Group 6

CASE TITLE: WHEN SUPPLY IS

OF PUBLIC INTEREST: ROCHE &
TAMIFLU
Prof in charge – Prof. Chetan Prabhu

Roll No. PRN Name

44199 21020141099 Namrata K

44209 21020141109 Komal Agrawal

44211 21020141111 Kshitiz Agarwal

44212 21020141112 Kshitiz Jaiswal

44215 21020141115 Lovish Kumar

44216 21020141116 Madhusudan Shah

44219 21020141119 Mainak Sarkar

44220 21020141120 Majety Mani Midhilesh

44223 21020141123 Mansi Nigam

44224 21020141124 Manvendra Pratap Singh

44241 21020141141 Neha Mishra

Q1. Discuss the reasons Roche decided to develop its oral drug Tamiflu and not a vaccine for
dealing with the influenza pandemic. What forecasting and delivery approach did it follow to
cater to worldwide demand and what specific challenges did it face in this process.

Roche chose to develop Tamiflu, an oral antiviral drug, rather than a vaccine to combat the influenza
pandemic because it provided an immediate response to the first wave of the pandemic, whereas vaccine
development takes time and could only begin once the pandemic had begun and the strain had been
identified. Furthermore, mass production would have taken more than six months to meet the demand.
When it came to vaccine development, there was a barrier in terms of production capacity.

To top it off, the oral medication was effective against both Type A and Type B influenza strains and
could be given for both prevention and treatment, whereas the vaccine could not.
Tamiflu's manufacturing method was hard and capital costly because it was an oral antiviral medication.
It took almost eight months to complete the manufacturing process. Roche had to begin developing the
medicine around ten to eleven months before the start of the winter flu season (taking into consideration
2-3 months lead time to start production).

Demand forecasts would be used to guide production. They would shelve their items and sell them
again the next season if the number of influenza cases was lower. The forecasting was done using
historical data that the company had on hand. Roche had data on the quantity of products sold in the
previous year for various regions and continents, and they could use this information to develop a time
series forecasting algorithm. Roche also had to use the qualitative method of demand forecasting to
predict demand for the following season.

They needed to enhance their capacity in the event of a pandemic, but they couldn't predict the demand
from various national governments. They had no choice but to rely on their judgement and go with a
qualitative forecasting strategy in such a situation. Roche opted to produce at risk in anticipation of
demand due to the length of the production cycle.
In terms of delivery, Roche used a first-come, first-served strategy for governments, based on the date
the order was placed. It was when the demand for Tamiflu outstripped their ability to supply it. Some
countries had to wait up to a year for the drugs to arrive.

The main challenges faced by Roche in this process were as follows:

• A limited capacity of production
• Lengthy production cycle time
• A complicated production process that made it difficult to respond quickly to a monumental
surge in demand
Roche also faced problems in capacity expansion due to the complications involved in steps 1 and 3,
namely extraction of shikimic acid and the conversion of epoxide into azide. For step 1, Roche was
dependent on the availability of a specific type of star anise in China, and for the third step, production
had to be done in small vessels as the process was hazardous, with a high risk of explosion.
Q2. Assess Roche’s supply chain network strategy to deal with the huge demand of Tamiflu when
the pandemic hit the USA and the global world.

Roche recognized that in the event of an avian flu pandemic, vaccination would be the best treatment
for controlling its spread; however, because it would take a significant amount of time to classify the
strains of the flu and develop a vaccine, antiviral drugs such as Tamiflu would be influential in halting
the pandemic's spread.

Roche made the decision to increase production capacity in small increments during 2004-2005, while
also collaborating with the US government to develop a pandemic preparedness plan. Following
Hurricane Katrina, the United States government directed Roche to produce 200 million treatments,
which was four times Roche's annual production capacity, with all of it manufactured in the United
States. This was a watershed moment for Roche, and it began taking significant steps to increase its
production capacity.

In 18 months, the team decided to increase production to around 300 million treatments. While the
majority of the production would take place in the United States, it would be available for purchase all
over the world.

Roche made the decision to expand its manufacturing plants all over the world while not using qualified
suppliers on a consistent or ongoing basis. However, if the need arises, the supplier's requirement, which
implied the supplier's capacity, should be used. Following these steps, the Roche team established an
8-month timeline, which seemed optimistic given that the process could have taken nearly two years.

