A Preview of What’s New for Frankfurt

A very warm welcome from the whole show team to this official Pre-Show Daily, designed to help you plan your visit to Germany. This year CPhI for pharmaceutical ingredients, ICSE for contract and outsourced services, and

P-MEC for pharmaceutical machinery and equipment will be co-located Oct. 25–27 at the Messe in Frankfurt. This year also marks the debut of InnoPack for innovative pharmaceutical packaging concepts, and we have an extensive program of new features for you to experience.

InnoPack is the evolution of the Packag-ing Zone that was introduced within ICSE last year and it has more than 80 confirmed exhibitors. The new event provides global resources for diverse, sophisticated, and sustainable pharma packaging products and services. InnoPack will also complement the strong industry focus on supply chain security through the Labelling Zone that will host companies with anti-counterfeiting and track-and-trace solutions. In addition to these features, InnoPack will host daily Innovation Briefs and Speakers’ Corners, covering current trends within the sector and will serve as the starting point of the Packaging Trail, returning for 2011, which allows visitors with packaging needs to eas-ily locate exhibitors offering these services throughout the co-located events.

The new LABWorld pavilion, being intro-duced within the P-MEC Europe event, has been introduced to highlight the growing number of exhibitors focused on smaller-scale analytical instrumentation, measuring and test-ing technologies, quality control, and other lab equipment. LABWorld will offer differentiation from the larger scale machinery suppliers that P-MEC has traditionally focused on.

Also new this year is the Lunchtime Education Series. Six information-packed, interactive sessions will be held across the three days, giving visitors the chance to analyse and discuss some of the key issues and trends facing the pharma market. Led by industry experts, topics include drug delivery and controlled release, pricing and reimbursement, excipient and intermediate sourcing, corporate social responsibility, GMP inspections in emerging regions, and opportunities and challenges for pharma mergers and acquisitions.

Following the success of the zoned layout last year in reducing the time visitors spent walking between stands, it is being repeated this time, with two further zones being added to CPhI—Generic APIs and Finished Dosage. There will be additional zones in ICSE, too—New Exhibitors, USA, Logistics and Supply Chain, and the General Floor.

A returning highlight of the show, of course, is the CPhI Innovation Awards. The winners will be announced at a ceremony on Oct. 25. Entries were submitted in an expanded range of categories, reflecting the zoned format, and came from exhibitors across all the co-located shows. Judged by an expert panel, the awards highlight achieve-ments, ideas, technologies and products that embrace innovation, and demonstrate tangible long-term benefits to the industry.

As we move toward the events, we are pleased to offer a glimpse of what’s new with the events and what to expect while on-site at CPhI Worldwide, ICSE, P-MEC Europe and Innopack for 2011. Looking forward to seeing you in Frankfurt!

Best Regards, Greg Kerwin, Pharma Portfolio Director

Innovation Awards:The FinalistsJohnson Matthey . . . . . . . . .2Glycotope . . . . . . . . . . . . . . .3Acuros . . . . . . . . . . . . . . . . . .33M . . . . . . . . . . . . . . . . . . . . .3Gerresheimer . . . . . . . . . . . .4PANATecs . . . . . . . . . . . . . . .4

UBM Calendar of Events 2011/2012 . . . . . . . . . . . .5

Frankfurt Celebrates Being Green . . . . . . . . .6–7

Frankfurt Gateway to CPhi Worldwide . . . . . . . . . . . . .8

AdvertisersAMRI Global . . . . . . . . . . .7Fabbrica Italiana

Sintetici . . . . . . . . . . . .8EVONIK Industries . . . . .9Aptalis Pharmaceutical

Technologies . . . . . . .10Pfizer . . . . . . . . . . . . . . .11

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Innovation Awards Finalists Revealed: Six Industry Advances Impress Judges

with Designs’ Commerical Potential

Once again, the CPhI Innovation Awards drew a wide range of entries from across the spectrum of exhibitors at CPhI Worldwide, ICSE, P-MEC Europe, and the new InnoPack. The awards, hosted in conjunction with media partner Manufacturing Chemist, were open to any company exhibiting at the events and six finalists were selected from these submissions. The selected finalists will make presentations in front of the judges on Tuesday, Oct. 25 from 10 am–12:50 pm on 51D02, and the winners will be announced during the Exhibitor Party that evening, which will be held from 5:30–7:30 pm in the Europa hall.

