Pharma Asia Sep-Oct 2011

A leading resource for the pharmaceutical industry

www.PharmaAsia.comSeptember-October 2011

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Drug counterfeiting: Under siege

Drug

Manufacturing

Moving up the compliance curve

Special Report

Modern drug testing

Drug

Development

Surviving difficult times

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www.PharmaAsia.comMay-June 2011

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Growth in Asia:New opportunities in drug development

Pharma IT

Pharma opens up to IT outsourcing

Special Report

China’s pharmaceutical industry goes from strength to strength

Drug Discovery

Proteomics in action: Opening doorways to new drugs

www.PharmaAsia.com22

PharmaAsia is published eight times a year by Ten Alps Communications Asia Pte Ltd, located at 67 Ubi Avenue 1, #06-06 StarHub Green North Wing, Singapore 408942. All rights reserved. Please address all subscription mail to PharmaAsia at the above address, or Fax (65) 6521 9766. PharmaAsia Volume 6, Number 5.

Contents

www.PharmaAsia.comSeptember-October 2011

08__ Country Analysis Vietnam: Boosting its domestic pharmaceutical

industry Rising presence of health issues such as gastrointestinal problems in the

country is creating a huge demand for drugs.

10__Drug Development Surviving difficult times While the global recession has exacerbated fi nancial pressures on

biopharmaceutical companies, those pressures create opportunities for the industry to reexamine and revamp the drug development process.

16__ Drug Manufacturing Drug counterfeiting: Under siege Asia’s pharmaceutical supply chains are constantly being invaded by

fake and sub-standard drugs. As protective regulatory policies are being erected, the industry also requires technology that can effectively combat the growing problem.

21__Special Report Modern drug testing TÜV SÜD PSB is equipped with modern analytical testing equipments

to help companies meet the necessary product quality and validation requirements for drugs and pharmaceutical products. Pharma Asia visited the facility in Singapore to fi nd out more.

24__ Drug Manufacturing Moving up the compliance curve How does a company move compliance from a traditional approach to

a fully effective quality system that is not only compliant but effi cient and integrated to key business processes? The following case study illustrates its transformation.


02__Editor's Column The other drug problem003__Top Of The News

27__Product Center

16

20

21


Editor’s Column

September-October 2011 • PharmaAsia

ISSN 2010-4251

EDITORIALGroup Editor

Raymond Foo, [email protected]

Editorial Advisors

Eize de Boer, PhD, Global Manager, Life Science Auditing, SGS. Ian Griffi ths, Medical Director, GSK International Medical, AP. Jasmin Patel, PhD, Managing Director, Fidelity Ventures. Jerold Martin, MSc, Senior Vice President, Scientifi c Affairs, Pall Life Sciences. Lee Babiss, PhD, President & Global Head, Pharma Research, Roche. Rama Shankar, Quality Performance Manager, TAP Pharmaceuticals Products Inc. Shama Kajiji, PhD, Director, Portfolio Franchise Management Department, Merck & Co.

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Raymond FooGroup Editor

There is a new front in the war on drugs, and it's not the kind of drugs one

might think. We're not talking about cocaine, heroin or methamphetamines.

This is about drugs that could wind up in every household’s medicine cabinet:

counterfeit prescription drugs.

According to WHO, counterfeit drugs are found everywhere in the world. They range

from random mixtures of harmful toxic substances to inactive, ineff ective preparations.

Some contain a declared, active ingredient and look so similar to the genuine product

that they deceive health professionals as well as patients. But in every case, the source

of a counterfeit drug is unknown and its content unreliable. These medicines are

always illegal and can result in treatment failure or even death. Eliminating them is a

considerable public health challenge.

Stringent regulatory control of medicines and enforcement by national medicines

regulatory authorities contributes signifi cantly to prevention and detection of

counterfeit drugs. However, the aim is to involve a range of stakeholders in collaborative

eff orts to protect people from buying and taking counterfeit drugs.

MSNBC reports that Pfi zer Inc and a pharmacy standards group are teaming to warn

consumers about the risks of counterfeit prescription medicines. The pharmaceutical

giant, whose impotence pill Viagra is widely counterfeited, and the US National

Association of Boards of Pharmacy have announced the start of an educational campaign

to explain the dangers of counterfeit drugs and help people fi nd legitimate pharmacies

online. The eff ort includes a website, a video series on a new YouTube channel and

takeovers of websites counterfeiters have previously used to sell fake Pfi zer drugs.

Here in Asia, counterfeit drugs remain a huge challenge. The region accounts for the

biggest share of the trade in counterfeit medicines, according to the Pharmaceutical

Security Institute. High prices of branded pharmaceuticals may be one of the reasons

that the counterfeit drug trade fl ourishes, not only in Southeast Asia, but in Western

countries as well.

The extent of the challenge means there is no ‘one size fi ts all’ solution. Besides

fostering cooperation between stakeholders and national enforcement agencies, the

other key objective should be the building of public and government awareness of the

seriousness of the problem. PA

The other drug problem

www.PharmaAsia.com 33

Top Of The News


Top Of The News

Prostate cancer drug granted patent in Singapore

Agilent and Chungnam University collaborate to further glycomics research

Pharmaron to host Merck Serono R&D laboratory in China

Ph a r m a ro n a n n o u n c e d a

s t r a t e g i c p a r t n e r s h i p

with Merck Serono, the

biopharmaceutical division of Merck

KGaA, Germany. In the framework of

this partnership, Pharmaron’s new

campus in the Beijing Economic and

Technological Development Area

(BDA) will serve as home to Merck

Serono’s China R&D Laboratory.

The focus of this laboratory will be

clinical bioanalysis and biomarker

characterization, allowing for the

identification of gene mutations

among the Chinese population,

early detection of disease processes,

and development of personalized

medicines for cancer and neuro-

degenerative diseases.

Pharmaron, a leading integrated CRO

in the US and China with expertise

from discovery to IND, recently

completed the first phase of its new

Beijing campus, which boasts over

600,000 square foot of space. This

new campus houses Pharmaron’s

elaborate drug discovery services area

including chemistry, DMPK, biology,

pharmacology and GLP Bioanalysis.

On August 31, 2011, Merck Serono and

Pharmaron celebrated the opening

ceremony of Merck Serono’s China

R&D Laboratory as the beginning of

this long-term collaboration between

the two companies.

Agilent Technologies

Inc and Chungnam

National University

announced an agreement to

develop new applications,

methods, technologies and

software tools in the field

of glycomics, the study of complex

sugars. The university aims to identify

and develop biomarkers for diseases

such as cancer, leading to development

of therapeutic antibody products.

The announcement marks the first

partnership of its kind for Agilent with a

university in Asia.

The research will be jointly led by

Professor Hyun Joo An, Department

of Analytical Science and Technology

at Chungnam National University’s

Graduate School of Analytical Science

and Technology (GRAST )

and Head of the new Asia

Glycomics Education Center,

a n d by R u d o l f G r i m m ,

Agilent’s Director of Science

and Technology and Manager

of Collaborations in the Asia

Pacific region. Grimm was appointed

adjunct professor by the university for

his work in this field. Both researchers

will define and conduct joint research

projects to develop new applications,

methods or analytical tools for glycan

analysis. Under the agreement, GRAST

will also develop glycomics training

courses for Agi lent ’s customers

and employees to help further the

advancement in the field, while Agilent

Life Sciences will utilize GRAST as its

strategic glycomics reference site in

Korea and Southeast Asia.

Ad a m i s P h a r m a c e u t i c a l s

Corporation announced the

technology which constitutes

its compound APC-200 was recently

granted patents in Singapore and South

Africa. According to the company, these

patents significantly strengthen the

Adamis APC-200 patent portfolio for the

use of APC-200 in the treatment of early

and late stage prostate cancer.

APC-200 is a small molecule formulation

that has been developed for oral

administration. Pre-clinical studies

confirming the use of APC-200 for the

treatment of prostate cancer were

pioneered by Dr George Wilding and his

team. Dr Wilding is the Assistant Dean for

Oncology and Director of the University

of Wisconsin Carbone Cancer Center.

The initial development of APC-200 is

intended for patients with castration-

resistant prostate cancer. However, APC-

200 has the potential to be beneficial to

patients in combination with androgen

deprivation therapy (ADT), or where ADT

has not been approved or is not effective

or tolerated.



Top Of The News

Nycomed and Almirall announce licensing agreement for antihistamine

GE Healthcare to invest US$1 billion in new oncology solutions

GE Healthcare

has announced

i ts p lans to

dedicate US$1 billion

of its total R&D budget

over the next five years to expand

its advanced cancer diagnostic and

molecular imaging capabilities, as well

as its world-class technologies for the

manufacture of biopharmaceuticals and

for cancer research.

