Optimizing Topical Drug Formulation and Manufacturing,” provides insight on recent advances in topical drug formulations, the latest regulatory/pharmacopoeial requirements in product quality and product performance, and strategies to optimize manufacturing for topical drug products.

Speakers include: Vinod Shah, PhD, chair of the Special Interest Group, Regulatory Science of the International Pharmaceutical Federation and distinguished pharmaceutical scientist and consultant to the US Pharmacopeia; Majella Lane, PhD, senior lecturer in pharmaceutics at the School of Pharmacy at the University of London; and Michael Lowenborg, R&D manager of formulation and process development at  DPT Laboratories.

Additional information and registration for the webcast may be found here.

After I kick-started the conference with a few choice words, notably the idea that many of those present would be unlikely to let me into their kitchens, let alone their sterile manufacturing facilities, the main event began.

Nick Maishman, senior director of parenterals at Pfizer took to the stage first and delivered a very imaginative presentation on the application of operational excellence (OE) within aseptic fill-finish. Using the analogy of Jonny Wilkinson’s kicking ability on the rugby field, Maishman described various states of process capability and process stability in terms of common or special cause variations. Maishman then went into some detail about Pfizer’s root cause analysis (RCA) strategy, which utilises the six sigma DMAIC approach and lean manufacturing principles, a combination that seems to define OE at Pfizer.

A panel discussion on the “regulatory minefield” followed. I was surprised by the openness of the panel but also of the delegates that contributed. Instead of placing regulatory authorities fully in the firing line, as can often be the case, here there was admission that industry too needs to take responsibility for moving forward with quality to address patient safety issues. I would like to thank all of those who contributed to an interesting and perhaps too short discussion.

Alexander Huber, director of sterile and topical plants at Novartis, and, coincidentally, editorial advisory board member of Pharmaceutical Technology Europe, was second to present and focused on operators, in particular “playing it safe” by using risk and people management successfully. Huber outlined some “pillars to success” an analogy that appeared in a number of presentations. The main concept here was ensuring that everybody in the organisation has some level of responsibility for quality and knowledge of risks, and that training and coaching are key to achieving this state.

Tim Simo, director projects, global technical services at Janssen-Cilag offered excellent insight into outsourcing strategies, in particular the idea of “big pharm to big pharma” in a time of overcapacity in some areas of the industry. What followed was a detailed description of a 12-month assessment process that saw 80 potential partners reduced to three over several distinct selection steps.

Philippe Juvin, quality operations director at Genzyme, managed to captivate and entertain the audience with a double-length talk on a bioburden reduction strategy that saw quality and production personnel working more closely together and get on “the shop floor” to fully-understand operator behaviour and the (sometimes unavoidable) errors made. It was a standout presentation that contained some surprises, such as gowning design changes that produced “wow”  level reductions in microbial excursions, and a very frank acknowledgment that the “human” in “human error” is only one part of a chain of events.

And all that was just day one. To get the full story next year, perhaps you’ll have to consider attending yourself… For more information about the Sterile Manufacturing CxO Dialogue and other events, click here.

Be sure to check out our special feature on cleanrooms, which will be available soon in the December issue of Pharmaceutical Technology Europe.

ICH Q6B, approved in 1999 by the three ICH regions, outlines specifications, test procedures, and acceptance criteria for biotech products. Q6B specifically calls for structural characterization and confirmation of the amino acid sequence and composition, terminal amino acid sequences, peptide map, sulfhydryl group and disulfide bridges, and the carbohydrate structure. With the more recent passage of the ICH quality guidelines, Q8, Q9, Q10 and the pending Q11, industry has even more information (as well as more expectation) on how to conduct a risk- and quality-based analysis of these products to ensure their safety.

A series of presentations on how to conduct biopharmaceutical characterization in detail was given yesterday in Valley Forge, Pennsylvania, by SGS Life Science Services and its recently acquired M-Scan Group, which focuses on mass spectrometry and gas chromatography for chemical analysis of both small and large molecule products.

Also discussed were biosimilars, which while making headway in Europe (14 have been approved since 2006), are still awaiting an implementation plan for approval in the US. Once that plan is in place—FDA continues to promise that it will be soon—bioequivalence, interchangeability, and comparability tests will become more commonplace. In the meantime, fully understanding and characterizing one’s product—down to the tiniest and most random chromatographic peak—remains a crucial part of the process and an expectation that is here to stay.

