Patricia Van Arnum was executive editor of Pharmaceutical Technology.

Patricia Van Arnum

Fine-chemical companies, contract manufacturers, and pharmaceutical/biopharmaceutical companies will be assembling later this month at 

, organized by UBM Live. The large exhibition featuring companies offering pharmaceutical ingredients and contract services will be held in Frankfurt, Oct. 22–24, with the exhibition starting on Tuesday Oct. 22 and the Pre-Connect Conference on Monday Oct. 21. The Pre-Connect conference will feature six modules covering six main topics: generics/supergenerics, drug delivery, biosimilars/biobetters, API sourcing in emerging markets, strategic partnering, and pharmaceutical packaging and labeling. 

Three other shows will be co-located with CPhI. The International Contract Services Expo (ICSE) features exhibitors offering contract services in drug development and formulation services, finished product manufacturing, clinical research, and pharmaceutical software/information technology. P-MEC is focused on pharmaceutical machinery and equipment, and InnoPack includes exhibitors focused on packaging solutions.  

CPhI Worldwide and its co-located exhibitions are expected to attract 30,000 attendees from 140 countries and 2200 exhibitors. Last year's installment of CPhI Worldwide in Madrid attracted 30,413 attendees, which included both visitors and representatives from exhibiting companies.  Attendees from Europe accounted for the largest number of attendees at approximately 60%, followed by attendees from Asia at nearly 24%, and attendees from North America at 7.5%. Among visitors, innovator pharmaceutical companies accounted for nearly 16% of the total and generic-drug companies 23%, according to information by ABC, an independent audit firm. 

The CPhI Pharma Awards will be announced on Tuesday Oct. 22. The awards recognize innovation in three main categories: formulation, process development, and packaging. The award for innovation in formulation will recognize advances in drug delivery, excipients, controlled release, stability or bioavailability. Innovation in process development involves developments in synthesis, crystallization, polymorphism, catalysis or green chemistry. The award for innovation in packaging will recognize advances in primary packaging, devices and technology, patient compliance, dispensers, or materials. 

Articles

A look at the happenings at this year's installment of CPhI Worldwide.

Pharmaceutical Companies and Their Suppliers Prepare for CPhI Worldwide

CDMOs and CMOs offering high-potency manufacturing and related services are expanding in response to increased demand for antibody drug conjugates and other highly potent compounds. Companies are expanding on both the API and finished product side for highly potent compounds.


In September 2013, Carbogen Amcis announced a series of investments aimed at enhancing its ADC capabilities. The investments include a $4-million cleanroom clinical-supply facility at its Bubendorf, Switzerland site and on the finished product side, a $950,000-upgrade of the sterile-manufacturing area at its facility in Riom, France. The upgrades at Riom include the implementation of a new vaporized hydrogen peroxide disinfection system and the installation of two new aseptic filling isolators.

In 2012, Carbogen Amcis and ADC Biotechnology (ADC Bio) partnered for ADC development and manufacturing services. ADC Bio is providing proprietary solid-phase immobilization technologies for conjugation and long-term storage of ADCs, and Carbogen Amcis is providing small- to large-scale GMP supply and the formulation of ADCs. ADC Bio also recently expanded its facility in St. Asaph, United Kingdom in northern Wales with the addition of a new technical service laboratory. Commissioned in April 2013, the additional facility at St. Asaph provides ADC screening, process development, and scale-up capabilites.

In January 2013, Lonza announced plans to invest CHF 14 million ($15 million) to expand ADC manufacturing capacity at its site in Visp, Switzerland. The expansion of the ADC facility will double the company's existing large-scale manufacturing capacity in Visp. The expansion is expected to be completed in the second quarter of 2014. 

In October 2012, Fujifilm Diosynth Biotechnologies formed a strategic alliance with Piramal for ADC production, whereby the two parties will offer contract development and manufacture of ADCs. Piramal offers ADC production at its site in Grangemouth, Scotland. Fujifilm recently announced an expansion of its cGMP manufacturing facilities at its sites in Research Triangle Park, North Carolina, and Billingham, UK. Novasep announced in 2012 a EUR 3-million ($3.9-million) investment to expand its highly potent API manufacturing capabilities at its Le Mans, France facility. Also, in 2010, SAFC opened a new $30-million high-potency manufacturing facility in Verona, Wisconsin.

