Results for “FDA drug manufacturing” 11 found
The Adderall Shortage: DEA versus FDA in a Regulatory War
A record number of drugs are in shortage across the United States. In any particular case, it’s difficult to trace out the exact causes of the shortage but health care is the US’s most highly regulated, socialist industry and shortages are endemic under socialism so the pattern fits. The shortage of Adderall and other ADHD medications is a case in point. Adderall is a Schedule II controlled substance which means that in addition to the FDA and other health agencies the production of Adderall is also regulated, monitored and controlled by the U.S. Drug Enforcement Administration (DEA).
The DEA aims to “combat criminal drug networks that bring harm, violence, overdoses, and poisonings to the United States.” Its homepage displays stories of record drug seizures, pictures of “most wanted” criminal fugitives, and heroic armed agents conducting drug raids. With this culture, do you think the DEA is the right agency to ensure that Americans are also well supplied with legally prescribed amphetamines?
Indeed, there is a large factory in the United States capable of producing 600 million doses of Adderall annually that has been shut down by the DEA for over a year because of trivial paperwork violations. The New York Magazine article on the DEA created shortage has to be read to be believed.
Inside Ascent’s 320,000-square-foot factory in Central Islip, a labyrinth of sterile white hallways connects 105 manufacturing rooms, some of them containing large, intricate machines capable of producing 400,000 tablets per hour. In one of these rooms, Ascent’s founder and CEO — Sudhakar Vidiyala, Meghana’s father — points to a hulking unit that he says is worth $1.5 million. It’s used to produce time-release Concerta tablets with three colored layers, each dispensing the drug’s active ingredient at a different point in the tablet’s journey through the body. “About 25 percent of the generic market would pass through this machine,” he says. “But we didn’t make a single pill in 2023.”
… the company has acknowledged that it committed infractions. For example, orders struck from 222s must be crossed out with a line and the word cancel written next to them. Investigators found two instances in which Ascent employees had drawn the line but failed to write the word.
The causes of the DEA’s crackdown appears to be precisely the contradiction in its dueling missions. Ascent also produces opioids and the DEA crackdown was part of what it calls Operation Bottleneck, a series of raids on a variety of companies to demand that they account for every pill produced.
To be sure, the opioid epidemic is a problem but the big, multi-national plants are not responsible for fentanyl on the streets and even in the early years the opioid epidemic was a prescription problem (with some theft from pharmacies) not a factory theft problem (see figure at left). Maybe you think Adderall is overprescribed. Could be but the DEA is supposed to be enforcing laws not making drug policy. The one thing one can say for certain is that Operation Bottleneck has surely been a success in creating shortages of Adderall.
The DEA’s contradictory role in both combating the illegal drug trade and regulating the supply of legal, prescription drugs is highlighted by the fact that at the same as the DEA was raiding and shutting down Ascent, the FDA was pleading with them to increase production!
For Ascent, one of the more frustrating parts of being told by the government to stop making Adderall is that other parts of the government have pleaded with the company to make more. The company says that on multiple occasions, officials from the FDA asked it to increase production in response to the shortage, and that Ron Wyden, the Democratic senator from Oregon, also pressed Ascent for help. They received responses similar to those the company gave the stressed-out callers looking for pills: Ascent didn’t have any information. Instead, the company directed them to the DEA.
Conditional Approval for Human Drugs
Recently a new drug to extend lifespan was granted conditional approval by the FDA–the first drug ever formally approved to extend lifespan! (By the way, the entrepreneur behind this breakthrough, Celine Halioua, is an emergent ventures winner for her earlier work rapidly expanding COVID testing. Tyler knows how to spot Talent!)
Great news, right? Yes, but there are two catches. First catch: the drug is for extending the lifespan of dogs. Second catch: Conditional approval is only available for animal drugs. Conditional approval was permitted for animal drugs beginning in 2004 for minor uses and/or minor species (fish, ferrets etc.) and then expanded in 2018 to include major uses in major species. What does conditional approval allow?
