FDA Postpones Inspections Delaying New Drugs and Creating Shortages of Old Drugs

by  Alex Tabarrok in

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.

Let the AZ Vaccine Go!

by  Alex Tabarrok

Finally the NYTimes has picked up on a story I have been shouting from the rooftops for months.

Tens of millions of doses of the coronavirus vaccine made by the British-Swedish company AstraZeneca are sitting idly in American manufacturing facilities, awaiting results from its U.S. clinical trial while countries that have authorized its use beg for access.

…About 30 million doses are currently bottled at AstraZeneca’s facility in West Chester, Ohio, which handles “fill-finish,” the final phase of the manufacturing process during which the vaccine is placed in vials, one official with knowledge of the stockpile said.

Emergent BioSolutions, a company in Maryland that AstraZeneca has contracted to manufacture its vaccine in the United States, has also produced enough vaccine in Baltimore for tens of millions more doses once it is filled into vials and packaged, the official said.

…But although AstraZeneca’s vaccine is already authorized in more than 70 countries, according to a company spokesman, its U.S. clinical trial has not yet reported results, and the company has not applied to the Food and Drug Administration for emergency use authorization. AstraZeneca has asked the Biden administration to let it loan American doses to the European Union, where it has fallen short of its original supply commitments and where the vaccination campaign has stumbled badly.

The administration, for now, has denied the request, one official said.

Some federal officials have pushed the White House to make a decision in the next few weeks. Officials have discussed sending doses to Brazil, which has been hard hit by a worsening coronavirus crisis, or the European Union or Britain.

The AZ vaccine could have saved thousands of lives in the US, if it had been approved earlier. But it’s not going to be approved in the US for months at best and with the ramp up in production of Pfizer, Moderna, J&J and now Novavax it’s no longer needed in the US. Let it go! Send it to Canada or Mexico or Brazil or COVAX.

In our Science Paper we estimate that another 1 billion courses of vaccine capacity are worth $1 trillion of additional global benefits. AZ has on the order of 50 million doses nearly ready to go and can produce in the US around 25 million doses a month so over a year that production is worth over $100 billion to the world economy, far higher than the modest cost of production! Instead of idling this capacity we should expand it even further as part of a plan to vaccinate the world.

It’s a Biden Plan to vaccinate the world or a Xi Jinping Plan and I’d rather it be a Biden Plan.

Why vaccination passports probably won’t work well

by  Tyler Cowen in

That is the topic of my latest Bloomberg column, here is one excerpt:

One issue is what exactly constitutes proof of vaccination. For my vaccinations, I have been issued a rather flimsy, easy-to-forge paper document from the Centers for Disease Control. Unlike a passport or a dollar bill, it has no embedded watermarks or other protections. Anyone with a moderately sophisticated copy machine could create many fake documents, or perhaps steal an existing stash of these documents and sell them on the black market. Once you have the documents, you can simply note that you have been vaccinated, and it is not easy for outside parties to dispute such claims.

Soon enough, of course, it may be easier for most adults to get a vaccine than to forge a vaccine passport. Still, U.S. laws and regulations work better when they can refer to clear, verifiable standards of evidence. It is hard to imagine a set of laws or procedures based on criteria so loose that they basically allow anyone to claim they are vaccinated. A more stringent standard, however, would be hard for most vaccinated Americans to meet.

Another knotty question is which vaccines will count for the passport. Pfizer’s, Moderna’s and Johnson & Johnson’s for sure, but what if you are a U.S. citizen living in Canada who received AstraZeneca’s vaccine, which has been approved by some 15 nations but not the U.S.? Is the federal government willing to tell a whole class of responsible individuals that they cannot fly on U.S. planes? Or will the vaccine-passport bureaucracy be willing to approve vaccines that the Food and Drug Administration will not?

These dilemmas can become stickier yet. What about Sputnik, the Russian vaccine, or the numerous Chinese vaccines, which are being administered around the world, including in Mexico?

