At the After Heparin conference in March, Prabir Basu of the National Institute for Pharmaceutical Technology and Education spoke about the slipping security in U.S. pharmaceuticals, and ways we can use science to mitigate the risks that have come with an increasingly off-shore supply chain.
PostScript talked with Basu again recently about the true costs of making drugs overseas, and how Heparin could be an early warning sign of a much larger crisis.
PS: You’ve called the safety and quality problems in overseas drug manufacturing “health care’s hidden crisis.” Why is that?
PB: Yes. There’s a lot of uncontrolled outsourcing of drug manufacturing, and as we know, the FDA only inspects less than 10 to 15 percent of those plants. And that doesn’t even include excipient suppliers. Being that dependent on sources outside U.S. raises the probability that one day, there could be a crisis many times bigger than Heparin. That could really set us back, and lead to a shortage of drugs in the U.S.
Here’s an analogy: For a long time people were talking about hazards of offshore drilling, but no one really took it seriously or had appreciation for the magnitude of disruption until the Gulf Coast spill. Heparin may just have been an early indication. They’ve found melamine in pet food, diethylene glycol in toothpaste, etc.
This is really the hidden crisis no one is talking about. We don’t even have capacity to manufacture life-saving vaccines in the U.S. anymore. I think pharmaceutical security is as important as defense or energy, but it’s taken a lot less seriously.
PS: How much of this problem is about cost?
PB: Well, manufacturing is about 30 percent of total cost of making a drug. The immediate reaction to lower cost is to outsource. But if we invested in science at the front end, studies have shown we could reduce the cost of manufacturing and save more money than with cheaper labor in foreign countries. Studies done by McKinsey and others have shown we could save $20 – $50 billion each year through improving the science of manufacturing and implementing Quality by Design (QbD). We’d be in investing in our own country creating jobs and have better regulatory control, since the FDA is really geared toward domestic oversight. The natural question to ask is whether the real saving in outsourcing is coming from cheap labor, or from the savings arising from avoiding FDA inspections.
PS: One of your recommendations at the After Heparin conference was to prohibit import any drugs into the U.S. that had been made in foreign plants not inspected by the FDA.
But the fact that the average foreign plant gets inspected by FDA once every 9 years is now a commonly cited statistic, and the agency has said it doesn’t see any way its inspectorate can get to all plants, even with a huge boost in resources. Now they are considering third-party inspections. Is that an acceptable solution to your mind?
PB: Well, as far as I know, right now if a pharma company wants to start importing an API from a foreign source, it isn’t always obligated to have that plant inspected by FDA. I think we need to change the law, so that APIs, excipients, intermediates or finished drugs cannot be imported without having the source first been inspected by the FDA.
Today we ensure quality by inspection. But we know FDA has trouble getting resources from Congress. Many talented people have been laid off recently in the pharmaceutical industry. It would take very little effort to train these people up. We [NIPTE] could work with the FDA to develop training programs that the agency could use to certify these people to be inspectors under FDA’s supervision.
But we also have to move from quality by inspection, to quality by design.
PS: So what is NIPTE’s aim?
PB: We believe that one of the ways to fix the quality and safety problem of our pharmaceuticals is to have proper science in place. In some ways, the pharma industry today could be compared with the auto industry 50 years ago: pretty happy with marketing and outsourcing and not investing in manufacturing science and technology.
And what happened? The auto industry essentially disappeared in this country a couple years ago. And drugs are a critical part of our life – we are very heavily dependent on a daily basis, perhaps more so than on cars.
The science I’m talking about consists of several things: design, manufacturing, how to detect impurities, etc. The [USP] methods are pretty antiquated, actually. There are newer methods and analytical tools–predictive models that relate raw material properties and operational variables to product performance, etc.— but they are not being used to design robust processes, which will have a much lower chance of failure.
PS: But isn’t that more about drug development than problems that happen during manufacture?
PB: Development and manufacturing are extremely interrelated. The Heparin crisis has taught us that there are very, very smart people trying to adulterate our drugs. We cannot lay back: we have to be smarter, think ahead and develop state-of-the-art technologies to anticipate and deal with problems that can occur. We have to have the science and technology to stop adulteration before it happens.
PS: In the scenario you’re describing, the manufacturer incurs savings from minimum regulation and the end user–the consumer–bears the cost. What can consumers do change the equation?
PB: Well, we need two things: to educate consumers, and to pressure our Congress to change the laws. A new bill is being proposed by Sen. Bennet to improve drug safety. Maybe it doesn’t go far enough, but it’s a good start.
When I look at my shirt, its tag tells me where it was made. Why shouldn’t I have that choice when I buy the most important things—the drugs that keep me alive? There should be labels showing country of origin for drugs, and a database where I as a consumer can go to see where each component is coming from, and better answer: do I feel safe enough to take that drug?
When an average citizen buys a drug from the pharmacy, she trusts the quality of that drug because she knows the FDA is there to ensure it’s safe. That citizen doesn’t know that the plant where an ingredient or final drug was made was never inspected by the FDA. There needs to be more education so that people are better aware of how our drugs sometimes get made in places where there is very little control and FDA supervision.
–Interviewed by Kate Petersen, PostScript blogger