Conditional Approval (CA) allows potential applicants (referred to from this point as “sponsors”) to make a new animal drug product commercially available after demonstrating the drug is safe and properly manufactured in accordance with the FDA approval standards for safety and manufacturing, but before they have demonstrated substantial evidence of effectiveness (SEE) of the conditionally approved product. Under conditional approval, the sponsor needs to demonstrate reasonable expectation of effectiveness (RXE). A drug sponsor can then market a conditionally approved product for up to five years, through annual renewals, while collecting substantial evidence of effectiveness data required to support an approval.
Here is where it gets even more interesting. Why does the FDA say that conditional approval is a good idea?
First, it’s very expensive for a drug company to develop a drug and get it approved by FDA. Second, the market for a MUMS [Minor Use, Minor Species, AT] drug is too small to generate an adequate financial return for the company. The combination of the expensive drug approval process and the small market often makes drug companies hesitant to spend a lot of resources to develop MUMS drugs when there is so little return on their investment.
By allowing a drug company to legally market a MUMS drug early (before it is fully approved), conditional approval makes the drug available sooner to be used in animals that may benefit from it. This early marketing also helps the company recoup some of the investment costs while completing the full approval.
…Similar to conditional approval for MUMS drugs, the goal of expanded conditional approval is to encourage drug companies to develop drugs for major species for serious or life-threatening conditions and to fill treatment gaps where no therapies currently exist or the available therapies are inadequate.
Sound familiar? These are exactly some of the points that I have been raising about the FDA approval process for years. In particular, by bringing forward marketing approval by up to 5 years, conditional approval makes it profitable to research and develop many more new drugs.
Conditional approval is very similar to Bart Madden’s excellent idea of a Free to Choose Medicine track, with the exception that Madden makes the creation of a public tradeoff evaluation drug database (TEDD) a condition of moving to the FTCM track. Thus, FTCM combines conditional approval with the requirement to collect and make public real-world prescribing information over time.
But why is conditional approval available only for animal drugs? Conditional approval is good for animals. People are animals. Therefore, conditional approval is good for people. QED.
Ok, perhaps it’s not that simple. One might argue that allowing animals to use drugs for which there is a reasonable expectation of effectiveness but not yet substantial evidence of effectiveness is a good idea but this is just too risky to allow for humans. But that cuts both ways. We care more about humans and so don’t want to impose risks on them that we are willing to impose on animals but for the same reasons we care more about improving the health of humans and should be willing to risk more to save them (Entering a burning building to save a child is heroic; for a ferret, it’s foolish.)
I think that the FDA’s excellent arguments for conditional approval apply to human drugs as well as to (other) animal drugs and even more so when we recognize that human beings have rights and interests in making their own choices. The Promising Pathways Act would create something like conditional approval (the act calls it provisional approval) for drugs treating human diseases that are life-threatening so there is some hope that conditional approval for human drugs becomes a reality.
Dare I say it, but could the FDA be lumbering in the right direction?
FDA Postpones Inspections Delaying New Drugs and Creating Shortages of Old Drugs
NYTimes: The Covid-19 pandemic has forced the Food and Drug Administration to postpone hundreds of drug company inspections, creating an enormous backlog that is delaying new drug approvals and leading the industry to warn of impending shortages of existing medicines.
…In an interview, F.D.A. officials said they sharply curtailed the inspections to protect their investigators, following guidelines from the Centers for Disease Control and Prevention, which discouraged federal employees from travel during the pandemic.
But some people in both industry and public health communities say that federal drug inspections are essential, and that the agency should bypass travel restrictions by taking precautions, including wearing proper personal protective equipment.
…In interviews, F.D.A. officials denied that the dramatic drop in inspections has slowed drug approvals. But a number of drug companies, including Spectrum Pharmaceuticals, Biocon Biologics and Bristol Myers Squibb, has issued statements noting deferred F.D.A. action because of the agency’s inability to conduct inspections.
