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Industry Focus
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Regina Kelder, Mary Parker

Why Does Drug Development Take So Long?

A survey found a gap between “common knowledge” and reality

The COVID-19 pandemic gave the world a crash course on drug development. People who were content to pick up prescriptions or grab some over-the-counter remedies were now more personally invested in finding out everything they could about the process, and scientific reporting flourished. Unfortunately, so did industries of misinformation.

A survey commissioned by Charles River Laboratories revealed the gap between what people think they know about the time and cost involved in developing a drug, and industry reality. The Health Care Collaboration survey was conducted online by The Harris Poll between May 11 and May 24, 2021 among 1,508 adults living in the US. Among the survey’s findings:

  • Just 10% of people knew that the typical drug development timeline is 10-15 years; the most common estimate—35% of respondents—thought it was between four and 10 years.
  • Only 6% of respondents knew that it cost as much as US$2.6 billion to bring a drug to market; the majority – 76% — thought it was less than $100 million.
  • On average, respondents thought that one third of drugs make it from conception to approval. In fact, only about .02% of drugs in development make it to market.

Drug safety takes time and money

Establishing a safety profile of a drug is a key reason why the process of drug development takes time. There are numerous studies that regulators require in determining if a drug is safe enough to be dosed in humans—and these safety studies continue throughout clinical trials and the drug’s lifecycle.

“It often comes down to being a choice – things can be done faster, but ultimately it is a balance between speed and the need for sufficient, accurate data,” says Michael V. Templin, PhD, Senior Scientific Director for Charles River’s Scientific Advisory Services. Templin provides drug development expertise and guidance to Sponsors of drugs, helping them plan their safety strategies. “Since these drugs are going into humans, we want them to be as safe as possible.”

Indeed, safety is one of the two main reasons a drug fails in clinical trials—the other being efficacy. “If we did safety faster, we will either cut corners by making studies smaller in scope or we find ways to reduce the time of ‘being human’ – arguing about the data and what it means,” says Templin.

Safety timetables are typically driving by regulators. It takes about 12-15 months to complete the preclinical safety tests that Sponsors need when determining whether to submit an Investigational New Drug Application (IND) to the US Food and Drug Administration for human trials. A typical small IND package requires anywhere from 9-12 studies.

The opportunities for shrinking the volume or timetable of studies are limited, said Templin. While it is possible to do some studies concurrently, many must be done consecutively because it saves money in case one study has ill effects. Labs also need the data from the first study to inform the design of the second. For instance, tox studies need to see toxicity over time and can’t be accelerated.

“For me, of the more key questions about how to reduce the time, is not to make the study shorter or less in scope,” said Templin. “It's to increase our efficiency as scientists about what we believe the data means and how we use it.”

Drug discovery begins with chemists and biochemists

The earliest stages of drug development are also arduous. Scientists rarely strike gold with the first molecule or the first drug target. And once they identify promising candidates, the process of optimizing them—that is refining the compound to improve its effectiveness and dimmish toxicity—takes time.

“It is iterative. For instance, for small molecule drugs, each week chemists look at the biological data and design novel molecules to improve on the compound, factoring in improvements like target inhibition, solubility, and half-life in the body,” says David Fischer, Executive Science Director, Discovery Services. “AI (Artificial intelligence) can help integrate and speed up all those difference biological parameters, but it is still a manual process that needs deep human expertise.”

Fischer says it typically takes 3-5 years for a small molecule drug to move from target validation to an optimized molecule – in other words the amount of time it takes to discover and refine the drug you intend to develop.

The process is a bit faster with gene therapies, and biologics in general, says Fischer, because “you can more accurately predict selectivity early on and understand the mechanism of action.”

In fact, Fischer views the growing field of biologics, cell therapies and gene therapies—as one area where we might see fewer failures and faster turnaround times. “I think the biggest impact that [genetic therapies and biologics] have is that the clinical chance of success may actually be higher,” he says. “And if it's higher you have less failures and thereby you reduce the time it takes from clinical to approval because you can focus on more of the successful programs rather than wasting a lot of time and exposing patients on clinical trials to candidate drugs that have a lower chance of success.”

About those COVID vaccines

So, given all that is required just during the preclinical process—how could we have gotten four very good vaccines into circulation in about a year? The simple answer is that the strategies and tools employed by the current COVID-19 vaccines have been refined for more than a decade on other indications. COVID-19 vaccine developers did not need to start from scratch—they already had blueprints that had been tested on other vaccine types, many of them viral based—and so could move their products to the clinic much faster. The massive amounts of collaboration also helped.

“When there’s precedent, it’s always easier,” says R. Mark Jones, Site Director for Charles River’s Biologics in Shrewsbury, MA who has extensive experience working on early-stage vaccine development. “In my previous position, I worked for roughly 8 years on a malaria vaccine. The first three years was focused on target selection to identify an acceptable biologic target to move to early-stage clinical trials. And we went from hundreds down to four or five, and then over the next two years, we went down to two. We spent half a decade to pick two targets,” he said. “If we flip back over to SARS-CoV-2, we already knew about the spike protein from the SARS coronavirus in 2003, and so we had two decades of people researching the spike protein on SARS, its family of viruses and types of viruses that fall into this category.”

The value of failing early in drug development

In any phase of drug development there is always the risk that the drug will be shown to be unsafe or ineffective for humans. But if those dangers can be identified early rather than during a clinical trial it can save the Sponsor money and time. “Time is really of the essence,” Jones said. “You want to be able to give the client the best advice possible. It's not always something that they want to hear, but it will help them in the long run because they won't waste time on something that it's not going to pass muster.”