The shortlisted entries, and ultimate winners, are chosen by a distinguished panel of judges, which has comprised the same group of senior industry personnel since 2007. Chaired by Hendrik Baumann of CU Chemie Uetikon, the panel also includes Zoran Buncic of Pliva, Didier Bensoussan of Dr Reddy’s Laboratories (UK), Hans-Leonhard Ohrem of Merck, Andreas Stolle of Saltigo and new jury member Michael Platscher of Merck and Cie.

This year’s six finalists are 3M Drug Delivery Systems, Acuros, Gerresheimer, Glycotope, Johnson Matthey, and PANATecs. All impressed the judges with their level of innovation and the commercial potential of their entries.

Efficient Marker for Protein Expression Johnson Matthey will present the Catalysts’ Colour-Tag-Protein technology, developed as an efficient marker for protein expression from 10-10:20 am. Biotechnological approaches are increasingly being used for the synthesis of chiral molecules in the pharma industry. It is important to optimize the manufacturing process to reduce production time and cut costs, and techniques such as promoter optimization, random mutagenesis, and the optimization of growth parameters are commonly employed to increase the economic viability of processes.

When engineering new enzymes, it is essential that protein expression

is measured, and the CTP technology was designed to facilitate this. The protein tag exhibits an intense yellow color that allows for easy detection and protein gels or protein purification are no longer required to determine expression levels. Even small quantities of protein can be easily quantified in the crude extract of cells, speeding up the whole process significantly.

The CTP itself is fused to a protein of interest via genetic methods, and it serves as a direct marker for protein expression. It comprises about 100 amino acids, and its high solubility also improves the solubility of the fusion protein. The yellow color is a result of a flavin adenine dinucleotide that has been covalently bound to the

protein backbone, making it simple to follow the level of protein expression by measuring the absorption of CTP at 460nm.

An advantage over the common expression marker green fluorescent protein is that it can be used in anaerobic conditions as well as aerobic, unlike GFP which only functions under aerobic conditions.

The method’s simplicity makes it suitable for use in automated high throughput screening methods in the optimization of protein production conditions. As an example, it has been used to determine the optimum expression conditions for Johnson Matthey’s X-Zyme libraries of alcohol dehydrogenases – expression levels for

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the enzyme were raised by an average 500 percent.

Optimizing Glycosylation of Antibodies, Other Glycosylated Biotherapeutics The GlycoExpress platform technology from Glycotope, designed to optimize the glycosylation of antibodies and other glycosylated biotherapeutics, will be presented from 10:30–10:50 am. Glycosylation is a post-translational modification whereby complex sugar chains are attached to the protein backbone. A vast number of proteins have carbohydrate functionality like this, ranging from a single glycosylation site on an antibody to the abundant glycosylation that can be seen on the extracellular matrix.

GlycoExpress was designed to optimize the glycosylation of antibodies and other glycosylated biotherapeutics. It is based on a set of human cell lines that were developed for screening the optimum glycosylation pattern and for producing the glyco-optimised biotherapeutics.

Historically, human biotherapeutics were mostly made in E. coli, yeast, or cell lines derived from insects, mice, or hamsters. However, these systems all tend to produce proteins with either no glycosylation or a different pattern from that found in humans. Even those rodent cell lines that confer a similar glycosylation pattern have a significantly increased likelihood of causing immunogenic reactions.

As GlycoExpress uses human cell lines, it provides humans glycosylation patterns. It is an entire set of human glycoengineered cell lines that differ only in the glycosylation pattern they create. A glycoprotein expressed in these cells will thus be available in various glycoforms, and bioassays allow the glycosylation pattern that gives the optimal product characteristics to be identified.

The key glycosylation parameters that can be modified on any recombinant protein are fucosylation, sialylation, galactosylation, antennarity, and the prevalence of bisecting N-acetylglucosamine. The degree of

sialylation and fucosylation can also be controlled by medium supplementation. The cell lines’ production features allow a cost-effective, stable, and reproducible process design, and because it has been used in creating the company’s clinical pipeline of biopharmaceuticals, it has been approved by various European regulatory authorities.

Continuous Delivery of Small Volume Parenteral Drugs A novel, disposable drug delivery device will be presented by Acuros from 11-11:20 am. The device was designed for the continuous delivery of small volume parenteral drugs in doses ranging from microlitres to millilitres per hour. Roughly half of all molecules in current pharma development pipelines are small volume parenteral drugs, and thus the demand for new devices to deliver them is growing. There is a particular challenge in providing continuous, precise delivery to the outpatient market, as evidenced by the latest developments in areas such as insulin pumps.