Do Americans really wish to create a country to which most foreigners would not be very welcome? Furthermore, what counts as proof of foreign vaccination? Some Asian countries, including China, are creating elaborate and supposedly secure vaccine verification systems, using advanced information technology. Good for them — but how would that connect with U.S. regulations? How many different passport systems would a flight attendant or gate agent have to read, interpret and render judgment upon?

The likely result of all this: Many foreign visitors to the U.S. would never quite know in advance whether they could board an airplane or attend a public event.

And how would the passport reflect any new vaccines deemed necessary? What if new Covid-19 strains require booster shots? What if you’ve had Covid and thus get only one shot for now rather than two, as many experts are recommending? What will happen as the number of vaccines around the world proliferates? Given the slowness of the FDA and CDC, it is hard to imagine any new U.S. approvals coming quickly. A vaccine passport system could end up being fetters not only for foreigners and anti-vaxxers but also for vaccinated Americans.

Recommended, there are additional arguments at the link.

Meng Wanzhou is still under arrest

by  Tyler Cowen in

Yes, the CFO of Huawei.  She has been held under house arrest by Canada since December 2018, under the supposition that she will be extradited to the United States to face trial.  Don’t we believe in something like a right to a fair and speedy trial?  Can she get that at this point?

I am not pleading for her innocence, rather this is a major foreign policy and tactical mistake.  How would the United States react if China held say Bill Gates, on the grounds that he had violated some extraterritorial Chinese law?  The U.S.-China relationship is the world’s most important, so why are we partially wrecking it over such a matter?

It is also an erosion of the rule of law in the United States and Canada.  You might plead “independent judiciary,” but when American law “goes extraterritorial,” as it has in this case, there are so many potential cases that the selection of charges and extradition requests cannot help but be political.  How many other people have acted to “conspire to circumvent U.S. sanctions against Iran”, as are the charges here?  Are they all being detailed and held?  This dilemma is a good reason to limit the reach of American law into extraterritorial matters, namely that there is no objective way to apply the law fairly and impartially against a very large number of (possible) foreign perpetrators operating overseas.  We go after corrupt soccer officials abroad but not corrupt chess officials at FIDE?

There is plenty of evidence (Bloomberg) that North American politicians have been interfering in this matter already, so to cancel the charges and release her would hardly be soiling our constitutional innocence.  Best would be if the Canadian government would step in and end the mess.

To be clear, I am supportive of the United States working very hard to make sure its allies do not install Huawei communications equipment, as that could compromise their and our national security.  Still, that is not the issue here and so it is time to free Meng Wanzhou.

Ordinary air pollution is still an underrated problem

by  Tyler Cowen in

That is the theme of my latest Bloomberg column, here is one excerpt:

More than 10 million people die each year from air pollution, according to a new study — far more than the estimated 2.6 million people who have died from Covid-19 since it was detected more than a year ago. And while Covid is headline news, ordinary air pollution remains a side issue for policy wonks and technocrats.

[To be clear, I am not seeking to minimize Covid as a major issue.]  And:

Why aren’t these deaths a bigger issue in U.S. political and policy discourse? One reason may be that 62% of those deaths are in China and India. The number of premature deaths due to particulate matter in North America was 483,000, just slightly lower than the number of measured deaths from Covid to date. An estimated 876 of those deaths were of children under the age of 4.

Another reason for the weak political salience of the issue may be its invisibility. Air pollution causes many deaths. But it is rare to see or read about a person dying directly from air pollution. Lung cancer and cardiac disease are frequently cited as causes of death, even though they may stem from air pollution.

Another problem is that the question of how to better fight air pollution does not fit neatly into current ideological battles. You might think Democrats would emphasize this issue, but much of the economic burden of tougher action would fall on the Northeast, a largely Democratic-leaning area.

And exactly how many people die each year from global warming?  Why not have a greater focus on ordinary air pollution?

Wednesday assorted links

by  Tyler Cowen

1. #Econtwitter to the Biden administration.

