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First across the line: the great generics race

In motor racing the 1980’s became known as the turbo-era. A period where a generation of super-fast, flame spitting, colourful race cars were born. But why the sudden change? Engine size, engine efficiency and particularly aerodynamics, all came to the fore.

Drivers were important, but it was mostly the new developments in turbo technologies that drove innovation. The prize for being first across the finish line on a Sunday afternoon directly lead to more car sales on a Monday morning, and it was the big corporations like Renault, BMW, Porsche and Ferrari that invested heavily in development to capitalise on this. But having a technological advantage wasn’t the only thing that won races. Every aspect of the machine was examined…

What did it take to win a race? Lancia Stratos was a company where the competition manager was looking for any advantage. He polled the entire racing crew to find out what they thought would make a winning car. It worked. They did have the advantage in their class of competition, winning for three years – but only three years…

However, with the faster cars came more accidents. With every change to design, potential risks needed to be balanced. New regulations came into effect. New limits were set on the cars. Minimum weights were introduced, along with many other regulations.

Big money poured into racing events, and with that came more and more competition to dominate racing. New companies entered racing and new markets opened up for Formula One in particular. The first Formula One race in Hungary was held in the 80s. Race organisers were looking for new markets to hold more races to make more money.

This very same drive to be the first across the line can be seen in the successful but aging asthma and COPD drugs market. New races are opening up in the generics category. Competitive companies have been anticipating the expiry of intellectual properties. The generics know that just building a fast car might not actually bring them victory. If the driver can’t control it or it doesn’t meet with race regulations, their efforts will fail. Why is it then that so many companies seem to have underestimated the time and effort required to develop devices for generic drugs?

“If it looks like a Porsche, it might not drive like a Porsche”

If it looks like a Porsche, it might not drive like a Porsche; if a generic drug is an exact copy of an existing compound then it should follow that the combination delivery technology (the inhaler) can also be a copy of the existing product.

The reality is that there is nothing generic about generic device development as there is nothing new about new device development. But to be real race competition, the generics have discovered that all device development projects need roughly the same amount of time and effort otherwise your ‘car’ might fail at the first hurdle and be disallowed.

Generic pharmaceuticals are an identical copy of existing drugs that are sold at much lower costs than the original but without the brand name. These are fully regulated, bioequivalent, chemically identical products that do the same job as their branded counterparts. In the U.S. alone generic drugs account for approximately 80% of the prescriptions written.

Companies who specialise in producing generics are legitimately able to market their own versions of the existing drugs when the patent protection on the existing ‘new drug’ has expired allowing full market competition to take place. The regulators understand the process and support it because the availability of cheaper generic drugs is a good thing for everyone.

Over the past ten years the development of generic drugs and device combinations has been a big topic in the respiratory market. The basic business model for generics companies is to produce an exact copy of an existing blockbuster drug formulation and obtain regulatory approval in time to launch – preferably on the day after the current license holder’s intellectual property expires.

“In the U.S. alone generic drugs account for approximately 80% of the prescriptions written”

Generic products are sold at a lower price than the branded product to encourage users and prescribers to switch brands. It is a high volume, low margin business that is heavily reliant on being the first to market.

The generics approach works well for pure pharmaceuticals (pills and some injectable drugs) but the development process seems to get more challenging when an existing branded drug is aligned (or combined) with a specific delivery technology or device, as is often the case with DPI (dry powder inhalers).

With inhaler device technologies, an in-depth understanding of the complex interactions between the device and the formulation is needed to understand why and how they work. Analytical tools such as CFD (computational fluid dynamics) and aerosol science are useful to give an understanding of device performance, but equally important is an understanding of the human usability aspects (why and how patients use the device) which is fundamental for regulatory authorisation.

The peculiarity in this rush by the generics to be first to market is that they are of course not the first. The first is always the original developer of the drug/device combination and their advantage often lies in their detailed knowledge of the device used to deliver the formulation, which ultimately governs the end performance. It is this profile that is often difficult to fully understand.

In some simple inhaler technologies it is relatively straight forward to use reverse engineering tools, such as 3D component scanning, in combination with CFD analysis to measure and understand the critical aspects of the air-path geometry – the route inside the device that the drug comes into contact with. However in more complex devices, such as those multi-dose versions that use complicated gearing and timing mechanisms to meter and release the drugs, reverse engineering alone can give a misleading result.

Typically, the developer will analyse the existing commercial device to understand the performance characteristics and traits. However, it is virtually impossible to tell if the commercial devices are operating at a nominal condition (in the middle of the design intent) or if they have components which are at the tolerance extremes. The physical differences are likely to be only fractions of one millimetre, which doesn’t sound like very much, but in order to produce a like-for-like performance copy an understanding of the nominal or median operating condition of the commercial device is necessary.

Another factor that is important in controlling the unit costs for the generic device is to understand the production tolerance window which allows the manufacturer to minimise (or better still prevent) rejects as early as possible in the production processes. When you consider that since 1995 GSK have made over 550 million of their ‘Diskus’ devices in the UK (and have produced over 1 billion worldwide) the balance of the device operating window and the control of production tolerances becomes very important for efficiency.

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On the whole, facsimile (like-for-like) copies of inhaler technologies are mostly confined to the markets outside of the USA and Europe. The preferred approach for generic inhaler devices for the more tightly regulated markets could be to develop a ‘performs-like’ and ‘operates–like’ but not a ‘functions-like device’.

Essentially a new device development that replicates the use steps of the predicate device – assuming that no critical use errors have been identified – but has a new internal ‘engine’ that has been developed from scratch with high scale production processes in mind. This gives the developer some scope to innovate and to avoid infringement of patents or copyright that may still be valid for the predicate device technology even though the pharmaceutical patents have expired.

In response to the inhaled generics, the original developers are also doing all they can to retain as much of their market share as possible via both litigation and extending patent protection but also with new technology development. Between the factions, this has set up an interesting and ongoing scuffle to outdo each other.

On one hand the generic drug developers are looking to create their replicate of the existing device performance, while in direct response the original developers are looking to retain market share of their existing asthma and COPD formulations by developing entirely new devices that pack in better usability, improved drug delivery efficiency and in some cases electronic intelligence and monitoring.

What has become clear is that both paths are costly. But what is fascinating is that the same drive and ambition in the race industry is the same in the medical device industry. Being first across the line isn’t just about being the fastest.

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