Pakistan Clinical Research Capacity

Pakistan

Located in South Asia, Pakistan shares an eastern border with India and a north-eastern border with China. Iran makes up the country’s south-west border, and Afghanistan rune along its western and northern edge. The Arabian Sea is Pakistan’s southern boundary with 1,064 km of coastline.

Pakistan displays some of Asia’s most magnificent landscapes as it stretches from the Arabian Sea, its southern border, to some of the world’s most spectacular mountain ranges in the north.

Pakistan is also home to sites that date back to word’s earliest settlements rivaling those of ancient Egypt and Mesopotamia.

Basic facts about Pakistan

Capital: Islamabad

Largest City: Karachi (about 17 million)

Total Population: 170 million

Area: 796,097 sq. km.

National language: Urdu

Official language: English

Imports: Industrial equipment, vehicles,

iron core, edible oil

Exports: Cotton, textile goods, rice, leather items, carpets, sports goods, handicrafts, seafood

Rawalpindi7%

Hyderabad7%

Karachi46%

Faisalabad11%

Islamabad4%

Lahore25%

Islamabad

Karachi

Lahore

Faisalabad

Hyderabad

Rawalpindi

799,000

9,269,265

5,129,214

2,280,360

1,447,957

1,406,214

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:

:

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Major Cities in Pakistan

Population in Major Cities

Growth rate: 8.4% this is the figure being talked about everywhere - making Pakistan the second fastest growing economy in the world, just behind China.

Inflation: 9.1%.

Per capita income: $736, almost 12 per cent higher than last years $657.

GDP: $123 billion.

Literacy rate: 52%

Health Budget: Rs. 38 billion (US$ 634 million)

Economic Survey of Pakistan

Health Infrastructure

Health Facilities

Hospitals in Public Health Sector 916Rural Health Centers 552Basic Health Units 5,301Dispensaries 4,582Registered Doctors 113,206Registered Dentists 6,127Nurses in Public Health Sector 48,446

Majority of doctors and hospitals are located in cities and towns – rural population has much less access to healthcare facilities

Clinical Research Capability and Infrastructure

Ethical Environment

Most of the tertiary care hospitals have there own ICH GCP compliant Ethics Committees

These committees meet on regular basis

Average approval timelines are between 4-6 weeks

Ethics committee fee ranges from US$ 500-3000

Regular reports need to be submitted to these committees on study progress and at closeout

Regulatory Approval Process

The clinical research wing of the ministry of health Pakistan takes care of the regulatory approval for CTM import as per Pakistan GCP guidelines

It is not necessary to obtain a separate approval for the export of biological materials from Pakistan

Import license is issued with the approval

The approval timelines are between 4-8 weeks

1. Investigator Brochure2. Final Protocol3. Informed consent form (English & Urdu)4. List of participating countries5. Phase of trial6. Quantity of Drugs to be imported on form-4 of drugs import & export rules 19767. Site of the trial8. C.Vs of investigators9. Ethical committee approval with complete composition of committee i.e., names and

designations of the members10. GMP certificate along with free sales certificate/ certificate of pharmaceutical product11. Preclinical and clinical data and safety studies.12. Summary of the protocol13. Summary of the Investigator Brochure 14. Adverse Event Reporting form15. No. of patients to be enrolled in each center16. Name of monitors/clinical research associate17. Evidence of registration in country of origin18. Copy of registration letter (if registered in Pakistan)19. Sample of label of drug20. Duration of trial21. Fee for clinical trial Rs. 5000/-

DOCUMENTS REQUIRED FOR REGULATORY APPROVAL

Approval Process – Phase I

No policy to process Phase I studies at the present:

WHY?

• Lack of infrastructure and specific facilities within the country

• Phase I studies are mainly concerned with the innovative drugs which are mainly dealt by the multinational companies with established research organizations and they have their own priorities to conduct such studies in their specific/notified regions.

