You are on page 1of 55
PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS R&C/AJ/PDS/1979 ISSUE 69 July 2011 PPPPHARMA

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
R&C/AJ/PDS/1979
R&C/AJ/PDS/1979
PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS R&C/AJ/PDS/1979 ISSUE 69 July 2011 PPPPHARMA
ISSUE 69 July 2011 PPPPHARMA CCCCHRONICLE Since 2009 Readers’ eaders’ eaders’ estimonials eaders’ Testimonials estimonials estimonials
ISSUE
69
July
2011
PPPPHARMA CCCCHRONICLE
Since 2009
Readers’ eaders’ eaders’ estimonials
eaders’ Testimonials estimonials estimonials
“I
“I
“I
“I enjoyed reading it and more important I could get some very interesting information in our field…”
“I
“I
“I
“It is always very interesting. Good continuation!”
“I
“I
“I
“It is very instructive and I think could be of interest to all of us.”
“ “ ...
...
...
I I I I
like the new look! I always forward your chronicle to my colleagues.”
“T“T“T“This effort is very informative and productive for Professional with special concern of up date for
Pharma Industries in the world; We are getting up date knowledge through this effort…”
“T“T“T“Thanks for sharing such an informative & well-presented material to keep us updated about the
Pharma Industry. Keep it up!”

1

For more information about PSI, please visit www.psiltd.com 2

For more information about PSI, please visit www.psiltd.com

2

For more information about PSI, please visit www.psiltd.com 3

For more information about PSI, please visit www.psiltd.com

3

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS C ONTENTS JULY 2011 INSIDE THIS

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

CONTENTS

JULY 2011

INSIDE THIS ISSUE:

CHRONICLE SPOTLIGHT NEWS FROM THE GULF INSIGHTS: Why Are Drug Prices Set So Unscientifically? PRODUCT LAUNCH FEATURE: Acquisitions, Not Research, Fuels New Drugs DRUGS ON THE WAY: Eli Lilly Plans 10 Drugs In Final-Stage Trials NEWS UPDATE FDA APPROVALS EMA NEWS FUNNY PHARMA CARTOON TIE-UPS & AGREEMENTS PHARMA ARTICLES UPCOMING FAIR INBANGKOK, THAILAND UPCOMING EVENT IN VIENNA, AUSTRIA

eyeforpharma ARTICLES

PHARMA ARTICLES

BUT……

...

MY

PROJECTS ARE SPECIAL

4

555515

151515

16161616

17171717

19191919

20202020

2121

21

21

2222—2222——26

—262626

2727—2727——29 —292929

30303030

3131

31

31

32323232

3333—3333——44

—444444

45454545

46464646

4747—4747——50

—505050

5151—5151——52

—525252

53535353

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS CHRONICLE SPOTLIGHT JULY 2011 F DA

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
CHRONICLE SPOTLIGHT JULY 2011
CHRONICLE SPOTLIGHT
JULY 2011

FDA APPROVES NOVARTIS’ ARCAPTA NEOHALER TO TREAT COPD

The U.S. Food and Drug Administration on Jul. 1, 2011 approved Arcapta Neohaler (indacaterol inhalation powder) for the long term, once-daily maintenance bronchodilator treatment of airflow obstruction in people with chronic obstructive pulmonary disease (COPD) including chronic bronchitis and/or emphysema.

COPD is a serious lung disease that makes breathing difficult. Symptoms can include breathlessness, chronic cough and excessive phlegm. Cigarette smoking is the leading cause of COPD, and is the fourth leading cause of death in the United States, according to the Centers for Disease Control and Prevention.

Arcapta Neohaler is a new molecular entity in the beta2-adrenergic agonist class that helps muscles around the airways of the lungs stay relaxed to prevent symptoms of COPD, such as wheezing and breathlessness. Arcapta Neohaler is not intended to treat asthma or sudden, severe symptoms of COPD.

"The approval of new long-term drugs for COPD that relieve breathing difficulty by opening airways provides another treatment option for the millions of people,” said Curtis Rosebraugh, M.D., M.P.H., director of the Office of Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research.

The safety and efficacy of Arcapta Neohaler was demonstrated in six confirmatory clinical trials that included 5,474 patients ages 40 and older with a clinical diagnosis of COPD. Those treated had a smoking history of at least one pack a day for 10 years and exhibited moderate-to-severe decreases in lung function.

Arcapta Neohaler carries a boxed warning that long-acting beta2 adrenergic agonists (LABA) increase the risk of asthma-related death. All LABA, including Arcapta Neohaler, should not be used in patients with asthma, unless used with a long-term asthma control medication. The FDA approved Arcapta Neohaler with a medication guide that includes instructions for use and information about the potential risks of taking the drug. The most common side effects reported by those using Arcapta Neohaler include runny nose, cough, sore throat, headache and nausea.

Arcapta Neohaler is marketed by Novartis Pharmaceuticals Corp. of East Hanover, N.J.

(Source: http://www.biospace.com/News/fda-approves-archimedes-pharmas-lazandar-first/225930/Source=TopBreaking FDA Approves Novartis Pharmaceuticals Corporation (NVS)'s Arcapta Neohaler to Treat Chronic Obstructive Pulmonary DiseaseJul. 1, 2011)

NEW STUDY: ZINC PREVENTS DIABETES DAMAGE

A new study led by an Indian professor has revealed that zinc keeps a protein called amylin in check and acts like a security guard in preventing major damage from diabetes.

Ayyalusamy Ramamoorthy, a professor of chemistry and biophysics at the University of Michigan, and his colleagues explained that in type two diabe- tes, amylin forms dense clumps that shut down insulin-producing cells, wreaking havoc on the control of blood sugar.

Amylin has been explained as something of a two-faced character. In healthy people who have normal levels of zinc in the insulin-producing islet cells of the pancreas, amylin actually pitches in to help with blood sugar regulation.

This is because in molecular terms, zinc prevents amylin also known as Islet Amyloid Polypeptide (IAPP) from forming harmful clumps similar to those found in Alzheimer's, Parkinson's, Huntington's and various other degenerative diseases.

However, in a zinc-starved cellular environment of someone with type two diabetes, amylin has no watchful guard. It is free to clump together with other amylin molecules in the molecular equivalent of a gang.

This clumping eventually leads to the formation of ribbon-like structures called fibrils, and because fibril formation has been linked to a number of human diseases, it was long assumed that fibrils themselves were toxic. The study shows that the binding of zinc in the middle makes one end of the amylin molecule, called the N-terminus become more orderly. This is significant, because the N-terminus is very important in clump formation and amylin toxicity, said Ramamoorthy.

The researchers also discovered that before amylin can begin forming fibrils, zinc must be rousted from its nesting place.

The study appears in the upcoming issue of the Journal of Molecular Biology.

(Source: http://timesofindia.indiatimes.com/life-style/health-fitness/health/Zinc-prevents-diabetes-damage/articleshow/9064976.cms Zinc prevents diabetes damageANI – Jul. 1, 2011)

5

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS CHRONICLE SPOTLIGHT JULY 2011 F DA

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
CHRONICLE SPOTLIGHT JULY 2011
CHRONICLE SPOTLIGHT
JULY 2011

FDA APPROVES JANSSEN’S XARELTO ® TO HELP PREVENT DVT

Janssen Pharmaceuticals, Inc. announced on Jul. 1, 2011 that the U.S. Food and Drug Administration (FDA) has approved XARELTO® (rivaroxaban

tablets), a novel, once-daily, oral anticoagulant for the prevention (prophylaxis) of deep vein thrombosis embolism (PE) in people undergoing knee or hip replacement surgery.

(DVT) which may lead to a pulmonary

“The approval of once-daily XARELTO® tablets will provide a new option to help protect patients from developing venous blood clots following knee or hip replacement surgery,” said Louis M. Kwong, M.D., Professor of Orthopedic Surgery at Harbor-UCLA Medical Center, who was involved with the rivaroxaban clinical trials program in this indication.

XARELTO® has a proven clinical benefit over one of today’s most widely used options in preventing these potentially life-threatening blood clots, and the use of a once-daily pill may play an essential role in helping to simplify clinical practice.”

According to the American Academy of Orthopedic Surgeons, more than 800,000 Americans undergo knee or hip replacement surgery each year. These procedures are associated with an increased risk for DVT, a blood clot that forms in a deep vein, usually in the leg. If all or part of a DVT breaks off, it can travel to the lungs and become a PE, where it may impact the flow of oxygenated blood and lead to potentially life- threatening consequences.

The American College of Chest Physicians recommends the use of blood thinners (anticoagulants) immediately following major orthopedic replacement surgery and extended use post-discharge (at least 10 days for knee replacement, and up to 35 days for hip replacement) to help reduce such risks; however, full compliance with these guidelines using previously available options has not been widely observed. DVT and PE are the leading causes of re-hospitalization following joint replacement surgery.

“The use of blood thinners has been shown to safely and effectively help keep people from developing preventable blood clots,” said Alan Brownstein, Chief Executive Officer of the National Blood Clot Alliance.

“The FDA approval of a new blood thinner, XARELTO®, offers a new option for patients seeking knee or hip replacement surgery, and we encourage people to discuss with their physicians the risk of blood clots and which blood thinner offers optimal protection as part of their pre- surgical consultation.”

Pivotal data from the XARELTO® Phase 3 clinical development program reflected in the approved label showed significantly greater efficacy of rivaroxaban, both in head-to-head comparison with enoxaparin and when comparing extended-duration (5 weeks) rivaroxaban with short- duration (2 weeks) enoxaparin, followed by placebo. In these trials, rivaroxaban and enoxaparin demonstrated similar safety profiles including low rates of major bleeding.

XARELTO® is approved for use at a 10 mg dose, once-daily for 35 days following hip replacement and for 12 days following knee replacement surgery.

To date, XARELTO® is approved in more than 110 countries worldwide and has been successfully launched in more than 80 countries by Bayer HealthCare. Janssen Pharmaceuticals, Inc. holds marketing rights for XARELTO® in the U.S.

The U.S. Bayer HealthCare sales force will support the Janssen Pharmaceuticals, Inc. sales force by detailing XARELTO® in designated hospital accounts.

“Shorter hospital stays following hip and knee replacement surgeries have made the prevention of venous blood clots an outpatient issue, and XARELTO® provides a safe and effective oral treatment option that can be easily transitioned from use in hospital to home,” said Paul Chang, M.D., Vice President, Medical Affairs, Internal Medicine, Janssen Pharmaceuticals, Inc.

“We’re pleased to make XARELTO® tablets available to physicians to help them better protect their patients from these highly preventable surgical complications.”

Please see full Product Information, or visit www.XARELTOhcp.com

(Source: http://www.biospace.com/News/fda-approves-novartis-pharmaceuticals-corporations/226000/Source=TopBreaking FDA Approves Janssen Pharmaceutica N.V.'s XARELTO(R) (rivaroxaban tablets) to Help Prevent Deep Vein Thrombosis in Patients Undergoing Knee or Hip Replacement SurgeryRaritan, New Jersey – Jul. 1, 2011)

6

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS CHRONICLE SPOTLIGHT JULY 2011 E LECTROMAGNETIC

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
CHRONICLE SPOTLIGHT JULY 2011
CHRONICLE SPOTLIGHT
JULY 2011

ELECTROMAGNETIC FIELDS CAN DISTURB LEARNING, STUDY SUGGESTS

The effects of high-frequency electromagnetic fields emitted by mobile phones on humans have been hotly debated for years. In a new study, neuroscientists from Ruhr-Universitaet-Bochum (RUB) in Germany have shed light on this question.

For the first time, they provide evidence that extremely high-powered electromagnetic fields can influence learning processes on the synaptic level within the brain, independent from other factors such as stress. However, such high levels are not encountered during typical use of mobile phones, the researchers note.

"For this effect, very high values are necessary. These do not occur during the daily use of mobile phones," explains Dr. Nora Prochnow, with RUB's Medical Faculty.

Mobile phone derived non-ionizing radiation can produce heat …

High-frequency electromagnetic fields (HEFs) are not only used in mobile phones, but also in a variety of other communication systems like radio, television or cordless telephone sets. Mobile phones of the so-called third generation utilize the UMTS technology (Universal Mobile Communication System) with a frequency of 1200 MHz and a relatively weak operating range (3.8-4.8 V/m). With increasing power, electromagnetic fields (EMFs) are able to elicit local warming of body tissues, being also described as a "thermal effect." Reportedly, mobile phones can cause local warming of the brain by less than 0.1°C. The effect on function and structure of the brain during long term use of mobile phones (e.g. > 30 min) remains unexplained until now.

… and might influence cellular activity

Furthermore, findings regarding the non-thermal effects of mobile phone emitted EMFs are unclear and contradictory. These comprise, for instance, an increase in permeability and fluidity of cellular membranes, which can be implicated in changes in ion-channel integration and metabolism, even without a detectable change in temperature. This may impair synaptic learning processes in the brain. Until now, experiments could not sufficiently answer the question of whether these effects are derived from non-thermal HEFs or from stress, as it can be induced by handling of the experimental animal (e.g. placing a rat into an unknown environment).

Stress or non-thermal EMF effect -- Scientists find out for the first time

To investigate this question, a new study was performed by scientists of the Department of Neuroanatomy and Molecular Brain Research (Professor Dr. med. Rolf Dermietzel) in cooperation with the Chair of Electromagnetic Theory of the University of Wuppertal.

For the experiment, rats were placed into differently powered non-thermal HEFs in the UMTS operating range. Synaptic learning and memory formation were analyzed by electrophysiological methods. Furthermore, all animals were tested for stress hormone release immediately following the HEF exposure.

Mobile phone use seems to be harmless -- critical values for occupational use have to be controlled precisely

The results: Although there was daily training and effortless contact to the exposure environment, increases in blood derived stress hormone levels could be detected for all exposed groups. The stress clearly influences learning and memory formation on the synaptic level in the rat brain. High- powered EMFs (SAR 10 W/kg) also have a significant effect on learning and memory formation. In contrast to this, weak EMFs (SAR 0 and 2 W/kg) lead to no detectable changes or impairments.

"These results cannot directly be transferred to humans," says Nora Prochnow. "But in the animal model, it can be demonstrated that neuronal mechanisms of synaptic learning can serve as a target for high powered EMFs."

However, there is no need for serious concerns: humans are not exposed to such high-powered EMFs during daily mobile phone use. Nevertheless, the matter has to be regarded differently in special occupational situations, for instance during the use of body worn antenna systems as it is common for security services or military purposes. Here, critical levels for occupational exposure may be reached more easily and have to be controlled carefully.

(Source: http://www.sciencedaily.com/releases/2011/06/110630091657.htm Electromagnetic Fields Can Disturb Learning, Study Suggests, but Only at Very High LevelsScienceDaily – Jul. 1, 2011 Story source: The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Ruhr-Universitaet-Bochum – www.ruhr-uni-bochum.de via AlphaGalileo www.alphagalileo.org)

7

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS CHRONICLE SPOTLIGHT JULY 2011 M ERCK

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
CHRONICLE SPOTLIGHT JULY 2011
CHRONICLE SPOTLIGHT
JULY 2011

MERCK SAYS GARDASIL, CUBICIN APPROVED IN JAPAN

Merck says Japanese regulators cleared HPV vaccine Gardasil, an antibiotic, and a cancer drug

Merck & Co. said on Jul. 1, 2011 that Japanese regulators approved three of its products, including the vaccine Gardasil, which protects against a virus that causes cervical cancer.

Merck said Gardasil was approved for the prevention of cervical cancer and precancerous lesions caused by four types of human papillomavirus. Its use was approved in women and girls age 9 and older.