This new device is driven by an os-motic actuation, and it has no battery or other power supply. With no electronic or mechanical components, the self-con-tained device gives a precise and stable flow rate. Selectable delivery rates and bolus dosages are also possible, and it is disposed of after a single use.

It uses standard primary packaging components, such as prefilled cartridg-es and syringes, and can be used for both the subcutaneous and intravenous administration of drugs such as insulin, analgesics, antibodies, and other biopharmaceuticals. As the device contains no ferrous materials, it is also suitable for use in MRI investigations.

The company believes it is the only small-volume drug infusion pump that is fully disposable, and which also takes advantage of standard prefilled car-tridges. Unlike common osmosis, the osmotic drive creates constant delivery rates by compensating for the dilu-tion process that usually takes place

in an osmotic process. As a result, the osmotic pressure remains constant throughout the whole delivery period.

As well as being easy to use, the cost-effective micropumps are customised to meet customers’ precise needs, with a range of feasible delivery rates from a few nanolitres a minute up to millilitres per hour. The total quantity of liquid drug the device can deliver is also variable, from 0.5ml up to 10ml.

Metered Dose Inhalers Track Status of Medication From 11:30–11:50 am, 3M Drug Delivery Systems will present its Integrated Dose by Dose counter that is designed to allow patients using metered dose inhalers to track the status of their medication so they can plan when they need a new one. The cost-effective counter was designed in response to the US FDA’s recommendation that MDIs should enable patients to track how many doses they have left. Unusually within the medical devices industry, the company commissioned an in-depth qualitative research program to gain patient insight into what they wanted from their inhaler.

Accuracy is essential—in particular, it should not under-count the doses, as this would leave the patient with an empty inhaler before the dose counter reaches zero. To achieve this, 3M designed a displacement driven mechanism that operates just ahead of the spray release, thus making un-dercounting impossible. While this is a complex mechanism, it also minimises the potential for over-counting.

It works by using a ratchet mecha-nism to split the count advance and reset into two stages, matching both the valve firing and refilling points. The resulting component has two adjacent rows of teeth, which led to the early de-velopment project being called “Shark.”

To ensure accuracy, the company also developed a theoretical analysis of design tolerances, and used X-ray com-puter tomography to check that the 3D

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geometry matched the computer-aided design. It also allowed the internal operating mechanism to be examined in a non-destructive way, which identi-fied a tiny defect that would prevent the counter from working correctly.

Importantly, it is integrated into a press-and-breathe MDI, making it com-patible with existing packaging lines. A modification to the system also enables an alternative display configuration to be used in markets where greater numbers of doses have to be counted, but with a lower display resolution. This involves a minimum number of parts having to be changed.

High Performance Vial for Parenteral UseA new high performance vial for parenteral use, based on multilayer

technology, will be presented by Gerresheimer from Noon–12:20 pm. The contain-er is made from a combination of the plastic COP, or cyclic olefin polymer, and polyamide. COP is known to be compatible with sensitive bio-pharmaceutical

drug formulations, is free from heavy metal ions, and its inert surface mini-mizes the risk of protein adsorption.

The polyamide, meanwhile, significantly improves the barrier properties compared to common vials made of COP or other polymers alone, thus preventing the ingress of air, bacteria and other contaminants. Made by the injection blow moulding process, an additional benefit is that the vials also retain the transparency of glass.

The different layers are consistent, which ensures the performance of each vial. The biocompatible COP is the only material that comes into contact with the drug solution, as the polyamide that confers strength and impermeability

is encased on both sides by COP. They have been designed to meet ISO stan-dards, so they are compatible with existing rubber closures and seals.

Another novel feature of the multilayer design is that it increases the impact resistance of the paren-teral container—this is five to 10 times higher than a glass vial, thus address-ing concerns about the security and sterility of the filled solution for injec-tion during transport and storage. This increased resistance to breakage also reduces production costs by minimiz-ing breakage during filling, stoppering, crimping, and transportation.

The impermeable nature of the polyamide layer increases shelf life over that seen with vials made from the standard COP, cyclic olefin copolymer, polyethylene, or polypropylene. Its oxygen barrier properties are about 30 to 40 times better than polymer monolayers. The puncture-resistant polyamide layer also helps protect hospital staff and patients from potential exposure to toxic drug solutions as a result of breakages. This ensures the vials are suitable for highly potent products such as cytotoxic drugs and hormone treatments.