Announced alongside a US$100 million

open innovation challenge in New York

City, the US$1 billion investment crosses

all lines of GE Healthcare’s global business

and is an example of the company’s

commitment to fighting cancer. The

investment will enable the company to

bring the most promising cancer ideas

to market, unleashing technologies that

improve accuracy of diagnosis to enable

more effective treatment decisions and

empower doctors and patients with

better information.

“We are committed to tackling cancer.

However, with a disease as complex and

multifaceted as cancer, solutions need

to be equally multifaceted and even

more integrated, combining imaging,

molecular diagnostics and healthcare IT,”

said John Dineen, President and CEO, GE

Healthcare. “As one of the most relevant

global cancer diagnostic companies, we

are devoting an even greater share of our

R&D budget to continue developing new

oncology solutions.”

Bristol-Myers Squibb and Ambrx announce collaboration for novel biologics programs

Bristol-Myers Squibb Company

and Ambrx Inc announced

a collaboration under which

Bristol-Myers Squibb will receive

exclusive worldwide rights to research,

develop and commercialize biologics

based on Ambrx’s research surrounding

the Fibroblast Growth Factor 21 (FGF-21)

protein, for potential use in treating type

2 diabetes, and the Relaxin hormone, for

potential use in treating heart failure.

Derivatives of FGF-21 and Relaxin

were developed using Ambrx’s unique

ReCODE platform technology to modify

the native proteins with amino acid

building blocks beyond the common

20 to engineer enhanced versions for

investigation for therapeutic use.

Under the terms of the agreement,

Bristol-Myers Squibb will make an

upfront payment of $24 million to

Ambrx. In addition, Bristol-Myers

Squibb will make potential milestone

payments and royalty payments on

worldwide sales for both programs.

Bristol-Myers Squibb and Ambrx will

also enter research collaborations for

both programs. FGF-21 is a naturally

occurring protein that has been

characterized as a potent metabolic

regulator, and has been shown to

lower blood glucose, elevate good

cholesterol and promote weight loss in

preclinical studies. The lead compound

in this program, ARX618, or PEG-FGF-21,

is in the final stages of preclinical

development.

Relaxin is a naturally occurring hormone

known for its role in pregnancy and

childbirth. Preclinical studies suggest

Relaxin may aid in the treatment of

heart failure by improving cardiac

function. This program is in preclinical

development.

Nycomed and Almirall announced

that they have signed a licensing

and supply agreement for

Almirall's R&D antihistamine ebastina,

under the trademark Kestine, indicated

for allergic rhinitis and chronic idiopathic

urticaria, in China and other key

emerging markets. Under the terms

of the agreement, Nycomed will have

exclusive commercialisation rights for

the existing Kestine product in China.

Additionally, Kestine will be launched in

Malaysia, Philippines, Singapore, Thailand

and Indonesia, with Nycomed becoming

marketing authorisation holder in

these territories. Financial details of the

agreement were not disclosed. According

to the companies, Kestine (ebastine) is a

product developed by Almirall's R&D and

which to date has been marketed in more

than 30 countries worldwide through the

company's own affiliates and licensees.

Its efficacy and safety are backed by

thorough, extensive research: over 100

clinical studies have been conducted on

over 15,700 patients.


Top Of The News


India generics companies lead pharmaceutical innovation in Asia PacificSignifi cant increases in investment and development of novel drug pipelines.

Multi-national pharmaceutical

companies are likely to

face increased competition

for new molecular entities from India-

based generics companies, according

to the 2011 CMR International Asia

Pacific R&D Pharmaceutical Factbook

released by CMR International, a

Thomson Reuters business.

According to the research contained

in the Factbook, India’s generic drug

companies are making significant

investments in innovative R&D and

have generated the largest new drug

pipelines among generics companies

worldwide in the years between 2006 and

2010.

India-based generics companies are now

leading the rest of the world’s generic

companies in discovering and developing

new biopharmaceutical entities that

have not been previously available for

therapeutic use in man. Although India

is reported to have nearly 90 innovative

products in the pipeline, almost half of

them are already in the preclinical phase.

The Asia Pacif ic Factbook also

reports that by continuing to shift

their operating model towards

participating in high risk, high-reward

drug patent challenges (known as

Paragraph IV challenges), India-based

generic companies are adopting an

increasingly aggressive approach to

securing market share. The change

in approach is highlighted by the 72

percent increase in the number of

Paragraph IV patent challenges raised

by Indian companies between 2009

and 2010.

GE Power & WaterWater & Process Technologies

New ASTM E2656 for On-Line TOC Demonstrating Process Control of TOC in Pharma Water

ASTM’s new E2656, Standard Practice for Real-Time Release Testing of Pharmaceutical Water for the TOC Attribute, explains how to achieve both accept-able water system process capability for the Total Organic Carbon (TOC) requirementand compliance with the critical new US FDA Process Validation Guidance Document.

To help you establish the scientific evidence that your water system can consistently deliver quality product, GE Analytical Instruments offers a range of products and services, including:

• World-class analytical instruments• Process validation services• Compliance with USP, EP, ChP, IP, and JP TOC requirements

Learn more. Contact [email protected] or visit www.geinstruments.com.

GE imagination at work



Top Of The News

Teva solidifies Japanese operations

Sinopharm upgrades supply chain system

Teva Pharmaceutical Industries

Ltd announced that it will

acquire the 50 percent interest

formerly held by Kowa Company Ltd in

Teva's Japanese joint venture for a total

purchase price of $150 million. With this

acquisition, Teva will own 100 percent

of the former joint venture, which will

immediately begin to do business as an

important and wholly-owned member

of the Teva Group.

Teva and Kowa announced the

establishment of Teva-Kowa Pharma

Co Ltd in September 2008, and have

since grown the joint venture into

one of the top 5 generic players in

Japan, in cooperation with Kowa.

The joint venture generated sales of

approximately $200 million in 2010.

SK biopharmaceuticals in collaboration agreement to study Lou Gehrig’s disease

In July 2011, Teva completed the

acquisition of Taiyo Pharmaceutical

Industry Co Ltd for $934 million. Taiyo is

the third largest generics manufacturer

in Japan with sales of approximately

$530 million in 2010.

Taiyo brings to Teva a portfolio of over

550 products and a strong presence

in all major channels of the Japanese

pharmaceutical market. Teva also gained

access to Taiyo's strong R&D team, local

regulatory expertise and a state of the

art production facility.

With this latest transaction, Teva's

operations in Japan are expected to

generate annual sales in excess of $800

million.

So u t h K o r e a n b i o t e c h S K

biopharmaceuticals announced

that they signed an agreement

to collaborate with the Mayo Clinic for

the discovery of new drugs targeting

Amyotrophic Lateral Sclerosis (ALS, Lou

Gehrig’s disease).

The collaboration aims to discover

innovative drugs that may aid in the

treatment of the disease. Current drugs

are known to extend a patient’s life by

only three months on average. Dr Jeong

Woo Cho, Vice President for the Drug

Development Business, said, “This is

the case of a happy marriage between

a specialty company with excellent

preclinical R&D and Mayo Clinic, a first-

class research institute focused on a

new scientific paradigm and equipped

to take on specialized clinical trials. The

collaboration aims to identify drug targets

that help treat this fatal disease.”

With their three-year collaboration, SK

biopharmaceuticals will work with Mayo

Clinic’s Leonard Petrucelli, PhD, Chair and

Professor of Neuroscience. Dr Petrucelli’s

laboratory has pioneered research in the

neurosciences field. The first phase of

the preclinical research collaboration will

focus on chemical compounds that target

TDP-43, a protein that is a prime suspect

in the disease.

Sinopharm Group’s distribution

centre in Hunan, China has

successfully upgraded its

supply chain technology platform

with the latest version of Manhattan

Associates’ Warehouse Management

system (WMS). Sinopharm expects the

system will play a vital supporting role

in helping it achieve its target of RMB

10 billion in revenue in the next five

years.

Sinopharm has invested nearly RMB

200 million in its Hunan distribution

centre, which opened in May this

year. The company said it is now able

to categorise products and manage

storage requirements to meet different

manufacturers’ needs, which is helping

make order picking more efficient and

optimising operating flow.

It also has the ability to analyse the

performance of the warehouse and

can identify areas where productivity

and service level improvements can be

made.

Sinopharm estimates the enhanced

capabilities offered by the new system

will deliver productivity improvements

of up to 30 percent.


Top Of The News


Merck and BGI establish strategic collaboration on biomarkers and genomic technologies

PPD expands clinical microbiology laboratory services globally

Sanofi Pasteur acquires worldwide license for acne vaccine

Sanofi Pasteur announced a

research and development

c o l l a b o r a t i o n w i t h t h e

University of California, San Diego

on an immunologica l approach

to acne prevention and treatment

targeting the specific neutralization

of Propionibacterium acnes factors in

inflammation.