Topical formulations can be used to treat local and systematic indications, offer ease of delivery, facilitate patient compliance, and avoid the problem of first-pass metabolism. Successfully developing a topical formulation requires an understanding of the physiochemical properties, such as release characteristics, composition of the drug-delivery system, and the nature of the drug-delivery vehicle. Manufacturing a semisolid dosage requires implementing a CMC (chemistry, manufacturing, and controls) strategy to ensure stability, photosafety, avoidance of product degradation, and minimization of process impurities. The Pharmaceutical Technology webcast, “Optimizing Topical Drug Formulation and Manufacturing,” provides insight on recent advances in topical drug formulations, the latest regulatory/pharmacopoeial requirements in product quality and product performance, and strategies to optimize manufacturing for topical drug products.

Speakers include: Vinod Shah, PhD, chair of the Special Interest Group, Regulatory Science of the International Pharmaceutical Federation and distinguished pharmaceutical scientist and consultant to the US Pharmacopeia; Majella Lane, PhD, senior lecturer in pharmaceutics at the School of Pharmacy at the University of London; and Michael Lowenborg, R&D manager of formulation and process development at  DPT Laboratories.

Additional information and registration for the webcast may be found here.

The fact is, industry seems to be tired of waiting for standard-setting bodies and regulators to take action on solving key challenges such as counterfeiting, economically motivated adulteration, the implementation of quality by design, and so forth. It’s not that the agencies and organizations aren’t working on these issues, but they have to do deal with more legal and governmental bureaucracy than do representatives from various companies sitting around a table over coffee or drinks.

In the latest issue of PharmTech, well-known academic leader Fernando Muzzio and his Rutgers colleague Mauricio Futran, offer a concrete plan to improving the state of the US manufacturing sector to keep up with global competition. Specifically, they propose the following: the creation of a long-term, strategically driven research center, bringing industry, academia, and government together; development of a well-funded, agile innovation ecosystem where technology customers and technology suppliers can work together effectively, with access to funding, and with minimal transactional overhead; establishment of a regulatory science center that can provide scientific support to the FDA and to ensure that regulations are updated, transparent, and promote higher quality standards while decreasing regulatory risk; and enabling training and educational programs that ensure a supply of properly skilled labor for all of the noted parties.

Other organizations seem to have some of the same ideas in mind. The University of Southern California just announced the establishment of an International Center for Regulatory Science to help meet the challenges caused by increasingly complex regulations that result from rapid changes in technology and economic globalization. According to a USC press release, Center Director Frances Richmond says that the center will “work to understand the problems facing both sides—the regulator and the industry—that could become bottlenecks to product development….. the Center will work not only with the FDA and US companies, but with their counterparts around the world in increasing speed while ensuring safety for medical product marketplace.”

Whether or not standard-setting bodies and regulators come up with solutions in the future to industry toughest problems, industry and academia seem determined to find some answers on their own. Hopefully, they will share those solutions with all the appropriate players so that pharmaceutical science can continue to advance on all fronts.

If you missed yesterday’s blog, the winner of the Innovation Awards was Glycotope for its GlycoExpress platform technology, which optimised glycosylation of antibodies and other biotherapeutics. The award was received by a very proud and happy Jens Pohl, managing director on Oct. 25, 2011.

In other news, UBM Live announced its plans for ICSE USA, which will debut at the Pennsylvania Convention Centre in Philadelphia and run from May 22-23, 2012. Apparently, 60.2 % of ICSE Europe visitors indicated that North America is the main target for business development, and ICSE USA seeks to address this trend. “ICSE USA’s introduction, in conjunction with Pharmapack North America, EAST Pack and MD&M is a win-win across the board. The combined events offer a platform for US companies that are working to address the upcoming blockbuster drugs [patent] expirations to connect with global business contacts and partner with and vice versa,” said Haf Cennyd, brand director of ICSE in UBM’s Show Daily magazine.

RX-360 in 2012

In a press conference Oct. 25, Guy Villax, board member of the RX-360 Consortium and CEO of Hovione, Portugal, was pleased to discuss the recent activities of RX-360 and the positive feedback received from medicines agencies. RX-360 brings together industry and regulators to address the issues of counterfeits and other interruptions to the supply chain, ultimately to protect the safety of patients. Villas was keen to note that RX-360 is a transversal trade organisation that is open to everyone, referring to membership trends in waves, the first being pioneers, the second a flood of suppliers, and the suspected third wave a deluge of generics companies. With current membership at 70 organisations globally, RX-360 has been working closely with regulatory authorities, including the FDA, EMA and WHO, and seems to have won positive feedback from everyone with hopes to expand further afield; Brazil is a target for 2012.

