Challenges in Export and Import of Temperature Controlled

Pharmaceuticals from India

Chilukuri Maheshwar Anglo Eastern Maritime Academy

10th Annual Cold Chain & Temperature

Management Global Forum Chicago, 24-28 September 2012

Movie clip

India - Among emerging economies

• BRIC: Brazil, Russia, India & China

• BRICS: Brazil, Russia, India China & South Africa

• BRIICS: Brazil, Russia, India, Indonesia, China & South Africa

• BRICKET • BRICM • BRICK • Next Eleven • CIVETS

Features of Emerging Economies Flips • Perceived as growth centres of the future • Drivers of future economic growth • Bullish investor confidence • Show higher economic growth rate compared to developed

countries • Expected to play a greater role in areas like financial markets,

consumption of goods and services, trade and commerce, sustainable development, innovation, infrastructure development and research.

Flops • Asia has lesser public spending ratios because of less extensive

public insurance coverage and benefit packages • Competing expenditure needs and constrained revenue raising

capacity

Public Health Care Spending

Challenges and Solutions - Emerging Economies

CHALLENGES • Lower average life expectancy

and Higher infant mortality • Limited funds to improve

health standards • Less extensive health coverage • Ill aligned incentives

(motivation) for health care providers

• Large informal labour market • Lower General awareness

levels about sanitation and hygiene

SOLUTIONS • Increase public health spending • Improve the general health safety

net • Importance and expansion of

primary and preventive health care • Incentives for health care providers • Focus on providing most essential

health services • Improve efficiencies of existing

health care systems by leveraging economies of scale.

INDIA’S SYMBIOTIC RELATIONSHIP WITH USA

• Over 40% of the generics prescribed are from India

• To ensure continued supply of the low cost quality generics from India, the US FDA has opened India office

• 1 out of 5 US FDA inspections for approvals are in India

• Share of generics in the overall US market expected to rise to 21-22% by 2015 from around 12-15% now.

• Which means pharma exports from India will double every three years

• Indian firms have about 35% of the total ANDA approvals in the US

• Based on their marketing and distribution networks and manufacturing capacities, Indian firms could see as much as 15-28% annual growth from the US, predict experts.

• To overcome the recent shortage of cancer drugs J & J’s Doxil in USA, the US FDA sought Sun Pharma’s help in providing their chemotherapeutic drug Lipodox from India

• This opens up opportunities for Indian drug generic makers as close to 287 essential drugs are estimated to be in short supply in the US.

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GLOBAL RECOGNITION

• Bill Clinton's foundation, Clinton Health Access Initiative (CHAI) got further discounts from Indian generic manufacturers that reduced the cost of combination drug treatments for AIDS, which can reach thousands of dollars per year in the West, to as low as $120 a year per patient.

• Many Indian companies are part of this agreement where Lamivudine, Stavudine, Zidovudine, Nevirapine will be supplied to a few African countries.

• India has highest number of approvals from the US President's Emergency Plan for AIDS Relief (PEPFAR).

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• India manufactures and exports medicines from all therapeutics groups.

• Many original innovator companies source their discovered drugs from Indian companies.

• India is a world leader in anti-AIDS and anti-TB segments and for some of the latest patented medicines like Glitazones, Celecoxib, Statins, Montelukast and many anti-cancer drugs

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ADVANTAGE INDIA

COLD CHAIN in Pharma

• Worldwide sales of vaccines predicted to rise

to $35 billion by 2014

• Huge growth of temperature sensitive

vaccines is driving the development of novel

technologies for transportation and logistics

such as thermo stable vaccines, solar “battery

free” refrigerators, “zero energy” cold chain

electric vehicles and longer-term passive

storage containers.

• Development of sub-sectors such as biotech,

medical devices, clinical trials and diagnostics

are fuelled by high levels of innovation.

leading to individual customer-centric

solutions

• India, with $ 2.36 bill. in biopharma market is

set to become one of top 5 producers of

biopharmaceuticals in the world by 2020.

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Pharma/Biotech Cold Chain

Process

COLD CHAIN IN PHARMA (contd…)

• Driven by regulations, more pharma products require

temperature control handling from refrigerated to ambient to

cold, broadening the cold chain market.

• Break in cold chain for most products may result in value

erosion financial loss, but break in cold chain of Pharma

products (vaccines, life saving drugs etc) could be fatal

for patients

• Retailers and Logistic providers may become the weakest

link in supply chain of drugs by the time it reaches the end

consumer, if proper care is not taken

• A study by UK-MHRA reveals that 43% of critical and major

product deficiencies are related to ineffective temperature

control and monitoring during storage and transportation.