The Ministry of Health, Labor and Welfare also approved Zolinza, an oral drug used for treatment of cutaneous T-cell lymphoma. The drug will be marketed in Japan by Taiho Pharmaceutical Co. The third approved was for Cubicin, an antibiotic that treats severe skin and bloodstream infections. Cubicin was developed by Cubist Pharmaceuticals Inc. Merck sells the drug outside the U.S.

Japan is the world's second-largest drug market after the U.S.

(Source: http://finance.yahoo.com/news/Merck-says-Gardasil-Cubicin-apf-2398153422.html?x=0&.v=1 Merck says Gardasil, Cubicin approved in JapanAssociated Press – Whitehouse Station, New Jersey Jul. 1, 2011)

ASTRAZENECA’S ENDING OF DOCTORS’ FREE TRIPS TO SPREAD

AstraZeneca PLC's decision to scrap payments for doctors to attend international medical congresses is ground breaking but necessary if the pharmaceutical industry wants to improve its tarnished image, said Richard Bergstrom, who heads the industry's European trade body. "I think others will follow," said Bergstrom, director general of the European Federation of Pharmaceutical Industries and Associations. AstraZeneca took the decision in April, partially in response to criticism of the pharma industry's potential influence on prescribers of medicines.

"We just wanted to tighten things up even further than the industry codes currently required or voluntarily suggest, because we never want to do anything that can be misinterpreted," an AstraZeneca spokesperson said, adding: "I think we're the first to go to this extent."

Congresses are held in Europe and the U.S. every year on subjects like diabetes, heart and lung disease and cancer, during which hundreds of specialist physicians are flown in at the expense of drug makers--a practice that has become increasingly criticized as healthcare costs have risen.

"We probably need to find ways of interacting which is more acceptable to society at large," said Bergstrom. The pharma industry is also keen not to be seen breaching new anti-bribery laws.

" AstraZeneca’s move probably reflects concern that such practices might run foul of legislation in the U.S., and now the new bribery act in the U.K., depending on how you do this, and depending on how you invite these physicians," said Bergstrom, a Swede and pharmacist by training.

"This trend is a wake-up call for the medical community and healthcare professionals who have gotten used to the fact the industry is paying for all this."

Bergstrom said that around half of all the congresses held around the world are related to life sciences.

"Congress organizers realize that we're in this together, and realize we need to take away the unnecessary things that are still remaining--the unnecessary social activities, and the gala dinners--they're just giving the wrong impression of a high science meeting. But some of doctors associations are responding very negatively, suggesting they regard this as something that they have a right to--getting the pharmaceutical industry's money to pay for their education. So some of them are in denial."

Britain's biggest drug maker, GlaxoSmithKline PLC, said it will continue funding trips for selected doctors to attend international medical congresses.

"Large, world-class, academic conferences such as ASCO [American Society of Clinical Oncology], ADA [American Diabetes Association] and ERS [European Respiratory Society] act as leading forums for discussion around serious diseases areas such as oncology, diabetes and respiratory disease. "Unfortunately, for many healthcare professionals the costs involved in attending these conferences may prove prohibitive without support," it added.

(Source: http://www.nasdaq.com/aspx/company-news-story.aspx?storyid=201106281208dowjonesdjonline000244&title=interview-astrazenecas-ending- of-doctors-free-trips-to-spread#ixzz1QhLBC6u4 INTERVIEW: AstraZeneca's Ending Of Doctors' Free Trips To Spread” by Sten Stovall Dow Jones Newswires – London Jul. 1, 2011)

8

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS CHRONICLE SPOTLIGHT JULY 2011 C ANADIANS

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
CHRONICLE SPOTLIGHT JULY 2011
CHRONICLE SPOTLIGHT
JULY 2011

CANADIANS WAIT MORE TO ACCESS LATEST DRUGS

CORCEPT SAYS FDA ACCEPTS CORLUX APPLICATION

Canada's federal and provincial governments are now taking more than two

and a half years, on average, to approve new prescription medicines, says a new report.

The federal regulator, Health Canada, takes an average of nearly 16 months to approve new drugs as safe and effective, after which the provincial governments typically spend another 15 months or more to decide whether new drugs will be eligible for public reimbursement under their drug plans, says the report, from free-market think tank The Fraser Institute.

This combination of federal and provincial decision-making creates delays or, more often, deprives patients of access to new medicines, it claims.

The Institute's research found that only 23% of new drugs approved as safe and effective by Health Canada in 2004 had been approved for either full or partial reimbursement under provincial drug plans as of June 9, 2011, compared to 98% that had been covered by at least one private insurer.

Moreover, Health Canada took longer to certify new drugs during 2006-2009 than the European Medicines Agency (EMA) and, during five of the last six years studied (2004-2009), its performance was worse than that of the US Food and Drug Administration (FDA).

The report's authors suggest two specific policy changes to make new medicines available more quickly to Canadians.

First, they say, Canada could speed up its regulatory processes by taking advantage of the knowledge and capacity of other jurisdictions, rather than attempting to duplicate the processes of the US FDA.

If Canada entered into agreements of "mutual recognition" with other countries, new medications already approved in those jurisdictions could be introduced onto the Canadian market far more rapidly, and vice versa, they add.

Corcept Therapeutics says FDA will make decision on Cushing's Syndrome drug Corlux by Feb. 17

Corcept Therapeutics Inc. said on Jun. 30, 2011 that regulators accepted its application to market the drug Corlux as a treatment for the rare disease Cushing's Syndrome. Corcept said the Food and Drug Administration expects to decide whether to approve Corlux by Feb. 17. The company filed for approval on April 15, and FDA reviews usually take about 10 months.

Cushing's Syndrome is caused when tumors cause a person's body to produce too much of the hormone cortisol. Its symptoms can include high blood sugar, high blood pressure, fatigue and muscle weakness. Corcept said about 20,000 people in the U.S. have the condition.

Earlier this month, Corcept reported results from late-stage testing that showed Corlux improved patients' blood sugar levels and blood pressure, and decreased body weight and waist circumference. If the drug is approved, Corcept will have seven years of marketing exclusivity because the FDA awarded Corlux orphan drug status, an incentive given to treatments for rare diseases. The company is also studying Corlux as a treatment for psychotic depression.

Corcept shares fell 13 cents, or 3.1 percent, to $4.12 in premarket

trading. The stock has traded between $2.76 and $5.07 in the last year.

(Source: http://finance.yahoo.com/news/Corcept-says-FDA-accepts-its- apf-38018945.html?x=0&.v=1 Corcept says FDA accepts its Corlux applicationAssociated Press – Menlo Park, California Jun. 30, 2011)

Second, government drug programmes could be replaced with means-tested subsidized access to private insurance, they suggest. A properly- regulated and competitive private-sector insurance market, in which universal access to catastrophic drug insurance would be facilitated through means-tested subsidies for those on low incomes, could make new medicines more readily available without increasing the burden on taxpayers, the report proposes.

In fact, only a very small percentage of Canadians actually face exorbitant drug costs, says the Institute; during 1997-2002, only 3% of Canadian house- holds spent more than 5% of their annual income on prescription drugs.

“Means-tested subsidies provided to those with low incomes, regardless of age, to purchase catastrophic drug insurance in a private, competitive insur-

ance market benefits recipients by giving them the choice of selecting the drug plan that meets their individual medical needs and financial abilities," said Mark Rovere, study co-author and associate director of health policy studies at the Institute.

Unlike the majority of public drug plans, which have small, flat co-payments, most private drug insurance plans include co-payments that are linked to the full cost of the prescription, and these encourage patients to make cost-efficient choices between alternative treatments, says the report. Con- sumer sensitivity to prices in turn creates incentives for physicians to prescribe treatment more efficiently and for drug manufacturers to invest effi- ciently in the development of new drugs, it adds.

"Allowing the private insurance market to compete through prices and service, thus eliminating government monopolies on drug prices and coverage, is the best policy choice for improving access to the newest prescription drugs," according to Mr Rovere.

(Source: http://www.pharmatimes.com/article/11-06-30/canadians_wait_more_than_30_months_to_access_latest_drugs.aspx Canadians ʺwait more than 30 months to access latest drugs" by Lynne Taylor World News – Jun. 30, 2011)

9

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS CHRONICLE SPOTLIGHT JULY 2011 J OHNSON

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
CHRONICLE SPOTLIGHT JULY 2011
CHRONICLE SPOTLIGHT
JULY 2011

JOHNSON & JOHNSON RECALLS EXTRA STRENGTH TYLENOL

J ohnson & Johnson on announced another Tylenol recall due to a musty moldy odor linked to a trace chemical.

The company's McNeil Consumer Healthcare unit is recalling one product lot of Tylenol Extra Strength Caplets made in February 2009 and distributed in the U.S.

The recall totals 60,912 bottles, each of which has 225 caplets.

McNeil said it has received a small number of reports about the pills' odor, which has been linked in past J&J recalls to the presence of trace amounts of "2,4,6-tribromoanisole." TBA is a byproduct of a chemical preservative sometimes used on shipping pallets.

Besides causing an unpleasant odor, TBA has been associated with temporary and non-serious gastrointestinal symptoms.

Since September 2009, New Brunswick, N.J.-based Johnson & Johnson has had about two dozen recalls of prescription and nonprescription medicines, replacement hips, contact lenses and diabetes test strips, including tens of millions of bottles of children's and adult Tylenol and Motrin.

The reasons have ranged from metal and other contaminants, to nauseating odors and packaging issues. Joint replacement systems so painful they required corrective surgery were also recalled, as were contact lenses that irritated eyes, along with potentially contaminated syringes full of the antipsychotic drug Invega.

The high-profile lapses have tugged at J&J's revenue, profit and stock price, as well as its once-stellar reputation.

J&J has said that it has inspected more than 100 plants around the world and invested millions to improve the quality of its manufacturing and satisfy federal regulators, who have three of its factories under scrutiny. The product lot number for the recalled Tylenol Extra Strength product can be found on the side of the bottle label - it is ABA619 300450444271.

Customers should stop using the product from the lot immediately and contact McNeil at www.tylenol.com instructions on receiving a refund or product coupon.

or by calling 1-888-222-6036 for

(Source: http://www.dddmag.com/news-JJ-Recalls-Extra-Strength-Tylenol-62911.aspx J&J Recalls Extra Strength TylenolDrug Discovery & Development – Jun. 29, 2011Primary source: Associated Press - Fort Washington, Pa)

STRIDES TO SET UP MANUFACTURING UNIT IN MALAYSIA

Bangalore-based Strides Arcolab on Jun. 29, 2011 signed an agreement to set-up biopharmaceuticals and sterile injectables manufacturing unit in a biotechnology park in Malaysia. The financial details were yet to be disclosed. The company's subsidiary Agila Specialties will set up a customized facility in biotech park, Bio-XCell Ecosystem in Johor in Malaysia. "Malaysia provides us with a strategic location to expand our manufacturing operations. The attractive financial incentives by the Malaysian government and presence of a pharma and biotech ecosystem are catalysts to our decision," said Adam Levitt, CEO-Americas of Strides. The project will be built by Bio-XCell to the design requirements by Strides and leased out to the company on a long-term basis.

The lease rentals are applicable from the date of commercialization, which supports the biotech strategy of Strides, where there is a long gestation period from development to commercialization, the company said.

In addition to Strides, Indian biotech firm Biocon, Metabollic Explorer from France, and Glycos Biotechnologies of US are some of the other companies, which will set up manufacturing units in the Bio-XCell Ecosystem.

(Source: http://www.business-standard.com/india/news/strides-to-setmanufacturing-unit-in-malaysia/139689/on Strides to set up manufacturing unit in Malaysia” by BS Reporter Mumbai, INDIA – Jun. 29, 2011)

10

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS CHRONICLE SPOTLIGHT JULY 2011 2 0

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
CHRONICLE SPOTLIGHT JULY 2011
CHRONICLE SPOTLIGHT
JULY 2011

20 EXPENSIVE DRUGS THAT COULD BANKRUPT MEDICARE

THE 20 MOST EXPENSIVE DRUGS IN AMERICA:

  • 1. Soliris, Alexion Pharmaceutical, $409,500 a year. Monoclonal antibody drug treats a rare disorder in which the immune system destroys red blood cells at night.

  • 2. Elaprase, Shire, $375,000 per year. Treats Hunter’s syndrome, a metabolic disorder.

  • 3. Naglazyme, BioMarin, $365,000 a year. Treats rare connective tissue disorder.

  • 4. Cinryze, ViroPharma, $350,000 a year. Treats hereditary angioedema, a rare, life-threatening genetic disorder that causes painful swelling.

  • 5. Arcalyst, Regeneron, $250,000 a year. An anti-inflammatory for patients with impaired immune systems.

  • 6. Myozyme, Sanofi, $300,000 per year. Treats Pompe disease.

  • 7. Cerezyme, Sanofi, $200,000 per year. Treats Gaucher disease.

  • 8. Fabrazyme, Sanofi, $200,000, per year. Treats Fabry disease.

  • 9. Aldurazyme, Sanofi, $200,000, per year. Treats Hurler syndrome.

    • 10. Provenge, Dendreon $93,000 per year. Treats prostate cancer.

    • 11. Erbitux, Eli Lilly, $80,000 per year. Treats

lung cancer.

  • 12. Folotyn, Allos Therapeutics, $60,000 per two-month treatment. Treats a rare type of lymphoma.

  • 13. Lemtrada (alemtuzumab), Sanofi, $60,000.* Treats M.S.

  • 14. Avastin, Roche, $50,000 a year. Treats colon cancer.

  • 15. Jevtana, Sanofi, $48,000 per year. Treats prostate cancer.

  • 16. Gilenya, Novartis, $40,000 per year. Treats multiple sclerosis.

  • 17. Zytiga, J&J, $40,000 per year. Treats prostate cancer.

  • 18. Xgeva, Amgen, $21,500 per year. Treats prostate cancer.

  • 19. Tofacitinib, Pfizer $20,000 a year.* An anti-inflammatory biologic.

  • 20. Fuzeon, Roche, $20,000 per year. Treats HIV.

Sources: Forbes, The New York Times, BNET, Bloomberg and the AP. *Not launched yet.

(Source: http://www.bnet.com/blog/drug-business/20-expensive-drugs-that-could-bankrupt-medicare/8885?pg=2&tag=content;drawer-container 20 Expensive Drugs That Could Bankrupt Medicare” by Jim Edwards Jun. 29, 2011)

PFIZER SUBMITS AXITINIB FOR ADVANCED RCC TO FDA

Pfizer says that axitinib, for the treatment of advanced kidney cancer, has been accepted for review by the US Food and Drug Administration.

The drug, which was filed in Europe at the beginning of June, is for previously-treated patients with advanced renal cell carcinoma, the most prevalent form of kidney cancer. The US submission is based on Phase III data, which found that axitinib extended progression-free survival (PFS) by 6.7 months compared with Bayer/Onyx's Nexavar (sorafenib), which extended PFS by 4.7 months. Axitinib is an oral drug which inhibits vascular endothelial growth factor receptors 1, 2 and 3, which can influence the spread and growth of tumors. Garry Nicholson, head of the drug giant's Oncology Business Unit, said the filing represents "a significant step towards accomplishing Pfizer's goal of bringing axitinib to advanced RCC patients who are in need of additional, effective treatment options". The company already has two kidney cancer treatments on the market - Sutent (sunitinib) and Torisel (temsirolimus). Pfizer noted that some 210,000 people worldwide are diagnosed with kidney cancer every year, and about 102,000 patients die of the disease. While "great advances have been made", five-year survival rates for patients with advanced RCC remain low, at around 20%.