Roche's next task was to build, register, and test the network, followed by implementing a production
plan that could clear the backlog. It was also necessary for the supply network to be qualified on a
global scale. Roche compiled a list of potential suppliers and included one extra supplier as a backup
for each step. Roche was able to qualify all of its suppliers and grow from a network of 12 entities to a
network of 28 entities. Some businesses also completed more than one production step.

It was difficult to increase the capacities in the Shikimic acid and Azide steps. They relocated the
fermentation process for Shikimic acid to a food chemical manufacturing firm, and they sponsored a
start-up capable of rapid technological transfer for Azide. The health authorities cooperated with
Roche's quick approach and accelerated the Tamiflu product approval process.

During 2005-2006, Roche worked with Government bodies and the WHO on preparedness planning
and tackled issues of affordability, access, and coverage around the world. Roche granted a sub-license
to HEC and Shanghai Pharmaceuticals in China and Hetero Pharmaceuticals in India.

Countries that did not follow US patent laws were asked to pay a token royalty, according to the
agreement. Roche had a technology transfer agreement with an African company, and Thailand
performed an in-country encapsulation. Taiwan has finally decided to purchase from Roche. This is
how countries gained access to the antiviral drug. A multi-tiered pricing strategy based on the country
of sale ensured the drug's affordability. In support of Southeast Asian and African countries, Roche
donated 2 million courses of treatment to the WHO. Roche created three types of formulations to ensure
easy administration and coverage for young children: powder, API, and syrup.
Q3. Elaborate on the elements of the New Supply Chain process Roche put in place wrt to new
suppliers. Identify any key bottlenecks in the process and what do you think it could have done
to better improve its supply chain network?

The WHO advised countries to maintain a stockpile in case of an epidemic. This prompted the countries
to approach Roche for vaccines for additional countries, posing challenges in terms of capacity
planning, as Roche was required to supply 300 million doses of vaccines, up from 55 million doses
previously. Because scaling up the internal facility was time-consuming and there was a high demand
for antiviral drugs, Roche decided to look into external suppliers who could be used as Tamiflu
manufacturing facilities. The Roche team worked toward two goals: first, to build, register, and test the
network, and second, to implement a production plan that would allow them to quickly clear the
backlog.

Furthermore, the qualification of the available network should support the qualification of the capability
of the supplier. Roche sifted through the many applicants to create a list of 19 potential suppliers, three
of whom were internal to Roche and sixteen of whom were external. They planned to include one
additional supplier for each process step in case one supplier did not qualify. Among the qualities that
Roche sought in its suppliers were quality, technical ability, capacity, and the speed with which that
capacity could be deployed. Roche was eventually able to qualify all of their suppliers, and their supply
chain was expanded from a network of 12 entities, 5 of which were internal to Roche (grey boxes), to
a network of 28 entities, 8 of which were internal to Roche (Some companies perform quite one
production step). As a result of this careful execution, Roche was prepared to quickly improve the
network and implement a production decision to eliminate the backlog. Roche also focused on
affordability by employing a multi-tiered pricing structure for developed, lower-middle- and low-
income countries.

The manufacturing locations, by process step, were as mentioned below:

Shikimic acid: China, France, Germany, Japan, US

Epoxide: Germany, India, Italy, Switzerland, US
Azide: Belgium, Germany, Korea, Switzerland, US
Active Ingredient: Switzerland, US
Encapsulation: France, Germany, Japan, Switzerland, US

The two key bottlenecks that Roche faced within the process were:
● Increasing capacity by an order of magnitude employing a combination of internal and external
production capabilities The standard time for the technology transfer was 12-18 months, and
governmental approval timelines of up to 24 months. Thus, the 18-month goal to accomplish
both was extremely aggressive
● Increasing capacity for shikimic acid production and therefore the azide step

To overcome these Roche looked out for partners outside of the pharmaceutical industry, transferring a
fermentation process to a corporation that manufactured food chemicals and also identified a
replacement supplier that had not previously been within the azide business but had the know-how and
therefore the infrastructure that might allow a rapid technological transfer.
Improvement Steps:

There are certain areas where Roche could have done better, those are highlighted below:
● Roche should have done forecasting of the availability beforehand by using technology.
● There was a delay in technology transfer for internal and external suppliers.
● The usage of higher technology would have reduced the time interval in manufacturing.