 Earlier this year, Catalent Pharma Solutions acquired an exclusive license to market Redwood Bioscience's proprietary SMARTag protein-chemical engineering technology used in site-specific protein modification and linker chemistry for ADCs. Catalent will have the exclusive right to sublicense the SMARTagtechnology and will work with Redwood to comarket the technology and support sublicense programs. As part of the collaboration, Catalent will also take a minority equity stake in Redwood, which may increase over time up to a potential acquisition.

Companies also are expanding high-potency manufacturing on the finished product side. Piramal Healthcare announced in September 2013 that it is investing $11 million at its facility in Morpeth, UK to triple production capacity for hormonal products, including contraceptive pills and hormone-replacement therapies. The expansion will increase the Morpeth site’s production capacity by approximately 2 billion tablets per annum. Work on the new suite, which will house formulation, packaging, coating, and tableting equipment, will begin at the end of 2013, with mechanical completion anticipated within 12 months and full operations expected to begin following a six-month validation period. 

This latest investment follows Piramal |Healthcare’s recent $2.5-million investment at its site in Grangemouth, UK, site to upgrade one of its ADC manufacturing suites from clinical phase to commercial grade. The upgrade will give Piramal two commercial-grade ADC suites at the Grangemouth facility while retaining clinical-phase manufacturing capacity in other suites at the site.

In July 2013, Almac’s Clinical Services business unit expanded its service offering for dispensing and bottling solid dosage products by introducing enhanced containment equipment and processes at its EU and US headquarters, respectively in Craigavon, Northern Ireland, and Souderton, Pennsylvania. 

In February 2013, Baxter International's BioPharma Solutions business began an approximately 1750-m

capacity expansion at the company's fill–finish cytotoxic contract manufacturing facility in Halle (Westfalen), Germany. This expansion follows previous expansions in Halle in 2007 and 2011.

 In April 2013, Goodwin Technology and Coldstream Laboratories agreed to develop and manufacture high-potency, highly cytotoxic materials, such as small molecules, protein toxins, cytotoxic ADCs, and other bioconjugates. GBI will use Coldstream's cGMP platform of services, including analytical testing, formulation, liquid or lyophilized fill–finish, storage and shipment of manufactured highly-potent bioconjugates.

In May 2013, Penn Pharma successfully completed the first batch of coated tablets at its new contained manufacturing facility in South Wales, UK. The facility is designed for the clinical and commercial manufacture of tablets and capsules. In November 2011, Metrics began offering neat API capsule-filling at its potent and cytotoxic facility in Greenville, North Carolina. The company secured a Capsugel Xcelodose system, a powder microdoser and automated encapsulator that places API directly into capsules with a high level of accuracy. Metrics also installed a custom-built isolation system for the equipment. The company offers dedicated and segregated potent and cytotoxic cGMP manufacturing for Phase I–III projects. It opened a new potent and cytotoxic drug-development facility in 2009 as part of an expansion of the company's Greenville facility.

In September 2013, Capsugel’s Dosage Form Solutions business unit announced it will increase it containment capacity at is facility in Ploermel, France to handle hormonal as well as high-potent compounds in softgel manufacturing. Upgrades include a high-precision dosing system and high-speed capsule printing capability. 

Other companies are positioned in both API and finished product manufacturing for highly potent compounds. For example, CordenParma has facilities in Plankstadt (Germany), Latina (Italy), and Boulder (Colorado) for manufacturing highly potent APIs and drug products. Aesica, based in Newcastle-Upon-Tyne, UK, opened a new high-potency manufacturing facility in Queenborough for formulated products in late 2011. The company later upgraded its UK-based API manufacturing facilities in Cramlington and Queenborough to manufacture high-potency APIs. 

Contract manufacturers of both APIs and finished products expand manufacturing capacity and services for high-potency manufacturing.

CMOs Invest in High-Potency Manufacturing

A review of activity thus far in 2013 shows measured investment by contract manufacturers of APIs and intermediates and fine-chemical producers. Certain companies have or are expanding manufacturing capacity, and others have partnered or made bolt-on acquisitions. 

 production plant in Nantong, China. The company broke ground for the new facility in July 2013. The plant will begin commercial production in mid-2014 and employ a workforce of about 300 by 2015. Siegfried is also proceeding with the construction of a new 100-m

 chemical plant in Zofingen, Switzerland. The new building will replace several older plants at the Zofingen site that no longer comply with efficiency requirements and generate high maintenance expenses. The two plants in Nantong and Zofingen are based on an identical technical concept to facilitate product transfers from a regulatory and technical perspective. A new administration building also will be erected in Zofingen. The new offices will be ready for occupation in the second half of 2015. 