In October, Spectrum announced that the F.D.A. had deferred action on its application for Rolontis, a treatment for cancer patients who have a very low number of certain white blood cells, because it could not inspect the manufacturing plant the company uses in South Korea.
In late December, Biocon Biologics notified shareholders that the F.D.A. deferred action on its joint application with Mylan for a proposed biosimilar to Avastin, a cancer drug.
Bristol Myers Squibb announced in November that the F.D.A. would miss its November deadline for taking action on a lymphoma treatment, lisocabtagene maraleucel because it could not inspect a third-party Texas manufacturing plant. The agency eventually did complete its inspection and approved the drug last month.
Grocery store workers are working, meat packers are working, hell bars and restaurants are open in many parts of the country but FDA inspectors aren’t inspecting. It boggles the mind.
Let’s review. The FDA prevented private firms from offering SARS-Cov2 tests in the crucial early weeks of the pandemic, delayed the approval of vaccines, took weeks to arrange meetings to approve vaccines even as thousands died daily, failed to approve the AstraZeneca vaccine, failed to quickly approve rapid antigen tests, and failed to perform inspections necessary to keep pharmaceutical supply lines open.
I am a long-time critic of the FDA and frankly I am stunned at the devastation.
How badly has the FDA been lagging?
As a Johns Hopkins scientist who has conducted more than 100 clinical studies and reviewed thousands more from the scientific community at large, I can assure you that the agency’s review can be done within 24 to 48 hours without cutting any corners. They just need to work harder.
Contrary to popular belief, the FDA process is not hands-on—it does not interview vaccine trial patients or look under a microscope at the immune cells. It’s doing a statistical analysis and looking at data. For the vaccine trial, the data set is small and straightforward. If my research team, normally tasked with analyzing data on millions of patients, was asked to review the smaller Pfizer vaccine study of 43,000 patients, it would take about one hour.
The FDA also reviews manufacturing data from Pfizer on how they made the drug. But not only can that data be reviewed in a few hours, it should have been done months ago when it was available. While the FDA was waiting for Pfizer’s long-term vaccine results to come in, the agency should have anticipated this step and done it early.
The final step of the FDA review is to look at the outcomes of the study volunteers, including rates and severity of infection and side effects in the vaccine and placebo groups. Again, there is no plausible reason why this basic analysis cannot be done in 24 hours. The FDA and external scientists have a simple task: confirm or reject the review already conducted by the trial’s independent data safety monitoring board before FDA submission.
That is from Marty Makary, who also details an ongoing history of FDA delays during the pandemic, starting with the very first Covid testing attempts from the University of Washington, which the FDA tried to nix, but continuing throughout. And:
FDA insiders say the agency and its approximately 17,000 employees were dark for the four-day Thanksgiving holiday, including those working on the vaccine approval.
For those of us who lived through the 2008 financial crisis (agencies other than the Fed were not on the ball in response), or who have studied (and indeed practiced) the economics of bureaucracy for forty years, or who know the extensive literature on how the FDA operates, will not be surprised by a lack of urgency. Or from the NYT:
Dr. Fauci said the politicization of the pandemic in his own country had led regulators to move a little more cautiously than the British, to avoid losing public support.
Sorry people, but I read that as “for political reasons we did not go more quickly.”
Here from Statnews journalists Matthew Herper and Nicholas Florko defend the FDA, going into considerable detail, do read it. Here is one excerpt, in direct contradiction to some of the above:
The agency’s staff “were eating turkey sandwiches on Thanksgiving while reviewing documents,” Peter Marks, who heads the FDA center conducting the vaccine reviews, said on a Thursday webcast run by the Journal of the American Medical Association.
Additionally, members of an FDA advisory committee that will convene Thursday to review the data and issue its recommendations, have expressed no desire to meet sooner. STAT spoke to four members of the panel and all said the agency should not try to move any faster.