• The process for approval has been initiated but not yet finalized (National and International assistance has been requested)

Complete Incomplete

New molecule Registered

Expert Evaluation

Rejected Approved

File sent to DDG (R&D)

Drugs Controller (R&D)

Director General (Health)

ADC (CT) License issued for the import

of drugs to conductClinical Trial

Firm informed about deficiencies

Rejection letter Issued with observationsof the Expert

Application & Protocol checked by ADC (CT)

Application & Protocol submission in the Clinical Trial Section

Approval Process (Phase-II & III)

Complete Incomplete

Expert Evaluation

Rejected Approved

DDG (R&D)

Drugs Controller (R&D)

Director General (Health)

ADC (CT)

Licence issued for the conduct of

Clinical Trial

Firm informed about deficiencies

Rejection letter Issued With Observationsof the Expert

Application & Protocol submission in the Clinical Trial Section

Scrutiny of Application by the ADC (CT)

Approval Process Phase IV

Timelines for Application Scrutiny/ Processing of Clinical Trial

Registered Molecule:

– Scrutiny of application………………………………7-10 working days

– Approval process from DG (Health)……………….7-10 working days

New Molecule:

– Scrutiny of application………………………………7-10 working days

– Expert opinion………………………………… ……40-50 working days

– Approval process from DG (Health)………….……7-10 working days

Note: In case of any clarification, processing is done accordingly

02468

101214161820

2003 2004 2005 2006 2007 2008

Clinical Trials Approved by Ministry of Health - Pakistan

Comparison of Phase II & Phase III Conducted in Pakistan

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2003 2004 2005 2006 2007 2008

Phase-IIPhase-III

COMPANIES CONDUCTING CLINICAL TRIALS IN PAKISTAN

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12

14

2003 2004 2005 2006 2007 2008

GSK

Novartis

Pfizer

BMS

Bayer

CRO/DRs

Abbott

COURIER SERVICES

All major courier services are operational in Pakistan i.e., FEDEX, TNT, World Courier etc. Biological specimens can be shipped overseas in Liquid Nitrogen,dry ice, with ice packs or at ambient temperature depending on the requirement of specific specimensSpecimens have reached destinations in the US from Pakistan within 48 hoursInternational safety guidelines are followed during transportation of biological specimens

Some Major Research Sites with Phase II and Phase III International Studies Experience

1. NORI, Islamabad2. Nishtar Hospital, Multan3. Aga Khan University Hospital, Karachi4. Jinnah Post Graduate Medical Centre , Karachi5. Dow University of health Sciences, Karachi 6. Jinnah Hospital, Lahore7. Lahore General Hospital, Lahore8. Services Hospital, Lahore9. Rawalpindi General Hospital, Rawalpindi10. Lahore General Hospital, Lahore11. Doctor's Hospital, Lahore12. Fountain House, Lahore13. Liaquat National Hospital, Karachi14. Ziauddin Hospitals, Karachi15. Al Shifa Hospital, Islamabad16. Bismillah Taqee Inst. of Health Sciences and Blood Diseases Ctr., Karachi17. BAQAI Hospitals, Karachi18. Liaquat National Hospital, Karachi19. National Medical Centre, Karachi20. Combined Military Hospital, Rawalpindi21. Shaukat Khanum Memorial Cancer Hospital, Lahore22. Cancer Research Group Foundation, Pakistan (working in > 20 hospitals in Pakistan)

Multinational Pharma in Pakistan involved in Clinical Research

GSK

Pfizer

Bayer

Novo Nordisk

Novartis

Sanofi-Aventis

Eli Lilly

Major Clinical Research Areas

Oncology

Neurology

Psychiatry

Endocrinology

Cardiovascular

Infectious diseases

Ophthalmology

Market potential is good for antibiotics, vaccines, analgesics, tranquilizers, hormones, anti-hypertensives, anti-ulcerants, cardiovascular, anti-cancer, psychiatric, contraceptives and birth control drugs.

CROs and SMOs in PakistanMultinational CROs

Parexel APEX International, Taiwan (working through Metrics Research)

Kendle International, USA (working through Metrics Research)

PRA International, USA (Agreement signed with Metrics Research as subcontractor)

Pharm-Olam International, UK (Agreement signed with Metrics Research as subcontractor)

Covance, USA (working indirectly, Metrics working at its sites as SMO)

Quintiles, USA (have hired local CRAs and will be opening offices soon)

PPD is planning to enter the market on their own

EPS International, Agreement signed recently

CROs and SMOs in Pakistan

Indigenous CRO/SMOMetrics Research (Pvt.) Ltd. www.mrcro.com

Have multinational collaboration with CROs and academic institutes

Have the capability to conduct and manage preclinical and Phase II,III and IV clinical research in major cities of Pakistan

Research cells established in various cities

Have the biggest clinical research team after GSK, Pakistan

Is the only certified clinical research training provider in Pakistan

Economy of Conducting CR Studies

US$ 1 = Rs. 80

40 to 50% economical than US and Europe

Clinical research personnel salary structure is less than India

Investigator fee is less than or comparable to India

All associated tests and scans are much cheaper than US and Europe

The Pakistan Advantage

A large diverse and heterogeneous population of Indo-European descent most of who are treatment naive