Cedarburg Hauser Pharmaceuticals upgraded its API plant in Grafton, Wisconsin. The upgraded facilities are expected to increase API production by 20–25%. Improvements to the plant include the addition of a 30-ton process chiller, an additional 200-kilowatt backup generator, and an industrial vacuum pump. The company also tripled its filtration capacity through the addition of new, large Aurora filters. 

In September 2013, International Chemical Investors Group (ICIG) agreed to acquire Allessa, a manufacturer of fine chemicals intermediates and specialty chemicals, headquartered in Frankfurt with production sites in Frankfurt’s vicinity in Fechenheim, Griesheim, and Hoechst. Allessa has more than 890 employees and an internal training center of more than 70 apprentices employed by the company.  The WeylChem Group, ICIG’s non-GMP fine chemicals platform, operates its plants in Griesheim and Hoechst as well, which also used to belong to the former Hoechst conglomerate, and any future cooperation between Allessa and the WeylChem Group, under one ownership, would result in additional synergies. 

Earlier in 2013, ICIG agreed to acquire from the Solvay Group Peptisyntha SA, the Brussels-based custom manufacturer of peptides. Upon closing of the deal, expected this fall, Peptisyntha will become a member of ICIG’s CordenPharma platform as its third site offering peptide manufacturing. Although the US sister company Peptisyntha Inc., located in Torrance, California, is not part of the transaction, certain customer relationships will be assumed by Peptisyntha in Brussels. 

Johnson Matthey’s Catalysis and Chiral Technologies business unit is expanding its existing specialty ligand manufacturing capability to include commercial-scale manufacturing up to 100 kg. The expansion is largely focused on the Buchwald ligands from the Massachusetts Institute of Technology.The Buchwald ligands are a class of bulky and electron-rich dialkylbiaryl monophosphine ligands, which are used for the 

generation of active catalysts. These ligands are used for coupling reactions in the manufacture of both pharmaceuticals and specialty chemicals and are more commonly offered at a research scale for use in the laboratory, according to the company. This is the third recent investment by the company, which has made investments at facilities in Taloja, India, last year and has further expansion underway in Royston, United Kingdom. 

In February 2013, Albemarle announced that its fine-chemistry services  business approved and began construction on another expansion of its Tyrone, Pennsylvania custom manufacturing facility. The $30-million expansion adds new capacity to the site for custom manufacturing projects, but also improves the infrastructure to allow for future expansions. The expansion follows an earlier expansion that began operation in November 2012. The first increment of new capacity will be operational late in the first quarter of 2014. 

Saltigo reported that it successfully passed a FDA inspection for its API production unit in Leverkusen, Germany and all the associated facilities. Also, Saltigo moved its corporate headquarters from Langenfeld to Leverkusen. The relocation of Saltigo’s corporate headquarters is part of a series of moves following the transfer of its parent company, Lanxess, headquarters to Cologne. In Leverkusen, business units and group functions from 11 different office buildings will move into four buildings belonging to Lanxess by the end of January 2014. 

Companies also are partnering to expand capabilities. Earlier this year, DSM Pharmaceutical Products signed a collaboration agreement with Chemtrix in the field of continuous flow chemistry. The collaboration is intended to provide equipment, development, and manufacturing services to the pharmaceutical industry. Also, Almac completed its knowledge-transfer partnership with Queens University Belfast, which was intended to develop, improve, and embed bioprocesses to facilitate the delivery of products for its biocatalysis business. The overall partnership aim was to allow technology transfer of fermentation and molecular/microbiology expertise from Queens University to Almac. Almac met the specific partnership objectives by not only sharing a program of work with academics at Queens, but also by attending training courses organized through University College London and embedding key learning back into the company. 

In February 2013, AMRI and Codexis formed  a SMARTSOURCING partnership. The collaboration will provide opportunities to combine the two companies’ capabilities and technologies for specific customer projects. Under the nonexclusive, two-year agreement, the companies will align their respective strengths to identify and implement new and improved manufacturing routes for select APIs with Codexis contributing directed evolution technology that enables enzyme discovery and optimization with AMRI’s process development and manufacturing capabilities, including using AMRI’s proprietary microbial strains. 