Acne vulgaris (acne) is one of the most

common skin diseases worldwide and

affects more than 50 million people in

the United States alone. The disease

has multiple, complex factors and is

associated in particular with the Gram-

positive anaerobic bacterium P acnes

that is a normal member of the human

skin microflora. Current treatment of mild

forms of acne involves killing P acnes

with bactericidal agents such as benzoyl

peroxide and oral or topical antibiotics,

all of which indiscriminately kill many

bacterial species and disrupt the normal

balance of the skin microflora. Long-term

use of antibiotics also leads to resistant

strains of P acnes.

According to Sanofi Pasteur’s estimates,

the annual worldwide market for

acne therapeutics is in excess of US$3

billion. The financial terms of the

agreement were not disclosed. The

agreement includes a two-year research

collaboration with Dr Chun-Ming Huang

and his associates at UC San Diego

School of Medicine for further research

and development. PA

PPD I nc announced i t has

expanded its clinical microbiology

laboratory at its global central

laboratories worldwide, strengthening

its laborator y testing ser vices in

infectious diseases, one of the largest

therapeutic areas for clinical research and

development. The company now offers a

full range of microbiology testing services

such as bacteriology, mycobacteriology

and testing of microbioterrorism

pathogens. The laboratory also provides

extensive virology testing, including real-

time polymerase chain reaction, viral

load, genotyping and single nucleotide

polymorphism analysis. The laboratory

has the capability to culture, quantitate,

identify and determine antibiotic

susceptibility and resistance for aerobic

and anaerobic organisms. PPD is already

running studies for staphylococcal and

yeast infections and for the presumptive

identification and quantification of

microbiota.

“Microbiology is an important compo-

nent of laboratory testing for infectious

diseases,” said Elena Logan, Senior Vice

President of Global Central Labs for

PPD. “Strengthening our microbiology

c a p a b i l i t i e s d e m o n s t r a te s P P D ’s

commitment to deliver a full range of high

quality global central laboratory services

and builds on our fully integrated clinical

research and development expertise

across all areas of infectious diseases.”

Merck and BGI announced

that they have established

a collaboration to focus

on the discovery and development of

biomarkers and genomic technologies.

Under the agreement scientists from

Merck and BGI will work closely together

to identify and characterize biomarkers

with an emphasis on drug discovery,

drug development and diagnostics

applications across a wide range of

therapeutic areas.

"This strategic collaboration

combines BGI's genomic

sequencing and analytic

capabilities with Merck's

expertise and experience in

drug development," said Dr

Jeffrey Chodakewitz, Vice President, Late

Stage Development, Merck Research

Laboratories. "By working together we

hope to apply BGI's comprehensive

next-gen sequencing solutions to

develop important new tools to aid

drug development and enable effective

tailoring of medicines to those patients

most likely to respond."

Under the terms of the agreement Merck

and BGI will each be permitted to propose

projects to be undertaken

under the collaboration.

Both Merck and BGI will

provide resources, expertise,

samples and other research

material as needed for the

collaboration.


Country Analysis


Demographically, Vietnam has a large and

young population, estimated to be the

eighth largest population in the Asia

Pacific region by 2016. The elderly population is

rising slowly, and will remain as one of the lowest

proportions in the Asia Pacific region. Rising drug

consumption and government investment make

Vietnam an attractive pharmaceutical market.

There are around 171 pharmaceutical companies

in Vietnam, out of which 9.0 percent are owned

by foreign investors and 4.0 percent are joint ven-

tures. About 28.0 percent of them have the Global

Manufacturing Practice (GMP) certification.

Local pharmaceutical production was valued at

nearly US$920 million and met 48.0 percent of

the nation's needs. Imported drugs account for

the remaining 52.0 percent. According to Deputy

Minister of Health, Cao Minh Quang, improving

the domestic pharmaceutical industry would

be the health sector's utmost priority in the

coming years in order to satisfy 70.0 percent of

the nation's demand by 2015. Health ministry

statistics show that the value of the nation's total

medicine consumption reached almost US$1.9

billion last year. The Ministry of Health forecasts

that the size of the Vietnam pharmaceutical

market will exceed US$2.0 billion and annual

growth will reach between 17-19 percent in 2011.

In 2010, about 22.0 percent of the population was

affected by gastrointestinal (GI) related problems

Vietnam: Boosting its domestic pharmaceutical industryRising presence of health issues such as gastrointestinal problems in the country is creating a huge demand for drugs.

Yamunah Kandasamy, Research Associate

– Healthcare, Frost & Sullivan

in Vietnam. Such a high percentage of population

suffering from this condition could be due to

the fact that people in Vietnam are increasingly

leading a busy and stressful lifestyle. With the

hectic lifestyle, they have less time for balanced

meals and exercise. People use more take-

away food deliveries, and many young urban

consumers eat at their desks at work. All of these

habits led to more digestion related problems and

gradually aggravates to more GI related issues.

Alcoholism appears to be another serious cause

of increase in gastrointestinal problems in

Vietnam. Statistics from the Vietnam Beverage

Association shows that 5.0 percent of citizens and

3.0 percent of mountaineers are alcoholics out of

total population of 89,571,130 in 2010.

According to Dr Pham Thi Thu Ho, VP of The

Vietnam Association of Gastroenterology, the

Gastrointestinal Department in Vietnam hospitals

have been burdened with male patients

having trouble with their livers or galls due to

overconsumption of alcohol.

Types of drug treatmentsThe availability of GI services in Vietnam is

relatively high and it is expected to be offered in

86.9 percent of hospitals. Only a small percentage

of doctors prefer the endoscopy procedure while

the majority prefers to prescribe patients oral

medication.


Country Analysis


Various drugs are available in Vietnam for GI related problems. Of

the drugs in the market, 45.0 percent are generic, 30.0 percent

are over-the-counter (OTC), and the remaining 25.0 percent are

patented. They are mostly classified into anti-diarrheal, anti-ulcer

drugs such as H pylori agents, H2 antagonists, prostaglandins

and proton pump inhibitors. Other categories include GI

anticholinergics, antispasmodics, GI motility drugs and laxatives.

Drugs in GI – opportunities and concernsVietnam's US$1.9 billion medicine consumption market

represents a good opportunity for medium to high return

market for drug makers. Demand for medicines is supported

by a thriving economy, political stability, growing private

consumption and health insurance. Despite a low per capita

spending, some research suggests that market growth could

have a CAGR of 14.6 percent against the government’s estimate

of 17-19 percent. With 22.0 percent of the population affected by

GI related cases in the country, and considering the fact that each

person affected by GI may have to receive a dosage of oral drugs

at various stages; this would boost the demand for drugs used for

treating GI conditions.

Since the country is depended on 52.0 percent of imported drugs,

the devaluation of its currency (dong) is a major area of concern.

The prices of pharmaceuticals are rising again in Vietnam. It costs

more for importers to purchase raw materials and finished drugs.

This is causing concern for patients that are already dealing

with constant inflationary pressures, predominantly affecting

essential items. Higher prices are then passed on to wholesalers,

retailers and ultimately the end users.

Future outlookThe Vietnam government will be consolidating and modernizing

existing hospital pharmacies in Ho Chi Minh City in the period up to

2020. Each province will also have additional provincial hospitals

to ensure that there will be one hospital with a pharmacy. Other

plans to develop Vietnam’s pharmaceuticals includes boosting

the manufacturing of essential drugs in order to cut prices,

stabilise the market and reduce the country’s dependence on

foreign pharmaceutical imports. Other targets include increasing

investment in scientific research and technological application

and expanding co-operation with foreign pharmaceutical

companies for efficient drugs. Foreign enterprises will be allowed

to import medicines from abroad. However, they will distribute

through Vietnamese distributors. Vietnam has pledged to set

import duties at less than 5.0 percent for pharmaceutical

products. In addition, drug tariffs are expected to average at 2.5

percent within five years of WTO’s accession.

Even though Vietnam’s health care service space is dominated by

public sector, there are a significant percentage of people that

spend out-of-pocket expenditure on availing treatment. The

growing healthcare insurance in the country, combined with

private spending provides a conducive environment for both

pharmaceutical companies and hospitals to offer more products

and services in Vietnam. PA

Percentage of hospitals with GI services (Vietnam), 2010

Percentage of drugs distributed in Vietnam for GI related problems (2010)

13.1%Without

GI

86.9%With GI

25.0Patented

30.0OTC

45.0Generic

APHAHazen

GardnerIodine Color NumberUS Pharmacopoeia

European Pharmacopoeia

Organising Your Colors

Into Numbers

Konica Minolta Sensing Singapore Pte Ltd10 Teban Gardens Crescent Singapore 608923 Tel: +65 6563 5533 Fax: +65 6560 9721www.konicaminolta.com/[email protected]

GIoIodid nen CCololor


Drug Development


Surviving diffi cult timesWhile the global recession has exacerbated fi nancial pressures on biopharmaceutical companies, those pressures create opportunities for the industry to reexamine and revamp the drug development process.