Q4. Examine the role played by WHO (World Health Organization) in dealing with the pandemic
situation. Assess its organizational structure, capability, co-ordination, influence and any
limitations to manage the supply-demand crisis of an oral drug or vaccine(s) in the world in the
face of a pandemic situation.

TIMELINE OF ACTIVITIES
On November 17, 2019, the first known case of Covid-19 was reported in China's Hubei province
(South China Morning Post). China, on the other hand, reported instances of pneumonia with an
unknown cause to the WHO on December 31, 2019. Covid-19 was designated a Global Health
Emergency on January 30 and a Pandemic on March 11, 2020, following repeated field visits, including
one led by director Tedros Adhanom personally.

ROLE PLAYED
The International Health Regulations, which have been in effect since 2005, are a legal structure that
represents the WHO's crisis work. Part states will surely disclose infections as soon as they occur under
these regulations, but if they fail to do so, or if they delay reporting, as China did with Coronavirus, the
association will have no hope of persuading them.

The organization received a lot of flak for its failure to criticize the Chinese government, especially
from Donald Trump, who went so far as to warn that America, WHO's greatest funder, would stop
funding the agency. Another point of contention has been the delay in calling Covid a global pandemic
and the consistent release of recommendations on the use of dexamethasone, a medicine with the ability
to treat critically ill patients.

Regardless of the many opinions to the WHO's COVID-19 response, it is undeniable that the
organisation has shown to be incredibly beneficial and the major thrust in the fight against Covid. To
be honest, almost every country on the planet has adopted a global health strategy or response measure
based on WHO guidelines. Furthermore, WHO's efforts in arranging vaccination campaigns to prevent
diseases including Diphtheria, measles, poliomyelitis, tetanus, tuberculosis, and whooping cough have
been notable. The World Health Organization (WHO) played a critical role in the eradication of
Smallpox.

COVAX- VACCINATION POLICY AT A GLOBAL LEVEL

The access to COVID-19 Tools (ACT) Accelerator, which was launched in April in response to the
epidemic by WHO, has COVAX as one of its three pillars. COVAX is concerned with speeding the
development and manufacture of Covid-19 vaccines, as well as ensuring fair access to and supply of
these vaccines to developing nations. In any event, there are two major flaws in the office.
Initially, it just allows antibodies to be measured in terms of population sizes, which isn't the most
accurate indicator of general well-being. Furthermore, it does not take into account a country's ability
to carry out large-scale vaccination campaigns. Vaccines must be stored at extremely low temperatures,
which are not available in developing nations. Blemishes Setting antibody appropriation goals based on
population size is flawed for a number of reasons.

ORANIZATIONAL STRUCTURE
There are 194 Member States, 150 Nation Workplaces, and six Provincial Workplaces in the
Organization. It is a bipartisan legislative organisation that collaborates with its member states, usually
through the Ministries of Health. The WHO is in charge of global health issues, including developing
the health research plan, establishing standards and principles, articulating evidence-based approach
alternatives, providing specialist assistance to countries, and monitoring and analysing health patterns.
Instead of receiving funding from countries, the WHO has relied on giver reserves — primarily from
wealthy nations and foundations such as the Bill and Melinda Gates Foundation.

As a result, 80 percent of WHO funding is currently tied to benefactor-selected initiatives. Work

programmes that are critical to the WHO's order are underfunded because they contradict with the
objectives of large funders, notably affluent and developed countries. As a result, other
intergovernmental organisations, such as the World Bank, and eventually large institutions have taken
over WHO's role as a global health pioneer.

Managing a Demand-Supply Shortage

The WHO is usually fully aware of any supply demand crisis in advance due to its regular monitoring
of the pandemic scenario. A behemoth like the WHO, on the other hand, simply cannot mitigate all
supply chain challenges that occur from a global pandemic due to its sheer size and various external
factors.
In the case of a supply-demand crisis, the WHO releases transparent instructions across all of its value
and supply chains. This is done after a thorough review of the medical equipment scarcity in any form.
From the expense of healthcare to the data used, everything is made public, including the findings of
scientific trials. Aside from that, additional operational costs are disclosed, including manufacturing
costs, supply chain mark-ups, and material and procurement costs. The WHO collaborates with
prominent scientists, businesses, and public health groups to provide a quick reaction to any pandemic
crisis that may emerge, with a focus on immunising patients as much as possible before releasing a fully
functional vaccine to the public. Once a vaccination is ready, the WHO tries to ensure that the most
vulnerable and affected people get it first.
It has formed a supply chain task force as part of its Strategic Preparedness and Response Plan to address
the lack of critical commodities such as clinical support equipment, supplies, medications, and vaccines.
The company intends to set up a hub-and-spoke distribution system with international consolidation
centres and regional staging areas along major distribution corridors. It also has the ability to transport
cargo between international and regional centres and then to countries via airlift. With these services in
place, WHO has demonstrated significant organisational capacities, including the ability to distribute
any critical medication or vaccination to countries in times of need.
Q5. Imagine, the current situation in India for vaccine suppliers Serum Institute of India (SII)
and Bharat Biotech and comment on the following broad areas: -
a) the manufacturing process of the Covishield and Covaxin vaccines wrt any technological
challenges present in these vaccine v/s any other vaccine for influenza.