A roundup of expansion activity of manufacturing capacity and service offerings from fine-chemical producers and contract API manufacturers.

Fine-Chemical Producers and Contract API Manufacturers Expand

AstraZeneca and Bristol-Myers Squibb have voluntarily recalled about 92,000 vials of their jointly marketed Type 2 diabetes treatment Bydureon (exenatide extended-release injectable suspension) in several European countries because some vials were not fully filled.

The affected batches were recalled in the United Kingdom, Germany, Romania, the Netherlands, Ireland, Sweden, Finland, and Spain, according to Bristol-Myers Squibb. The Bydureon recall was issued after a review of manufacturing records indicated at least one of the batches may have had a very small number of under-filled vials, according to an 

alert distributed by the UK Medicines and Healthcare products Regulatory Agency (MHRA)

. The affected lot (C164827) was a 4 x 1 single-dose kit (1 vial and 1 syringe) with an expiration date of Aug. 31, 2015. It was first distributed on July 12, 2013. The low fills impact approximately 0.2% of the batch and range between 30% and 75% of the labeled dose. MHRA is advising that remaining stocks of the affected batch should be quarantined and returned to the original supplier for credit. 

No batches distributed in other markets were affected and the companies don't expect any supply issues. There is little evidence that patient safety would be compromised as a result of injecting an under-filled vial, and any health consequences would likely be minimum, according to Bristol-Myers Squibb.

Bydureon is part of the diabetes alliance between AstraZeneca and Bristol-Myers Squibb. Bristol-Myers Squibb acquired Bydureon through its 2012 acquisition of Amylin Pharmaceuticals. AstraZeneca and Bristol-Myers Squibb formed a diabetes alliance in 2007 for certain drugs and later expanded that collaboration following Bristol-Myers Squibb's acquisition of Amylin to include the diabetes portfolio of Amylin, including Bydureon. 

AstraZeneca, Bristol-Myers Squibb recall certain lots of of their antidiabetes drug Bydureon (eventide) due to manufacturing records that batches may contain underfilled vials.

AstraZeneca, Bristol-Myers Squibb Recall Certain Lots of Bydureon

	Product quality is of paramount importance to pharmaceutical manufacturers, and implementing a strategy for impurity control is crucial. Organic impurities cover a wide spectrum of compounds that have varying structures, behaviors, and characteristics. Organic impurities can result from the manufacturing process, storage conditions, or degradation resulting from light, heat, and other external factors. Deciding what technology or analytical methods to use to detect and measure organic impurities is a challenge. 

“Meeting Regulatory and Technical Requirements for Organic Impurity Analysis

, on Tuesday Sept. 24 at 11:00 AM EDT to 12:00 PM EDT to provide insight on the regulatory, compendial, and ICH requirements for organic impurity control and analysis as well as best practices in analytical method development, method selection, and method validation for detecting and quantifying organic impurities in drug substances and drug products.

	The panelists for the webcast will be: Timothy Watson, PhD, and research fellow in the GCMC Advisory Office at Pfizer and a member of the PhRMA Expert Working Group on the ICH Q11 regulatory guidance document for drug substances; Mark Argentine, PhD, senior research advisor, analytical sciences R&D with Eli Lilly; and Hildegard Bruemmer, PhD, operational laboratory manager, SGS Life Science Services, Berlin. The panelists will provide insight on the regulatory and compendial requirements for organic impurity control and analysis in drug substances and drug products. They will also share insight on selecting the appropriate analytical methods for the detection, analysis, and quantification of organic impurities and offer related case studies on how best to ensure product quality.

	Audience members may ask questions of the panelists during the 

 Information on how to register for the webcast, “

Meeting Regulatory and Technical Requirements for Organic Impurity Analysis

” for Tuesday Sept. 24 at 11:00 AM EDT to 12:00 PM EDT and for on-demand viewing is available 

Product quality is of paramount importance to pharmaceutical manufacturers, and implementing a strategy for impurity control is crucial.

Meeting Technical and Regulatory Requirements for Organic Impurity Control and Analysis

Looking at the first eight months of 2013, mergers and acquisitions (M&A) in the biopharmaceutical industry have increased on both a value and volume basis compared to the same period last year. Although there were no megamergers in the industry, there were several noteworthy deals, including Amgen’s proposed $10.4-billion acquisition of the biopharmaceutical company Onyx Pharmaceuticals. Additionally the number and value of deals involving a single innovative drug or part of the company were up significantly in 2013 thus far, reflecting the tactical nature of biopharmaceutical dealmaking. 