Giving examples of potentially adulterated acetonitrile and the effects of the tsunami and subsequent radiation leaks in Japan earlier this year, one of RX-360’s aims is to provide early identification of issues followed by rapid response, disseminating information through the website and social media channels at virtually no cost.

RX-360 has recently concluded its Audit Pilot, which aims to improve efficiency in the system through two routes. Sharing of redacted supplier audits through a secure database is the first, with joint audits offering further opportunities; sponsor companies can plan ahead through RX-360 and request joint audits to be conducted by a vetted third party auditor. The audit campaign will be rolled in 2012, and is particularly relevant as the Falsified Medicines Directive (FMD) will make it mandatory to conduct audits of all API suppliers every three years.

EXCiPACT – International Pharmaceutical Excipients Certification

RX-360 also sets standards of quality and offers best practice examples, providing summaries of proposed, draft and enacted legislation. Notably, RX-360 has adopted the EXCiPACT standard for excipients, another NPO initiative whose representative, Folker Ruschatz, BASF Pharma presented at a press conference organised by the European Fine Chemicals Group (EFCG). Ruschatz, an EFCG board member, stressed that excipients need to be as closely monitored as APIs in the supply chain, and will also be impacted by the FMD. One of EXCiPACT main objectives is to make risk assessments easier, requesting an increase in periodical, physical audits whilst also reducing the economic burden. Ensuring that cGMP and cGDP standards are set for today and the future, the last year has seen EXCiPACT raising funds with plans to establish an advisory board and begin operations on Jan. 25, 2012. Once again, feedback has been very positive from regulatory bodies, and I hope to be able to report progress at PharmTech.com.

Finally, Guy Villax graced the stage for a second time on behalf of EFCG, this time to talk about the FDA’s proposed Generic Drug User Fee Act (GDUFA, seemingly pronounced ger-doo-fer), which seeks to raise funds of $299 million for FDA “to allow the FDA to do their job on a global scale.” This means, from the Vilax’ point of view, that FDA will be able to accelerate the approval process, promote faster access to lower-cost, higher-quality medicines, and level the playing field―all major steps forward for generics. Watch this space for news and upcoming information.

Thank you for reading, and see you in Madrid in 2012!

The rationale for such an approach is clear. One needs to only look  down the rows of the more than 1800 exhibitors at CPhI to see the requisite  for contract-service providers and suppliers to achieve competitive advantage through product and service differentiation. For pharmaceutical companies, among the more than 25,000 attendees at CPhI, the decision of with whom to partner is crucial for successfully implementing their drug-development and manufacturing strategies.

The strategic partnership model was discussed at a conference session at CPhI. Moderated by Jim Miller, president of PharmSource Information Services and contributing editor to Pharmaceutical Technology, the panel featured presentations from Sanjit Singh Lamba, managing director of the  Knowledge Center for Eisai, Massimiliano Brescia, global pharmaceutical operations at Abbott, and  Philip Pratten, vice-president of business development, contract pharma services with Alkermes.  The panelists discussed the drivers behind the adoption of strategic partnerships and best practices in optimizing such relationships.

For pharmaceutical companies, they face ongoing pressure to reduce costs while maintaining quality and security of supply, are seeking to   reduce their supplier base to more efficiently manage their drug-development activities and manufacturing network on a global basis, and want to gain continuous improvement and innovation in technology, processes, and  project management. For contract service providers, such strategic partnerships are a way to meet the expanding and diverse needs of pharmaceutical customers  by building long-term and stable relationships. The panelists shared perspectives on performance metrics, communication approaches, and best practices in technology transfer in meeting the evolving needs of pharmaceutical companies.

So what is the take-away? Effective relationship builing, project-management competency, continuous-improvement strategies, and supplier innovation are evermore important elements of the toolboxes of contract-service providers.

Those following us on Twitter (PharmTech.com/twitter) will already know the winner of the Innovation Awards, but for those who do not, I will enlighten you, though you will have to provide your own virtual drum roll…

The bronze prize went to Johnson Matthey for its colour-tag protein (CTP) technology, which was developed to provide an efficient way of measuring protein expression. CTP technology, as its name suggests, uses a protein tag that exhibits an intense yellow colour and allows even small amounts of protein to be quantified in a crude extract of cells, significantly speeding up the screening process.