My view is this: if your agency is saying “usually we move five to ten times more slowly,” it is highly unlikely their current procedures are optimized for speed. It is fast organizations that are good at moving fast, right Usain Bolt?
We’re now at the point where Covid-19 is the single leading cause of death in this nation.
Drug Shortages Caused by the FDA
Shortages of drugs, especially generic injectables, continue to cause significant harm to patients. A new Congressional report offers the best account to date of the shortages and provides details confirming my earlier post. The story in essence is this:
The FDA began to ramp up GMP rules and regulations under the new commissioner in 2010 and 2011 (see figure at left (N.B. this includes all warning letters not just GMP so it is just illustrative, AT added). In fact, the report indicates that FDA threats shut down some 30% of the manufacturing capacity at the big producers of generic injectables. The safety of these lines was not a large problem and could have been handled with a targeted approach but instead the FDA launched a sweep against all the major manufacturers at the same time. These problem have been exacerbated by a change in Medicare reimbursement rules and by the rise of GPOs (buying groups) which reduced the prices of generics. Thus, in response to the cut in capacity, firms have shifted production from less profitable generics to more profitable branded drugs, so we get shortages of generics rather than of branded drugs.
Add to these major factors a few unique events such as the FDA now requiring pre-1938 and pre-62 drugs to go through expensive clinical trials, the slowdown of ANDAs and crazy stuff such as DEA control over pharmaceutical manufacturing and you get very extensive shortages.
Drug Shortages
WP: Doctors, hospitals and federal regulators are struggling to cope with an unprecedented surge in drug shortages in the United States that is endangering cancer patients, heart attack victims, accident survivors and a host of other ill people.
Currently there are about 246 drugs that are in short supply, a record high. These shortages are not just a result of accident, error or unusual circumstance, the number of drugs in short supply has risen steadily since 2006. The shortages arise from a combination of systematic factors, among them the policies of the FDA. The FDA has inadvertently caused drugs long-used in the United States to be withdrawn from the market and its “Good Manufacturing Practice” rules have gummed up the drug production process and raised costs.
Here, for example, is an analysis from the summary report on drug shortages by the American Society of Health-System Pharmacists (ASHP), the American Society of Anesthesiologists (ASA), the American Society of Clinical Oncology (ASCO), and the Institute for Safe Medication Practices (ISMP).
Several drug shortages (e.g., concentrated morphine sulfate solution, levothyroxine injection) have been precipitated by actual or anticipated action by the FDA as part of the Unapproved Drugs Initiative, which is designed to increase enforcement against drugs that lack FDA approval to be marketed in the United States. (These drugs are commonly called pre-1938 drugs, referring to their availability prior to passage of the Food, Drug, and Cosmetic Act of that year.) Some participants noted that the cost and complexity of completing a New Drug Application (NDA) for those unapproved drugs is a disincentive for entering or maintaining a market presence. Other regulatory barriers include the time for FDA review of Abbreviated New Drug Applications (ANDA) and supplemental applications, which are required for changes to FDA-approved drug products (e.g., change in source for active pharmaceutical ingredients API, change in manufacturer). Manufacturers described this approval process as lengthy and unpredictable, which limits their ability to develop reliable production schedules.
and on GMP:
Manufacturing-related causes that contribute to drug shortages are multifactorial. Inability to fully comply with GMP, which results in production stoppages or recalls, was considered a major cause.
John Goodman at the Health Affairs Blog explains the details:
The Federal Food and Drug Administration (FDA) has been stepping up its quality enforcement efforts — levying fines and forcing manufacturers to retool their facilities both here and abroad. Not only has this more rigorous regulatory oversight slowed down production, the FDA’s “zero tolerance” regime is forcing manufacturers to abide by rules that are rigid, inflexible and unforgiving. For example, a drug manufacturer must get approval for how much of a drug it plans to produce, as well as the timeframe. If a shortage develops (because, say, the FDA shuts down a competitor’s plant), a drug manufacturer cannot increase its output of that drug without another round of approvals. Nor can it alter its timetable production (producing a shortage drug earlier than planned) without FDA approval.