• WHO recently maintained that 25% of all vaccine products

arrive at their final destination in a degraded state.

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COLD CHAIN in Pharma (contd…)

• The distribution process must be validated to ensure that

there is no negative impact to the safety, efficacy or quality

of the drug substance

• GMP environment requires that all processes that might

impact the safety, efficacy or quality of the drug substance

must be validated, including storage and distribution of the

drug substance.

• More than 50% of the problems faced by manufacturers

and retailers in cases of rejections of pharma products as

‘not of standard quality’ by regulatory authorities is due to

not giving due importance to Good Distribution & Storage

Practices.

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‘Cold’ Chain System

• High protection is good, but appropriate protection is better!

• Majority of commonly recommended vaccines require storage

temperatures of 35

F - 46

F (2

C - 8

C) and must not be exposed to

freezing temperatures, which can irreversibly reduce the potency of

vaccines.

• Physical changes are not always apparent after exposure to freezing

temperatures and visible signs of freezing are not necessary to result

in a decrease in vaccine potency.

• An estimated 17%--37% of providers expose vaccines to improper

storage temperatures, and refrigerator temperatures are more

commonly kept too cold than too warm

• Although the potency of the majority of vaccines can be affected

adversely by storage temperatures that are too warm, these effects are

usually more gradual, predictable, and smaller in magnitude than

losses from temperatures that are too cold.

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Pharmaceutical Cold Chain

• Complex drugs and pharmaceutical products market expected to grow to U.S. $900 billion by 2012 and $1.2 trillion by 2014.

• Life-saving products like vaccines : $35 billion market by 2015 • 25 percent of all healthcare products are temperature-

sensitive, meaning they require refrigeration during transportation and storage from manufacturer to end user.

• By 2014, $16 billion worth of biological and vaccine shipments will require temperature-controlled rooms during transit.

• Short window of viability, which makes rapid transport essential.

• Monitoring temperatures and maintaining the proper packaging environment during transport are critical to maintaining the viability of these high-value shipments.

Pharma Markets and Vaccines • Effective cold chain shipping is critical, as pharma

and biopharma cold chain shipments in markets worldwide are expected to grow dramatically in future.

• Emerging Economies are the drivers of volumes • South Asia seen as the fastest growing cold chain

shipment volume region • Cold Chain Infrastructure less developed here,

losses maximum in this region • One of the first and foremost tools for preventive

health care is Vaccination. • In 2005, nearly half of all vaccines got ruined in

transit due to poor cold chain services: WHO

India: Polio Vaccination Movement

• 1996: Polio Eradication Program started

• 2000: Expected Global Eradication of Polio

• 2007: 866 Polio cases reported

• Fresh Polio cases are still being reported.

• One of the reasons for the failure of Polio Vaccination program in India is the absence of an effective cold chain which rendered the vaccine ineffective

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CHALLENGES UNIQUE TO INDIA

• In the hot climate of India it is definitely a challenge maintaining product temperature throughout the distribution network, with external temperatures easily over 30

C

• India's cold-chain market is still in its developing stages, and thus there is a lack of temperature-sensitive services from the point of origin to the point of consumption.

• Sub segments like medical devices, biotech, clinical trials etc. to which India contributes about 8% of world's pharma output is expected to grow to a $ 50 billion market by 2020.

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Why such losses in this region?

• High Ambient temperature • Poor transport infrastructure • Lack of knowledge and awareness • Poor roads and poor connectivity • Dusty atmosphere • Non availability of refrigerated carriers • Difficult Geographical terrain • Cold Chain Infrastructure is a Non priority sector for the

administration as there are more important priority areas where funds need to be deployed

• Less evolved cold chain shipment regulations • Unreliable grid power

Addressing the Challenges

• Understanding and compliance of Multiple international and country specific cold chain shipment regulations

• Set up a cold chain infrastructure in place

• Training of the various stakeholders including public at large

• Establishing a network of partners who can look after the cold chain shipment at various stages before reaching the end consumer

Distribution Chain

Distribution Challenges

• Distribution in emerging markets presents three particular challenges: • Improving forecast accuracy and data reliability for estimating vaccine or drug demand • Maintaining product stability throughout the distribution chain, including requirements for cold-chain continuity • Managing the dispensing of medical products to patients in the “last mile” of the distribution chain (i.e., the stage where products are delivered from the wholesaler or pharmacy to the consumer).

How to handle the Last Mile?

