Is India about to become the next hotbed for original pharma research?

Pass the paracetamol.

The Indian pharmaceutical industry could be about to step up to the big league with the launch of a new original diabetes drug, Lipaglyn, developed by homegrown pharma group Zydus Cadilla. With annual revenues of $1bn, Zydus’ chairman and managing director Pankaj Patel, expects the new drug, which tackles both high blood sugar and cholesterol in a single pill, to more than double that amount, calling it a potential “blockbuster”.

Due to be released in the coming months in India, it will take another 3-5 years of clinical trials before being cleared for sale in the more tightly regulated western markets. After years of the Indian pharma industry producing cheap knock-offs of western medicines, it is “time for India to give back,” according to Patel, “(having) benefited for years from the research and development efforts in other countries.”

This reputation for a culture of imitation drug production has led to repeated accusations from western pharma companies of poor IP protection by Indian authorities. US giant Pfizer, among others, have called on lawmakers to do more to protect the millions spent on R&D, which will not be turned into revenues if the Indian generics market is allowed to continue churning out cheaper alternatives. This culminated in US Secretary of State John Kerry discussing the issue with Indian policymakers during his recent visit to the country.

But that has still not stopped some companies falling foul of the Indian system, with the Supreme Court rejecting Novartis’ bid to protect its new leukemia drug with a patent in January, paving the way for India’s pharma companies to produce generic versions at a fraction of the cost. Gleevec, which can cost up to $31,000 a year in India is now being undercut by the generic version, which costs just $2,100 a year.

Still, Zydus’ Lipaglyn could be the start of a move from generics manufacture to original research across the rest of the Indian pharma industry. G. Shah, secretary-general of the Indian Pharmaceutical Alliance, sees this latest development as critical if Indian pharma companies, such as Glenmark and Biocon are to compete on the world stage; “Our credibility is at stake now… People have been branding us as a copycat industry, and this is a departure from that,” he said. “We are not just copycats, but we are transforming into creating original research products also.”

Zydus have spent close to $450m developing new drugs since 2001, while Glenmark spent nearly $1billion on R&D in the last year alone. However, not everyone shares this enthusiasm, with Gayatri Saberwal of the Institute of Bioinformatics and Applied Biotechnology, Bangalore, last year voicing his concern over the Indian pharma sector’s R&D abilities. Based on analysis of the patents being granted in the sector, he found a tiny minority were for genuinely original research, thus making the “prospects for original drug discovery in India poor,” he said. “There is probably a long way to go for Indian companies to undertake highly innovative work”.

Just what success the Indian industry is able to achieve internationally will not become apparent on these shores for some time yet, with the development of news drugs taking years. So we will have to stick to our tried and tested remedies in the short term at least, just as the Indian generics industry will also continue to cause a headache for western pharma companies until their original research starts to bear fruit. Pass the parcetamol.

Photograph: Getty Images

Mark Brierley is a group editor at Global Trade Media

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Inside Big Ben: why the world’s most famous clock will soon lose its bong

Every now and then, even the most famous of clocks need a bit of care.

London is soon going to lose one of its most familiar sounds when the world-famous Big Ben falls silent for repairs. The “bonging” chimes that have marked the passing of time for Londoners since 1859 will fall silent for months beginning in 2017 as part of a three-year £29m conservation project.

Of course, “Big Ben” is the nickname of the Great Bell and the bell itself is not in bad shape – even though it does have a huge crack in it.

The bell weighs nearly 14 tonnes and it cracked in 1859 when it was first bonged with a hammer that was way too heavy.

The crack was never repaired. Instead the bell was rotated one eighth of a turn and a lighter (200kg) hammer was installed. The cracked bell has a characteristic sound which we have all grown to love.

Big Ben strikes. UK Parliament.

Instead, it is the Elizabeth Tower (1859) and the clock mechanism (1854), designed by Denison and Airy, that need attention.

Any building or machine needs regular maintenance – we paint our doors and windows when they need it and we repair or replace our cars quite routinely. It is convenient to choose a day when we’re out of the house to paint the doors, or when we don’t need the car to repair the brakes. But a clock just doesn’t stop – especially not a clock as iconic as the Great Clock at the Palace of Westminster.

Repairs to the tower are long overdue. There is corrosion damage to the cast iron roof and to the belfry structure which keeps the bells in place. There is water damage to the masonry and condensation problems will be addressed, too. There are plumbing and electrical works to be done for a lift to be installed in one of the ventilation shafts, toilet facilities and the fitting of low-energy lighting.

Marvel of engineering

The clock mechanism itself is remarkable. In its 162-year history it has only had one major breakdown. In 1976 the speed regulator for the chimes broke and the mechanism sped up to destruction. The resulting damage took months to repair.

The weights that drive the clock are, like the bells and hammers, unimaginably huge. The “drive train” that keeps the pendulum swinging and that turns the hands is driven by a weight of about 100kg. Two other weights that ring the bells are each over a tonne. If any of these weights falls out of control (as in the 1976 incident), they could do a lot of damage.

The pendulum suspension spring is especially critical because it holds up the huge pendulum bob which weighs 321kg. The swinging pendulum releases the “escapement” every two seconds which then turns the hands on the clock’s four faces. If you look very closely, you will see that the minute hand doesn’t move smoothly but it sits still most of the time, only moving on each tick by 1.5cm.

The pendulum swings back and forth 21,600 times a day. That’s nearly 8m times a year, bending the pendulum spring. Like any metal, it has the potential to suffer from fatigue. The pendulum needs to be lifted out of the clock so that the spring can be closely inspected.

The clock derives its remarkable accuracy in part from the temperature compensation which is built into the construction of the pendulum. This was yet another of John Harrison’s genius ideas (you probably know him from longitude fame). He came up with the solution of using metals of differing temperature expansion coefficient so that the pendulum doesn’t change in length as the temperature changes with the seasons.

In the Westminster clock, the pendulum shaft is made of concentric tubes of steel and zinc. A similar construction is described for the clock in Trinity College Cambridge and near perfect temperature compensation can be achieved. But zinc is a ductile metal and the tube deforms with time under the heavy load of the 321kg pendulum bob. This “creeping” will cause the temperature compensation to jam up and become less effective.

So stopping the clock will also be a good opportunity to dismantle the pendulum completely and to check that the zinc tube is sliding freely. This in itself is a few days' work.

What makes it tick

But the truly clever bit of this clock is the escapement. All clocks have one - it’s what makes the clock tick, quite literally. Denison developed his new gravity escapement especially for the Westminster clock. It decouples the driving force of the falling weight from the periodic force that maintains the motion of the pendulum. To this day, the best tower clocks in England use the gravity escapement leading to remarkable accuracy – better even than that of your quartz crystal wrist watch.

In Denison’s gravity escapement, the “tick” is the impact of the “legs” of the escapement colliding with hardened steel seats. Each collision causes microscopic damage which, accumulated over millions of collisions per year, causes wear and tear affecting the accuracy of the clock. It is impossible to inspect the escapement without stopping the clock. Part of the maintenance proposed during this stoppage is a thorough overhaul of the escapement and the other workings of the clock.

The Westminster clock is a remarkable icon for London and for England. For more than 150 years it has reminded us of each hour, tirelessly. That’s what I love about clocks – they seem to carry on without a fuss. But every now and then even the most famous of clocks need a bit of care. After this period of pampering, “Big Ben” ought to be set for another 100 or so years of trouble-free running.

The Conversation

Hugh Hunt is a Reader in Engineering Dynamics and Vibration at the University of Cambridge.

This article was originally published on The Conversation. Read the original article.