Thus, it’s not any one thing that is causing the shortages but an accumulation of rules and regulations. The system plods along when all is normal, but when a novel situation develops the market can no longer adapt quickly and efficiently. As Michael Mandel puts it:
No single regulation or regulatory activity is going to deter innovation by itself, just like no single pebble is going to affect a stream. But if you throw in enough small pebbles, you can dam up the stream. Similarly, add enough rules, regulations, and requirements, and suddenly innovation begins to look a lot less attractive.
Add to all these pebbles the fact that various price controls have become more binding over time and thus have reduced the profits from being in the business at all and you have a recipe for deadly shortages.
Shout it From the Rooftops and Sometimes People Will Listen
Shout it from the rooftops and sometimes lots of other people will start shouting and then sometimes other people will listen!
The U.S. will begin sharing its entire pipeline of vaccine from AstraZeneca once the COVID-19 vaccine clears federal safety reviews, the White House told The Associated Press on Monday, with as many as 60 million doses expected to be available for export in the coming months.
The move greatly expands on the Biden administration’s action last month to share about 4 million doses of the vaccine with Mexico and Canada. The AstraZeneca vaccine is widely in use around the world but not yet authorized by the U.S. Food and Drug Administration.
…About 10 million doses of AstraZeneca vaccine have been produced but have yet to pass review by the FDA to “meet its expectations for product quality,” Zients said…That process could be completed in the next several weeks. About 50 million more doses are in various stages of production and could be available to ship in May and June pending FDA sign-off.
Let’s also get our J&J vaccine factories up and running and soon we will have Moderna and Novavax to export as well. Keep it coming! An American plan to vaccinate the world.
In praise of Alex Tabarrok
Here’s a question I’ve been mulling in recent months: Is Alex Tabarrok right? Are people dying because our coronavirus response is far too conservative?
I don’t mean conservative in the politicized, left-right sense. Tabarrok, an economist at George Mason University and a blogger at Marginal Revolution, is a libertarian, and I am very much not. But over the past year, he has emerged as a relentless critic of America’s coronavirus response, in ways that left me feeling like a Burkean in our conversations.
He called for vastly more spending to build vaccine manufacturing capacity, for giving half-doses of Moderna’s vaccine and delaying second doses of Pfizer’s, for using the Oxford-AstraZeneca vaccine, for the Food and Drug Administration to authorize rapid at-home tests, for accelerating research through human challenge trials. The through line of Tabarrok’s critique is that regulators and politicians have been too cautious, too reluctant to upend old institutions and protocols, so fearful of the consequences of change that they’ve permitted calamities through inaction.
Tabarrok hasn’t been alone. Combinations of these policies have been endorsed by epidemiologists, like Harvard’s Michael Mina and Brown’s Ashish Jha; by other economists, like Tabarrok’s colleague Tyler Cowen and the Nobel laureates Paul Romer and Michael Kremer; and by sociologists, like Zeynep Tufekci (who’s also a Times Opinion contributor). But Tabarrok is unusual in backing all of them, and doing so early and confrontationally. He’s become a thorn in the side of public health experts who defend the ways regulators are balancing risk. More than one groaned when I mentioned his name.
But as best as I can tell, Tabarrok has repeatedly been proved right, and ideas that sounded radical when he first argued for them command broader support now. What I’ve come to think of as the Tabarrok agenda has come closest to being adopted in Britain, which delayed second doses, approved the Oxford-AstraZeneca vaccine despite its data issues, is pushing at-home testing and permitted human challenge trials, in which volunteers are exposed to the coronavirus to speed the testing of treatments. And for now it’s working: Britain has vaccinated a larger percentage of its population than the rest of Europe and the United States have and is seeing lower daily case rates and deaths.