Covishield and covaxin manufacturing process occurs in 5 steps –

1. Metal preparation
2. All machine components and septic parts (like stoppers, caps etc.) are washed and sterilized at 142
degree Celsius for 30 minutes
3. Formulation of the vaccine: Concentrated drug substance from the upstream process which is purified
and ready for formulation in the blending area. Here formulation buffers and drug substrates are blended
to produce the drug formulation
4. Dilution and filling into vials in the Isolator Filling line. Each vial consists of 10 doses
5. Screening of vials into doses

The Process's Major Challenges and Strategies for Covishield: -

1. The ChAdOxl viral vector technology was used to develop the Covishield vaccination. A
innocuous adenovirus that causes the common cold in chimps was modified to generate this
platform. ChAdOx1 was chosen because it may elicit a significant immune response and since
it is not a reproducing virus, thus it cannot infect people. Thousands of people had already been
exposed to it in clinical trials for various diseases, including Middle Eastern respiratory
syndrome (Mers), which is caused by a different type of coronavirus.
2. Stages of vaccine trials: Vaccine trials are usually divided into three stages. Phase 1 evaluates
the vaccine's safety and tolerability, as well as the immunological response. Phase 2 entails
testing on a wider, more diverse group of people to determine the best dose and timing. The
goal of Phase 3 is to assess a vaccine's safety and efficacy in a large number of people,
frequently in various places. This is usually determined by comparing the number of cases of
the disease seen in those who receive the vaccine vs those who do not. To expedite the
development process for Covishield, combined phase 1 and 2 as well as phase 2 and 3 trials
were conducted.
3. Due to the short timelines in which SII signed technology transfer agreements with their
numerous partners, scaling up the process, having several runs, and demonstrating consistency
was rather difficult. To meet this problem, a crucial technique was to optimise production
capabilities at specific factories in order to leverage resources for large-scale research.

Covaxin contains the following ingredients. –

1. 6 microgram of SARS CoV-2 antigen that has been inactivated by the complete virion
2. Gel of aluminium hydroxide
3. TLR 7/8 agonist (15 micrograms) (imidazoquinolinone)
2.25 mg 2-phenoxyethanol
5. 0.5 mL phosphate buffer saline
6. Virus that has been inactivated or destroyed

Key Strategies and Challenges in the Process for Covaxin

 1. There was a public outcry after the initial supply of vaccines since the quality of the vaccines
produced did not meet expectations. This was addressed by focusing on knowledge transfer
agreements with Haffkine and BIBCOL, as well as enhancing quality control methods at their
facilities.
2. Covaxin accounts for almost a tenth of the covid-19 vaccine doses now delivered, with
Covishield, made by Serum Institute of India, accounting for the remainder. Bharat Biotech's
vaccine, which was developed in India, has so far been a distant second. The main cause for
this has been Covaxin's low production rate: while Covaxin produces just 10 million doses
per month, Serum Institute produces 90-100 million doses of Covishield per month. Covaxin
was awarded an emergency use licence in "clinical trial mode" in January, despite the fact that
efficacy evidence was still pending. The Indian FDA gave full emergency authorization to the
vaccine after the manufacturer announced an interim efficacy of 80.6 percent, and its uptake
increased. Capacity, on the other hand, remained a significant stumbling block.