The failure of the US bank Bear Stearns in

the third quarter of 2008 was one of several

events that set off a global banking/credit

crisis, a crisis that applied recessionary pressures

to every major economy worldwide. As credit

became less available and more restrictive,

funding for biotechnology ventures dried up, and

some biotech companies disappeared. Earnings

pressures, exacerbated by the burgeoning

recession, drove massive change across the

biopharmaceutical industry, signaling the final

death knell for the blockbuster era. Faced with

high development costs, scientific challenges,

changing regulations, and a number of high-

profile product withdrawals, many companies felt

compelled to devise a new drug development

model, even as they continued to pour money

into research and development (R&D).

As the industry began to tighten its belt,

contract research organizations (CROs) looked

inward to find ways to optimize their internal

processes to become more efficient. This process

of introspection has yielded a renewed focus

on technology, development of new business

models, and strengthening of continuous

improvement initiatives as biopharmaceutical

companies devise new strategies to rebuild their

pipelines.

Cost-cutting and riskmanagementMany companies implemented cost-cutting

and risk management strategies that focus their

energies on compounds and therapeutic areas

with great potential or unmet medical needs.

Biopharmaceutical companies also deployed

variable cost structures, which are less prone

Dalvir Gill,PhD, President,

Late Stage Development,

PharmaNet

to pipeline variations, by increasingly using

outsourcing to shift fixed costs onto CROs.

Others, in an effort to rationalize their pipelines

and therapeutic focus, are dropping compounds

– some are dropping entire therapeutic areas

– and/or reprioritizing development projects.

Many companies are undergoing organizational

restructuring, in some cases leading to significant

headcount reductions and facility closures.

In addition to cutting costs, many companies

are spending differently. Some are moving more

aggressively to restock their pipelines through

acquisitions, licensing deals, and partnerships.

Others are shifting their focus from discovery to

development or from small molecules to biologic

products. In some cases, organizations are

creating entire departments or business units that

primarily use external expertise and manpower

to provide operational and intellectual “muscle”,

thus acting as “virtual” pharma companies.

Rethinking the innovationprocessAs companies seek to accelerate drug

development, many are taking a fresh look at the

innovation process. In some cases this has led to

a relaxed “guardianship” of intellectual property

(IP), with information shared more freely. Several

of the largest biopharmaceutical companies

have established collaborations to share assays

and compound libraries with government and

academic research organizations, as well as with

smaller biotech companies, in an effort to identify

earlier drug candidates. This relaxed approach

to guarding and sharing IP is taking place even

as the industry continues to consolidate, a trend

that was evident before the recession. Many


Drug Development


Outsourcing has emerged as a crucial cost-containment strategy for biopharmaceutical companies.

companies view consolidation as a means to obtain, size, scale,

and market share, thus shoring up their competitiveness amid

economic uncertainty.

Such rethinking of the innovation process goes hand-in-hand

with more aggressive outsourcing strategies. Partnering with

CROs has become more prevalent as drug makers continue to

seek ways to cost-effectively increase the volume of quality

clinical and preclinical data while reducing time to market. This

trend has led to a stronger focus on preferred providers with

whom companies can leverage relationships and infrastructure

to create integrated systems to share information, along with

harmonized standard operating procedures and business

practices.

All these efforts to revamp the innovation process have largely

been fueled by an intensifying focus on technology, as evidenced

by widespread adoption of genotyping for pharmacogenomics,

personalized medicine initiatives, and exploration of

nanotechnology. Rather than employing technology to speed

up what was essentially a shotgun approach, companies are

increasingly using advanced technologies to more quickly and

efficiently target drug candidates to specific disease pathways,

Figure 1: Money raised by biotechnology companies 2010 versus 2009

thereby facilitating development of therapeutic compounds

with favorable efficacy and safety profiles in specific patient

populations.

Yet even as consumers worldwide continue to feel the pinch

of economic stress, the recession appears to have bottomed

out in most countries, and some economies are experiencing

modest growth. Consequently, biopharmaceutical companies

are executing on previously announced strategies, and program

priorities have been clarified, resulting in more focused pipelines

and an uptick in projects across the industry. As shown in

Figure 1, investment in US biotech rebounded strongly in 2010

(particularly during the second quarter), aided in no small part by

the Affordable Care Act, by which the US government granted a

$1 billion tax credit to biomedical companies with fewer than 250

employees. Thus, as the nascent signs of an economic recovery –

however anemic – become more evident, the industry is looking

to CROs for more efficient and effective buying processes and

methods to streamline development.

The impact on CROsAs noted above, outsourcing has emerged as a crucial cost-

containment strategy for biopharmaceutical companies, thus

fueling CRO hiring. In the second quarter of 2010, the CRO

hiring rate significantly outpaced pharma hiring, and was 250

percent greater than those of medical device and supply firms.

The growth in CRO hiring is largely due to a strong recovery in

late-stage development (phase 2-4 studies), although this is

slightly offset by a slower recovery in phase 1, and a flat to slightly

declining market for toxicity studies. Project cancellations have

normalized across the industry, and in the third quarter of 2010

the top 10 CROs all reported strong book to bills ranging from

1.0 to 1.5, with an average of single-digit revenue growth across

the industry.

Many CROs, by virtue of their diverse client rosters and range

of therapeutic experience, can often cast wider nets than some

biopharmaceutical companies, and often have more recent



Drug Development

experience in a particular area of research. Consequently, clinical

trial sponsors increasingly recognize that working with CROs

is key to developing sound protocols and boosting patient

recruitment. CROs can help sponsors adapt to the changing

clinical trial environment through greater use of technology,

flexible staffing approaches, novel approaches to registrational

trials, and assistance with phase 4 studies. Unlike phase 3

studies, which generally have complicated protocols designed

to secure marketing approval, phase 4 trials are often meant to

answer questions about a product’s post-marketing use, safety

and effectiveness. CROs with the right expertise can thus help

companies streamline phase 4 studies to address the protocol

objectives in a more focused manner, making these studies’

designs far less complicated to implement.

At the same time, CROs need to rethink their relationships

with sponsors to address their new approaches to product

innovation and development. Some CROs are adopting risk-

sharing models whereby they invest in the development of novel

drug candidates, which, if successful, may generate revenue

through milestones, payments, and royalties. Such models may

incorporate time-based incentives and disincentives, upfront

discounts with downstream benefit if a product is approved, or

asset transfers with service contracts.

Emerging marketsBiopharmaceutical companies continue to invest in R&D on a

global basis, as lackluster growth in traditional markets is offset

by rapid growth in emerging markets. CROs with a presence

in emerging markets will thus be well-positioned to capitalize

on this trend. The BRIC quartet (Brazil, Russia, India, and China)

is expected to dominate future R&D growth. Supported by

improving infrastructure, emerging economies in Asia are

expected to have double-digit growth (15-20 percent), compared

to the 1-2 percent expected in traditional markets.

Some Asian countries are already reaping the benefits of clinical

trial activity. Clinical trial initiations in South Korea rose by 150

percent from 2006 to 2009. In India, R&D spending by the top

25 drug companies rose nearly 17 percent in 2008-09, and the

country’s pharma market is predicted to reach the $55 billion

sales level by 2020. Additionally, the Indian government plans to

establish a $640 million venture capital fund to encourage drug

discovery and strengthen the country’s pharma infrastructure.

Meanwhile, pharma investment in emerging markets continues

apace. Eli Lilly has invested $1.27 billion in the US-Russia Health

Sciences Forum. GSK acquired the Argentine firm Laboratorios

Phoenix in 2010. Sanofi-aventis opened an R&D center in China

Figure 2: What changes is your company making to improve the effi ciency of its work with sponsors? (survey of 88 companies)


Drug Development


in 2010 and is pursuing R&D activities in Russia, South Korea,

and India. Merck CEO Kenneth Frazier recently hailed emerging

markets such as China and Latin America as major contributors

to the company’s long term success, with growth in those regions

predicted to reach 25 percent over the next three years. Not to be

outdone, Pfizer is looking to expand research collaborations in

China, India, Korea, Japan, and Australia.

Leveraging preferred supplierrelationshipsPreferred supplier relationships are a key strategy of

biopharmaceutical companies as they seek to maximize the

outcomes of their partnerships with CROs. These alliances allow

the partners to leverage business processes, joint accountability,

information technology infrastructure, and communications

across projects, thus enhancing efficiency.