(Source: http://www.pharmatimes.com/Article/11-06-29/Pfizer_submits_axitinib_for_advanced_RCC_to_FDA.aspx Pfizer submits axitinib for advanced RCC to FDA” by Kevin Grogan World News – Jun. 29, 2011)

11

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS CHRONICLE SPOTLIGHT JULY 2011 H YDERABAD

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
CHRONICLE SPOTLIGHT JULY 2011
CHRONICLE SPOTLIGHT
JULY 2011

HYDERABAD FIRM LAUNCHES TRACKING TOOL FOR PHARMA INDUSTRY

Goose, a city-based business re-engineering solutions provider, on Jun. 28, 2011 announced the launch of an indigenously developed product to help pharma industry meet the new regulatory packaging guideline, detect counterfeit drugs and protect their brand reputation.

'Procon Tracker' is a new addition to Goose's wide range of solutions adopted by several leading global pharma companies to increase business process efficiency, Goose said in a statement here. Deb Pattnaik, Founder of Goose, said the recent directive from the government to pharma industry to implement track and trace automatic identification process to offset counterfeits opens an opportunity for his firm's new product.

"We found the pharma industry is eager to meet the new regulatory compliance norms deadline without disrupting packaging quality process and Procon Tracker is designed precisely to meet these expectations."

A Centre for Medicines in the Public Interest report has estimated that globally counterfeit pharmaceutical commerce will grow to become 16% of the aggregate size of the legitimate industry, a 6 percentage point rise from 2004. This illegal business will generate $75 billion in revenues for its owners in 2010, a 92% increase from 2005, Pattnaik said, quoting the report.

"We are excited about the potential of Procon Tracker and its addition to a wide range of high performance solutions we offer to the global pharma industry," he said. According to him, Goose expects wide acceptance and adoption of Procon Tracker in the industry.

(Source: http://www.business-standard.com/india/news/hyderabad-firm-launches-tracking-tool-for-pharma-industry/139657/on Hyderabad firm launches tracking tool for pharma industryPress Trust of India – Hyderabad, INDIA Jun. 28, 2011)

NUTRA PHARMA ANNOUNCES JORDAN DISTRIBUTOR FOR NYLOXIN PAIN RELIEVERS

Nutra Pharma Corp., a biotechnology company that is developing treatments for Multiple Sclerosis (MS), Human Immunodeficiency Virus (HIV),

Adrenomyeloneuropathy (AMN) and Pain, announced on Jun. 28, 2011 that it has selected Medicinesconsult to serve as the exclusive distributor in Jordan for its Nyloxin-branded pain relievers.

Nutra Pharma continues to increase awareness internationally and while we are establishing the framework for international distribution of our pain relievers,” commented Rik J Deitsch, Chairman and CEO of Nutra Pharma Corporation. "Medicinesconsult has already begun the registration process for our Nyloxin products in Jordan and will begin an aggressive marketing campaign throughout the Middle East once they have regulatory clearance,” he added.

Medicinesconsult is known for their highly experienced management and consultant marketers who have broad experience in the medical field, including: prescription and OTC drugs, biotech products, medical equipment and medical devices. Medicinesconsult works directly with the Jordanian Ministry of Health, Military and Governmental Hospitals, private hospitals, and other health institutions in Jordan with the mission to provide the Jordanian market, as well as the Middle East and North Africa markets, with high quality medical products for human use.

Recently, the Jordan Food and Drug Administration (JFDA) have warned the public against extensive use of painkillers containing paracetamol (acetaminophen) because of the associated risk of liver damage. Additionally, it was reported in the November 1, 2010 issue of The Jordan Times that although Jordanians consume the most painkillers in the region, more needs to be done to improve access to necessary drugs. According to the Jordanian Pain Society (JPS), Jordan was ranked 59th internationally and first regionally in the consumption of painkillers in 2008.

According to JPS Secretary General Ahmad Khatib, more efforts are needed to improve access to painkillers in Jordan to reach international averages. General Khatib noted that the sub-average rates are due to the belief of health institutions and physicians that the use of painkillers leads to addiction and their related refusal to prescribe the drugs to their patients -- hence the necessity for a non-addictive alternative.

Nyloxin™ is an over-the-counter (OTC) pain reliever clinically proven to treat moderate to severe (Stage 2) chronic pain. Nyloxin™ is currently available in the United States as an oral spray for treating back pain, neck aches, headaches, joint pain, migraines, and neuralgia, and as a topical gel for treating joint pain, neck pain, arthritis pain, and pain from repetitive stress. In addition to its everyday strength formulation, Nyloxin™ is also offered in an extra strength formula for more advanced, Stage 3, chronic pain.

Previously, Nutra Pharma announced agreements with distributors in Mexico, Colombia, Venezuela and Lebanon. The drug registration process for

both Cobroxin® and Nyloxin™ are currently being pursued in more than 20 countries. For additional information about Nutra Pharma, visit: http:// www.NutraPharma.com

(Source: http://www.nutrapharma.com/newsroom/display.php?newsid=181 Nutra Pharma Announces Jordan Distributor for Their Nyloxin Pain RelieversCoral Springs, Florida – Jun. 28, 2011)

12

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS CHRONICLE SPOTLIGHT JULY 2011 F O

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
CHRONICLE SPOTLIGHT JULY 2011
CHRONICLE SPOTLIGHT
JULY 2011

FO R J A PA N E S E M & A , I N T E G RA T I O N I S T H E K E Y

Japan has about 2,400 drug manufacturers. Sounds like an industry ripe for consolidation? But Japanese drugmakers with the resources to snap up smaller companies don't want domestic buyouts. They're looking overseas for deals.

Take Takeda Pharmaceutical, which recently agreed to buy the Swiss drugmaker Nycomed for $13.7 billion. As the Financial Times reports, CEO Yasuchika Hasegawa dislikes the idea of buying a fellow Japanese pharma. "We are not interested," he told the newspaper. "I'd rather spend my time on a more rewarding opportunity [overseas] in terms of return on investment. I don't see [opportunities] domestically."

One reason is government regulation. Were Takeda to buy up some smaller Japanese drugmakers, it would find its freedom to integrate operations rather limited. It's tough to lay off redundant staff, for instance, the FT notes. So, restructuring to cut costs and generate the ROI Hasegawa cites just isn't as straightforward as it can be when buying an overseas firm. Not that it's easy; just listen to Takeda EVP Frank Morich, who's charged with bringing Nycomed into the fold. The two companies are very different, and Takeda wants to keep Nycomed's more entrepreneurial-minded managers to handle its far-flung operations with a high degree of local autonomy. "The vital condition for achieving this is to have enough trust between where those other decisions are made and Tokyo," Morich says. "I see that as my main role. That these guys get the trust, that they get enough freedom from Tokyo--and that I ensure that is not read the wrong way in Tokyo."

(Source: http://www.fiercepharma.com/story/japanese-ma-integrations-key/2011-06-28 | For Japanese M&A, integration's the key” by Tracy Staton | Jun.

28, 2011)

MEDPRO SAFETY INTRODUCES HYPODERMIC SAFETY SYRINGE

MedPro Safety Products, Inc., a leading developer of transformational technologies that enable safer medication delivery and blood collection, on

Jun. 27, 2011 announced the introduction of its hypodermic safety syringe. The device incorporates a proprietary safety shield that is automatically released during the administration of medicine, covering the needle as it is removed, and thereby enhancing patient and operator safety.

The passive (automatic) hypodermic safety syringe provides unique features and benefits. The passive safety mechanism is integrated into the syringe and is activated through the normal process of medication delivery. The shield is automatically deployed over the contaminated needle, reducing the chances of a needlestick injury. It prevents recapping, removal and reuse of the syringe with the engagements of its auto-disable feature and reduces the chance of blood or drug splatter. The device is easy to use and provides an unobstructed view of the patient during an injection.

"The passive hypodermic safety syringe is the latest offering in our efforts to expand our patented passive safety technology across a broad range of products," said Craig Turner, CEO of MedPro Safety Products. "This development demonstrates the strength of our research and development effort. We are in various stages of discussions with several potential partners to explore the commercialization of the hypodermic safety syringe…”

(Source: http://www.marketwatch.com/story/medpro-safety-products-introduces-passive-hypodermic-safety-syringe-2011-06-27?reflink=MW_news_stmp MedPro Safety Products Introduces Passive Hypodermic Safety SyringeLexington, Kentucky – BusinessWire Jun. 27, 2011 Primary source: MedPro Safety Products, Inc. - http://www.medprosafety.com)

SUN PHARMA GETS FDA APPROVAL FOR MIGRAINE INJECTION

U.S. largest regional market for contract manufacturing.

Drug firm Sun Pharma on Jun. 23, 2011 said it has received the US health regulator's approval for the launch of its generic Sumatriptan Succinate injections, used in the treatment of migraines and headaches, in the American market. The Mumbai-headquartered firm's US subsidiary has received approval from the US Food and Drug Administration (USFDA) to market Sumatriptan Succinate injections in strength of 6 mg (base)/0.5ml, Sun Pharmaceutical Industries said in a statement.

"Annual sale for Sumatriptan Succinate injections in the US is approximately USD 190 million," the company said. Generic Sumatriptan Succinate injections are equivalent to GlaxoSmithKline's Imitrex Stat dose system in the same strength, it added.

"Sumatriptan Succinate injection is indicated for the acute treatment of migraine attacks with or without aura and the acute treatment of cluster headache episodes," it said.

(Source: http://articles.economictimes.indiatimes.com/2011-06-23/news/29690320_1_usfda-approval-injections-treatment-of-migraine-attacks Sun Pharma gets USFDA approval for migraine injectionPTI – New Delhi, INDIA Jun. 23, 2011)

13

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS CHRONICLE SPOTLIGHT JULY 2011 O RCHID

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
CHRONICLE SPOTLIGHT JULY 2011
CHRONICLE SPOTLIGHT
JULY 2011

ORCHID CHEMICALS, PHARMA LTD CLEAR U.S. FDA INSPECTION

Chennai-based pharma company Orchid Chemicals and Pharmaceuticals Ltd has said its Cephalosporin API manufacturing (antibiotic) complex in

Alathur, Chennai, has successfully cleared the USFDA inspection that it went through. The company announced this to the stock exchanges on Jun. 22,

2011.

"This test is conducted to show that our products and plant meet the required global standards," the company spokesperson told ET.

The facility has a capacity of 800 tonnes per annum. The oral and sterile Cephalosporin APIs produced here cater to developed markets such as the US, Europe and Japan.

This mandatory and routine test would enable Orchid continue with its supplies to those markets.

(Source:

http://articles.economictimes.indiatimes.com/2011-06-22/news/29689999_1_orchid-chemicals-cephalosporin-apis-chennai-based-pharma

Orchid Chemicals, Pharmaceuticals Ltd clear USFDA inspectionET Bureau – Chennai, INDIA Jun. 22, 2011)

NOW CHECK GENUINENESS OF PHARMA PRODUCTS THROUGH SMS

US-based Sproxil on Jun. 21, 2011 announced the launch of its operations in India and unveiled a product to check the drug counterfeit market.

Mobile Product Authentication (MPA) enables consumers to verify the authenticity of a pharmaceutical product by sending the unique code on the drug as a free text message to the manufacturers in real time, Sproxil CEO Ashifi Gogo told reporters.

Sproxil established the first national mobile-based anti-counterfeit service in Africa and has already sold millions of anti-counterfeit labels which provide services to several global pharmaceutical companies, the company said.

India has one of the largest pharmaceutical markets in the world, but is plagued by counterfeit (spurious) medicines made elsewhere that tarnish brand India, Gogo said. "Our services enable Indian companies to reduce the presence of counterfeit medicines by connecting companies directly to their consumers in a scalable manner, using mobile phones", he added.

Sproxil recently received $1.8 million from Acumen Fund, a non-profit global venture fund, to expand operations in India (which would get the lion's share) and Eastern African countries such as Kenya, Tanzania and Uganda. The company said MPA product delivers automatic protection, simple labels and back-end analytics, and enables consumers to SMS an item-unique code for a rapid response that confirms a brand's genuineness.

(Source: http://articles.economictimes.indiatimes.com/2011-06-21/news/29683507_1_sms-anti-counterfeit-labels Now check genuineness of pharma products through SMSPTI – Bangalore, India Jun. 21, 2011)

EU REGULATORS APPROVE MARKETING OF DIABETES DRUG BYDUREON

European Union regulators have approved the first once-per-week diabetes medication, the companies that developed the drug said on Jun. 21, 2011.

Eli Lilly and Co., Amylin Pharmaceuticals Inc. and Alkermes Inc. said they received marketing approval for Bydureon, a drug that is intended to help patients control their blood sugar in combination with other diabetes medications. The drug is designed to increase the body’s insulin production.

Bydureon is a version of Lilly and Amylin’s diabetes drug Byetta, which was approved in the U.S. in April 2005 and in Europe in November 2006. Byetta, or exenatide, is taken twice a day. Alkermes, based in Waltham, Mass., created the technology that gradually releases the drug over the course of a week. Common side effects of Bydureon included mild to moderate nausea, vomiting, diarrhea, and constipation.

The companies have not received approval to sell Bydureon in the U.S. The Food and Drug Administration declined to approve Bydureon in October, asking the companies to run a thorough study that evaluated effects of bigger doses of Bydureon on patients’ heart rates. The agency also requested results from a study intended to evaluate the efficacy, and labeling of the safety and effectiveness, of the commercial formulation of Bydureon.

Lilly, Amylin and Alkermes plan to submit that information in late 2011. Lilly is based in Indianapolis, and Amylin is headquartered in San Diego.

(Source: http://www.washingtonpost.com/business/lilly-and-partners-say-eu-regulators-approved-marketing-of-once-a-week-diabetes-drug-

bydureon/2011/06/21/AGMbQAeH_story.html

Lilly and partners say EU regulators approved marketing of once-a-week diabetes drug Bydureon

Associated Press – New York, USA Jun. 21, 2011)

14

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS CHRONICLE SPOTLIGHT JULY 2011 S ANOFI

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
CHRONICLE SPOTLIGHT JULY 2011
CHRONICLE SPOTLIGHT
JULY 2011

SANOFI ENTERS INTO RESEARCH COLLABORATION WITH AUDION THERAPEUTICS

Over 500 Million Patients Suffer from Hearing Loss Worldwide with No Currently Available Disease-Modifying Treatments

Sanofi announced on Jun. 17, 2011 that it has entered into a two-year research collaboration with the biopharmaceutical company Audion Therapeutics (Audion) to develop potential treatments for hearing loss through the optimization of small molecules by using a regenerative medicine approach.

This collaborative research will utilize technology developed at the Massachusetts Eye and Ear Infirmary in the Eaton-Peabody Laboratory, one of the world's largest basic research facilities dedicated to the study of hearing and deafness, by investigator and Audion co-founder Dr. Albert Edge, who has strong expertise in stem cells and inner ear biology. Audion licensed Dr. Edge's technology from Mass Eye and Ear. Under the terms of the agreement, Sanofi has an option to license technology rights from Audion related to research conducted under the collaboration.

"We are very excited about this collaboration with Sanofi that validates our thinking around developing small molecule regenerative drugs for the treatment of hearing loss," said RolfJan Rutten and Helmuth van Es, founders of Audion Therapeutics. "Sanofi's interest in the hearing loss field plus its vast experience and infrastructure in small-molecule drug discovery make them the perfect partner to move this program forward as diligently as pos- sible."

"Our new relationship with Audion demonstrates our commitment to work with partners on conditions with unmet and growing medical needs, such as hearing loss," said Elias Zerhouni, M.D., President, Global Research & Development, Sanofi. "This collaboration is a multi-disciplinary approach with our internal Aging Therapeutic Strategic Unit and our Early-to-Candidate Unit working together to advance novel therapies in the field of otolaryngol- ogy using the most advanced technologies available to study cochlear biology."