 A Burrill & Company analysis of overall M&A activity for innovative therapeutics companies during the first eight months of 2013 shows that total deal value increased 12.3% to $31 billion in 41 transactions compared to $27.6 billion in 38 transactions during the same period a year ago, according to a Sept. 3, 2013 press release by Burrill & Company. The Burrill & Company analysis further showed that upfront money in private company transactions increased and that more transactions involved a single innovative drug asset or part of a company. 

In 2013, average upfront payments represented 42% of the total potential values of transactions, compared to average upfront payments representing 26% of total potential transaction values in 2012. Overall, the number of privately held innovative therapeutics companies fell to 30 in the first eight months of 2013 compared to 39 in 2012, nearly a 25% decline, according to the Burrill analysis. “The resurgent IPO [initial public offering] market is providing alternatives to privately held biotechs that can access capital with attractive valuations,” said G. Steven Burrill, CEO of Burrill & Company, a global financial services firm focused exclusively on the life sciences, in the company’s September press release. “At the same time, though, acquirers are focusing more on buying assets rather than companies,” he added. The analysis found that a total of 55 transactions thus far in 2013 valued at $31.8 billion involved a single innovative drug asset or part of a company, compared to 26 such transactions worth $4 billion during the first eight months of 2012. Overall, life sciences M&A transactions were up 13.3%percent globally to $91.6 billion during the first eight months of 2013 compared to the period a year ago.

Thus far in 2013, there have been several noteworthy transactions. Amgen’s proposed $10.4-billion acquisition of the biopharmaceutical company Onyx Pharmaceuticals, is the largest therapeutics transactions of the year. In August 2013, seeking to build its oncology drug portfolio, Amgen agreed to acquire the biopharmaceutical Onyx Pharmaceuticals for $10.4 billion ($9.7 billion net of estimated Onxy cash). The deal is expected to close in the fourth quarter of 2013, subject to customary closing conditions and regulatory clearance. Onyx Pharmaceuticals has a growing multiple myeloma franchise, which includes Kyprolis (carfilzomib) for injection already approved in the United States. Onyx holds global rights to Kyprolis, excluding Japan. Kyprolis has orphan-drug designation in the United States with exclusivity until July 2019, and patents in the US that extend until at least 2025. In addition, Onyx has three partnered oncology assets: Nexavar (sorafenib) tablets (an Onyx and Bayer HealthCare Pharmaceuticals compound), anoral kinase inhibitor, approved in the US for unresectable hepatocellular carcinoma and advanced renal cell carcinoma; Stivarga (regorafenib) tablets (a Bayer compound), an oral kinase inhibitor, approved in the US for for metastatic colorectal cancer; and palbociclib (a Pfizer compound), an oral, small molecule cyclin-dependent kinase 4/6 inhibitor, now in Phase III trials, to treat ER+, HER2-negative advanced breast cancer. Amgen says that the acquisition of Onyx will add to Amgen's late-stage pipeline. This pipeline includes nine innovative products for which registration-enabling data are anticipated by 2016. Four of these products are oncology products. Onyx's pipeline complements Amgen's oncology portfolio, according to Amgen.

Also, in August 2013, Amgen closed on its deal with the French pharmaceutical company Servier under which Amgen has obtained commercial rights in the US to Servier's oral drug, approved in the European Union as Procoralan (ivabradine), for chronic heart failure and stable angina in patients with elevated heart rates. Amgen also received an exclusive option to develop and commercialize Servier's investigational molecule, S38844, for cardiovascular diseases in the US Currently, S38844 is in Phase II studies for the treatment of heart failure. Through the collaboration, Servier obtained an exclusive option to commercialize omecamtiv mecarbil in Europe. Omecamtiv mecarbil is an activator of cardiac myosin, which is currently being tested for potential applications in the treatment of heart failure in patients with systolic dysfunction.

Thus far, AstraZeneca has been active on the M&A front. In August 2013, MedImmune, the company’s biologics arm, agreed to acquire the biopharmaceutical company Amplimmune for $500 million with $225 million upfront and the rest contingent on the achievement of specified milestones. Amplimmune is a Maryland-based developer of cancer immunotherapeutics. The deal, which is subject to customary regulatory closings, is expected to close in the third quarter of 2013.