In a recent Avoca Group survey of 88 CROs, more than half

indicated they were increasing their pursuit of preferred

providerships (Figure 2). The Avoca Group also polled

management personnel at 72 biopharma-sponsor companies,

69 percent of whom responded that they presently have

preferred provider arrangements; 42 percent indicated that

at least three quarters of their clinical research expenditures

went to preferred providers in 2009. When asked what they

always expect from preferred providers in 2010 and beyond,

more than half of respondents from sponsor companies cited

factors such as discounted rates, increased senior management

oversight, formal performance measurement/management,

and preferred access to specific staff members (Figure 3).

Notably, the percentage of sponsors that always expect formal

relationship management programs from preferred providers

has doubled since 2007-09. Additionally, 55 percent of sponsor

respondents indicated that they currently use measurement of

key performance indicators (KPIs) to evaluate clinical service

providers’ performance; however, only 30 percent of those who

use KPIs felt those indicators provided an adequate reflection of

providers’ true performance, including the quality of deliverables.

The Avoca Group data underscore the importance of establishing

the right partnership structure, with shared governance and

sponsor access to CRO management. While metrics provide

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JOIN YOUR PEERS AT LOGIPHARMA ASIA AND GAIN NEW INSIGHTS INCLUDING HOW: • AstraZeneca benchmarks its supply chain infrastructure with international standards • Abbott Healthcare who acquired Piramal’s generics business developed an effective consolidated supply chain strategy in Asia• GS1 standards were successfully deployed to enhance supply chain management and increase operational efficiency• The Pharmaceutical Export Promotion Council is helping to tackle your challenges with the new GMP regulations in India by 2012• USP-China, U.S.Pharmacopoeia identifies solutions to adhere to China’s 12th five-year plan and new GSP and GMP regulations in China for 2012• PT Kalbe Farma develops collaborative supply chain planning systems between local suppliers and distributors in Indonesia• Roche Diagnostics benchmarks their monitoring practices to create a good cold chain in Asia• Eli Lilly and Watson Pharma handle the new changes of GSP and GMP regulations in China and India with little negative impact on their supply chain business • Johnson & Johnson and Pfizer implement effective solutions to reduce costs and balance risk across their supply chain• DSM, Cipla and Cadila Pharmaceuticals tackle the challenges of India’s logistic infrastructure development • Singapore Health Services, one of Singapore’s leading healthcare groups shares their strategies on how best to ensure end-to-end supply chain optimisation

EFFECTIVE COLD CHAIN MANAGEMENT FOCUS DAY | NOVEMBER 22, 2011

With a full day consisting of case studies, roundtables and panels, you are guaranteed to walk away with actionable insights to enable you to gain greater control of your cold chain.

• Stuart Anderson, Head of Global Supply Chain, Enabling Capabilities, AstraZeneca

• Viliam Kovac, VP Global Supply Chain Quality, Roche Diagnostics

• Marco A Vega, Head of Quality, Eli Lilly China

• Siddhartha Pahwa, President - Supply Chain, Generic & Newten, Abbott Healthcare

• Rajesh Pednekar, Head of Supply Chain, Pfizer

• Neeraj Bhargava, Regional Logistics Procurement Director, Asia Pacific, Johnson & Johnson

• Chandramouli NV, Head of Demand & Supply Chain AMEA, DSM

• Shivraj Dasari, Vice President, Quality Management and Regulatory Affairs, Inno Bio Ventures

• Hemant Deshpande, Head of International Logistics, Cipla

• Amrendra Singh, Deputy, General Manager – Supply Chain, Cadila Pharmaceuticals

• Tuti Susilowati G, General Manager Supply Chain, PT Kalbe Farma

• Lok Mun Leng, Assistant Director, Procurement, Singapore Health Services

• Vijay Kaul, Vice President Supply Chain, Unilever

• Gerry A Mattios, Expert Principal, Bain & Company

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Leading pharma government and standards authorities include:

• Dr PV Appaji, Executive Director, Pharmaceutical Export Promotion Council, India

• Dr John J. Hu, VP, General Manager, USP-China

• Wong Tack Wai, Executive Director, GS1, Singapore

Leading experts include:

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Session 1: The myths that cause cold chain management to failSession 2: Cold Chain re-engineering - challenging the myths, re-thinking, revitalising and adapting the best cold chain management practice

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an indication of performance, other “softer” factors may also

impact the relationship. Experience suggests that a more subtle

approach to relationship management can positively impact

the success of the partnership. Such an approach depends on

robust business systems supported by operating procedures that

clearly define roles and responsibilities. Successful relationship

management must also take into account the vested interests

of team members, both within the sponsor company and the

CRO. Project teams must be empowered to resolve issues in a

collaborative way, and team members must be encouraged to

avoid assigning blame and to share successes.

SummaryIn the past year and a half, the biopharmaceutical industry has

undergone a historic period of change. Evolving business models

are being developed to accelerate drug development and make

it more cost-effective. As those business models become more

widely adopted, sponsor companies and CROs need to address

new relationship paradigms for preferred partnerships, which

appear to be gaining favor as the clinical trials environment

continues to change. The changing environment places a

premium on performance metrics, and CROs can add measurable

value to the drug innovation and development process. As the

role of CROs continues to expand, CROs will increasingly be

regarded as an extension of their sponsors, a characterization

that should help the industry continue to thrive well into the 21st

century. PA

Preferred supplier relationships are a key strategy of biopharmaceutical companies as they seek to maximize the outcomes of their partnerships with CROs.

Figure 3: What does your company expect from preferred providers in 2010 and beyond?

Drug Development

DownstreamBioProcessing& Single-use Systems Asia 2011

Main Conference Date: 1 December 2011

Post-conference Workshop: 2 December 2011

Venue: Amara Hotel, Singapore

Eliminating Downstream Process Bottlenecks through Process Optimisation,

Implementation of Innovative Technologies and Single-Use Systems

T: F: E: W:

Expert speaking faculty includes:Peter Kumpalume

Head of PurificationGlaxoSmithKline, United

Kingdom

Dr. Susanna Leong

Assistant ProfessorNanyang Technological

University, Singapore

Dr. Fei Xu

Head of Purification Process DevelopamentA-bio, Singapore

Dr. Frank Ho

VP Bioprocess DevelopmentA-bio, Singapore

Dr. Ashok Patra

Group Leader, Downstream ProcessingPanacea Biotec Ltd, India

Ying Wang

Chief EngineerNCPC GeneTech

Biotechnology Development,

China

Jason Li

Director, Downstream Process DevelopmentGenor BioPharma Co. Ltd.

Wison Group, China

Tushar Joglekar

Assistant Manager Process DevelopmentSerum Institute of India

Sudip Kumar Majumder

Principal Scientist Intas Biopharmaceuticals, India

Bin Xi

Director of Industrial DevelopmentZensun Sci & Tech Co., Ltd,

China

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Attend this event and hear downstream bioprocess experts address

Advanced technologies in separation and filtration processes that will enhance your production processes

Developing downstream biomanufacturing flexibility – Future-proofing facilities for multiple product lines and higher titers

Examining the latest chromatography technologies and their impact on purification processes

Evaluating the implementation of acidification for reducing impurity levels and improving throughput in harvest operations

Downstream scale-up evaluation for high-titer mammalian-based processes: Platform strategies for improved clarification and purification throughput

Developing new disposable technology platforms and strategies to increase flexibility and to optimise cost throughout manufacturing operations

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Drug Manufacturing

Asia is fast becoming a hotbed for

pharmaceuticals manufacturing, with

China and India taking the lead. China's

pharmaceutical industry is projected to grow

at an average annual rate of about 22 percent

from 2010 to 2019, according to the Southern

Medicine Economic Research Institute (SMERI).

IMS Health supports this, stating that the world's

third-largest pharma market is projected to

grow by 25 to 27 percent, to more than US$50

billion. India’s pharma market is also undergoing

rapid expansion, with a growth rate of about

Didier Lacroix, Senior Vice President,

Cognex Inc

Drug counterfeiting:Under siegeAsia’s pharmaceutical supply chains are constantly being invaded by fake and sub-standard drugs. As protective regulatory policies are being erected, the industry also requires technology that can effectively combat the growing problem.

10 percent, according to Pharmaceutical Drug

Manufacturers.

Market expansion however, also comes with its

own set of challenges – counterfeit drugs.

China: Rooting out the weedsChina is taking active steps to combat its domestic

counterfeit drug problem. According to a report

in January 2011 by www.china.org.cn, more than

60 tons of fake and substandard pharmaceuticals

and medical equipment worth 40 million yuan



Drug Manufacturing

(US$6 million), were destroyed in a move to crack down on

counterfeit drugs. The State Food and Drug Administration

(SFDA) claims that the destroyed products were confiscated by

Beijing's municipal drug supervision bureau, and included about

130 kinds of drugs such as fake Viagra and capsules for diabetes.