2. Data on Long Covid.

3. Work and writing habits of Harlan Coben (NYT).

4. How vaccine production was accelerated, from the policy side (NYT).

5. Register for my Saturday chat with Patrick Collison, through Oxford and Works in Progress.  And Dutch inventor of the audio cassette tape passes away.

6. Ross Douthat on January 6th.

7. One-way interviews.

My excellent Conversation with John Cochrane

by  Tyler Cowen in

Here is the audio, transcript, and video.  So many good parts it is hard to excerpt, here is part of the summary:

John joined Tyler to apply that habit of mind to a number of puzzles, including why real interest rates don’t equalize across countries, what explains why high trading volumes and active management persist in finance, how the pandemic has affected his opinion of habit formation theories, his fiscal theory of price level and inflation, the danger of a US sovereign debt crisis, why he thinks Bitcoin will eventually die, his idea for health-status insurance, becoming a national gliding champion, how a Renaissance historian for a father and a book translator for a mother shaped him intellectually, what’s causing the leftward drift in economics, the need to increase competition among universities, how he became libertarian, the benefits of blogging, and more.

Here is one bit from John:

COCHRANE: You ask two questions here. One is active management, and the other is trading. I’d like to distinguish them. It’s a puzzle in the Chicago free market sense.

Let me ask your question even more pointedly. If you believe in efficient markets, and you believe in competition, and things work out right, we’ve scientifically proven since the 1960s, that high-fee active managers don’t earn any more than a proverbial monkey throwing darts in a well-managed slow index. So why do people keep paying for high-fee active management?

Chicago free market — we’re not supposed to say, “Oh, people are dumb for 40 years — 50 years now,” [laughs] but there’s a lot of it. It’s one of those things. Active management is slowly falling away. The move towards passive index investment is getting stronger and stronger.

There’s a strong new literature, which I’ll point to. My colleague here, Jonathan Berk, has written some good articles on it. This is the puzzle of efficient markets. If everybody indexed, markets couldn’t be efficient because no one’s out there getting the information that makes markets efficient. Markets have to be a little inefficient, and somebody has to do the trading.

Your second question is about trading. Why is there this immense volume of trading? When was the last time you bought or sold a stock? You don’t do it every 20 milliseconds, do you? [laughs]

I’ll highlight this. If I get my list of the 10 great unsolved puzzles that I hope our grandchildren will have figured out, why does getting the information into asset prices require that the stock be turned over a hundred times? That’s clearly what’s going on. There’s this vast amount of trading, which is based on information or opinion and so forth. I hate to discount it at all just as human folly, but that’s clearly what’s going on, but we don’t have a good model.

Self-recommending.

What I’ve been reading

by  Tyler Cowen in

1. Cat Jarman, River Kings: A New History of the Vikings from Scandinavia to the Silk Roads.  An excellent history of what the title claims, starting from an archaeological point of view and incorporating many of the latest discoveries.  The book is especially good at telling the reader how we know what we know about the Vikings: “Sweden has the highest quantity of Islamic dirhams in the whole of Europe after Russia.”

2. Jesse Singal, The Quick Fix: Why Fad Psychology Can’t Cure Our Social Ills.  An overdue and very well-executed look at how many of the problems in social psychology run deeper than just the replication crisis.  It covers topics of self-help books, posing and power, superpredators, bias tests, and much more.  It seems the core problem is that if the general public cares about an area, it is much harder to get accurate information about those same questions — I have noticed the same tendencies in economics.

3. Eric Herschthal, The Science of Abolition: How Slaveholders Became the Enemies of Progress.  A good survey of the scientific arguments against slavery, covering Benjamin Franklin, Benjamin Rush, the Lunar Society, and the technologists, among others.  The 2021 gloss would be “the Progress Studies people were especially anti-slavery.”  But why so little about the economists such as Smith, Malthus, and Mill, among others, all strongly opposed to slavery?