The acquisition will strengthen MedImmune’s oncology pipeline by obtaining multiple early-stage assets for its immune-mediated cancer therapy (IMT-C) portfolio, including AMP-514, an antiprogrammed cell death 1 monoclonal antibody (mAb). AMP-514 is in late-stage preclinical development, and Amplimmune expects to file an investigational new drug filing before the end of 2013. Other Amplimmune assets include multiple preclinical molecules targeting the B7 pathways.

Founded in 2007 and headquartered in Gaithersburg, Marlyand, Amplimmune is focused on developing costimulatory/co-inhibitory molecules that rebalance the immune system and are intended for treating cancer, autoimmune disease, infectious disease, and transplantation. Amplimmune has three biologic product candidates: AMP-224 is in Phase Ib trials in cancer; AMP-110 for autoimmune diseases in partnership with Daiichi Sankyo; and AMP-514 for cancer. The acquisition builds on MedImmune's oncology R&D activities. MedImmune’s oncology research is focused on IMT-C, a therapeutic approach that may lead to durable and prolonged response rates across a range of cancer types. IMT-Cs are being designed for the immune system to counteract the tactics employed by cancer cells to avoid detection and attack the body. MedImmune's clinical-stage program includes tremelimumab, an anti-OX40 mAb, and MEDI-4736, an anti-PD-L1 mAb. The acquisition of the Amplimmune technology and pipeline strengthens AstraZeneca's and MedImmune portfolio to enable the use of data-driven combinations of IMT-C molecules as well as combinations with highly targeted small molecules.

In another deal, in June 2013, AstraZeneca completed its $1.2-billion acquisition of Pearl Therapeutics, which is focused on the development of inhaled small-molecule therapeutics for respiratory disease. The acquisition gives AstraZeneca access to a potential new treatment for chronic obstructive pulmonary disease currently in late-stage development and inhaler and formulation technology that provides a platform for future combination products. The $1.2-billion deal included $560 million in upfront payments, $450 million in deferred compensation contingent on reaching certain development and regulatory milestones, and $140 million in sales payments, contingent on reaching sales thresholds. 

In May 2013, AstraZeneca agreed to acquire Omthera Pharmaceuticals, a specialty pharmaceutical company based in Princeton, New Jersey, focused on the development and commercialization of new therapies for abnormal levels of lipids in the blood for $323 million ($260 million in cash and $63 million for Omthera’s cash balance). Omthera’s investigational product, Epanova, being developed for the treatment of patients with very high triglycerides, is a omega-3 free fatty acid composition that has been shown to bolster levels of eicosapentaenoic acid and docosahexaenoic acid in the blood. In addition to the cash payment, each Omthera shareholder will receive contingent value rights of up to approximately $4.70 per share, equating to approximately $120 million in total, if specified milestones related to Epanova are achieved, or if a milestone related to global net sales is achieved. This will bring the total potential acquisition cost to approximately $443 million. The transaction is expected to close in the third quarter of 2013. Also in April 2013, MedImmune, the biologics arm of AstraZeneca, acquired AlphaCore Pharma, an Ann Arbor, Michigan-based biotechnology company focused on the development of ACP-501, a recombinant human lecithin-cholesterol acyltransferase (LCAT) enzyme.

In a move to bolster its oncology portfolio, Johnson & Johnson completed its $1-billion acquisition of Aragon Pharmaceuticals, a privately held pharmaceutical discovery and development company focused on drugs to treat hormonally driven cancers. The acquisition includes Aragon’s androgen receptor antagonist program. Aragon’s lead product candidate is a second-generation androgen receptor signaling inhibitor, ARN-509, in Phase III development for castration-resistant prostate cancer (CRPC). Under the terms of the agreement, Johnson & Johnson is making an upfront cash payment of $650 million, plus additional contingent payments of up to $350 million based on reaching predetermined milestones.

In May 2013, GlaxoSmithKline acquired Okairos, a Swiss privately held developer of vaccine platform technologies for EUR 250 million ($325 million) in cash. GSK plans to use the vaccine platform in its of new prophylactic vaccines (designed to prevent infection) as well as new classes of therapeutic vaccines (designed to treat infection or disease). The deal also includes a small number of early-stage assets.

Mergers and acquisition activity on both a volume and value basis is up thus far in 2013 comparative to 2012.