It has also been reported by www.asianews.it that a Hangzhou-

based crime syndicate has sold counterfeit and ineffective drugs

for years. The patent rights are held by Bayer, Nova, Roche and

AstraZeneca, and are worth tens of millions of yuan. The group

posted sales information online to indicate that the drugs had

been smuggled in from India and Peru – countries where real

drugs can be manufactured without paying patent duties – and

then sold for 10 percent of the original price. A reality check

however, revealed that the drugs were counterfeits that had

been manufactured in China at locations such as Yixing (Jiangsu).

While being ineffective and unsafe, the drugs are not lethal.

By the time the scandal was exposed in 2009, the organisation

had earned more than 7.5 million yuan, with export sales to

locations such as Peru and India.

Taking a long term approach in dealing with the problem, the

SFDA announced a supplementary notice in the first quarter of

2011 to promote the electronic supervision of essential drugs. All

imported bid-winning essential drugs are required to be entered

into the network and be coded accordingly. The management

of printing/pasting electronic supervision codes have to be

standardized on some packages.

Mandatory serialization on sellable pharmaceutical product

units is required by December, 2011 and all products that are

manufactured in China must have GS1 barcode labels. Imported

products may have Health Industry Business Communications

Council (HIBCC) barcodes for now, but will soon have to be

mandated to the GS1 standard.

India: Wolves in sheep’s clothingIndia is becoming a center for counterfeit and substandard

medicines, according to the Washington Post. Such fake drugs

are well-packaged and are often labelled with reputable brand

names like GlaxoSmithKline, Pfizer and Novartis. These drugs are

sold to the local Indian consumer market and are also exported

Facilitate innovation and manufacturing of affordable high quality vaccines and

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Dr Scott Liu,President and CEO,Henlius Biopharmaceuticals Inc., USA

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30+ case studies

20+ hours of networking time

4 conferences and workshops

1 superb learning and networking

Dr Li Shi,CEO,Shanghai Zerun Biotechnology, China

Dr Christian H. Leist,Head of BioProcess Development & Technology Platform Manager,Novartis Pharma AG, Switzerland

Dr Su Chen,CEO,Chengdu Kanghong Biotechnology Co., China

29 Nov to 1 Dec 2011, Shanghai, China

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to developing nations. The government claims that 0.4 percent

of the country's drugs are fake and that substandard drugs make

up about 8 percent. On the other hand, independent estimates

range between 12 to 25 percent.

The illegal activities include attaching fraudulent labels on

expired products and putting water into vials. Adding minimal

quantities of real ingredients in packages of actual drugs and

filling medicine packets with chalk powder are also other

examples of illegitimate drug manufacturing activities.

In response to the exacerbating problem, the Indian government

has announced that all pharmaceutical export shipments must

have a track and trace system. Exporters of pharmaceutical

products are required to affix barcodes on their export products

to facilitate the tracking and tracing of their products as per GS 1

global standards.

GS1 GTIN is required on primary packaging (level below the retail

packaging). While Data Matrix is the preferred carrier, EAN/UPC,

GS1-128 and GS1 Databar are also acceptable.

GS1 GTIN is required on secondary packaging, as well as

expiration date and batch/lot number. The GTIN on the secondary

level packaging must be different from the GTIN on the primary

package, as well as the GTIN on the higher-level shipper pack.

GS1-128, GS1 DataMatrix or GS1 DataBar are all acceptable for

secondary packaging.

Carton/Shipper-level packaging must also contain GTIN,

expiration and batch information.

For primary packaging (example: blister strips, vials and bottles),

2D barcodes are required with effect from July 1, 2012). For

secondary packaging, 2D or 1D barcodes are required with effect

from January 1, 2012). For tertiary packaging (example: shipper or

carton), 1D barcodes are needed from October 1, 2011 onwards.

The original deadline of July 1, 2011 for pharma exporters to affix

barcodes on their export products has been extended to Oct 1,

2011 for 1D barcodes.

The barcodes need to encode a unique product identification

code, batch number, expiry date and serial number.

South Korea: Catching crimeSouth Korea is one of the world’s leading drug counterfeiters,

where only 20 percent of counterfeit/recalled drugs are ever

recovered. In 2010, South Korea revealed that it had seized

US$5.58 billion worth of counterfeit goods since 2006, which

includes a substantial quantity of fake medicines, according to

The Partnership For Safe Medicines.Org. Based on a report that

was submitted by the Korea Customs Service to the Strategy and

Finance Committee of the National Assembly, fake drugs worth

US$157.8 million have been seized by Korean authorities since

2006.

It is estimated that the quantity of counterfeit Erectile Dysfunction

(ED) medication that is smuggled into the country is 23 times

greater compared to the five years before 2010. The National

Tax Service (NTS) detected 18 cases of smuggled impotence

medicine totalling 90.6 billion won (US$77 million) for the first

six months of 2010.

More than 99 percent of the smuggled medications were

fake versions of ED drugs, which were alleged to have been

manufactured in China.

In its war against drug counterfeiting, the government has

mandated that 50 percent of all drugs sold in the country have

Radio Frequency Identification (RFID) tags by 2015, and that

pharmacies be equipped to read the tags to authenticate them.

However, many pharma industry experts believe that the cost

of RFID is too prohibitive for its implementation on such a wide

scale – and even if the technology is used, it will most likely be

accompanied with a barcode.

South Korea is enforcing the requirement for all drugs to have a

GS1 barcode (GTIN-13, GTIN14 or GS1-128). Specified drugs must

have GS1-128 codes with lot number and expiry date in 2012 and

special drugs in 2013.

Verifying the sourceToday, one of the most important applications for the

pharmaceutical industry is product authentication or ePedigree.

Authentication is essentially being able to verify that a medicinal

product is genuine, and comes from the manufacturer or other

legal source within the supply chain. This application requires

Drug Manufacturing

Today, one of the most important applications for the pharmaceutical industry is product authentication.



coding, marking, serial number aggregation,

and multiple vision systems and ID readers

for barcode reading, offline verification and

online mark quality assessment along the

production line. These applications seek

item-level serialization on every bottle, carton

or blister pack and Data Matrix has been

adopted as the standard. Serialized items are

associated with larger case and pallet lots in a

parent child relationship.

Vision and ID products verify that the correct

information has been printed (a US FDA

requirement) and also determine the overall

quality of the printed characters or codes.

Print quality verification can be accomplished

in-line and is valuable in diagnosing printing problems with

equipment or substrates.

Vision systems like In-Sight from Cognex use a patented PatMax

algorithm to locate and verify printed characters even when they

Drug Manufacturing

are moving within the field of view. The algorithm tolerates wide

positional and size variances in characters to consistently and

reliably verify each character. The pharma code is read and can be

verified by the camera itself or it can be sent to any programmable

logic controller (PLC), computer etc, for further processing.

Print quality verifi cation is valuable in diagnosing printing problems with equipment or substrates.

TherapeuticsDISTINGUISHED PANEL OF SPEAKERS

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29 Nov to 1 Dec 2011, Shanghai, China

Dr Jian Ni,CEO and Chief Scientist,Human antibodomics (Suzhou Industrial Park) Inc, Su Zhou, China

Dr Allan Riting Liu,Vice President, Wanbang Biopharm,Shanghai Fosun Pharma Group, China

Dr Zhu Zhenping,Executive Vice President Global Biologics R&D Kadmon Pharmaceuticals, China

Dr George Wang, Senior Director Analytical Sciences Formulation & Quality Genor Biopharma, China

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In addition to ePedigree, machine vision products solve many

other problems. Vision can be used to improve product and

package quality at just about every station on the pharmaceutical

line. Applications include checking container orientation,

verifying code quality and label accuracy at printing and marking

stations. Vision can also detect chipped tablets or inspect for

container flaws prior to filling. It can inspect package integrity,

missing capsules in a blister or under-filled vials.

It can also be used for simple inspections such as checking for

the presence of cotton, caps, seals and tamper-evident bands,

inserts and outserts, as well as for more detailed inspections such

as cap skew, safety ring integrity or label position. Machine vision

can also be used to guide robotic pick and place, or to determine

package position or orientation.

In labeling and marking applications vision can inspect for

label correctness, placement, wrinkles and tears and verify print

graphic quality. It can also be used in secondary packaging and

palletizing applications.

With rising demands for patient safety and better products,

manufacturers in Asia need to work hand-in-hand with regulatory

authorities. Via the adoption of technology that satisfies both

production requirements and government legislation, the

pharma industry can finally get the upper hand in the fight

against drug counterfeiting. PA

Inspecting vial stoppers using machine vision to ensure that they are properly seated prior to sealing.