Detecting Materials Containing Protease Contamination PANATecs will present the P-Check technology, designed to detect materials containing protease contamination from 12:30–12:50 pm. If there are protease impurities present in the raw materials used in enzyme immunoassays, they can significantly impact assay performance. This risk can be decreased if the protease impurities in incoming protein-based raw materials are controlled, and if

protease inhibitors are included in the assay formulations

Many different proteases might be found in raw materi-als, and it is important to test the quality of the protein-based materials. The test should be as sensitive and universal as possible, and

could be used to support the choice of protease inhibitors

or the selection of protease-free protein based raw materials. Proteases

also pose a problem for biopharma-ceutical products. They can destroy the product, or even endanger patients, if they are injected alongside the drug. Pro-tease testing is important for both protein diagnostic testing, and in the production of biopharmaceuticals.

The P-Check system is based on fluorescence resonance energy transfer,

or FRET, technol-ogy. If a protease is present, it will split the substrate peptide, and a flu-orescence signal is emitted. It uses newly developed labelled substrate peptides, which contain sufficient points of attack to be able to detect

most known—and unknown—proteases. By using an additional peptide library containing up to 2.47 million sequence variants, it can be greatly extended.

The technique has sensitivity in the nanogram range for known proteases. Contamination was found to differ between raw materials, and this corre-lated with assay performance. Protease activity in contaminated raw materials could be suppressed to various degrees by using different chemical inhibitors or by thermal treatment. The technique is suitable for the control of incoming protein-based raw materials used for enzyme immunoassays, as well as for the optimization of protease inhibitor use or the thermal treatment to deactivate proteases. •

Attend the Finalist

Presentations on Tuesday, Oct. 25, from 10 am to 12:50 pm

on 51D02 to find out more about these exciting innovations. If you’re

not able to attend the Exhibitor’s Party at the Europa Hall from

5:30–7:30 pm when the results are announced, you can find out all

about who won the awards in the Show Daily on

Wednesday.

Wolfgang Dirk, Gerresheimer Plastic

PackagingProduct Manager

Parenteral and Business Development

Thomas Flad, Co-founder and

currently director of sales and marketing

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Gardens, Not Walls! Frankfurt Celebrates Birth as Green City

Frankfurt’s former city walls are celebrating an historic birthday. Two hundred years ago, the City of Frankfurt enacted the so-called Wallservitut, an easement with which they moved to protect the parklands along the course of the former mediae-val city fortifications from destruction. This edict also helped to lay the founda-tion for further natural development within the city. Today, Frankfurt is one of Germany’s “greenest” urban centers, featuring more than 50 parks and gar-dens within its city districts.

Today, the Anlagenring—a section of the former city walls now landscaped—forms a five-kilometer-long semicircle around the city center. Visitors taking a walk along this green ring will come across fountains, ponds, ancient trees, modern sculptures, monuments and memorials, many of which serve as re-

minders of Frankfurt’s colorful history. The demolition of the former city walls had helped to bring about the estab-lishment of English-style landscape gardens, which were continuously expanded over time. The former course of the star-shaped city fortifications is still recognizable upon closer examina-tion of a city map.

Starting at the massive euro symbol situated in front of the European Central Bank, Frankfurt’s green ring takes visitors past the Beethoven Memorial and Heinrich Heine Memorial to one of the city’s most beautiful locations: Opera Square and Alte Oper, Frankfurt’s grand old opera house and one of the city’s premier landmarks. A few hundred metres further on, one comes across the Nebbiensche Gartenhaus. This oasis of green, built in classicistic style in 1810, was one

of the first glasshouses to be erected along the green pathway. Today, it is available for special-event hire. From here, it is not far to the Eschenheimer Tor, the only remaining city gate of the former mediaeval walls. Continuing on, one arrives at the Odeon, a popular dance club. Originally, this classicistic-styled structure was built by order of the Bethmanns, a famous Frankfurt banking family. For many years, it served as the home of the Museum of Sculptures. Taking a few steps away from the beaten track, walkers will arrive at the nearby Bethmann Park and its Chinese Garden, which was designed according to the principles of Feng Shui. Having returned to the green lane, one comes across Frankfurt’s most beautiful “outhouse.” Nowadays, these monument-listed former public toilets with their chapel-

Gardens, Not Walls! Frankfurt Celebrates Birth as Green City

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like dimensions are home to a cocktail bar named Lala Mamoona. The gabled roof and half-timbered framework provide an excellent background for the lounge music and relaxed atmosphere of this popular location.