Against Regulatory Nationalism
I’ve long argued that if a drug or medical device is approved in another country with a Stringent Regulatory Authority it ought to be approved in the United States. But, of course, the argument is even stronger in the other direction. Drugs and devices approved in the United States ought to be approved elsewhere. Indeed, this is how much of the world actually works because most countries do not have capability to evaluate drugs and devices the way the FDA or say the EMA does. Although it’s the way the world works, few will admit it because that would violate pretensions of regulatory nationalism. Moreover, keeping up with pretenses means transaction costs and unnecessary delays.
The price of such regulatory nationalism can be very high as indicated in this interview with Adar Poonawalla, chief executive of the Serum Institute of India (SII), the world’s largest producer of vaccines.
Some people think the reason that rollout has been slow in many countries is because the developers who hold the patents on the vaccines have licensed too few manufacturers to make them. Do you agree?
No. There are enough manufacturers, it just takes time to scale up. And by the way, I have been blown away by the cooperation between the public and private sectors in the last year, in developing these vaccines. What I find really disappointing, what has added a few months to vaccine delivery – not just ours – is the lack of global regulatory harmonisation. Over the last seven months, while I’ve been busy making vaccines, what have the US, UK and European regulators been doing? How hard would it have been to get together with the World Health Organization and agree that if a vaccine is approved in the half-dozen or so major manufacturing countries, it is approved to send anywhere on the planet?
Instead we have a patchwork of approvals and I have 70m doses that I can’t ship because they have been purchased but not approved. They have a shelf life of six months; these expire in April.
Did you get that? Regulatory nationalism has added months to vaccine delivery and now threatens to put to waste millions of stockpiled doses.
Addendum: See also Scott Sumner on the costs of regulatory nationalism.
The economics of biosimilars
If I understand correctly, a biologic is “any medicinal product manufactured in, extracted from, or semisynthesized from biological sources,” and a biosimilar is a copy of a biologic. Think of a biosimilar as harder to make than a generic drug and also requiring separate FDA approval. Here is Wikipedia:
Unlike the more common small-molecule drugs, biologics generally exhibit high molecular complexity, and may be quite sensitive to changes in manufacturing processes. Follow-on manufacturers do not have access to the originator’s molecular clone and original cell bank, nor to the exact fermentation and purification process, nor to the active drug substance. They do have access to the commercialized innovator product.
Here is a Rand piece on the potential cost savings from biosimilars (pdf), but in percentage terms they do not become nearly as cheap as generic drugs, maybe 65-85% of the price of the original.
Zarxio was the first biosimilar approved by the United States, and the global biosimilars market could hit $55 billion by 2020. Here is yesterday’s FT story about biosimilars draining away sales.
Here is a paper by Blackstone and Fuhr:
Various factors, such as safety, pricing, manufacturing, entry barriers, physician acceptance, and marketing, will make the biosimilar market develop different from the generic market. The high cost to enter the market and the size of the biologic drug market make entry attractive but risky.
Will cell therapies, which are relatively new and also hard to copy with biosimilars, save Big Pharma from the forthcoming patent cliff?
Biosimilars will become a bigger issue soon:
There are 11 biologic drugs that will face biosimilar competition in the next several years, according to data compiled by Evercore ISI. These drugs, which treat ailments from cancer to rheumatoid arthritis, raked in more than $50 billion combined in 2014.
The FDA is outlining biosimilar approval pathways, although the issue seems to be receiving almost zero attention from the outside world.
Marcia Angell’s Mistaken View of Pharmaceutical Innovation
At Econ Talk, Marcia Angell discusses big Pharma with Russ Roberts. I think she gets a lot wrong. Here is one exchange on innovation.
Angell: The question of innovation–you said that some people feel, economists feel, [the FDA] slows up innovation: The drug companies do almost no innovation nowadays. Since the Bayh-Dole Act was enacted in 1980 they don’t have to do any innovation….