Drug Manufacturing



Modern drug testingTÜV SÜD PSB is equipped with modern analytical testing equipments to help companies meet the necessary product quality and validation requirements for drugs and pharmaceutical products. Pharma Asia visited the facility in Singapore to fi nd out more.

With more than 40 years of

experience in testing, TÜV SÜD PSB

provides a comprehensive range

of pharmaceutical testing services covering

chemical analysis and testing of pharmaceutical

products and raw materials according to BP,

USP, and EP methods, microbiological testing,

preclinical testing services and environmental

monitoring. Its laboratories are also accredited to

the requirements of ISO 17025 by the Singapore

Laboratory Accreditation Scheme (SAC-SINGLAS).

In January 2010, this quality and safety

testing, inspection, certification and auditing

organization was officially listed as one of WHO’s

Prequalified Quality Control Laboratories of

Pharmaceuticals. This qualification recognizes

that TÜV SÜD PSB’s laboratories are in compliance

with recommended standards governing Good

Practices for National Pharmaceutical Control

Laboratories (GPCL) and Good Manufacturing

Practices (GMP) for the testing and analysis of

pharmaceutical products.

Testing fertility drugsAccording Lim Hwee Jen, Product Manager,

Chemical and Materials – Food and Pharmaceu-

ticals, drugs are tested according to inter-

Special Report



Special Report

national pharmacopeia standards at

TÜV SÜD PSB. She took Pharma

Asia through the various steps of

fertility drug testing using the USP

method. The products tested were

Levonorgestrel and Ethiny Estradiol

tablets. The process is as follows:

• Prepare a deaerated mixture

containing 350 mL of acetonitrile,

150 mL of methanol, and 450 mL of

water.

• Prepare a concentration of 15 μg per mL and 3 μg per mL of

USP Norgestrel RS and USP Ethinyl Estradiol RS respectively.

• Assay preparation – Transfer 10 tablets, equivalent to about

3 mg of levonorgestrel, to a 200-mL volumetric flask. Dilute

with Mobile phase to volume, sonicate to disintegrate the

tablets. Centrifuge and filter with 0.45 membrane filter, and

use the clear, supernatant.

• Chromatographic system – The liquid chromatograph

is equipped with a 215-nm detector and a column that

contains packing L7. The flow rate is about 1 mL per minute.

Chromatograph the Standard preparation, and record the

peak response as directed.

• Separately inject equal volumes of the Standard preparation

and the Assay preparation into the chromatograph, record

the chromatograms, and measure the responses for the major

peaks.

Drugs are tested according to international pharmacopeia standards atTÜV SÜDPSB.

1.

2.

3.

4.


Special Report


Building on a strong heritagePharma Asia spoke to Chong Kok-Yoong, Vice President, Food and Pharmaceutical Industries, Strategic Business Development, TÜV SÜD PSB, to fi nd out more about the organization:

PA: Tell us more about TÜV SÜD PSB and the customers

that you service.

Chong: TÜV SÜD PSB is a 145 year-old company that started

in Germany. Today, it is a truly international company with 600

locations worldwide. We are in the CTCT (consulting, training,

certification and testing) business-to-business arena.

Our customers are organizations and corporations who buy

medicines or pharmaceuticals products. Specifically, they are

international buying bodies such as UN agencies that buy in

bulk. They need these drugs to be tested and verified before

they distribute them to various governments of developing

countries around the world, such as Cambodia and Myanmar

in Southeast Asia.

Besides the aid agencies, we also have business from Big

Pharma companies. They use us as an external laboratory

to complement and support what they do in-house. We

provide them independent verification on drugs that

they are developing. In most cases, their laboratories

are quite tight in terms of schedule so they sub-

contract to us to ease their workflow.

PA: What kinds of inspection are carried out in

your labs?

Chong: Our pharmaceutical testing is fairly wide

ranging. At present, we specialize in testing birth

control pills and malaria tablets. We check, for example,

the concentration of the active ingredient in the drug

against what is labeled. Organizations also utilize our

services to do packaging and environmental testing. We

would check on the functionality and tightness of blister

packaging for capsules, for example, to meet a certain

standards. They cannot be too loose that damage can

occur during transportation. In environmental testing, we

would check on the parameters like quality of air in

the manufacturing environment.

PA: Tell us more about the international prequalification

programme that TÜV SÜD PSB received in 2010?

Chong: This is prestigious as not more than 10 organizations

globally have received this accreditation and TÜV SÜD PSB

is one of them. In fact, we are the only non-government

laboratory to receive this accreditation. The accreditation

process was stringent, and took place in two main areas –

chemical testing and microbiological testing. We had to show

proper documentary evidence on how we conduct a test. Are

our personnel trained? Do we have a quality system based on

good laboratory practices (GLP)? Meeting these requirements

as well as our conformance to the ISO 17025 standard formed

the basis of our qualification.

PA: What do you think made the difference for TÜV

SÜD PSB in receiving the -qualification?

Chong: We have been in the drug testing business for

a long time. We also have a strong reputation in

the market for our technical know-how and

credibility. I believe that our heritage and

previous government links also had a part to

play in our qualification. We used to be called

SISIR back in the 70’s when we first started

as a standards organization in Singapore

specializing in various types of testing. From

SISIR, the organization became PSB Corporation

which was then acquired by TÜV SÜD PSB five

years ago.

I am sure the TÜV SÜD PSB brand, our network of

worldwide locations with a total of 16,000 employees

had a part to play in our qualification as well.

But we are not resting on our laurels. In terms of

future strategic development, we are maintaining

and will continue to look for interested parties who

need testing services to work with us. PA



Drug Manufacturing

Robert A Rhoades, Vice President, Quality

and Compliance, Consulting at Quintiles

Moving up thecompliance curveHow does a company move compliance from a traditional approach to a fully effective quality system that is not only compliant but effi cient and integrated to key business processes? The following case study illustrates its transformation.

A mid-sized specialty pharmaceutical

company was mired with a disjointed

collection of some 4,500 procedures

across their global R&D organization. Despite

the procedural and country-specific focus, the

company lacked alignment with regulatory

requirements, found it difficult to execute global

projects due to varying business processes, and

was replete with inefficient, non-value added

activities. The company was operating at Stage

2 on the compliance maturity curve (Figure 1) –

functioning, but at risk of sliding to Stage 1 and

into trouble.

Starting with a global, top-down regulatory

assessment, the company developed a global

quality system with activity-based procedures

and processes focused on regulatory compliance.

As a result, the number of procedures was reduced

96 percent from 4,500 to less than 200 (Figure 2),

with equally significant reductions in procedure

maintenance and training requirements. All

staff now operate under the same procedures,

wherever they go in the company. Responsibilities

for critical processes involving regulatory risk,

such as pharmacovigilance, were modeled and

are now clear and fully integrated. These changes

Figure 1: Ascending the compliance maturity curve



Drug Manufacturing

were managed through extensive involvement of affected

stakeholders, development of a web-based portal for employees

to see at a glance all of their quality and compliance related

responsibilities, and visibility to key performance metrics.

Talking points were developed for presentation in regulatory

audits so that staff could clearly explain how 96 percent of

the procedures in the former quality system were eliminated

without sacrificing compliance. Moreover,

the company was able to demonstrate how

quality and compliance were enhanced

by sharing improvements in meaningful

quality indicators and metrics. The company

passed two stringent regulatory inspections

with no observations noted, and is currently

evaluating how the same model can

be applied to other types of regulatory

requirements, including financial, labor,

environmental, and data security.

These improvements brought the company Figure 2: Streamlined R&D SOP

not only to a fully compliant state, but also achieved greater

rewards because of the critical attention given to align quality

processes with the product development cycle. R&D concurrently

aligned to a stage-gate governance model driven by meaningful

metrics that support pipeline decision making. By focusing on

science-driven development supported by the incorporation of

key metrics designed to facilitate “fail fast” strategies, the company

is innovating more quickly. By deconstructing processes into

detailed activities, drivers and owners, new

processes are in place for key disciplines

supporting product development, such

as Medical Affairs and Medical Safety.

Moreover, by eliminating unnecessary

procedures and tasks, the organization

was poised to return to its core mission:

to focus on science and the development

of products addressing unmet needs. The

company’s pipeline has never been more

robust. Product quality and credibility

with regulators has improved. Sustainable

compliance has been achieved.

