Archive | February, 2015

In The Hindu: Medicines in India, For India

I write in The Hindu on what it takes to get a drug from the lab to the market. Here is the full piece along with hyperlinked references.

January marked an important breakthrough in the fight against tropical diseases. Researchers at the International Centre for Genetic Engineering and Biotechnology (ICGEB) in Delhi found a drug candidate that prevented the TB and Malaria pathogens from infecting human blood cells.

This cutting edge research took place not just in India, but for Indian challenges — whose solutions have global implications. Further, Anand Ranganathan and his colleagues did not just find this drug candidate, but also helped develop processes to develop these drug leads. It also happened thanks to a combination of a UN facility set up decades ago, attracting top global research talent to come back to India and work here. And the research was funded not just through international sources, but also a ‘Grand Challenge Programme’ on vaccines set up by the Department of Biotechnology, Government of India. Much of this success is a delayed fruit of a biotechnology push in India that started in the mid 1980s, which has gained in strength over time.

However, the discovery of the drug candidate ‘M5 synthetic peptide’ is the beginning of a long road and not the end. The process of drug discovery here is not yet complete, and has to be succeeded by more research and a host of clinical trials. Here is a plausible set of intermediate steps before a new TB or Malaria drug enters the market from the work of Ranganathan and others.

The ICGEB researchers have attempted ‘rational drug design’, where they have not only found a drug candidate, but have done so while identifying what protein target it interacts with in the body, and the mechanism it uses to prevent disease. The first steps forward for all interested researchers in the field will likely be to study further how the peptide drug candidate works, what its structure is, what the key biochemical interactions are, and how its target proteins behave.

While the drug candidate might work well in a test tube or an agar plate, its efficacy in the human body is an entirely different story. At this stage, whether the peptide can be easily absorbed by the body or be happy in blood, whether it finds the right targets, has no side effects or toxicity, are all unknown. Researchers, including those in private pharmaceuticals, can start developing variants of the M5 peptide that might have more desirable properties and have higher efficacy, and a good number of promising drug candidates might be patented by public sector researchers or pharmaceutical companies, depending on who discovers their utility.

It is after this that pre-clinical trials start on promising compounds, from tests in mammals to finally humans. Phase I clinical trials are typically about testing safety among healthy people, moving to phase II which are small trials of efficacy among patients. The last and the most expensive — Phase III, involves large, double-blind tests to determine both safety and efficacy among large groups of people.

The entire process of drug development is one of attrition, where a hundred lead compounds might trickle down to one or two medicines. It can take a decade or more, and cost in the order of a billion dollars, or 6000+ crore rupees.

Science is often described in popular retelling in a triumphalist manner, when in reality research involves many misses by researchers, incremental progress, and the eventual success of someone who stands on the shoulders of many giants.

For this process to happen, you need to have a robust research ecosystem, adequate funding, and good pipelines that ensure minimum friction in the development of drug candidates and lead compounds into medicine that you can buy at the corner shop.

The challenge in India is that tropical diseases have often been neglected by big pharmaceuticals because the size of the drug market is lower, with people having lower incomes in tropical countries. Further, companies are uncertain about intellectual property rights on essential drugs, unsure about whether they can recover high sunk costs in this inherently risky proposition. It is no surprise that big Indian corporations have stayed away from pharmaceutical R&D, finding more secure avenues for a return on their investment.

Policymakers in India will need to strike the right balance between public funding, and the role and return on private investment on drug development. Greater clarity on India’s eminent domain and compulsory licensing positions could make foreign-patented drugs more costly for India, but might spur R&D on tropical and endemic diseases in the long run.

Further, the unwritten compact in developed countries on drug development is that a thick layer of public funds pay for the basic research up to and including drug candidate discovery. It is over and above this that private pharmaceuticals come in, patent drugs and develop them.

Indian funding on basic research and drug discovery remains minuscule in comparison, with the entire Department of Biotechnology budget being lesser than 1500 crore rupees in 2014-15, or about 250 million dollars. The Government of India’s spending on drug development is broadly of the same order of magnitude of what is spent by the Gates Foundation and others on drugs for tropical diseases, and both the quality and quantity of public spending has to dramatically improve if we want more drug candidates against TB, Malaria, Dengue, Cholera and other diseases.

One way to increase the funding is to redirect extensive funds that go towards large healthcare subsidies, so that future drugs can be both better and cheaper.

India also has the opportunity to re-examine how clinical trials are governed. While we want ethical and safe practices in clinical testing, American or European regulations have accumulated some extra bureaucracy and regulations along the way. India can also set new standards on transparency so that new research is easy to discover, verify and build on.