Availability of evaluable patients in numerous therapeutic categories

Relatively fast pace of recruitment

Low cost in conducting clinical trials

A willing population eager to participate in novel drug therapies

A government that is proactive that supports and encourages induction of trials such as the ministry of health, trade development authority of Pakistan, higher education commission, and the ministry of labor and manpower

English cultural and colonial influence with English as the co-official language and business language of communication

The Pakistan Advantage

GCP compliant sites committed to upholding international conventions and ethical standards

Lack of regulatory hurdles due to an increasingly accommodating regulatory environment

Relaxed duties and taxes on import of test articles and supplies

Pakistan’s highly talented English speaking workforce with international post graduate experience

Extremely labor and investment friendly environment of Pakistan

Low manpower costs

High quality of service

Good infrastructure with large tertiary care setups

External Economic Drivers for Pharmaceutical Setups

Approximately 56,000 doctors - both general physicians and specialists - whose prescriptions are the main sales drivers for the industry

A cut in government duties on pharmaceutical raw materials and packing materials

Export opportunities due to WTO implementation

Manufacturing and marketing of cheaper new generic drugs by National Companies

Tax holidays for setting up of new pharmaceutical plants

Government setting up new industrial estates specifically for the pharmaceutical industry

5 Key Reasons to Invest In PakistanGeostrategic LocationLocated in the heart of Asia, Pakistan is the gateway to the energy rich Central Asian States, the financially liquid Gulf States and the economically advanced Far Eastern tigers. This strategic advantage alone makes Pakistan a marketplace teeming with possibilities.

Trained and Talented WorkforceEnglish is the official language and primary means of communication at businesses and educational setups

Economic OutlookPakistan had one of the fastest growing economies of the world having touched a GDP growth rate of 8.4% in 2005. Today Pakistanhas 170 million consumers with an ever growing middle class. Foreign investment had risen sharply from an average of $400 million in the 1990s to over $ 3.5 billion in 2005-06. Fiscal deficit had declined from an average 7% of GDP in the 1990s to around 3% in recent years. And FOREX reserves had increased from $3.22 billion in 2000-1 to $13.14 billion in 2005-6.

5 Key Reasons to Invest In Pakistan

Investment PoliciesCurrent investment policies have been tailor made to suit investor needs. Pakistan’s policy trends have been consistent with liberalization, de-regulation, privatization, and facilitation being its foremost cornerstones.

Financial MarketsThe capital markets are being modernized, and reforms have resulted in development of infrastructure in the stock exchanges of the country. The Securities and Exchange Commission has improved the regulatory environment of the stock exchanges, corporate bond market and the leasing sector. Whilst the CentralBoard of Revenue has facilitated structural reform in tax and tariffs and the State Bank of Pakistan has invigorated the banking sector into high returns on investment.

The outsourcing opportunities exist in:

Contract research & development

Bulk drug & formulation manufacture

Co-marketing & sales

Clinical trials including

Technical services like data management

Expertise in herbal and nutraceuticals

Primary packaging materials

Software development

Outsourcing Opportunity

Pakistan Diseases Profile

Top causes of Morbidity and Mortality

Mental IllnessThere are one million severely mentally ill and over 10 million individuals with neurotic mental illnesses within the country (10% among men and 25% among women)Traffic AccidentsFurthermore, 1.4 million road traffic crashes were reported in the country in the year 1999. Of these, 7000 resulted in fatalities.Substance Abuse4.8 million in the year 2000 (growth rate of 7%)HIVHIV/AIDS - adult prevalence rate: 0.1%HIV/AIDS - people living with HIV/AIDS:74,000 HIV/AIDS - deaths: 4,900

CAD26.9% in men and 30.0% in womenOne in four middle-aged adults in Pakistan has prevalent CAD

STROKESRaised blood pressure has been observed in 23-64% of the patients suffering from stroke31-42% were found to be suffering from diabetes33-53% of stroke patients were current smokers11-17% were found to be overweightMajority suffered from cardiac disease (46%) and hyperlipidemia (30%)Carotid artery stenosis was observed in 8%

Top causes of Morbidity and Mortality

Top causes of Morbidity and Mortality

Data on biological risk factors of coronary heart disease and stroke

There were an estimated 5.5 million men and 5.3 million women with hypertension in the years 1990-94

The prevalence of hypertension over the age of 15 years was reported at 17.9%, with a higher prevalence observed in urban areas (21.5% vs. 16.2%)

Over the age of 45 years, prevalence was reported at 33%, implying that one in every three Pakistanis over the age of 45 years suffers from high blood pressure A.