(Source: http://www.pharmaceuticalonline.com/article.mvc/Sanofi-Enters-Into-Research-Collaboration-0001 Sanofi Enters Into Research Collaboration With Biopharmaceutical Company Audion Therapeutics To Develop Potential Treatments For Hearing LossPRNewswire – Paris Jun. 17, 2011)

NOVARTIS BEGINS CONSTRUCTION OF PHARMA FACILITY IN ST. PETERSBURG, RUSSIA

Novartis held a groundbreaking ceremony to announce the start of construction of a pharmaceutical manufacturing plant in St. Petersburg, Russia.

The construction of this facility represents the most significant Novartis investment in Russia to date. This facility will further expand the company's capabilities to produce and deliver both innovative pharmaceuticals and high-quality generics to Russian patients.

The new greenfield facility will be built in the Novoorlovskaya Special Economic Zone (SEZ), located to the north of the St. Petersburg city center. Once completed and approved for commercial production, which is expected in 2014, the state of-the-art facility will use cutting-edge technologies to produce approximately 1.5 billion units per year. It will also be an attractive workplace for local talent, employing more than 350 highly qualified professionals who will have access to world-class training and development programs at Novartis.

"The establishment of the new Novartis manufacturing facility demonstrates our commitment to invest in the Russian healthcare infrastructure and to contribute to the long-term goals of improving healthcare in Russia, set by the government", said Joseph Jimenez, CEO, Novartis AG. "The plant in St. Petersburg is the latest step in our strategy to bring both innovative pharmaceuticals and low cost, high quality generics closer to patients and customers in Russia."

The groundbreaking ceremony was attended by Minister of Economic Development of the Russian Federation, E. Nabiullina, Governor of St. Petersburg V. Matvienko, Novartis AG CEO Joseph Jimenez and other Novartis collaborators and key representatives from the Russian government and the Swiss embassy.

“Novartis decision to launch drug production in Saint-Petersburg is an outstanding example of a successful collaboration between Russia and foreign investors in the high-technology and innovation sphere, creating new job opportunities for local talent", said Valentina Matvienko, Governor of St. Petersburg. "We're looking forward to help Novartis in solving one of the key challenges on the government agenda - modernization of healthcare".

This facility is part of a USD 500 million five-year investment into Russian healthcare infrastructure announced by Novartis in December 2010. This comprehensive partnership addresses three core areas, which are local manufacturing, R&D collaborations and public health development in Russia.

Novartis and its predecessors have been active in Russia since the 1860s, and today the company is one of the key players in the Russian pharmaceuticals market. Novartis currently employs over 2,000 professionals in Russia across all business divisions, spanning Pharmaceuticals, Alcon, Sandoz, Consumer Health and Vaccines & Diagnostics.

(Source: http://www.pharmanews.eu/novartis/831-novartis-begins-construction-of-new-state-of-the-art-pharmaceutical-manufacturing-plant-in-st- petersburg-russia Novartis begins construction of new state-of-the-art pharmaceutical manufacturing plant in St. Petersburg, RussiaJun. 17, 2011)

15

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS NEWS FROM THE GULF JULY 2011

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
NEWS FROM THE GULF JULY 2011
NEWS FROM THE GULF
JULY 2011

PRICES OF 565 VITAL MEDICINES REDUCED

Patients suffering from a range of serious illnesses, including diabetes and anxiety disorders, will benefit from a 20 per cent reduction in costs.

Patients suffering from a range of serious illnesses, including diabetes and anxiety disorders, will benefit from a 20 per cent reduction in costs on an average for their medication from September 1.

This follows a Ministry of Health directive to make 565 pharmaceutical drugs cheaper and more accessible to the public.

“Our adoption of the decision to approve the reduction of the prices of the pharmaceutical drugs is a practical step towards providing comprehensive health care to all members of our society. This is part of the ministry’s vision and mission to put health, disease prevention and treatment as our national priorities,” UAE Health Minister Dr Hanif Hassan said at a Press conference on Jun. 27, 2011.

He said the price reduction was a result of a “fruitful cooperation between the Ministry of Health and pharmaceutical companies to provide patients with care and support”.

Sixty-seven drugs by pharmaceutical majors like Pfizer and Merck Sharp & Dohme are part of the first batch of roughly 20 per cent of a price cuts across the board, effective from July 1.

The price cut on the remaining 498 drugs will be effective from September.

Al Baraha Pharmacy’s Assistant Pharmacist, Mohanan T, commented on the potential impact the reduced prices may have on pharmacies across the UAE. “This initiative is a breakthrough for patients, even though it may mean less of a profit for pharmacies,” he said.

After working in the field for the past 12 years, Mohanan noted the relatively costly nature of medicines in the UAE. “Compared to other countries, medicines in the UAE are still on the higher side, but that is because almost all drugs are imported from all over the world. With the Ministry of Health tying up with international drug companies, prices can steadily be decreased with time, which is good for patients who don’t have insurance. An average type-2 diabetes patient can spend more than Dh500 a month on medication alone, so these kinds of price reductions can really make a difference,” he said.

According to Mohanan, the most popular prescription drugs include Lipitor by Pfizer aimed at patients with heart disease and high cholesterol levels; Xanax by Pfizer, used to treat moderate to severe anxiety disorders and panic attacks; and Januvia by Merck Sharp & Dohme, used in conjunction with exercise and dietary restrictions to lower blood sugar levels in adults with type-2 diabetes. All three of the top-sellers will sell cheaper from July.

From September, 103 drugs under GlaxoSmithKline, will be available at reduced prices for the general public.

Other firms supporting price reductions include Alcon Pharmaceuticals Ltd, AstraZeneca, Bayer Schering, Boehringer Ingelheim, Bristol-Myers Squibb, Chauvin Pharmaceuticals Ltd., Eli Lilly, Ferring Pharmaceuticals, H. Lundbeck A/S, Hoffmann-La Roche Ltd., Janssen-Cilag, Les Laboratories Servier, Merck Serono, Novartis Pharma AG, Sanofi Aventis, and Valeant Pharmaceuticals.

Once the directive by the Ministry of Health is announced to all pharmacies and hospitals, price stickers and inventory lists will need to be revised.

“We will need to wait for official instructions on how to treat old stock ordered before the directive. Some pharmacies may choose to absorb 20 per cent of the price until new shipments come in, but it depends on a lot of factors and we cannot be sure,” Mohanan added.

(

S

o

u

r

c

e

:

http://www.khaleejtimes.com/DisplayArticleNew.asp?

section=theuae&xfile=data/theuae/2011/june/theuae_june782.xml | Prices of 565 vital medicines reduced” by Praseeda Nair | Khaleej Times – Jun. 28, 2011)

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS NEWS FROM THE GULF JULY 2011

Pharmaceutical Solutions Industry Tel: +966 2 6361383 Fax: 966 2 6379460 P.O. Box 17476 Jeddah 21484 Kingdom of Saudi Arabia. For more info, visit www.psiltd.com

16

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS INSIGHTS JULY 2011 W HY ARE

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS INSIGHTS JULY 2011
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
INSIGHTS
JULY 2011

WHY ARE DRUG PRICES SET SO UNSCIENTIFICALLY?

For an industry rooted in science, why are drug prices set so unscientifically?

The pharmaceutical market does not follow the basic laws of economics. If it did, there would be, at least in each country, one set, limited price range for each drug, dictated by supply, demand and other market fundamentals.

Instead, we seem to have chaos. Prices that U.S. consumers pay for name-brand and generic drugs vary widely depending on one’s insurance carrier.

I tested this recently by trying to use two different insurance cards to order an asthma inhaler: in one case, the cost was $250, in the other, $46. (It would have cost even more than $250 without insurance—a sobering thought.)

U.S. prices remain far above those in other countries. Can the U.S. consumer’s willingness to pay more for pharmaceuticals, indefinitely, be assumed?

But variability is also seen outside the U.S. A recent European Union study found that prices for 150 name brand medications varied by 24% across member states, and that generic drug prices could vary by a factor of 16!

In May, a group of pharma CEOs spoke candidly about drug pricing at the Reuters Health Summit. After reading a report on it, blogger Jim Edwards’ take on the meeting —“Four Pharma CEO’s Admit They Jack Up Prices For the Hell of It”—didn’t seem far from the truth.

AstraZeneca CEO David Brennan noted the lack of transparency on pricing in the U.S., Reuters reported. Shire CEO Angus Russell was quoted as saying, “Prices were just shoved up every year to make more money and meet earnings.”

“The industry has been in volume decline for three years—it’s been propped up on price,” said Tim van Biesen, head of Bain & Co’s healthcare practice, as quoted by Reuters. “You have to ask how long that can continue.”

There is a call for more transparency about all things, but particularly drug pricing. Last month, UNICEF began to publish the prices that drug manufacturers quote for vaccines.

In addition, in the U.S., a group of Democratic Congressmen wrote to drug manufacturers asking them to clarify the means by which they are establishing prices for new drugs. One of the two drugs targeted is Avanir Pharmaceuticals’ neurological treatment, Nuedexta.

Nuedexta is reportedly a combination of quinidine and dextromethorphan, both inexpensive ingredients, and the lawmakers asked why a product made with $20 worth of ingredients was being sold for $600. They demanded cost figures for clinical trials and post-market studies,

marketing budgets, and details on how the price was established.

Newspapers and blogs also discussed the high prices for some newly approved drugs, including Optimer’s Dificid and Vertex’s Incivid, and the fact that price isn’t being openly shared, up front, with the groups who need that information most: physicians and patients.

As consumers become better educated about drug effects, how willing will they be to pay much more for a drug that may, in some cases, provide only marginally better performance?

In Europe, the move is toward “Value Based Pricing.” This approach, critics argue, is keeping the latest innovations from patients. Others say it is keeping prices, and manufacturer hype, down to manageable levels.

Last year, in the U.K., the National Institute for Health and Clinical Excellence (NICE) failed to recommend three new cancer drugs because the treatments were too expensive relative to the benefit they offered.

NICE is said to be working on a value-based approach, set to take shape by 2014. Germany has also drafted a “value-based” set of requirements for drug manufacturers. Can the U.S. be far behind?

Undoubtedly, this developing trend will add to the challenges of getting new drugs approved. However, it will also force drugmakers to ensure that new drugs convey additional value to physicians and patients to justify a higher price.

(Source: http://www.pharmamanufacturing.com/articles/2011/091.html Drug prices? eenie meenie miney mo” by Agnes Shanley, Editor-in-Chief)

17

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS ANALYSIS JULY 2011 M EN’S WAISTLINES

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS ANALYSIS JULY 2011
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
ANALYSIS
JULY 2011

MEN’S WAISTLINES COULD BE KEY TO HEALTH

Men can gain significant health benefits

from watching their waist size and, if necessary, losing some flab around the middle, the American Dietetic Association says.

“Just as it’s important to know your blood pressure, cholesterol, blood sugar and weight numbers, men need to know their waist circumference. So, get out the tape

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS ANALYSIS JULY 2011 M EN’S WAISTLINES

measure,” registered dietitian and ADA spokesman Jim White said in an ADA news release.

For an average male, a waistline of 40 inches puts him into the “disease-risk zone,” the experts warned.

Excess abdominal fat, as opposed to fat elsewhere on the body, increases men’s risk for health problems such as diabetes, heart disease and some types of cancer. This fat around internal organs is known as visceral fat.

To correctly measure your waist size, wrap the tape measure over bare skin on your natural waistline, a little above the belly button at the narrowest part of your torso. Don’t hold the tape measure too loose or too tight, White said.

“Eating better, decreasing stress levels, engaging in physical activity and getting at least seven to nine hours of sleep every day can help keep a man’s midsection under control,” registered dietitian and ADA spokesman Manuel Villacorta said in the news release.

Villacorta

suggested

reducing

portion sizes, cutting back on alcohol and

exercising regularly.

 

(Source: http://news.health.com/2011/06/20/mens-waistlines-could-be-key-to- health/#more-46431 Men’s Waistlines Could Be Key to HealthHealthDay News – Jun. 20, 2011 Primary source: American Dietetic Association, news release – Jun. 15, 2011)

DID YOU KNOW?

Abou t Hearing Loss: Hearing loss is the most prevalent inner ear disorder and

the World Health Organization estimates that 500 million people worldwide have a mild to moderate to severe or greater hearing loss. Of people aged 65 to 74, nearly 33 percent have hearing loss and close to 50 percent of people over the age of 75 are affected. Of people over the age of 85, almost everyone is affected to some extent.

Estimates are that the number of people in the world with age-related hearing loss is expected to increase to 900 million by 2050. However, the incidence is rising rapidly among younger people as well, due to frequent exposure to excessive noise. Estimates from the National Institutes of Health and the Centers for Disease Control and Prevention place the total annual costs of hearing loss at approximately $50 billion per year in the U.S. alone. There are currently no prescription products for a disease modifying treatment for hearing loss.

18

QUOTE & UNQUOTE

To me, the most important part of intelligence is being able to recognize and acknowledge what you don’t know and what is possibly unknown by anyone. I think that understanding my own limits and acknowledging the things that I don’t know—as well as being able to discuss and interact with scientists to deter- mine the extent of our current knowledge and understanding on a particular topic—has served me well as both an entrepreneur and life science executive.

Randal J. Kirk

Sr. Managing Director & CEO—Third Security, LLC

www.thirdsecurity.com

(Abstract from the source: Through The Eyes Of A Billion- aire Life Sciences Investor” by Cliff Mintz, Ph.D. Life Sci- ence Leader – www.LifeScienceLeader.com June 2011)

“For our industry to regain public trust, we must con- stantly examine how we interact with our customers, how we communicate with patients and providers, how we fund activities, and how we share information. We also need to do a better job of informing those we serve about how we operate now. We also need others in healthcare to stand with us and embrace a values-based approach to our inter- actions and recognize and respond to how we've changed. By doing these things, we can assure the public that our industry—an industry that has brought so much benefit to so many—is conducting its business with focus on the patient, with transparency, with integrity, and with respect. In this way we will be worthy of trust.”

(Abstract from the source: http://pharmexec.findpharma.com/ pharmexec/Commentary/Restoring-Public-Trust-in-Pharma/

ArticleStandard/Article/detail/716295?

contextCategoryId=48158

Restoring

Public

Trust

in

Pharma” by Deirdre Connelly, President, North American Pharmaceuticals at GlaxoSmithKline Pharmaceutical Executive – Apr. 1, 2011)

Strategic alliances are an important area for improving pharma R&D and bringing medicines to patients. The pharmaceutical industry needs to go through this transformation. There are huge pressures facing pharma now, such as increasing costs and devel- opment times. Strategic alliances are one of the ways we’re fixing R&D, so we can speed the delivery of novel medicines to pa- tients.”

Adrienne Takacs, Ph.D.,

Senior Advisor & Alliance Executive—Eli Lilly and Company.

(Source:

op-

http://www.lifescienceleader.com/index.php?

tion=com_jambozine&layout=article&view=page&aid=4276&It

emid=56 Strategic Alliances: The Cure For What Ails Pharma?” by Sara Gambrill Life Science Leader – May

2011)

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS PRODUCT LAUNCH JULY 2011 B AUSCH

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
PRODUCT LAUNCH JULY 2011
PRODUCT LAUNCH
JULY 2011

BAUSCH & LOMB TO LAUNCH OPHTHALMIC DROPS IN INDIA

Bausch + Lomb, through a strategic agreement with Micro Labs, is set to launch ophthalmic pharmaceutical business in India.

The agreement will provide the Rochester-based global eye health company with manufacturing capabilities in India to accelerate the launch of new prescription and over-the-counter ophthalmic drops including Moxisurge, Aquasurge, Aquasurge Max, Bromvue, Ketovue and Moxisurge-KT.

Bausch + Lomb will also set up sales and marketing teams, and deliver practitioner and patient education programs in relation to eye care.

As part of the agreement, Bausch + Lomb will source ophthalmic solution products from Micro Labs and, market and sell them in Asia Pacific.

The companies will partner over manufacturing technology for the production of eye drops. They will also conduct ophthalmic pharmaceutical products research and development for emerging markets.

