How exactly does a medicine get approved? (Part 1 of 5)


I really wanted to write a post about pediatric medicines and the unique challenges that are faced in developing them. As a parent, I want the best science-based medical treatment for my children, and as such it’s important to understand what barriers exist to developing new ones. It’s also important to understand what the data really says about use of a given product in a child.

Unfortunately, that post first requires a basic understanding of how medical products are created for adults. So here we go on a long and rambling road through the land of drug and medical device regulation. As the entire discussion ended up rather long, I’m breaking it up over several weeks.


Disclosure: During the day, I work at a large medical device manufacturer, where we produce orthopedic implants (hips, knees, elbows, trauma plates, scoliosis rods, etc.). The vast majority of our products are only used in adults, so I have effectively no financial incentive for promoting pediatric products. One of my myriad functions is to develop the clinical and regulatory plan for new product options; understanding the time and cost required to obtain FDA or similar clearance can dramatically impact how a firm prioritizes a development project. Therefore I do have a personal financial interest in medical products, though my direct contact with pediatric products is effectively zero.

Drug and device regulation was born from a sordid era of snake oil elixirs, sham therapies, predatory sales tactics, and ill-conceived tonics. It is also filled with little-known heroes, most notably Dr. Harvey W. Wiley, who championed the world’s first food and drug safety regulations and led the FDA through its tumultuous birth, and Dr. Frances Oldham Kelsey, who almost single-handedly opposed thalidomide’s approval in the US, protecting an untold number of children from birth defects.

Today, medical regulators–be they the US FDA, the EU MDD, Health Canada, the Australian Therapeutic Goods Authority, the Chinese FDA, or any of dozens of others–are tasked with evaluating the demonstrated safety and efficacy of a product against the potential risks of its use or misuse. Manufacturers gather comparisons to similar products, bench test data, animal test data, and human clinical data to support their product, requiring years of work and millions of dollars of investment. They have to recoup this investment by selling the product before patents or other market exclusivities expire.

Consider these data from an investment standpoint: in general, over 80% of molecules that enter clinical trials will be abandoned due to safety or efficacy concerns. Only about one in three drugs pass Phase II testing; of those, two in three pass Phase III (large-scale) testing. From 2003 to 2011, roughly one in ten drugs successfully passed from Phase I testing to FDA approval. Overall, only roughly one in 10,000 molecules survive the entire path from initial discovery to approved drug. Once on market, most drugs have five to seven years before generic competitors are allowed, at which point sales volumes and prices plummet. Devices follow a similar pattern at a different scale, with a large portion of novel device concepts failing during development and evaluation.

For the remainder of these posts, I will focus on the US FDA’s approach to regulation. I’ll point out major differences as they arise, but be aware that every jurisdiction offers subtle variations that can be important. I won’t be talking about homeopathic products (which are overseen by FDA, but in a very different way) or GMO foods (which are an incredibly complex situation, with input from FDA, USDA, EPA, and others). Leave those for another time.


Next time: medical maggots!


Topher is a nerd, scientist, bioengineer, photographer, costumer, dog trainer, beer brewer, and a lot of other nouns. He has too many degrees and too many hobbies because it’s all fun and interesting, and … squirrel!

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