A while back I had a post about an article that compared airplane design to drug design. I discussed the challenges in drug design compared to airplane design and why the former is much less predictable than the latter, the short answer being "biological complexity".
Now the analogy surfaces again in a different context. C & EN has an interview with Kiran Mazumdar-Shaw, CEO of India's largest biopharmaceutical company Biocon. Shaw is an accomplished woman who does not hold back when she laments the current depressing state of drug development. I think many of us would commiserate with her disappointment at the increasing regulatory hurdles that new drugs have to face. But at one point she says something that I don't quite agree with:
Mazumdar-Shaw dismisses the argument that drugs create a public safety imperative mandating stricter oversight than many other regulated products. “So you think passenger safety is any less important than patient safety?” she asked. Yet aircraft makers don’t face a 12-year, all-or-nothing proposition when designing, developing, and commercializing an airplane. Nor, she added, does Boeing have to prove that it is making something fundamentally different than what Airbus already has on the market.
To which my counter-question would be, "What do you think is the probability of unforeseen problems showing up in aircraft design compared to drug design"? I see a rather clear flaw in the analogy; aircraft design is not as tightly regulated because most aircraft work as designed and the attrition rate in their development is quite low. The number of failures in aircraft development pale in comparison with the number of Phase II failures in drug development. In fact as the article quoted in my previous post described, these days you can almost completely simulate an aircraft on a computer. Regulatory agencies can thus be much more confident and insouciant about approving a new airplane.
This is far from the case for drugs. First of all there is no clear path to a drug's development and in the initial stages most people don't have a clue as to what the final product is going to look like. But more importantly, designing drugs is just so much riskier than designing aircraft that regulatory agencies have to be more circumspect. How many times do drugs show all kinds of side-effects which would never have been predicted at the beginning? How many times do drugs show side-effects that would not even have been imagined at the beginning? It's this almost complete lack of prediction driven by the sheer complexities of biology that distinguishes drugs from airplanes.
In another part of the interview Mazumdar-Shaw voices her impatience with regulators' recalcitrance to adopt new technologies. The example she gives is of Hawk-Eye, a computer that tracks a tennis ball's movement and makes it easier to call out the result of a disputed bounce. Just like sports authorities are reluctant to use these technologies to override the flaws in human judgement, Mazumdar-Shaw thinks regulators are reluctant to use new technologies to overcome the limitations of human judgement. The point is not irrelevant but the truth is that decision making in drug development is far more complex than decision making in tennis tournaments. For Hawk-Eye to track tennis balls is a simple matter of physics, and it can do this with high accuracy. Contrast this with drug development where the "event" to be analyzed is not the bounce of a ball but the efficacy of a drug in a large clinical trial as assessed by a variety of complex statistical measures. In addition, approving a drug is inherently more subjective, being based on efficacies of existing therapies, the exact numerical superiority of the extra benefits, cost and patient populations. Good luck writing a computer problem that could possibly assess this morass of sometimes conflicting information and reach an informed judgement.
I think many of us are frustrated with the increasing regulatory hurdles that new drugs face and we all wish that the process was smoother. Personally I don't think that the FDA's systems for assessing risks is as finely attuned to potential benefits as it should be. But I don't find myself following Mazumdar-Shaw in advocating for drug approvals that are as easy as aircraft approvals. The former is science and engineering. The latter is science with a healthy dose of intuition and art. And some black magic.
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