(Source: http://www.pharmaceutical-business-review.com/news/bausch-lomb-partners-with-micro-labs-to-establish-pharma-business-in-india-010711 |“Bausch + Lomb partners with Micro Labs to establish pharma business in India” by PBR Staff Writer |Pharmaceutical Business Review – Jul. 1,

2011)

MEDPRO SAFETY INTRODUCES PRE-FILLED SAFETY SYRINGE

MedPro Safety Products, Inc., a leading developer of transformational technologies that enable safer medication delivery and blood collection, on Jun. 28, 2011 announced the introduction of its pre-filled safety syringe (PFSS).

The device contains a precise dose of pharmaceutical stored within a syringe system equipped with MedPro's unique, fully passive safety mechanism that reduces and potentially eliminates the risk of needlestick injury.

Pre-filled syringes represent an approximately 2.6 billion unit annual market growing at approximately 14% (Pre-filled Syringes, Greystone Associates, February 2008). There is no fully passive pre-filled safety syringe currently commercially available in the U.S. and the MedPro product represents the first truly passive market entry. Current estimates indicate that only 15% of the pre-filled market segment has converted to any type of safety solution.

The PFSS is comprised of two unique parts:

  • (a) A standard glass or plastic cartridge that will act as both a pre-filled medicament reservoir and syringe plunger, and

  • (b) A plastic safety syringe that incorporates a fully passive (or automatic) safety deployment system.

The PFSS device offers significant benefits to healthcare safety, both for the patient and the healthcare professional. The automatic activation of a safety shield as a needle is removed protects the operator from the contaminated needle and prevents a needlestick injury. The shield also reduces the chance of blood or drug splatter.

The prefilled cartridge offers patient safety through exact dosage control and the theoretical reduction of medicine delivery errors. It also saves time in drug preparation and delivery.

The PFSS is designed to be compatible with existing pharmaceutical filling technology for ease of adoption and operational efficiencies, and the glass cartridge is consistent with current industry standards.

"The pre-filled safety syringe is another example of the Company's strategy to expand our unique patented passive safety technology across platforms," said Craig Turner, CEO of MedPro Safety Products.

"The PFSS can deliver a wide range of biotech and pharmaceutical products. We are currently in various stages of discussions with several potential partners to explore the commercialization of the PFSS in several markets…”

(Source: http://www.marketwatch.com/story/medpro-safety-products-introduces-pre-filled-safety-syringe-2011-06-28?reflink=MW_news_stmp MedPro Safety Products Introduces Pre-filled Safety SyringeLexington, Kentucky – BusinessWire Jun. 28, 2011 Primary source: MedPro Safety Products, Inc. - http://www.medprosafety.com)

19

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS FEATURE JULY 2011 A CQUISITIONS, NOT

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS FEATURE JULY 2011
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
FEATURE
JULY 2011

ACQUISITIONS, NOT RESEARCH, FUELS NEW DRUGS

Outside business deals rather than internal research projects are stocking the new drug cabinets of major pharmaceutical companies, analysts for Fitch Ratings said on Jun. 27, 2011 in a global health care business report.

Thanks to acquisition and licensing deals, the multinational drug makers, taken as a whole, are on pace to meet last year’s level of 21 new drug approvals by the end of the year in the United States and Europe, the Fitch report said.

But at the same time, 15 possible new drugs have hit major hurdles since the beginning of the year, mostly because of unfavorable clinical trials, the analysts said.

The largest drug companies started at least 22 new projects in their late-stage pipelines since the beginning of the year, Fitch said, but mostly from business deals rather than internal R&D.

The companies’ setbacks in their own labs are well known in the industry, notably at Pfizer, which has announced plans to slash research by as much as $2.9 billion the next two years.

Pfizer, Eli Lilly and Johnson & Johnson have each added three or more new experimental drugs to their late-stage development plans since the beginning of the year, Fitch said.

Two of Lilly’s were diabetes drugs licensed from Boehringer Ingelheim in January. Pfizer acquired three new pain medicine candidates – called Remoxy, Oxecta, and ALO-02 — when it bought King Pharmaceuticals for $3.6 billion in October 2010. J&J acquired a yellow fever vaccine in late development with the $2.4 billion takeover of the Dutch biotechnology company Crucell and licensed another experimental drug from Sweden’s Medivir.

In another analyst report with a broad view of the industry recently, Dr. Timothy Anderson of Bernstein Research looked at the prospects for nine major pharmaceutical companies to 2020.

His June 16 investor note found some companies with good long-term prospects from existing products, while others fall off the “patent cliff” as generic competition is expected to pound their sales.

The three companies with the best sales prospects to 2020 are GlaxoSmithKline, Novartis and Bristol-Myers Squibb, Bernstein reported.

Those with the “most troubling revenue outlook” are, by far, Eli Lilly and AstraZeneca. This chart from Bernstein shows “base” pharmaceutical revenues to 2020, normalized to 2010:

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS FEATURE JULY 2011 A CQUISITIONS, NOT

Source: Bernstein Research, based on company reports and Bernstein estimates and analysis

(Source: http://prescriptions.blogs.nytimes.com/2011/06/27/acquisitions-not-research-fuels-new-drugs/?scp=8&sq=drug&st=cse Acquisitions, Not Research, Fuels New Drugs” by Duff Wilson Prescriptions –The Business of Health Care Jun. 27, 2011)

20

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS DRUGS ON THE WAY JULY 2011

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
DRUGS ON THE WAY JULY 2011
DRUGS ON THE WAY
JULY 2011

ELI LILLY PLANS 10 DRUGS IN FINAL-STAGE TRIALS BY YEAR END

Eli Lilly & Co., the drugmaker slated to lose U.S. patent protection on its biggest-selling medicine Zyprexa in October, said it will have at least 10 new therapies in final-stage studies by year’s end.

Lilly has 33 drugs in the second and third stages of clinical trials, including medicines for cancer, diabetes and Alzheimer’s disease, up from seven in 2005, the Indianapolis- based company said on Jun. 30, 2011 in a statement.

The drugmaker confirmed its forecast of at least $20 billion in annual revenue and $3 billion in full-year net income from 2011 to 2014. Lilly’s 2010 net income was $5.07 billion with sales of $23.1 billion.

Patent expirations on Zyprexa and other drugs are estimated to reduce annual sales by about $7 billion from 2010 to 2014, Lilly said in the statement released before its investor meeting in New York. New products will help growth return after 2014, the company said.

Zyprexa had $5.03 billion in sales last year.

“With our pipeline maturing, we will be in a position where we will resume a good growth trajectory as we come out” of the patent-expiration period, Chief Executive Officer John C. Lechleiter said in an interview on Jun. 30, 2011.

Growth in the emerging markets, Japan and in Lilly’s Elanco animal-health unit may generate more than $4 billion of additional revenue by 2015, the company said. Earnings per share are expected to decline from 2011 to 2012, rise in 2013 and decline again in 2014, the company said.

NEGATIVE VIEW

“Expectations are pretty low,” said Les Funtleyder, a portfolio manager with Miller Tabak & Co., in a telephone interview on Jun. 29, 2011. “The street is about as negative as you are going to get for a pharma company.”

Lilly rose 19 cents to $37.46 at 9:43 a.m. in New York Stock Exchange composite trading. The shares had gained 6.4 percent in trading this year before Jun. 30, 2011.

Growth-oriented investors “have a hard time reconciling” Lilly’s strategy of shrinking first and growing later, he said. “I am looking for an articulation of their strategy.”

Lilly faces generic competition in 2013 for the antidepressant Cymbalta, the company’s second-biggest seller at $3.46 billion, and in 2014 to its $1 billion osteoporosis drug, Evista.

$34 BILLION

U.S. drugmakers face patent losses this year to products with $34 billion in yearly sales. Sales at risk from generic rivals will increase to $147 billion by 2015, according to Bloomberg data.

In the statement, Lilly said it had fully enrolled patients in two final-stage trials of solanezumab, the company’s experimental Alzheimer’s drug. The company expects to complete the studies in the first half of 2012.

Three phases of clinical trials are generally required for U.S. regulatory approval of new drugs.

Lechleiter reiterated the company’s opposition to a large merger and said Lilly is seeking smaller deals that would “complement or supplement assets we already have.”

The CEO cited Lilly’s January partnership with German drugmaker Boehringer Ingelheim GmbH to develop and sell diabetes treatments as the type of deals the company favors.

“We see these large-scale combinations as solving short- term problems,” Lechleiter said. “We think they are a distraction.”

(Source: http://www.bloomberg.com/news/2011-06-30/eli-lilly-plans-10-drugs-in-final-stage-trials-by-end-of-2011.html?cmpid=yhoo |“Eli Lilly Plans 10 Drugs in Final-Stage Trials by Year End” by Robert Langreth |Story Editor: Reg Gale |Bloomberg – New York |Jun. 30, 2011)

21

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS NEWS UPDATE JULY 2011 P HARMA

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
NEWS UPDATE JULY 2011
NEWS UPDATE
JULY 2011

PHARMA TRADERS MUST FOLLOW INT’L STANDARDS: TDAP CHIEF

Pakistani Pharma traders should follow international standards in terms of products’ acceptability in global market to boost pharmaceutical industry.

Tariq Iqbal Puri, Chief Executive Trade Development Authority of Pakistan (TDAP) addressing 1st Pharma Summit on Jun. 15, 2011 said the role of PPMA’s leadership in awakening the need to revamp the pharma industry is laudable.

He informed the audience about the role being played by TDAP for the growth of export from pharma industry by extending different subsidies. He said realizing the importance of international accreditation, TDAP approved subsidy for UK MHRA Gap-Analysis at the behest of PPMA.

TDAP created a Pharma Cell in TDAP for the promotion of export from the pharma industry.

Prompted by this realization, Pharma Cell of TDAP has

organized two workshops on ‘WHO Pre-Qualification Program and Export Opportunities’ in Karachi and Lahore. “We have to remain globally competitive by revamping the industry to meet international standards,” he said.

Sindh Health Minister, Dr Saghir Ahmad assured government support for establishment of FDA-approved drug manufacturing plants in the province. He said government was committed to assisting industries creating employment opportunities and earning foreign exchange for the country. Talking about devolution of health sector to the provinces, with specific reference to registration of drugs, their licensing, pricing and quality control, he said these issues have been discussed with the federal government and a clear picture would appear in the next few months. Saghir Ahmed offered to facilitate PPMA in issues that were believed to be hindering progression and strengthening of local pharmaceutical industry.

About Appellate Board handling complaints against drug industry and regarding matters related to pricing of drugs, he said there has to be a balanced representation of all the provinces in boards to be established in each province.

Mirza Ikhtiar Baig, advisor to Prime Minister said the conference would be helpful for the growth and development of pharma industry. He asked the PPMA to provide him with the list of pharmaceutical products intended for zero-rating for export to China. This list, he said was being currently prepared by the government. He mentioned there were good opportunities for pharmaceutical exports to Yemen and Morocco. He asked the PPMA to procure government support and capture this big market share.

Dr Shahzeb Akram, Vice Chairman of PPMA suggested pharma family to join hands in procurement of FDA and WHO approved plants. He mentioned

the country was about to have a WHO approved Drug Testing Lab in Lahore at its Sunder Industrial Estate. He said this lab would become functional in

2012.

Haroon Qasim Chairman PPMA appreciated the role played by TDAP for the support of pharma industry of Pakistan.

(Source: http://www.dailytimes.com.pk/default.asp?page=2011\06\16\story_16-6-2011_pg5_6 Pharma traders must follow int’l standards: TDAP chiefStaff Report – Jun. 16, 2011 Karachi, PAKISTAN)

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS NEWS UPDATE JULY 2011 P HARMA

Pharmaceutical Solutions Industry

Tel: +966 2 6361383 - Fax: 966 2 6379460

Kingdom of Saudi Arabia.

For more info, visit www.psiltd.com

22

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS NEWS UPDATE JULY 2011 S TUDY:

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
NEWS UPDATE JULY 2011
NEWS UPDATE
JULY 2011

STUDY: CANCER DRUGS APPROVED IN U.S. BEFORE EUROPE

New cancer medicines typically reach the U.S. market several months before they go on sale in Europe, according to a study published amid a debate about access to new drugs.

The findings released on Jun. 16, 2011 counter a common belief among doctors, academics and investors that new oncology drugs often win approval in Europe first, said researchers from the nonprofit advocacy group Friends of Cancer Research. Each of the 23 cancer drugs cleared by the United States and Europe over a seven-year period debuted in the U.S. market, the study found. Drugmakers usually submitted their medicines to the U.S. Food and Drug Administration first, and the FDA review period was generally shorter at around six months. In Europe, the median review time was nearly a year, at 350 days.

"To patients battling cancer, with no treatment options, access to new medicines five-and-a-half months sooner is a very important and potentially life- saving difference," said Ellen Sigal, who chairs and founded the cancer group.

The findings were published online in the journal Health Affairs.

The researchers analyzed regulatory review times for 35 new cancer drugs approved in either the United States, Europe or both between 2003 through 2010. Twenty-three medicines won clearance in both regions.

Europe cleared three medicines the FDA did not approve. The FDA gave a green light to nine drugs that did not reach the European market. The researchers did not analyze the reasons for the conflicting decisions.

FDA Commissioner Margaret Hamburg, in a statement, said the findings "reflect FDA's commitment to foster access to effective therapies in a responsive and timely manner."

The agency has drawn fire from some manufacturers as being too cautious in analyzing cancer and other drugs as well as medical devices. Some critics say the FDA is harming innovation and U.S. competitiveness with unnecessarily tough requirements. The medical device industry has argued vocally that the FDA is driving companies to Europe where developers see a quicker path to the market. Consumer advocates and others, meanwhile, argue that the FDA may sacrifice safety for speed and should demand more data from companies.

Dr. Janet Woodcock, the FDA's top drug official, said the agency was "not in a race with other regulatory agencies." But she said the cancer drug findings could help dispel an "urban myth" that the United States was routinely falling behind Europe on approval decisions.

"FDA review of cancer drugs is efficient. It is rapid. The real problems are in the scientific development programs and scientific uncertainty" about how to attack cancer,” she said.

For investors, the findings show "there are certain things that are working quite well" in the United States, said Jonathan Leff, managing director of healthcare at private equity firm Warburg Pincus.

He pointed to the FDA's accelerated approval process, a program designed to bring new drugs for serious diseases to the market quickly based on early data.

Investors worry, however, that the FDA will require companies to produce more data to show safety and effectiveness for cancer drugs as the agency has in other areas.

"The fear this is bleeding over into oncology is palpable," Leff said.

The study's authors said their results showed the need for Congress to adequately fund the FDA. They planned a briefing for congressional staff on the findings on Jun. 16, 2011. Republican lawmakers in the U.S. House of Representatives have proposed steep cuts to the FDA's budget.

"Strong public and congressional support is desperately needed for the FDA to continue this trend and to improve its scientific foundation," Sigal said.

The study was published online by Health Affairs at http://content.healthaffairs.org/cgi/content/abstract/hlthaff.2011.0231

(Source: http://www.chicagotribune.com/business/yourmoney/sns-rt-us-cancer-drugs-apptre75f1cd-20110616,0,7505467.story Study: Cancer drugs approved in U.S. before Europe” by Lisa Richwine Edited by Tim Dobbyn Reuters – Washington Jun. 16, 2011)

23

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS NEWS UPDATE JULY 2011 C ADILA

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
NEWS UPDATE JULY 2011
NEWS UPDATE
JULY 2011

CADILA TO BUY ASSETS OF U.S. - BASED NESHER

Cadila Healthcare Ltd., a part of the Zydus Group, on Jun. 17, 2011 said its U.S. unit has agreed to acquire the assets of U.S.-based pharmaceutical company Nesher Pharmaceuticals Inc. for an undisclosed amount.