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Drug Manufacturing

How to support sustainable compliance• Ensure that every member of the organization has a

basic understanding of what regulations are intended to

accomplish

• Establish systems – interlinked sets of processes and

procedures – that help the organization respond quickly

when things don’t go as planned and that prevent those

situations from recurring

• Establish reliable and thorough information pathways

that keep management informed of the various aspects

of a product’s life cycle

• Maintain a knowledgeable staff commensurate in

number and skill level with the products you make and

market

• Ensure that every individual in the company understands

a few fundamental concepts: change control, corrective

and preventive action, root cause and validation

• Establish and maintain a simple, logical and complete

documentation program

SummaryQuality problems or enforcement actions may drive a company

to begin its journey up the compliance maturity curve, but the

best time to take action is before such problems surface. Timely

and proactive efforts to drive sustainable compliance minimize

the risk of quality problems or enforcement action (see Figure

3). Importantly, when not distracted fighting fires, leaders have

the relative luxury to practice the art of compliance – to think

more strategically and design and implement a Stage 4 solution.

Sustainable compliance is the art and science of managing a

business with a clear view of the regulatory requirements that

govern all businesses in this industry. It is a fundamental part

of the healthcare industry – and one that can profoundly affect

the financial health of the enterprise. It is a component of the

business that deserves as much attention to excellent planning

and flawless execution as any other. Done well, it provides

competitive advantage, growth and financial health for the

shareholders; done poorly, it can mean interruption of supply

to customers, long-term decline of a firm’s credibility and the

ultimate demise of the business enterprise. Understanding

compliance as a core business process and integrating it into the

way the organization lives and breathes is the way to success. PA

Figure 3: Where is your company on the compliance maturity curve?



Product Center

Faster pipetting The lightweight, cord-

less design of the

Thermo Scientifi c S1

Pipet Filler enables fast

and effi cient pipetting

over longer periods of time with

maximum comfort. It features a volume

range of 1 to 100 ml and a large backlit

LCD display with battery-charge and

speed-set indicators so users can confi rm

– at a glance – whether there is enough

power to complete the current run. A

lithium-ion battery provides 15 hours of

continuous use.

The S1 Pipet Filler includes separate

aspiration and dispense speeds with

eight diff erent options for precise

performance. Five color options and

an identifi cation area make it easy to

personalize each pipet fi ller. Finally,

each S1 Pipet Filler is supplied with a

table and wall-mounted holder, a 1

mL pipet support, a power supply and

international power adapters. Innovative

“mobile” solution increases data integrity,

eliminates human error, whilst ensuring

patient safety.

Thermo Fisher Scientifi cwww.thermofi sher.com

Accurate color measurementKonica Minolta Sensing Singapore introduces Spectrophoto-

meter CM-5, a bench top spectrophotometer designated for

the pharmaceutical industry. It off ers easy standalone operation

with advance functionality. The innovative operation of CM-5

makes color measurement simple with 3 easy steps. Simply

switch on its power, position the sample to be measure and press

a button to start measuring. It also has a wizard function which

provides step by step guidance to aid users in their instrument

settings, making it well suited for inexperienced users.

CM-5 has a LCD screen and keyboard which can display numeric

data, spectral graphs and colorimetric plots, making it a

standalone spectrophotometer that does not require a separate

computer. The versatility of

the top port design supports

measurement of solid objects,

pills, granules, and pastes. It

also integrates a sliding body

panel which reveals a large transmittance chamber with no

sides, capable of measuring liquids, fi lms or plates up to 60mm

thick. Addressing a wide range of measuring needs, liquid color

measurement in both US Pharmacopeia and EU Pharmacopeia

are available in CM-5, providing great ease of use to the

pharmaceutical industry’s users.

Konica Minolta Sensing Singapore www.konicaminolta.com/instruments

High resolution dataAgilent Technologies Inc introduced the

SureScan Microarray Scanner, the latest

innovation in scanner technology and

the foundation of Agilent’s complete

microarray solution for both gene

expression and CGH/cytogenetics

research applications. The new SureScan

system delivers high sensitivity, wide

dynamic range and high resolution,

providing researchers with the greatest

degree of confi dence in their microarray

results. In addition, the manufacturing

process used on the SureScan Microarray

Scanner is ISO 13485 certifi ed.

The SureScan system off ers a streamlined

workfl ow, allowing researchers to

continuously load microarray slides

while the instrument is operating. With

the system’s random scanning capability,

they can also reprioritize and rearrange

the scan queue order at any point

during the operation. Raw image data is

automatically loaded into Agilent Feature

Extraction software, eliminating manual

transfer. The compact Microarray Scanner

(16.5 in. high, 17 in. wide and 26 in. deep)

conserves bench space. The system also

combines a newly designed slide cover

and a built-in ozone barrier system

to minimize dye signal degradation,

protecting valuable samples. Extremely

sensitive results are achieved by the

dynamic autofocus mechanism in

conjunction with a detection limit of

as low as 0.01 fl uorophores per square

micron. These enable users to capture

quality data from samples with both low

and high signals.

Agilent Technologieswww.agilent.com

30 Micron Feature at 5 Micron Resolution. 30 Micron Feature at 2 Micron Resolution.



Product Center

Proteomics mass spectrometry

Safe, precise fi lling Bosch Packaging Technology

presents the new MLF 40x0

for the safe fi lling and

capping of injection bottles

in the two to fi ve milliliter

format. This new unit, based

on the MLF 30x0 series,

handles up to 200 pieces per

minute and provides gentle

and safe container transport.

High quality is assured

through the optimized 100 percent in-

process weight control (IPC), for precise

tare and gross weighing.

The MLF 40x0 is continuously fed from

a turntable, or a transport belt, with

the incoming containers individually

transferred to the indexing transport

system via a servo-controlled segmented

star wheel. At the outfeed of the

machine, the containers are transferred

by another segmented star wheel to a

continuous stream and conveyed onto a

transport belt or a tray. The fi lling station

of the MLF 40x0 is available in a four or

Scientists at ETH Zurich and AB SCIEX are working together

to deliver a new mass spectrometry-based technique for

scientists to get quantitation on every peptide in a single

proteomics sample analysis. SWATH Acquisition is said to be

a breakthrough for proteomics mass spectrometry users to

conduct comprehensive quantitation on the entire proteome.

As a next step in its MRMAtlas collaboration with ETH Zurich,

AB SCIEX is developing enhanced MS/MSALL functionality

to enable SWATH Acquisition on the AB SCIEX TripleTOF 5600

System for scientists to utilize around the world.

SWATH Acquisition is being developed in collaboration

with ETH Zurich to provide a new type of system for future

proteomics research that is expected to generate new and

exciting proteomics discoveries and overcome the diminishing

scientifi c returns that iterations on current mass spectrometry

platforms are delivering. A key advantage of the technique is

that it provides a complete quantitative and qualitative archive

of the sample that can be retrospectively interrogated in-silico,

as new hypotheses are developed.

This new technique is said to be a perfect complement

to the MRMAtlas, which is a database that provides mass

spectrometry-based assays to a large proportion of the human

proteome. Scientists around the world can use this atlas to

signifi cantly advance biomarker research, protein-based drug

development and fundamental biological and biomedical

research. The MRMAtlas provides simple, validated assays

expanding into “never-before-seen” areas of the proteome. With

SWATH Acquisition on the TripleTOF 5600 System, the MRMAtlas

will be more valuable to a greater number of scientists.

AB SCIEXwww.absciex.com

eight pitch design, with a horizontal

fi lling needle motion, depending upon

the volume of the containers. In addition

to the standard rotary valves piston

pump system, all current fi lling systems,

such as Time to Peak Filling (TPF) or

rolling membrane pumps, are available.

The MLF 40x0 uses “Clean Feed” sorting

equipment, for the loading of stoppers

and caps into the sorting bowls. Along

with low loading heights the laminar

fl ow is less aff ected and the particle

generation is minimized.

Bosch Packaging Technologywww.bosch.com

Monitoring critical drugs Dyzle has launched its new leading edge

solution for the pharmaceutical industry

– the PharmaTag. The approach is simple:

a thin measuring device, the size of a

credit card, travels with the product

during its entire journey. Upon arrival, it

provides the receiver with the shipment

temperatures for its entire transport

chain. If the vaccine temperature has

been exposed during transportation, this

is instantly alerted to the hospital with

an alarm on the PharmaTag and this can

be automatically communicated to all

stakeholders in the transport chain over

the internet. The product owners and the

logistics service provider can then use

this data to implement improvements in

their cold chain.

Dyzle www.Dyzle.com

A Leading Resource for the Pharmaceutical Industry• Published eight times a year

• Distributed to 6,000* qualified readers across Asia

• Coverage on drug discovery, clinical trials, pharma IT and more

• Available in print, e-book, e-newsletter and web formats

A Leading Resource for the Pharmaceutical Industry

* Publisher’s own data as at July 2011

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Pharma Asia Sep-Oct 2011