Top causes of Morbidity and Mortality

Obesity In the age group of 25-44 years, 9% of the rural men were overweight compared with 22% of the urban men; for women, prevalence of overweight in rural areas was 14% versus 37% in urban areasWhen stratified by age, sex and residence, prevalence of overweight was highest (40%) in urban females aged 45-64 year

Dyslipidemia7.3 million people has high blood cholesterol levels31% of the adults have raised blood cholesterol

Top Causes of Morbidity and Mortality

Rheumatic FeverUrban: 22/1000Rural: 5.7/1000

Diabetes Overall prevalence: 11.47%

Tobacco Use in Pakistan54% men and 20% women using tobacco in one form or the other

ThalassemiaFive thousand children in Pakistan are born with thalassemiamajor every year5-6 per cent of Pakistan’s population is carrier of thalassemiagene

Top causes of Morbidity and Mortality

Hemophilia10,000 cases of hemophilia A and 2,000 case of hemophilia B in the country

Malaria131,179 confirmed cases of malaria from public sector sources in 2003

TuberculosisTuberculosis is responsible for 5.1% of the total national disease burden; its incidence is reported at 177/100,000 population whereas the annual mortality on its account has been estimated at 67,500

Hepatitis B and CCommon cause of acute hepatitis in PakistanHepatitis B positive male volunteer blood donors in Karachi has recently been estimated at 2%Sero-prevalence of HCV in blood donors has been reported at 1.8%

Blindness1.5 million blind people within the country

Leprosy1/100,000

Cancer in Pakistan

Incidence of cancer in Pakistan is 730,956/annum

The population of Pakistan has been reported to have the highest rate of breast cancer of any Asian population and one ofthe highest rates of ovarian cancer worldwide

Recessively inherited genes may contribute to breast and ovarian cancer risk in Pakistan

Incidence of Cancer in Pakistan

In Pakistani men the 7 most common cancers are:

1. Lung Cancer (18% of all cases)

2. Lymphomas - Hodgkin's disease or Non-Hodgkin's lymphomas (13%)

3. Prostate cancer (8%)

4. Leukemia (6%)

5. Bowel cancer (8%)

6. Bladder cancer (5%)

7. Head, Face and Neck cancers (lip, mouth or throat) (5%)

Incidence of Cancer in Pakistan

In Pakistani women the 7 most common cancers are:

1. Breast cancer (34% of all cases)

2. Cervical cancer - cancer of the neck of the womb (6%)

3. Lymphomas - Hodgkin's Disease or Non-Hodgkin's lymphoma (6%)

4. Ovarian cancer (6%)

5. Leukemia (5%)

6. Bowel cancer (4%)

7. Head, Face and Neck cancers (lip, mouth or throat) (4%).

Incidence of Cancer in Pakistan

Cancer Treatment Facilities

CANCER RESEARCH GROUP (CRG) DATAFifteen Common Tumor in Male & FemaleTotal Patient 45883 1995 - 2000

67075134

4863

3155

1915 18561463 1346 1247 1169 1071 1024 858 672

225

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2000

3000

4000

5000

6000

7000

Brea

stLy

mph

oma

H&N

Bron

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STS

Leuk

aem

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CNS

Ovar

yUr

inary

Blad

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Cerv

ix

Liver

Colo

nPr

osta

teGa

ll Blad

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Bone

CANCER RESEARCH GROUP (CRG) DATATen Common Tumor in FemaleTotal Patient 209031995 - 2000

6707

15901346

1169 1155 697 672664 467 293

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6000

7000

Brea

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H&N

Ovar

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Cerv

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Gallb

ladd

erLe

ukae

mia

Bron

chus

CNS

CANCER RESEARCH GROUP (CRG) DATATen Common Tumor in MaleTotal Patient 249801995 - 2000

3979

3273

2688

1247 1218 1192 1170 1071858 813

0

500

1000

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2000

2500

3000

3500

4000Ly

mph

oma

H&N

Bron

chus

Urina

ry B

ladde

r

STS

Leuk

emia

CNS

Liver

Pros

tate

Colo

n

Demographics of Cancer in Pakistan

Total Population in Pakistan : 170 Million