Cadila Healthcare said the acquisition of Nesher--the generic unit of KV Pharmaceutical--will allow its U.S. unit to make and sell generic controlled substances in the country, which otherwise cannot be imported. The acquisition includes Nesher's existing and future portfolio of generic drugs, certain manufacturing facilities and a research and development laboratory, Cadila Healthcare said in a statement. The company said the deal entails the assumption of certain liabilities of Nesher, but didn't elaborate.

Cadila Chairman Pankaj Patel said the development gives the company access to a "difficult-to-develop product pipeline, expertise and infrastructure that will add value to our operations in the U.S."

Nesher's pipeline of generic drugs include eight existing filings with the U.S. drug regulator and five products under development.

The deal also includes supply and technical services agreements whereby certain products of KV Pharmaceutical will be manufactured by Zynesher Pharmaceuticals USA LLC, a unit of Zydus Pharmaceuticals USA Inc. Annual sales of controlled substances medications in the U.S. are estimated at $7 billion, the statement added.

(Source: http://www.marketwatch.com/story/cadila-to-buy-assets-of-us-based-nesher-2011-06-17 Cadila to buy assets of U.S.-based Nesher” by Rumman Ahmed MarketWatch – Bangalore, INDIA Jun. 17, 2011)

ASTRAZENECA GRABS RUSSIAN OPPORTUNITY

Question: When does a threat become an opportunity?

Answer: When it is in your interests.

That is how AstraZeneca interpreted Russia’s past warnings that global pharmaceutical companies would be punished if they didn’t build operations inside Russia and transfer technology there.

“I was here a couple of years ago and had that conversation with a couple of ministers and ultimately we came back with a plan on how to do it. We recognized that would be an opportunity for us,” AstraZeneca’s CEO David Brennan said in an exclusive interview about the drug maker’s strategy for Russia, which was unveiled on Jun. 16, 2011.

AstraZeneca announced that it plans to build a research and development hub in St. Petersburg in the coming year. The move by the U.K.’s second- largest drug maker strengthens its investments in Russia—now targeted at $1.2 billion over the next five years–and supports the Russian government’s strategy to modernize and develop the country’s pharmaceutical sector.

The company has already begun building a new £$150 billion manufacturing facility in the country’s central Kaluga region to supply Russia with locally manufactured medicines. That looks like a win-win proposition for a company that sees Russia, Brazil and China as key to growing its revenue and business base.

“It will position us well,” said Mr. Brennan. “We’re not the leading foreign drug company in Russia but we will certainly be very active on the ground, with a couple of hundred new employees with our new manufacturing facilities, some research activities, as well as a strong marketing and sales organization. From my perspective, that’s a pretty complete picture for a country like this.”

Given that the Russian government plans to invest heavily in the pharmaceuticals industry and sees the sector as a key one for restoring the country’s industrial strength, AZ’s move looks pretty smart.

But it isn’t alone in spotting the opportunity Russia offers. Several pharmaceutical companies have already pledged to build manufacturing plants in Russia over the past 18 months including Sanofi, Nycomed and Novo Nordisk.

“This is essentially a land grab by drug makers”, said Peter Cartwright, an associate with Fiske. “Everyone has already piled into China and Brazil. “Russia, by comparison, is more or less untouched by big drug makers despite the country’s many attractions: a relatively receptive government, an ageing population and a huge need for quality medicines. There is also much to be gained from establishing greenfield sites with your own locally-based management. That is much easier than having to work with a local partner who might not do what you want all the time.”

(Source: http://blogs.wsj.com/source/2011/06/16/astrazeneca-grabs-russian-opportunity/?mod=yahoo_hs AstraZeneca Grabs Russian Opportunity” by Sten Stovall Jun. 16, 2011)

24

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS NEWS UPDATE JULY 2011 A PP

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
NEWS UPDATE JULY 2011
NEWS UPDATE
JULY 2011

APP PHARMA TO PLUG $38M INTO EXPANDING NY MANUFACTURING SITE

APP Pharmaceuticals plans on investing $38 million to expand a manufacturing facility in Grand Island, NY, to increase its production of injectable genetic drugs. It will thus add 90 jobs to its existing workforce of 580 at the plant.

APP, a wholly owned subsidiary of Fresenius Kabi Pharmaceuticals Holding, will expand its production site by 13,000 square feet and add six new production lines for injectable products. The expansion is anticipated to begin this month and take two years to complete.

At Grand Island, APP manufactures a variety of injectable pharmaceutical products for the North America market. The products encompass four therapeutic areas: anti-infectives, critical care, analgesia/anesthesia, and oncology.

“Through the expansion, the site will significantly contribute to the continuous local supply of high-quality injectable generics for the U.S. and Canada,” states Michael Schönhofen, president, science, production, and technology for Fresenius Kabi.

Based on its promise of the new and retained jobs, APP has won nearly $1.2 million in tax credits over five years through New York state’s Excelsior Jobs Program; 2,000 kW of lower-cost power through the state Power Authority; and local property tax, sales tax, and mortgage tax abatements through the Erie County Economic Development Corp.

APP owns two manufacturing plants in Grand Island—one of 210,000 square feet, the other 148,000 square feet—as well as 120,000 square feet of warehouse and administrative space.

(Source: http://www.genengnews.com/gen-news-highlights/app-pharma-to-plug-38m-into-expanding-ny-manufacturing-site/81245307/ APP Pharma to Plug $38M into Expanding NY Manufacturing SiteGEN News Highlights – Jun. 15, 2011)

VIROPHARMA’S CINRYZE GETS NOD FROM EUROPEAN COMMISSION

Biotechnology company ViroPharma Inc. said on Jun. 15, 2011 it received European approval for Cinryze, an intravenous treatment for a genetic disease that can cause dangerous swelling in the throat and extremities.

The company said the European Commission approved Cinryze for the prevention and treatment of angioedema attacks in adults and adolescents. The commission also authorized properly trained patients to administer Cinryze to themselves.

Hereditary angioedema, or HAE, affects at least 10,000 people in Europe. Patients with it can experience unpredictable and potentially deadly swelling attacks that can affect the larynx, abdomen and face.

“Many patients experience frequent or severe attacks that are not only disabling and potentially fatal, but also lead to constant anxiety about when an attack will occur significantly impacting patients’ ability to conduct normal and productive lives,” Konrad Bork of the Department of Dermatology of Johannes Gutenberg University in Mainz, Germany, said in a prepared statement.

“The approval of Cinryze in Europe provides a very important new option to meet the needs of these severely afflicted HAE patients.” Cinryze is already approved in the United States and generated $57 million in sales during the first quarter.

HAE is a variable disease due to a deficiency of C1 inhibitor, a human plasma protein that prevents swelling. Cinryze helps to control HAE by increasing functional C1 inhibitor activity.

ViroPharma said Cinryze is the first and only FDA-approved C1 inhibitor approved on clinical data supporting its effectiveness in the prevention of attacks of this potentially dangerous genetic disease. The approval of Cinryze follows the positive opinion adopted by the Committee for Medicinal Products for Human Use in March.

Cinryze is now approved throughout all the member states of the European Union as well as in the European Economic Area, namely Norway, Iceland and Liechtenstein.

“The approval of Cinryze throughout Europe is an important milestone for ViroPharma in our evolution as an international biopharmaceutical company that delivers novel solutions that address the unmet medical needs of patients living with few, if any, clinical treatment options,” said Vincent Milano, ViroPharma’s president and chief executive.

(Source:

http://www.pennlive.com/newsflash/index.ssf/story/viropharma-drug-gets-ok-from-europe/d61345adcf0a4c6a83472c6e3e0d1a15

ViroPharma drug gets OK from Europe” by Gretchen Metz Daily Local News Uwchlan – Jun. 15, 2011)

25

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS NEWS UPDATE JULY 2011 M ERCK

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
NEWS UPDATE JULY 2011
NEWS UPDATE
JULY 2011

MERCK TEAMS WITH HANWHA TO DEVELOP BIOSIMILAR ENBREL

Merck & Co. is teaming up with Korean firm Hanwha Chemical to develop a biosimilar form of Pfizer and Amgen’s TNF-blocker, Enbrel (etanercept),

which has a patent expiry date looming in October 2012. The collaboration will focus on Hanwha’s HD203 candidate, which is currently undergoing a Phase III trial in Korea. The study is comparing HD203 with Enbrel as combination therapy with methotrexate in the treatment of rheumatoid arthritis. Clinical trials with HD203 have yet to be initiated in the U.S.

Under terms of the deal Merck will carry out clinical development and manufacturing of HD203, and has rights to commercialize the drug globally, except in Korea and Turkey, where Hanwha has retained marketing rights. Korea-based Hanwha will also receive an up-front payment from Merck, along with technology transfer and regulatory-associated milestones, plus tiered sales royalties.

Enbrel is currently approved in various markets globally for the treatment of rheumatoid arthritis and polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, and plaque psoriasis. Originally developed by Immunex, Enbrel is marketed by Amgen in the U.S. and Canada, and by Pfizer in all other approved markets.

For the three months ended March 31 2011 Amgen reported Enbrel sales of $875 million, up 9% on equivalent 2010 sales. The drug is Amgen’s second biggest sales earner, behind Neulasta/Neupogen. Sales of Enbrel by Pfizer in non-U.S./Canadian markets were also up 9% during Q1 2011, at $870 million. The drug is currently Pfizer’s third highest-ranking in terms of global sales, even excluding the U.S. and Canadian markets.

(Source: http://www.genengnews.com/gen-news-highlights/merck-co-teams-with-hanwha-to-develop-biosimilar-enbrel/81245290/ Merck & Co. Teams with Hanwha to Develop Biosimilar EnbrelGEN News Highlights – Jun. 13, 2011)

US A D D S F OR M A L D E H Y D E T O L I S T OF C A R C I N OG EN S

The government on Jun. 10, 2011 added formaldehyde, a substance found in plastics and other commonly used products, to a list of known carcinogens and warned that the chemical styrene might cause cancer.

In a report prepared for the Secretary of the Department of Health and Human Services (HHS), scientists warned that people with higher exposure to formaldehyde were more at risk for nasopharyngeal cancer, myeloid leukemia and other cancers.

"There is now sufficient evidence from studies in humans to show that individuals with higher measures of exposure to formaldehyde are at increased

risk for certain types of rare cancers ...

,"

the Report on Carcinogens said.

Formaldehyde is a colorless, flammable, strong-smelling chemical widely used to make resins for household items, such as composite wood products, paper product coatings, plastics, synthetic fibers, and textile finishes. It is also commonly used as a preservative in medical laboratories, mortuaries, and some consumer products, including hair-straightening products.

The report, produced by the National Toxicology Program (NTP), also added styrene to the list of substances that were reasonably anticipated to be human carcinogens. Styrene is a synthetic chemical used in the manufacture of products such as rubber, plastic, insulation, fiberglass, pipes, automobile parts, food containers, and carpet backing. The greatest exposure to styrene in the general population is through cigarette smoking, the report said.

The American Chemistry Council (ACC), an industry group, lashed out at the report, saying it was concerned that politics may have hijacked the scientific process. "Today's report by HHS made unfounded classifications of both formaldehyde and styrene and will unnecessarily alarm consumers," Cal Dooley, president and CEO of the ACC, said in a statement.

Jennifer Sass of the National Resources Defense Council, a U.S. environmental group, praised the government for publishing the report in the face of what she described as pressure by chemical companies to prevent its release. "The chemical industry fought the truth, the science, and the public -- but, in the end our government experts came through for us, giving the public accurate information about the health risks from chemicals that are commonly found in our homes, schools, and workplaces," Sass wrote in a blog.

The report also listed aristolochic acids, found in some plants, as a known carcinogen and added the fungicide captafol, some inhalable glass wool

fibers, cobalt-tungsten carbide, riddelliine and

o-Nitrotoluene to the list of substances reasonably anticipated to be carcinogens. It, however, said

listing the substances did not in itself mean they would cause cancer. Amount and duration of exposure, and susceptibility to a substance were among

the many factors that affected whether a person developed cancer, it said. The report is available at ntp.niehs.nih.gov/go/roc12

(Source: http://www.reuters.com/article/2011/06/11/us-usa-health-cancer-idUSTRE75A0KN20110611 U.S. adds formaldehyde to list of carcinogens” by Paul Simao, Americas Desk Reuters – Washington Jun. 11, 2011)

26

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS FFFF DADADADA APPROVALS APPROVALS APPROVALS APPROVALS

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

FFFFDADADADA APPROVALS

APPROVALS

APPROVALS

APPROVALS

JULY 2011

FDA APPROVES RECTIV FOR PAIN ASSOCIATED WITH ANAL FISSURES

ProStrakan Group plc, a subsidiary of Kyowa Hakko Kirin Co. Ltd., and an international specialty pharmaceutical company, today announces that it

has received approval from the U.S. Food and Drug Administration (FDA) for Rectiv™ (nitroglycerin) Ointment 0.4 % for the treatment of moderate to severe pain associated with chronic anal fissures. Rectiv will be the only FDA approved prescription product for patients with this condition.

"The pain associated with anal fissures can be unrelenting and debilitating. Prompt initiation of treatment by primary care practitioners, gynecologists,

gastroenterologists and surgeons alike is critical to a patient's wellbeing," said Scott Berry MD, FACS, colorectal surgeon and the principal investigator on one of Rectiv's clinical trials.

"Now we have an effective and easy-to-use topical ointment which allows grateful patients to resume their daily lives."

Anal fissures are fairly common, with approximately 700,000 people in the U.S. receiving a diagnosis or treatment for an episode each year. An anal fissure is a small tear in the skin that lines the anus, and can occur in a number of ways such as passing large or hard stools, straining during a bowel movement, or following an episode of diarrhea. When an anal fissure occurs, it typically causes severe pain and bleeding with bowel movements. Chronic anal fissure has been shown to impact significantly on patients' quality of life. An episode can take six to eight weeks to heal; and if healing does not occur then surgery may be required.

Peter Allen, Chairman of ProStrakan, said: "The market in the U.S. for a prescription medicine to treat chronic anal fissure pain is significant and, having successfully marketed this product in Europe for some years, we are pleased that it will now be made available to patients in the U.S."

"We will now evaluate the most efficient way of bringing this product to market and making it available as widely as is necessary."

ProStrakan expects Rectiv to be available in the U.S. in the first quarter of 2012. Marketed under the name Rectogesic®, the product is already approved in the EU and marketed by ProStrakan in all major European countries, where sales grew by 15% in 2010 to $14.4 million (9.3 million Pounds Sterling). The product has also been out-licensed outside Europe by ProStrakan to commercial partners in 34 countries worldwide.

(Source: http://www.news-medical.net/news/20110622/FDA-approves-ProStrakans-Rectiv-for-pain-associated-with-anal-fissures.aspx FDA approves ProStrakan's Rectiv for pain associated with anal fissuresJun. 22, 2011)

LUPIN GETS FDA NOD TO MARKET GENERIC LEVAQUIN TABLETS IN US MARKET

Pharma major, Lupin Ltd. said its US subsidiary Lupin Pharmaceuticals, Inc. had obtained final approval from the United States Food and Drugs Administration (US FDA) for its abbreviated new drug application (ANDA) to market a generic version of Ortho McNeil's Levaquin (levofloxacin) tablets.

The company said the commercial shipment of the product had commenced. Lupin's levofloxacin 250mg, 500mg and 750mg tablets are the AB-rated generic equivalent of Levaquin, a synthetic broad spectrum antibacterial agent used to treat or prevent infections that are proved or strongly suspected to be caused by susceptible bacteria. As per IMS Health sales data, Levaquin tablets had annual sales of around $1.6 billion for the twelve months ended March 31 this year.