Getting 21st century medical solutions to India’s health concerns is a long slog. The new potential cure for TB and malaria gives us a chance to think through how to develop medicines in India, and for India.

Hindu_Feb14_PavanSrinath_MedicinesFromLabtoMarketRead the article in The Hindu on their website.


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In Mint: Let India’s urban poor pay for good water

I write in Mint this week on how thinking along the lines of micro finance principles can change how we approach water pricing. Instead of an ideological stand on keeping water free, it’s better to ask how we can make clean water cheaper and more affordable for urban India’s most deprived.

In microfinance, people also acknowledge that it costs more to lend to the poor. When most people have to take a big loan from a bank, they have a steady income to show. They have a credit history. They also have assets they can pledge as surety, in case they default on the loan. The poorest of the poor don’t have salaries to showcase. They don’t have assets to pledge. The risk of defaulting on a loan is higher, and it is humane that they be allowed to default when the circumstances are dire. By allowing microfinance institutions to charge higher interest rates, the policies allow them to service these needs.

Similarly, the costs of supplying water for a city’s poor can be high. People often don’t have address proofs or any proofs of legal residence, making installing water connections harder. Getting even basic piping to reach the heart of a slum is not always cheap, given that there is hardly any road space to dig up. Maintaining pipes is even tougher. Installing and maintaining water meters is difficult, thereby making bill collection costlier.

It is highly disingenuous to ignore all these real issues and shout for a right to free water.The better approach is to ask, “how can we make water cheaper for the poorest?” And that line of thinking can birth an entirely new range of solutions.

Read the full article at Live Mint, February 13, 2015.

Live Mint e-Paper - Mint - 14 Feb 2015 - Page #11 Pavan Srinath


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India’s unusual trade pattern with the United States

Richard Rossow (via Milan Vaishnav) shared the latest US-India trade in goods data updated by the US Census Bureau.

India has a running trade deficit in goods: where it imports more goods than its exports. It is wrong to simplistically judge whether a trade deficit is good or bad – however, India does do ‘better’ when it comes to its services.

However, today this blogger learnt that the trade relationship that India has with the United States of America is quite different from that with many other big trading partners. India’s large software and services exports to the US are well-known, but India exports more goods to the US as well. Little wonder that American businesses lobby hard in Washington to be able to trade more and operate more in India.

In 2014, for the first time since 2006, India’s exports to the US are more than double its imports. It is currently unclear as to what to attribute this towards and pass judgement on whether this is a good or a bad thing. The broad trends in the two economies in the last 4 years has been one of revival and renewed growth in the United States, and faltering growth and investment in India.

India-US Trade1The timeline of imports and exports from the 1980s onwards has a few points of interest from recent years. The most prominent of these is the dip in 2009 of both Indian exports and imports, with the former affected far more than the latter. This was preceded by a sharp rise in 2007 in Indian goods imports from the US.

While Indian exports to the US bounced back since 2010, Indian goods imports plateaued in 2011 and have dropped a little in real terms since then.

The USTR website on India-US trade relations says that India’s largest goods exports to the US are precious stones (diamonds), pharmaceuticals, mineral fuel, organic chemicals and others. India’s largest goods imports are again precious stones (diamonds and gold), aircraft, machinery and optical and medical instruments.

A closer examination of export and import trends in types of goods (using the US Census Bureau’s “end use” dataset) provides the following:

1. Since 2009, the largest growth in highly traded Indian goods exports to the US as of 2013 are:
– Petroleum products, other
– Tobacco, waxes, etc
– Fish and shellfish
– Fuel oil

2. Since 2009, the largest growth in highly traded Indian goods imports from the US as of 2013 are:
– Complete military aircraft
– Gem diamonds
– Nonmonetary gold
– Newsprint
– Parts for military-type goods

3. Since 2009, the largest fall in highly traded Indian goods imports from the US as of 2013 are:
– Civilian aircraft, engines, equipment, and parts
– Chemicals-fertilizers
– Steelmaking materials
– Computers
– Drilling and oilfield equipment

I encourage readers to comment on the significance of some of these observed changes.

There’s a lot more information waiting to be unearthed from these datasets, including information on when Indian defence imports of US equipment really increased and to what extents. The defence angle is particularly interesting as the Indian ministry of defence is quite opaque in defence spending and is known to defer capital payments while making large announcements.

Readers are welcome to use the full rich XLS spreadsheet that I have compiled on all the data from the US Census Bureau relevant to the last couple of decades of India-US trade.

Addendum: The US$-Indian Rupee exchange rate has been steadily rising, making imports from the US less competitive. This could perhaps explain a part of the slump in US goods imports by India.

PS. All years used in this post are calendar years and not financial years.

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