4. Christine Perkell, editor, Reading Vergil’s Aeneid: An Interpretative Guide, and David Quint, Virgil’s Double Cross: Design and Meaning in the Aeneid. Two books, excellent in their own right, and an antidote to the common view that everything in the humanities is bankrupt these days, or just “French theory,” or whatever.  Of course you have to read them at the same time you are studying The Aeneid.

5. Natsume Soseki, Kokoro.  From 1914, very retro in its aesthetic, it deals with modernization, the nature of friendship, and yes “the meaning of life.”  Simple and charming in a way that contemporary authors find difficult to match.  From 1984 to 2004 the author appeared on the Japanese one thousand yen note.

Dr. Seuss as a policy issue

by  Tyler Cowen in

That is a Substack essay from Matt Yglesias, and open source at that.  Excerpt, using quotation marks rather than forcing further indents on the segment:

“To me, there’s something attractive about the “constitutional copyright” idea of returning to the 1790 Copyright Act rule. But there’s also something attractive about the idea of an author retaining control over their works during their lifetime. There’s also something to be said for the idea that if you publish something and then get hit by a bus the next day, maybe that happenstance shouldn’t cut your heirs out of the downside. Mashing that all together might leave you with life of the author OR 28 years, whichever is longer.

I think it’s hard to specify the exact right number (Rufus Pollock tries with some fancy math and comes up with 15 to 38 years), but these two points from Hal Varian’s paper on copyright terms seem relevant:

  • “Fewer than 11 percent of the copyrights registered between 1883 and 1964 were renewed after 28 years.”
  • “Of the 10,027 books published in 1930, only 174 were still in print in 2001.”

It is just super-rare for old works to have large commercial value. But Xing Li, Megan MacGarvie, and Petra Moser show that copyright extensions have a big impact on consumer prices. And I would argue the cultural cost is higher.”

There is much more at the link.

Jiaolong, China’s Private City

by  Alex Tabarrok in

Shruti Rajagopalan and I wrote about India’s private cities, Guragaon and Jamshedpur in Lessons from Gurgaon, India’s Private City. One thing we discovered was that transaction costs prevented private developers from coordinating on infrastructure such as sewage and electricity even though that was clearly the efficient solution and there was plenty of time to bargain. We suggested larger purchases–such as at Disneyland–were necessary to internalize the externalities.

In The Contractual Nature of the City, Qian Lu looks at Jiaolong, an unusual private city in China. Jiaolong is small, about 4.3 square km and a population of 100,000 but all the infrastructure including electricity, sewage, roads, apartments, shopping malls, aquarium, office buildings, and hotels have been built privately. The firm in charge, Jiaolong Co., has planning rights and crucially it collects 25% of all property tax which means it internalizes part of the increase in value generated by its investments.

Jiaolong is a city built and operated by a business corporation. This is rare in China because in most cases the local city government is in charge of urbanization. In almost all cities, government makes land and city planning, takes farmers’ land, builds city infrastructure, sells land to housing developers and manufacturers, operates police stations, hospitals, schools and universities. By holding the monopoly power of coercion, the government is able to pool together resources by fiat and hold transaction costs low.

… The urbanization of Jiaolong is not based on coercive power, but by a series of contracts with Shuangliu government, firms, farmers, residents and other relevant parties. As the central contractor, Jiaolong Co. is able to simplify the contractual web and reduce coordination cost. The essential contracts are the investment contract with the county government to transfer planning rights, and a series of contracts with the government and firms to share tax. Tax sharing contracts define the income rights for Jiaolong so that Jiaolong could share the surplus of urban development and infrastructure construction. Sharing contracts also motivate Shuangliu government to provide public services including protection of property rights. A series of contracts transfer planning rights, land use rights, and income rights to Jiaolong Co., and thereby endogenize the externality of infrastructure building and urban development. From the perspective of institutional change, Jiaolong offers a case of contract-based rather than coercion-based urbanization, the latter being the typical approach in China.