The end of the green ring is now only 750 meters away. The former municipal library, rebuilt in 2005 and now the home of the Frankfurt House of Literature, today presents itself as a beautiful café with an attached beer garden, inviting visitors to a refreshing respite. Those fit enough are urged to continue on down Frankfurt’s unique and very natural riverside promenade, which runs along both sides of the River Main. From here, beautiful views of the city’s skyline and surrounding area are guaranteed; in fact, they are best enjoyed from one of the riverside establishments while drinking a glass of Frankfurt apple wine.

Frankfurt’s Anlagenring, the first such landscaped parklands to partially encircle a city center in Germany, raised many eyebrows throughout Europe at the time of its creation. This green ring was instrumental in commencing the establishment of a series of parks and gardens that helped to transform Frankfurt am Main into a truly green city—a fact that often escapes attention due to the many other highlights found in the Main metropolis.

With such an impressive skyline, it is hard to believe that the business and banking city of Frankfurt is also home to several nature reserves, such as Enkheim Moor in the city’s northeast, Schwanheim Forest in the southwest and Fechenheim Forest to the east.

Two hundred years after the creation of the the green ring, Frankfurt’s “GreenBelt” has established itself as the city’s premier place of rest and rec-reation. Fully completed in 1991, it now encircles the city at a length of some 80 kilometres and consists of hiking and cycling paths as well as countless other recreational opportunities. During summer, the GreenBelt’s many public gardens attract visitors with their im-

pressive variety of flora – be it Mediter-ranean, like at the Gardens of Niece at the banks of the River Main, baroque-style as at the Bolongaro Gardens, or spacious as the English landscaped parks of old, such as Grüneburgpark and Ostpark.

One location that’s particularly attractive all year round is the Palmen-garten. Founded in 1868 with the kind donations of Frankfurt’s citizenry, these magnificent botanical gardens are home to some 3,000-odd species and varieties of plant. Here, visitors have

the unique opportunity of experiencing plant life representing the most diverse climate zones.

Frankfurt is also home to Germany’s largest city forest, a 5,000-hectare wood that extends from the airport to the city districts of Oberrad, Sach-senhausen and Niederrad. Recently, during Whitsuntide, Frankfurt locals once again headed to the city forest to celebrate their “national holiday”, the Wäldchestag, or “Forest Day.” This festival is unique to Frankfurt and has been taking place since 1792. •

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Frankfurt is Colorful “Gateway” to CPhI Worldwide Conference 2011

After a successful event in 2008, UBM Live is pleased to return to Frankfurt to once again host CPhI Worldwide and co-located events at the Messe Frankfurt, Germany. Often considered the “Gateway to Europe,” Frankfurt is well suited to provide a

venue for the event’s line-up. The city has the largest airport in Europe and offers easy accessibility via train, taxi, and foot and has a plethora of attrac-tions to offer to guests. With a history dating back as far as the 1st century, Frankfurt has long been a popular

international destination for both busi-ness and personal travel needs.

Frankfurt is located in the southwest part of Germany on both sides of the River Main and boasts many famous attractions. Known as a “green” city,

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Frankfurt is home to many lush gardens that offer guests with scenic areas to walk and relax in. One such marvel, located in the southern part of the city, is the Frankfurt City Forest (Frankfurter Stadtwald) that is Germany’s largest forest within a city. The area is also home to many museums, churches, and historic areas that are pedestrian friendly.

While travelling through the city, tourists will also take in views of Frankfurt’s famous skyscrapers, and can even visit the Main Tower that of-fers a restaurant on the 53rd floor and scenic observation deck on the 55th

floor. Other popular visits or attractions include city sightseeing tours and trips to the Applewine District (Sachsenhau-sen) where travellers can sample the traditional local beverage, thought to date back to the 16th century.

This is just a preview of the avail-able attractions here in Frankfurt. For more information, please visit: http://www.frankfurt-tourismus.de/. We hope that you have some time to enjoy this lovely city, and above all, thank you for joining us for CPhI Worldwide, ICSE Europe, P-MEC Europe, and InnoPack 2011 here in Frankfurt. •

http://www.frankfurt-tourismus.de/http://www.aptalispharma.com/http://www.showpress.com

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