Challenges

• Smaller Quantities

• Lack of availability of recognised Cold Chain

• Field Difficulties

• Dusty atmosphere

• High ambient Heat

• Language Barrier

• Social Barriers

• Unavailability of Grid Power

Opportunities

• Extension of Cold Chain right till the end

• Innovative Methods of Maintaining Cold Chain

• Indigenous Methods of Preservation

• Innovation and use of Technology in communication

Pharmaceutical Sector vs Agricultural Sector

• Economic Losses more severe in Pharma sector

• Administering a damaged vaccine or drug is far more dangerous

• Erosion of the sense of security in vaccination

• Pharma Volumes smaller to justify air transportation over ocean transportation

• Urgency of requirement in case of vaccines and drugs

Features of an Effective Cold Chain

• Temperature Measurement, Monitoring, Control and Recording

• Traceability

• Accountability

• Transparency

• Effective Communication

• Networking and Involvement

The Pharma Export Process

Partners in Temperature Controlled Pharma Products Export Process

• Manufacturer • Ground Transport • Airport • Airline • Destination Airport • Forwarder’s Terminal • Intermediate Stops & Transfers • Distributor’s Warehouse • Consumer Outlet • End Consumer

Challenges in the Export Process - Manufacturer

• Good Quality Raw Materials,

• Controlled Manufacturing Practices,

• Cleanliness,

• Dust Free Atmosphere,

• Strict Quality Control

• Good Packaging,

• Traceability

• Storage in Required Temperature and Atmospheric Conditions

Challenges in the Export Process – Ground Transport

• Delicate Handling while loading into truck

• Correct Stacking and Stowage inside the Truck

• Transportation under Required Temperature and Atmospheric Conditions

• Prevent deterioration and Ensuring Durability of the Packaging

Challenges in the Export Process – Departure Airport

• Delicate handling during unloading from the truck

• Storage under Recommended Temperature and Atmospheric Conditions during the waiting period

• Careful handling during transfer into the aircraft

Challenges in the Export Process – Airline

• Correct Stacking and Stowage inside the Aircraft

• Adequate Lashing and Securing of the Packages to prevent movement and vibration

• Maintenance of Correct Temperature and Atmospheric Conditions during the flight

• Regular Monitoring and Recording of Temperature and other conditions

Challenges in the Export Process – Destination Airport

• Delicate handling during unloading from the aircraft

• Storage under Recommended Temperature and Atmospheric Conditions during the waiting period of arrival formalities and documentation

• Careful handling during transfer into the Forwarder’s Terminal

Challenges in the Export Process – Forwarder’s Terminal

• Maintenance of Correct Temperature and Atmospheric Conditions during the period of stay in Forwarder’s Terminal

• Regular Monitoring and Recording of Temperature and other conditions

Challenges in the Export Process – Intermediate Stops & Transfers

• Careful handling during transfers

• Correct Stacking and Stowage during transfers

• Adequate Lashing and Securing of the Packages to prevent movement and vibration during transfers

• Maintenance of Correct Temperature and Atmospheric Conditions

• Monitoring and Recording of Temperature and other conditions

Challenges in the Export Process – Distributor’s Warehouse

• Maintenance of Correct Temperature and Atmospheric Conditions during storage

• Monitoring and Recording of Temperature and other conditions during storage

• Maintaining Traceability

• Cleanliness and Dust Free Atmosphere

Challenges in the Export Process – Consumer Outlet

• Maintenance of Correct Temperature and Atmospheric Conditions during storage

• Monitoring and Recording of Temperature and other conditions during storage

• Maintaining Traceability

• Cleanliness and Dust Free Atmosphere

• Careful handling

• Easy Accessibility

• Simple and Efficient Documentation during Dispensing

Challenges in the Export Process – End Consumer

• Maintenance of Correct Temperature and Atmospheric Conditions during storage

• Small quantities – easy to store and handle

• Careful handling

• Maintaining the Required Documentation and Records

Remember, The Process ends only after the product is finally used by the End Consumer

Introspection • Do we have something in Pharma Supply Chain identical to

360 Quality and Zero Damage Concepts in Northern Europe for Perishable Export Cargo

• Do we have a clear understanding of the export process? • Have we identified and enpowered all the partners in the

Supply Chain? • Have responsibilities been clearly identified? • Is there Transparency? • Is there Accountability? • Is there Traceability? • Does free flow of communication exist? • Finally, are we always keeping the end consumer in sight all

through the process?

End Consumer

This could be our End Consumer!

Acknowledgements

• UK P&I Club • Cold Chain India Summit 2012 Hyderabad, 7th -

8th June 2012: VISIONING INDIA AS GLOBAL

GENERICS SUPPLIER: DAARA B PATEL SECRETARY – GENERAL, INDIAN DRUG

MANUFACTURERS’ ASSOCIATION (IDMA) MUMBAI, INDIA

Thank you

Namaste