The silver award went to Acuros for a novel device designed for the continuous delivery of small volume parenterals. Using standard primary packaging components, the device is fully disposable and requires no power supply—instead, osmotic actuation drives the device and provides a precise and stable flow rate.

And finally, the gold award was given to Glycotope for its GlycoExpress platform technology, designed to optimise glycosylation in antibodies and other biotherapeutics. The technology is based on an entire set of human glycoengineered cell lines that express proteins exhibiting different glycosylation patterns; bioassays then identify the pattern that provides the optimal product characteristics.

The six finalists for the Innovation Awards were judged not only on the level of innovation but also, crucially, on the commercial potential of the technology by a distinguished panel chaired by Hendrik Baumann of CU Chemie Uetikon.

Before the main awards, a Sustainability Award was presented to Solvias, a privately held company based in Basel, Switzerland that delivers customised solutions for drug development.

Congratulations to all winners!

In tomorrow’s blog, I will share news from the press room, including developments from the RX-360 consortium, an update from EXCiPACT, and the European Fine Chemical Group’s stance on the proposed Generic Drug User Fee Act (GDUFA), as well as other news from the show floor.

How has the show been for you? Let us know in our quick survey. We’ll be publishing some of the responses anonymously in our next newsletter.

Somehow, I found myself at the boarding gate having fast-tracked through security with speed usually reserved for animals of the four-legged variety. Time for a coffee even―especially as one of the runways at Heathrow was closed causing delays to all in- and outbound flights. Not going well.

Nevertheless, I found myself stood in Frankfurt  Messe on October 24 considering my options and hoping I would still be able to make the CPhI pre-show conferences planned for the day before the main events. Success!

I was fortunate enough to attend a conference entitled “The challenges and opportunities in biosimilars and biobetters,” which offered a rare glimpse into the strategies, concerns and successes to be had in this contentious area. Moderated by Alan Sheppard of  IMS Health the conference brought together several schools of thought on the topic, which perhaps mirror the global view. Sheppard classified current thinking on biosimilars under three headings: a mirage, an opportunity with some way to go, and something just around the corner. And taking into account the presentations that followed, perhaps it is a little of all of these things.

Genentech’s (Roche Group) Gautam Ganguly gave an excellent, high level account of some of the current challenges of entering the biosimilar market, the level of uncertainty in the US regulatory framework a notable example. The big question here was “how similar is similar?” and the answer is somewhat unclear and product dependent. Ganguly pointed out that, because of complex manufacturing,  “the process is the product” with each stage conferring unique properties on the resulting biologic making biosimilars very distinct from small molecule generics. Ganguly also noted the companies entering the biosimilars space, making it seem crowded, with traditional innovators, CMOs and generics companies all vying for the same unpredictable market.

Frederico Pollaro from Richter-Helm BioTec posed the question “make or buy?” and provided some case study examples as to his group’s decision-making processes. The key message here was the importance of being aware of the timeline involved and asking if your target biosimilar will still be an attractive option 10 years down the road; new therapies, price erosion and market instability all factors to consider. Pollaro also made clear the opportunity, given the right target, to expand the market and take advantage of potential volume growth.

The final presentation in the conference was delivered by Anjan Selz of Finox Biotech and was, I suspect, inspirational to most. Describing his company as a renegade virtual biotech, Selz wowed delegates with the story of how Finox moved from cell bank to Phase III in just four years, comically noting that “we haven’t made any money yet!” Once again, choosing the target carefully was a key message. For Finox, picking a niche product with lower levels of competition was the route taken; follicle-stimulating hormone (FSH), with its specialised market and motivated, informed patients offered a strong business case further justified by its successful history. Selz said that the key to success was creating a differentiating factor, whether through improved stability, formulation, delivery or branding, because to physicians “FSH is FSH” and the word biosimilar has no meaning.

Tomorrow (today for you), the co-located events of CPhI Worldwide, ICSE, InnoPack and PMEC and a horde of attendees will descend on the Messe―the anticipation (and sawdust) is palpable.

How was the start of the show for you? Let me know in the comments box or give us your opinion in our quick survey. We’ll be publishing some of the responses anonymously in one of upcoming newsletters.