(Source: http://www.rttnews.com/Content/IndianNews.aspx?Id=1651268&SM=1 Lupin Gets US FDA Final Nod To Market Generic Levaquin Tablets In US Market” by RTT Staff Writer Jun. 22, 2011)

WATSON LABORATORIES GETS FDA NOD FOR NABUMETONE TABLETS

Watson Pharmaceuticals, Inc. on Jun. 17, 2011 announced that its subsidiary, Watson Laboratories, Inc., has received approval from the United States Food and Drug Administration (FDA) for Nabumetone Tablets USP, 500 mg and 750 mg. Watson expects to launch the product shortly.

Nabumetone had total U.S. sales of $58 million for the twelve months ending April 30, 2011, according to IMS Health. Nabumetone is indicated for the relief of signs and symptoms of osteoarthritis and rheumatoid arthritis.

(Source: http://ir.watson.com/phoenix.zhtml?c=65778&p=irol-newsArticle&ID=1575067

Watson's Nabumetone Tablets Receive FDA Approval

PARSIPPANY, N.J., - Jun. 17, 2011 PRNewswire via COMTEX Primary source: Watson Pharmaceuticals – www.watson.com)

27

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS FFFF DADADADA APPROVALS APPROVALS APPROVALS APPROVALS

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

FFFFDADADADA APPROVALS

APPROVALS

APPROVALS

APPROVALS

JULY 2011

FDA APPROVES INFANT DOSE OF DRUG FOR CYSTI C FIBROSIS

The FDA has approved the first infant-specific dosage of pancrelipase (Creon) to treat exocrine pancreatic insufficiency (EPI) common in cystic fibrosis.

The new dosage of Creon Delayed-Release Capsule contains 3,000 units of lipase, which allows for more precise dosing at feeding, a statement from manufacturer Abbott said.

Pancrelipase is indicated to improve food digestion in patients who cannot digest food properly because of EPI and should be taken with each meal and snack. EPI is common among patients with cystic fibrosis but is also associated with pancreatic cancer, gastrointestinal surgery, and chronic pancreatitis.

"We know that the need for consistent, precise dosing of pancreatic enzyme replacement therapy is critical for infants and children living with cystic fibrosis," Eugene Sun, MD, vice president of Abbott, said in the statement.

The original FDA approval for Creon in 2009 was based on the results of three clinical studies of 103 patients with EPI to an endpoint of coefficient of fat absorption. Studies one and two measured drug effects in patients with EPI due to cystic fibrosis, while the third study examined patients with EPI due to chronic pancreatitis and pancreatectomy. In the first two studies, those in the pancrelipase group had average coefficients of fat absorption of 89% and 83%, versus 47% in the placebo group.

In the third study, average change in coefficient of fat absorption was greater in patients with lower run-in period coefficient of fat absorption values than in those with higher run-in period values.

Adverse events related to pancrelipase include fibrosing colonopathy, flatulence, headache, stomach pain, dizziness, hyperglycemia, and hypoglycemia. The drug may cause an allergic reaction, including severe stomach pain, worsening of gout, swollen joints, troubled breathing, skin rash, or swollen lips. The capsules should not be crushed or chewed, as they may cause mouth irritations.

(Source: http://www.medpagetoday.com/PublicHealthPolicy/FDAGeneral/27094FDA Okays Infant Dose of Drug for CF” by Cole Petrochko, Associate Staff Writer MedPage Today Washington - Jun. 16, 2011)

FDA APPROVES NDA FOR TWO HYDROCODONE COUGH AND COLD MEDICATIONS

The U.S. Food and Drug Administration (FDA) has approved Optimer Pharmaceuticals' antibacterial drug DIFICID (fidaxomicin) tablets for the treatment of Clostridium difficile-associated diarrhea (CDAD) in adults 18 years of age and older.

Cypress Pharmaceutical announced recently that the Food and Drug Administration (FDA) approved a new drug application (NDA) for Zutripro (hydrocodone bitartrate, chlorpheniramine maleate and pseudoephedrine HCl) Oral Solution (CIII) and Rezira (hydrocodone bitartrate and pseudoephedrine HCl) Oral Solution (CIII). Both products are indicated for the relief of cough and symptoms associated with the common cold.

Zutripro and Rezira Oral Solutions are the only FDA approved hydrocodone cough and cold combinations containing a nasal decongestant. The approval of Zutripro™ and Rezira™ Oral Solutions marks the first NDA approval by the FDA for a liquid hydrocodone cough medication since 1990.

These products will be marketed by Hawthorn Pharmaceuticals, a subsidiary of Cypress Pharmaceutical, Inc.

"Currently, there are very few prescription products for patients suffering from cough and the symptoms associated with the common cold," said Chris Smith, EVP of Sales for Hawthorn Pharmaceuticals. "With Zutripro™ and Rezira Oral Solutions, healthcare practitioners finally have more options when treating patients suffering from a cough and symptoms associated with the common cold. Additionally, Zutripro and Rezira both contain a decongestant which is very beneficial considering the fact that one of the most common symptoms of the common cold is nasal congestion.”

Zutripro and Rezira Oral Solutions are available through all national drug wholesalers, as well as chain drug stores and other distribution channels and will begin shipping immediately. Zutripro and Rezira Oral Solutions are available by prescription only in the United States. ZUTRIPRO (hydrocodone bitartrate, chlorpheniramine maleate and pseudoephedrine hydrochloride) Oral Solution (CIII) is indicated for the relief of cough and nasal congestion associated with common cold and relief of upper respiratory allergy symptoms including nasal congestion in adults 18 years of age and older.

Visit www.hawthornrx.com for complete prescribing information on both products.

(Source: http://www.pharmaceuticalonline.com/article.mvc/FDA-Approves-NDA-For-Two-Hydrocodone-Cough-0001? sectionCode=Freeform1&templateCode=LifeScienceSponsor&user=20&source=nl:31109 FDA Approves NDA For Two Hydrocodone Cough And Cold MedicationsPrimary source: Cypress Pharmaceutical – Jun. 15, 2011)

28

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS FFFF DADADADA APPROVALS APPROVALS APPROVALS APPROVALS

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

FFFFDADADADA APPROVALS

APPROVALS

APPROVALS

APPROVALS

JULY 2011

BRISTOL-MYERS GETS FDA OK ON NEW TRANSPLANT DRUG

The first new type of drug in more than a decade for keeping transplanted kidneys functioning won approval from federal regulators on Jun. 15, 2011.

The Food and Drug Administration approved Nulojix, developed by Bristol-Myers Squibb Co., for preventing rejection of a transplanted kidney in adult patients, despite concerns about serious possible side effects. It was approved for use along with other medicines that suppress the immune system, including corticosteroids.

Without immune suppressants, a patient's body would reject the new kidney as a foreign object and attack it. If other drugs can't counteract that rejection, the kidney could stop its crucial job of filtering toxins from the blood, and the patient would have to undergo hours-long dialysis three times a week. Even with the best care, about half of patients either die or have their new kidney stop working in roughly 8 to 10 years, said Dr. Brian Daniels, senior vice president for global development and medical affairs at New York-based Bristol-Myers.

"This is the first meaningful alternative in over a decade for patients, and one that provides potential for long-term survival" of transplanted kidneys, Daniels told The Associated Press in an interview.

Besides having a new mechanism of action, Daniels said Nulojix kept kidneys functioning better over three years in the company's two large, final-stage studies, compared to the standard treatment, cyclosporine. He said in a small number of patients getting Nulojix in a separate study and followed for up to eight years, kidney function had yet to decline significantly.

Nulojix, given through 30-minute intravenous infusions once a month for life, works by inhibiting the activation of T cells, which are key to triggering an immune system response to a perceived invader.

Bristol-Myers said it expects to launch the drug in early July. So far, it is not disclosing the expected price. Nulojix, also known by the chemical name belatacept, is an alternative to some older immune suppressants, which cause headaches and nausea and, occasionally, kidney toxicity.

The approval comes 3 1/2 months after a panel of FDA advisers voted 13-5 to approve Nulojix despite concerns about higher rates of severe kidney rejection than older drugs have. The drug carries a boxed warning, the most serious type, that it can increase risk of a type of cancer in which white blood cells grow out of control after an organ transplant, a condition called post-transplant lymphoproliferative disorder. There is a second boxed warning that Nulojix, as well as other immune suppressants, increases risk of other cancers and serious infections. Nulojix can also cause other side effects. Common reactions in studies that included more than 1,200 patients included anemia, constipation, kidney and bladder infections, and swollen legs, ankles or feet. In addition, all transplant patients are at risk of infection, so they should not get live vaccines. Those taking Nulojix also should limit time spent in sunlight because of the risk of skin cancer.

More than 89,000 patients in the United States are waiting for a kidney transplant, according to the Organ Procurement and Transplantation Network. (This version to kidney toxicity in 9 th paragraph. Corrects to 13-5 in 10 th paragraph)

(Source: http://finance.yahoo.com/news/BristolMyers-gets-FDA-OK-on-apf-591147682.html?x=0&.v=6 Bristol-Myers gets FDA OK on new transplant drug” by Linda A. Johnson, AP Business Writer Associated Press – Trenton, N.J. Jun. 15, 2011)

AUROBINDO PHARMA GETS US FDA NOD FOR RAMPIRIL CAPSULES

Aurobindo Pharma has obtained the approval from the US drug regulator to make and market Ramipiril capsules, a company statement said.

The drug used for the treatment of congestive heart failure (CHF) and hypertension (high blood pressure) will be available in 1.25mg, 2.5mg, 5mg and 10mg strengths. Ramipiril is remake of Altace manufactured by American drug maker King Pharmaceuticals.

Ramipiril falls under the Cardiovascular ( CVS) therapeutic segment and its market size is estimated at $95 million for the 12 months ending September 2010, according to IMS data.

Cardiovascular disease is still the world's leading cause of death, even after a couple of decades of declining death rates. Expenditures for cardiovascular drugs account for about one-fifth of total expenditures for all types of drugs.

Aurobindo now has a total of 138 ANDA approvals (108 Final approvals and 30 tentative approvals) from US Food and Drug regulator. Over the last one year, the company filed 1270 formulations dossiers across several therapeutic segments in other key regulated markets including multiple registrations in European Union.

(Source: http://articles.economictimes.indiatimes.com/2011-06-10/news/29643102_1_usfda-nod-final-approvals-tentative-approvals Aurobindo Pharma gets USFDA nod for Rampiril Capsules” by Deepika Amirapu ET Bureau – Hyderabad, INDIA Jun. 10, 2011)

29

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS EMA NEWS JULY 2011 C HMP

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
EMA NEWS JULY 2011
EMA NEWS
JULY 2011

CHMP RECOMMENDS NOVARTIS DRUG VOTUBIA ® FOR APPROVAL IN EU

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS EMA NEWS JULY 2011 C HMP

If approved, Votubia (everolimus) will be first medication in EU for subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC)

CHMP opinion based on Phase II study of 28 patients showing 33% experienced a SEGA tumor reduction of 50% or greater at six months

relative to baseline Brain surgery is only treatment option in EU for growing SEGAs, benign brain tumors that primarily affect children and adolescents

Worldwide regulatory submissions for everolimus to treat this patient population are under way; first approval received in the US in 2010 as Afinitor ®

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for Votubia ® (everolimus) tablets for the treatment of patients aged 3 years and older with subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC), who require therapeutic intervention but are not amenable to surgery. If approved, Votubia will be the first medication available for these patients in the European Union (EU).

Tuberous sclerosis complex, also known as tuberous sclerosis (TS), may cause benign tumors to form in vital organs and can affect many different parts of the body, most commonly the brain. Signs of TSC vary depending on which system and which organs are involved. SEGAs, or benign brain tumors, occur in up to 20% of patients with TSC.

Tuberous sclerosis complex is also associated with a variety of resulting disorders including seizures, swelling in the brain (hydrocephalus), developmental delays and skin lesions. Currently, brain surgery is the only treatment option for patients in the EU with growing SEGAs associated with TSC.

The CHMP positive opinion is for a conditional approval based on a prospective, open-label, single-arm, Phase II study of 28 patients. Results showed that 78% of patients (21 of 27) experienced a reduction of 30% or greater in the size of their largest SEGA and 33% (9 of 27) experienced a reduction of 50% or greater at six months relative to baseline.

"The positive CHMP opinion for Votubia is encouraging as it may lead to the approval of the first medication in the European Union for patients with this challenging disease," said Hervé Hoppenot, President of Novartis Oncology.

"Our focus on tuberous sclerosis complex research reflects the commitment Novartis has made to develop innovative therapies to help address unmet medical needs."

The European Commission generally follows the recommendations of the CHMP and delivers its final decision within three months of the CHMP recommendation. The decision will be applicable to all 27 EU member states plus Iceland and Norway.

Regulatory approvals have already been granted for

SEGA associated with TSC in the United

States, Switzerland, Brazil, Colombia, Guatemala, the

Philippines and South Korea. Additional submissions to global regulatory agencies are under way worldwide.

Everolimus targets mTOR, a protein that acts as an important regulator of tumor cell division, blood vessel growth and cell metabolism. Tuberous sclerosis complex is caused by defects in the TSC1 and/or TSC2 genes.

When these genes are defective, mTOR activity is increased, which can cause uncontrolled tumor cell growth and proliferation, blood vessel growth and altered cellular metabolism, leading to the formation of benign tumors throughout the body, including the brain.

By inhibiting mTOR activity in this protein pathway, everolimus may reduce cell proliferation, blood vessel growth and glucose uptake related to SEGA associated with TSC.

Tuberous sclerosis complex is a genetic disorder affecting approximately one to two million people worldwide. In Europe, the prevalence in the general population is estimated to be nearly nine cases per 100,000.

(Source: http://www.novartis.com/newsroom/media-releases/en/2011/1525934.shtml Novartis drug Votubia® recommended by CHMP for approval in the EU for children and adults with SEGA associated with tuberous sclerosisBasel - Jun. 24, 2011)

30

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS F UNNY PHARMA CARTOON JULY 2011

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

FUNNY PHARMA CARTOON

JULY 2011

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS F UNNY PHARMA CARTOON JULY 2011

“I s that a controlled document?”

(Source: http://www.pharmamanufacturing.com/articles/2010/155.html Submitted by Dominic Tunzi)

AN S W E R F R O M T H E E X P E R T

Q: When a high-visibility project is not going according to plan, how do you get leaders to talk about it?

The secret is amazingly simple: Be candid. Get the stakeholders together, and lead an honest discussion of the circumstances. Sometimes it helps to have each stakeholder take a quiet moment before the discussion begins to write a brief description of the problem along with an assessment of exactly what they could do make a contribution to the issue.

Then have each person sequentially read their comments aloud for the group. It is important for the facilitator of this kind of meeting to call this “tactical” session as early as possible, make sure that all stakeholders are in attendance, and then keep the discussion moving. It is also important in critical situations to avoid blaming and to seek constructive solutions. Many times, the simple act of articulating the problem can quickly lead to a situation. In real-life situations, long delays, avoidance, and interpersonal triangulation are the poison trilogy for problem solving.

David Frew

Dr. David Frew is a visiting professor at Mercyhurst College in the Graduate Organizational Leadership (MSOL) Program. He has served as a consultant to GE Crotonville, NASA, and dozens of other regional, national, and international clients.

(Source: Ask The BoardLife Science Leader – www.LifeScienceLeader.com June 2011)

COMPANY PROFILE: WHO’S WHO?

About Boehringer Ingelheim: The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 42,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine. As a central element of its culture, Boehringer Ingelheim pledges to act socially responsible. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavors.