Q5. Imagine, the current situation in India for vaccine suppliers Serum Institute of India (SII)
and Bharat Biotech and comment on the following broad areas: -
b) the supply chain strategy adopted by SII and Bharat Biotech to deal with supply of
Covishield and Covaxin respectively, and comment on any shortcomings in the strategy
adopted.
The dosages of both Covaxin and Covishield were directly delivered to states free of charge in the
first two phases for frontline and healthcare personnel, as well as for anyone over 45. SII and Bharat
Biotech supplied 50% of their vaccine doses to the Government of India in a month for Phase III
for adults under 45, which the Government of India will distribute at cost to state governments and
private hospitals under the new Liberalized Pricing and Accelerated National Covid-19 Vaccination
Strategy. As a result, both the government and private hospitals can purchase the remaining 50%
of jabs produced from the producers.
Both vaccine makers give 50% of their supply to the federal government and the other 50% to state
governments and private institutions under this method. The shots will remain free at government
facilities in all states under the new pricing model for all those who are eligible for vaccination.
Covishield is sold by SII to the Centre for Rs 150 per dose and to the states for Rs 300 per dose.
For states, the cost of Covaxin is Rs 600 per dose. It is much pricier for private facilities, with
Covishield costing Rs 600 and Covaxin costing Rs 1200.

The vaccine charge at private facilities, on the other hand, would be managed, according to the
regulation. Four government medical store depots (GMSDs) in Karnal, Mumbai, Chennai, and
Kolkata acquire vaccines from producers, making up India's vaccine distribution network. Around
53 state vaccine depots acquire their supplies from these GMSDs or from producers directly.
Vaccines are subsequently distributed via insulated vans from state vaccine stockpiles to regional,
district, and sub-district cold chain sites.

Due to a vaccine shortfall in certain Indian states, the immunisation programme for people aged 18
to 44 years old, which began on May 1, was delayed or slowed. The most pressing issue raised in
regards to COVID-19 vaccine production was the lack of supplies. While this was completely
unforeseen, the delays and issues put a significant strain on the supply chain. India's decision to
export vaccines to other countries was hasty, as the combined production of Covishield (100 million
per month) and Covaxin (8-9 million per month) is insufficient to meet domestic demand, let alone
 build an export surplus. To ensure continuous and seamless production, India must now invest in
growing manufacturing capacity and performing clinical trials. To boost vaccine manufacturing,
the Union and state governments should seek public-private partnerships, advanced purchase
agreements, incentives, and advantages with concessional loans, rather than relying on a single
manufacturer.
Due to a variety of factors, including a lack of raw materials, restricted manufacturing capacity,
inadequate transportation and logistics infrastructure, and insufficiently qualified staff, the supply
scenario for Covid vaccine in India has been uncertain. On the demand side, while the population
numbers are set, demand remains uncertain at the micro level due to complications experienced by
some patients, misinformation about the vaccine's efficacy, and new information about the highly
mutant strain of the virus, all of which add to scepticism about the overall vaccination program's
effectiveness.

Q5. Imagine, the current situation in India for vaccine suppliers Serum Institute of India (SII)
and Bharat Biotech and comment on the following broad areas: -
c) What improvements would you recommend to alleviate the supply -demand issue?

In India, Covid-19 vaccines are in insufficient supply, putting everyone at risk. That's because new
strains of the virus will emerge if large populations aren't vaccinated, including some that are resistant
to present vaccines.
We need to do more than wring our hands. Right now, we can take actions to bring order to the
vaccination market, remove bottlenecks, and increase availability and access to the Covid-19 vaccine
portfolio.

The following are some recommendations: -

1- Make the raw material flow more efficient.

The Covid-19 vaccine portfolio is complicated, requiring specialized manufacturing capacity as well as
reagents and equipment manufactured in the United States and Europe. Consumables, single-use reactor
bags, filters, culture media, and vaccine components are all part of the vaccine materials sector. Export
limitations on raw materials, equipment, and finished products hurt the entire vaccination supply chain,
and everyone suffers in the long run.

2. Streamline Regulatory Processes

Before vaccines are certified for use in a country, each country's drug regulatory agency evaluates them
for safety, quality, and effectiveness on a regular basis. This function is carried out by the Food and
Drug Administration (FDA) in the United States and the European Medicines Agency in EU member
countries, for example. The requirement that a company do clinical trials on local individuals and then
have its regulator examine the data before allowing the use of a vaccine in each nation or bloc, however,
delays the introduction of new vaccines.

Investing in manufacturing capacity alongside clinical studies, as evidenced by Operation Warp Speed
in the United States, makes a tremendous difference in getting large quantities of vaccines fast.
Expanding vaccine manufacturing capacity should be supported by governments and international
public-private partnerships.