Roberts: But let’s just get a couple of facts on the table…[The] research and development budget of the pharmaceutical industry is, in 2009, was about $70 billion. That’s a very large sum of money. Are you suggesting that they don’t do anything–that that’s mostly or all marketing? That they are not trying to discover new applications of the basic research? It seems to me basic research is an important part. Putting that research into a form that can make us healthier seems to be a nontrivial thing. You think they are–what are they doing with that money?
Angell: If you look at the budgets of the major drug companies–just go to their annual reports, their Security and Exchange Commission (SEC) filings, you see that Research and Development (R&D) is really the smallest part of their budget. If you look at the big companies you can divide their budget into 4 big categories. One is R&D, one is marketing and administration; the other is profits, and the other is just the cost of making the pills and putting them in the bottles and distributing them. The smallest of those is R&D.
Notice that Angell first claims the pharmaceutical companies do almost no innovation then, when presented with a figure of $70 billion spent on R&D, she switches to an entirely different and irrelevant claim, namely that spending on marketing is even larger. Apple spends more on marketing than on R&D but this doesn’t make Apple any less innovative. Angell’s idea of splitting up company spending into a “budget” is also deeply confused. The budget metaphor suggests firms choose among R&D, marketing, profits and manufacturing costs just like a household chooses between fine dining or cable TV. In fact, if the marketing budget were cut, revenues would fall. Marketing drives sales and (expected) sales drives R&D. Angell is like the financial expert who recommends that a family save money by selling its car forgetting that without a car it makes it much harder to get to work.
Later Angell tries a third claim namely that pharma companies do no innovation because their R&D budget is mostly spent on clinical trials and, “it’s no secret how to do a clinical trial.” I find this line of reasoning bizarre. I define an innovation as the novel creation of value, in this case the novel creation of valuable knowledge. Is Angell claiming that clinical trials do not provide novel and valuable knowledge? (FYI, I have argued that the FDA is overly safety conscious and requires too many trials but Angell breezily and nastily dismisses this argument). In point of fact, most new chemical entities die in clinical trial because what we thought would work in theory doesn’t work in practice. Moreover, the information generated in the clinical trials feeds back into basic research. Angell’s understanding of innovation is cramped and limited, she thinks it begins and ends with basic science in a university lab. Edison was right, however, when he said that genius is one percent inspiration and ninety-nine percent perspiration–both parts are required and there is no one-way line of causation, perspiration can lead to inspiration as well as vice-versa. Read Derek Lowe on the reality of the drug discovery process.
Angell infuses normative claims to the industrial organization of the pharmaceutical industry. Over the past two decades there has been an increase in the number of small biotechnology companies, often funded by venture capital. Most of the small biotechs are failures, they never produce a new molecular entity (NME). But a large number of small, diverse, entrepreneurial firms can explore a big space and individual failure has been good for the small-firm industry which collectively has increased its discovery of NMEs. The small biotechs, however, are not well placed to deal with the FDA and run large clinical trials–the same is also true of university labs. So the industry as a whole is evolving towards a network model in which the smaller firms explore a wide space of targets and those that hit gold partner with one of the larger firms to pursue development. Angell focuses in on one part of the system, the larger firms and denounces them for not being innovative. Innovation, however, should be ascribed not to any single node but to the network, to the system as a whole.
Angell makes some good points about publication bias in clinical trials and the sometimes too-close-for-comfort connections between the FDA, pharmaceutical firms, and researchers. But in making these points she misses the truly important picture. Namely that new pharmaceuticals have driven increases in life expectancy but pharmaceutical productivity is declining as the costs of discovering and bringing a new drug to market are rising rapidly (on average ~1.8 billion per each NME to reach market). In my view, the network model pursued on a global scale and a more flexible and responsive FDA, both of which Angell castigates, are among the best prospects for an increase in pharmaceutical productivity and thus for increases in future life expectancy. Nevertheless, whatever the solutions are, we need to focus on the big problem of productivity if we are to translate scientific breakthroughs into improvements in human welfare.