In 2010, Boehringer Ingelheim posted net sales of about 12.6 billion euro while spending almost 24% of net sales in its largest business segment Prescription Medicines on research and development. For further information, please visit www.boehringer-ingelheim.com

31

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS T IE-UPS & AGREEMENTS JULY 2011

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

TIE-UPS & AGREEMENTS

JULY 2011

LUPIN, NATCO TIE UP TO MARKET BREAST CANCER TABLETS

Drug firms Lupin Ltd and Natco Pharma on Jun. 23, 2011 said that they have entered into an alliance to jointly market generic Lapatinib Ditosylate tablets, used for treating breast cancer, in the American market.

Natco has filed an abbreviated new drug application (ANDA) seeking United States Food and Drug Administration ( USFDA) approval for marketing these tablets in the strength of 250 mg, Natco and Lupin Ltd said in separate statements. "Natco has partnered with Lupin for marketing of the product," Natco Pharma said in a filing to the Bombay Stock Exchange (BSE). Lapatinib Ditosylate tablets are sold under the brand name Tykerb in the American market. The patent of Tykerb is with Glaxo. "Tykerb had sales of USD 113.6 million as of March, 2011, according to IMS health," Lupin said. "Natco and Lupin believe that they are the first to file an ANDA containing a paragraph IV certification for Lapatinib," it added.

This means that once their ANDA is approved, the firms could have 180 days' exclusivity for the product in the US.

(Source: http://articles.economictimes.indiatimes.com/2011-06-23/news/29694483_1_natco-pharma-breast-cancer-tablets Lupin, Natco tie up to market breast cancer tabletsNew Delhi, INDIA – Jun. 23, 2011)

LIGAND ENTERS INTO CAPTISOL ® SUPPLY AGREEMENT WITH MERCK

Ligand Pharmaceuticals Incorporated announced on Jun. 20, 2011 that it has entered into a Captisol ® supply agreement with Merck & Co., Inc. for an undisclosed program.

Ligand will supply clinical and commercial supplies of Captisol and, if the program is approved for commercialization, expects to deliver multiple metric tons of Captisol annually. Financial terms of the deal were not disclosed.

“We are extremely pleased to enter into a long-term commercial supply agreement for this Captisol-enabled program,” said Matt Foehr, Executive Vice President and Chief Operating Officer of Ligand Pharmaceuticals.

“This collaboration with Merck is a good example of the type of relationships we try to build with our partners. Merck used Captisol to reformulate a drug in their portfolio and performed initial proof of concept under a research use agreement.”

“This announcement marks the natural transition of the program to a full commercial supply relationship as commercialization approaches,”

added Mr. Foehr.

“This deal has the potential to add meaningful revenue to the Ligand business in the coming years and extends the already significant partnering relationship that we have developed with Merck over the past few years.”

About Captisol® : Captisol is a patent protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. This unique technology was originally developed by Ligand’s subsidiary company CyDex Pharmaceuticals and has enabled five FDA approved products, including Pfizer’s VFEND ® IV and Prism Pharmaceuticals’ NEXTERONE ® .

There are currently over twenty Captisol-enabled ® products in development, including Onyx pharmaceuticals’ carfilzomib program.

About Ligand: Ligand Pharmaceuticals is located in La Jolla, California on the cliffs just above Torrey Pines Beach. Founded in 1987, Ligand is a biotech company with a rich heritage in drug discovery and development. Ligand has used its drug development expertise to produce over 40 clinical candidates, 22 INDs, and 5 approved drugs. That's a level of productivity that ranks near the top of the biotech industry. Today, Ligand is operating with a business model that is based upon the concept of developing or acquiring royalty revenue generating assets and coupling them to an efficiently lean corporate cost structure. Ligand's goal is to produce a bottom line that supports a sustainably profitable business.

For more information, visit www.ligand.com

(Source: http://www.istockanalyst.com/business/news/5240600/ligand-enters-into-captisol-r-commercial-supply-agreement-with-merck Ligand Enters into Captisol ® Commercial Supply Agreement with MerckBusiness Wire – Jun. 20, 2011)

32

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS PHARMA ARTICLES JULY 2011 Q bD

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
PHARMA ARTICLES JULY 2011
PHARMA ARTICLES
JULY 2011

QbD FOR BETTER METHOD VALIDATION AND TRANSFER

Just as process validation can benefit from a QbD and a product lifecycle approach, so can analytical method validation and transfer

More companies in the pharmaceutical industry today are adopting the principles of Quality by Design (QbD) for pharmaceutical development and manufacturing.

Described in ICH Q8, Q9 and Q10 guidance documents, QbD enables enhanced process understanding, and a more systematic and scientific approach to development, so that better controls may be implemented. The end goal is more robust manufacturing processes than those that typically result from traditional approaches to drug development.

The QbD framework has many implications for manufacturers and regulators alike. This article describes how analytical methods can be viewed as "processes" and QbD concepts applied, to improve both method validation and transfer. Its goal is to stimulate thinking and discussion on how analytical method validation and transfer could evolve as industry increasingly adopts Quality by Design concepts.

But QbD cannot be considered without examining validation within a product lifecycle framework. The U.S. Food and Drug Administration (FDA) attempted to do just that in a recent draft guidance designed to help achieve the goals of its “Pharmaceutical GMP's for the 21st Century – A Risk Based Approach”.

This guidance addresses some of the problems with traditional approaches to process validation, which were articulated by Moheb Nasr nearly five years ago. Too narrow a focus on a "three-batch" approach to validation has encouraged a "don't rock the boat" mindset within the industry that can fail to foster continuous improvements in quality or efficiency.

The Need for Real World Verification

The same problems can be seen in analytical method validation and transfer, where the focus often shifts from ensuring the robustness of the method itself to ensuring the robustness of the documentation, and how well it will withstand regulatory scrutiny.

Methods for pharmaceutical products are normally validated by experts who have developed the method in accordance with ICHQ2 guidance (Validation of Analytical Procedures: Text and Methodology) or USP <1225> (Validation of Compendial Procedures). However, validation can be treated as a one-off event, with little consideration given to verifying how well the method will perform at everyday, "real world" operating conditions.

All too often, regulators and industry use ICH Q2 or USP <1225> in a “check box” manner without considering the intent of these guidances, or the philosophy of method validation.

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS PHARMA ARTICLES JULY 2011 Q bD

33

Continued on page 34

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS PHARMA ARTICLES JULY 2011 Continued from

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
PHARMA ARTICLES JULY 2011 Continued from page 33. . ‘QbD For Better Method Validation And Transfer’
PHARMA ARTICLES
JULY 2011
Continued from page
33. .
‘QbD For Better Method Validation And Transfer’

These issues continue after the method has been validated, when it is transferred to another laboratory. This transfer step requires that the knowledge of how to operate the method be transferred to those who will use it routinely, and that an exercise be performed, documenting that similar results have been obtained by both parties.

The transfer exercise is usually performed by the most competent analytical staff in the receiving laboratory, yet it may have little relationship with how the method will be used in routine, day to day operations. It may come as little surprise, then, that most methods fail to perform as intended in the receiving laboratory, triggering efforts to identify variables that are causing the discrepancies, and repeated, costly testing and documentation.

The roots of method transfer failures can usually be traced to insufficient consideration of the routine operating environment during the method validation exercise, and lack of an effective process for capturing and transferring the tacit knowledge of the development analysts.

A QbD Framework for Analytical Method Life Cycle Management

If an analytical method is viewed, simply, as a process, whose output is data of acceptable quality, QbD concepts designed for manufacturing processes can be applied to analytical methods. Thus, the concepts of lifecycle validation that are being developed for manufacturing processes might also be applied to analytical methods.

Quality by Design (QbD) is defined as “a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding based on sound science and quality risk management”. And FDA has proposed a definition for process validation that is “the collection and evaluation of data, from the process design stage throughout production, which establishes scientific evidence that a process is capable of consistently delivering quality products.” When considering a lifecycle approach to method validation, a similar definition could be adopted “The collection and evaluation of data and knowledge from the method design stage throughout its lifecycle of use which establishes scientific evidence that a method is capable of consistently delivering quality data.” From these definitions, it can be seen that there a number of key factors that are important in a QbD\Lifecycle approach. These include:

The importance of having predefined objectives

The need to understand the method, or being able to explain the method performance as a function of the method input variables

The need to ensure that controls on method inputs are designed such that the method will deliver quality data consistently in all the

intended environments in which it is used The need to evaluate method performance from the method design stage throughout its lifecycle of use.

In alignment with the approach proposed in the draft FDA guidance for process validation, a three-stage approach could be taken with method validation. (See chart.)

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS PHARMA ARTICLES JULY 2011 Continued from

34

Continued on page 35

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS PHARMA ARTICLES JULY 2011 Continued from

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
PHARMA ARTICLES JULY 2011 Continued from page 34. . ‘QbD For Better Method Validation And Transfer’
PHARMA ARTICLES
JULY 2011
Continued from page
34. .
‘QbD For Better Method Validation And Transfer’

Stage 1 – Method Design: Define method requirements and conditions and identify critical controls Stage 2 – Method Qualification: Confirm that the method is capable of meeting its design intent. Stage 3 – Continued Method Verification: Gain ongoing assurance to ensure that the method remains in a state of control during routine use.

STAGE 1 - METHOD DESIGN

The Method Design stage includes establishing the method performance requirements, developing a method that will meet these requirements and then performing appropriate studies to understand the critical method variables that must be controlled to assure the method is robust and rugged. The method design stage can be an iterative process, which is repeated as required in accordance with the lifecycle phase of the product.

Method Performance Requirements

Utilizing a QbD approach, it is essential at this stage that sufficient thought be given to the intended use of the method and that the objectives or performance requirements of the method be fully documented. This represents the Analytical Target Profile (ATP) for the method. To draw a parallel to qualification of new analytical equipment, the ATP for the method is effectively the equivalent of a User Requirement Specification that would be produced to support qualification of new analytical equipment (or the Design Qualification as defined in USP <1058>).

To build the ATP, it is necessary to determine the characteristics that will be indicators of method performance. Typically, these characteristics will be a subset of those described in ICH Q2, such as accuracy or precision. It is important, however, not to use the ICH Q2 characteristics in a check box manner but to consider the method's intended use. For example, the characteristics that are critical to the performance of an HPLC assay method intended to be used to quantify the active ingredient within a tablet might be quite different from those of an NIR method intended to be used to measure the end point of a blending operation. In the second case, accuracy may not be a critical method performance requirement in determining homogeneity.

Once the important method characteristics are identified, the next step is to define the target criteria- in other words, how accurate or precise the method should be. A key factor in choosing the appropriate criteria is the impact of method variation on the overall manufacturing process capability. Knowledge of the proposed specification limits and the expected process mean and variation is helpful in setting meaningful criteria.

Method Development

Once the ATP has been defined, an appropriate technique and method conditions must be selected in order to meet the requirements of the ATP. While method development is a very important part of the method lifecycle, it is not necessary to elaborate here since it has been extensively addressed in the literature.

Method Understanding

Based on an assessment of risk (i.e. the method complexity and the potential for robustness and ruggedness issues) one can perform an exercise focused on understanding the method to better understand what key input variables might have an impact on the method's performance characteristics. From this, one can identify a set of operational method controls. Experiments can then be run to understand the functional relationship between method input variables and each of the method performance characteristics. Knowledge accumulated during the development and initial use of the method provides input into a risk assessment (using tools such as the Fishbone diagram and FMEA), which may be used to determine which variables need studying and which require controls.

Robustness experiments are typically performed on parametric variables using Design of Experiments (DoE) to ensure that maximum understanding is gained while minimizing the total number of experiments. Depending on the type of method, surrogate measures of characteristics such as accuracy or precision may be evaluated. An example might be peak resolution in a chromatographic method. It follows that well designed System Suitability requirements can be a valuable tool for assuring that a method is operating in a region where the ATP requirements will be met.

When developing an understanding of the method’s ruggedness, it is important to consider variables that the method is likely to encounter in routine use, such as in situations involving different analysts and different instruments. Tools such as measurement system analysis can be useful in providing a structured experimental approach to examining such variables.

Method Design Output

A set of method conditions will have been developed and defined which are expected to meet the ATP. Those conditions will have been optimized based on an understanding of their impact on method performance.

35

Continued on page 36

PPPP HARMA CCCC HRONICLE AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS PHARMA ARTICLES JULY 2011 Continued from

PPPPHARMA CCCCHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS
PHARMA ARTICLES JULY 2011 Continued from page 35. . ‘QbD For Better Method Validation And Transfer’
PHARMA ARTICLES
JULY 2011
Continued from page
35. .
‘QbD For Better Method Validation And Transfer’

STAGE 2 - METHOD QUALIFICATION

Once a set of operational method controls has been determined during the design phase, the next step is to qualify that the method will operate as intended. In a similar manner to equipment qualification, method qualification can be broken down into the stages of method installation qualification (MIQ), method operational qualification (MOQ), and method performance qualification (MPQ).

Method Installation

Qualification focuses on ensuring that the facility where the method will be used is prepared to use it. This process includes ensuring that the analytical equipment is qualified and that appropriate knowledge transfer and training of analysts has been performed.

The method conditions and detailed operating controls, along with all the knowledge and understanding generated during the design phase, must be conveyed to staff at the facility in which the method will be used. Performing a “method walkthrough” exercise with both the development and routine analytical teams can be extremely valuable in ensuring all tacit knowledge about the method is communicated and understood.

The extent of the IQ phase may vary depending on the level of pre-existing knowledge of the routine testing laboratory with the product, method or technique. For example, the laboratory that originally developed the method may merely ensure that other personnel who will use the method are trained.

The Method Operational Qualification phase is focused on demonstrating that the method meets its design intent. It is similar to “traditional method validation.” In the lifecycle approach, however, the focus is not about performing the traditional check box exercise to demonstrate compliance with ICH Q2. Instead, it is about demonstrating that the method meets the specific requirements that have been pre-defined in the Analytical Target Profile. A fundamental principle of this stage is that it should build on information that may have been generated in experiments already performed; for example, evidence of the selectivity or limit of quantification of a method may already exist from studies performed as part of method design.

The final stage in the qualification phase is to perform a MPQ exercise. At this stage, the actual manufactured supply samples are tested in facility, equipment and by personnel that will be used for routine analysis. The method should be operated exactly in accordance with the defined method controls and local operating procedures. As with the IQ stage above, the extent of the PQ exercise could vary, and would include for example confirming system suitability criteria are being routinely met.

STAGE 3 - CONTINUED METHOD VERIFICATION

The goal of this stage of the method lifecycle is to continually assure that the method remains in a state of control. This should include an ongoing program to collect and analyze data that relate to method performance---for instance, by setting criteria for replication of samples or standards during the analysis, by trending system suitability data or by trending the data from the regular analysis of a reference lot.

This activity aligns with the guidance in USP chapter 1010 on system performance verification. Close attention should also be given to any out of specification (OOS) or out of trend (OOT) results generated by the method once it is being operated in its routine environment. Ideally, using the new approach, laboratories should encounter fewer OOS results. If they do, it will be easier for staff to determine their root cause.

Change Control

During the lifecycle of a product, both the manufacturing process and the method are likely to experience a number of changes brought through unintentional deviations, continuous improvement activities or the need to operate the method and\or process in a different environment. It is essential that all changes to the method operating conditions be considered in light of the knowledge and understanding that exists on the method performance.

If the method operating conditions are modified such they fall outside the known method operable region (determined as part of ‘method understanding’ during the original design phase) then the Method Qualification should be revisited. Likewise if the process changes and samples contain analytes at levels outside those covered in the method operational qualification exercise or have new interferences, a new ATP would need to be generated and a partial re-qualification exercise will be required to ensure the method is still capable of producing consistent and reliable results for the extended range or modified sample.

Where a method needs to be transferred to new location, appropriate Method Installation Qualification activities (including knowledge transfer) will

need to be performed in addition to a Method Qualification exercise. Consistent with QbD principles, the extent of re-qualification should be driven by scientific principles, as described previously.

36

Continued on page 37