Archives For FDA Regulation

[TOTM: The following is part of a blog series by TOTM guests and authors on the law, economics, and policy of the ongoing COVID-19 pandemic. The entire series of posts is available here.

This post is authored by Jacob Grier, (Freelance writer and spirits consultant in Portland, Oregon, and the author of The Rediscovery of Tobacco: Smoking, Vaping, and the Creative Destruction of the Cigarette).]

The COVID-19 pandemic and the shutdown of many public-facing businesses has resulted in many sudden shifts in demand for common goods. The demand for hand sanitizer has drastically increased for hospitals, businesses, and individuals. At the same time, demand for distilled spirits has fallen substantially, as the closure of bars, restaurants, and tasting rooms has cut craft distillers off from their primary buyers. Since ethanol is a key ingredient in both spirits and sanitizer, this situation presents an obvious opportunity for distillers to shift their production from the former to the latter. Hundreds of distilleries have made this transition, but it has not without obstacles. Some of these reflect a real scarcity of needed supplies, but other constraints have been externally imposed by government regulations and the tax code.

Producing sanitizer

The World Health Organization provides guidelines and recipes for locally producing hand sanitizer. The relevant formulation for distilleries calls for only four ingredients: high-proof ethanol (96%), hydrogen peroxide (3%), glycerol (98%), and sterile distilled or boiled water. Distilleries are well-positioned to produce or obtain ethanol and water. Glycerol is used in only small amounts and does not currently appear to be a substantial constraint on production. Hydrogen peroxide is harder to come by, but distilleries are adapting and cooperating to ensure supply. Skip Tognetti, owner of Letterpress Distilling in Seattle, Washington, reports that one local distiller obtained a drum of 34% hydrogen peroxide, which stretches a long way when diluted to a concentration of 3%. Local distillers have been sharing this drum so that they can all produce sanitizer.

Another constraint is finding containers in which to the put the finished product. Not all containers are suitable for holding high-proof alcoholic solutions, and supplies of those that are recommended for sanitizer are scarce. The fact that many of these bottles are produced in China has reportedly also limited the supply. Distillers are therefore having to get creative; Tognetti reports looking into shampoo bottles, and in Chicago distillers have re-purposed glass beer growlers. For informal channels, some distillers have allowed consumers to bring their own containers to fill with sanitizer for personal use. Food and Drug Administration labeling requirements have also prevented the use of travel-size bottles, since the bottles are too small to display the necessary information.

The raw materials for producing ethanol are also coming from some unexpected sources. Breweries are typically unable to produce alcohol at high enough proof for sanitizer, but multiple breweries in Chicago are donating beer that distilleries can bring up to the required purity. Beer giant Anheuser-Busch is also producing sanitizer with the ethanol removed from its alcohol-free beers.

In many cases, the sanitizer is donated or sold at low-cost to hospitals and other essential services, or to local consumers. Online donations have helped to fund some of these efforts, and at least one food and beverage testing lab has stepped up to offer free testing to breweries and distilleries producing sanitizer to ensure compliance with WHO guidelines. Distillers report that the regulatory landscape has been somewhat confusing in recent weeks, and posts in a Facebook group have provided advice for how to get through the FDA’s registration process. In general, distillers going through the process report that agencies have been responsive. Tom Burkleaux of New Deal Distilling in Portland, Oregon says he “had to do some mighty paperwork,” but that the FDA and the Oregon Board of Pharmacy were both quick to process applications, with responses coming in just a few hours or less.

In general, the redirection of craft distilleries to producing hand sanitizer is an example of private businesses responding to market signals and the evident challenges of the health crisis to produce much-needed goods; in some cases, sanitizer represents one of their only sources of revenue during the shutdown, providing a lifeline for small businesses. The Distilled Spirits Council currently lists nearly 600 distilleries making sanitizer in the United States.

There is one significant obstacle that has hindered the production of sanitizer, however: an FDA requirement that distilleries obtain extra ingredients to denature their alcohol.

Denaturing sanitizer

According to the WHO, the four ingredients mentioned above are all that are needed to make sanitizer. In fact, WHO specifically notes that it in most circumstances it is inadvisable to add anything else: “it is not recommended to add any bittering agents to reduce the risk of ingestion of the handrubs” except in cases where there is a high probably of accidental ingestion. Further, “[…] there is no published information on the compatibility and deterrent potential of such chemicals when used in alcohol-based handrubs to discourage their abuse. It is important to note that such additives may make the products toxic and add to production costs.”

Denaturing agents are used to render alcohol either too bitter or too toxic to consume, deterring abuse by adults or accidental ingestion by children. In ordinary circumstances, there are valid reasons to denature sanitizer. In the current pandemic, however, the denaturing requirement is a significant bottleneck in production.

The federal Tax and Trade Bureau is the primary agency regulating alcohol production in the United States. The TTB took action early to encourage distilleries to produce sanitizer, officially releasing guidance on March 18 instructing them that they are free to commence production without prior authorization or formula approval, so long as they are making sanitizer in accordance with WHO guidelines. On March 23, the FDA issued its own emergency authorization of hand sanitizer production; unlike the WHO, FDA guidance does require the use of denaturants. As a result, on March 26 the TTB issued new guidance to be consistent with the FDA.

Under current rules, only sanitizer made with denatured alcohol is exempt from the federal excise tax on beverage alcohol. Federal excise taxes begin at $2.70 per gallon for low-volume distilleries and reach up to $13.50 per gallon, significantly increasing the cost of producing hand sanitizer; state excise taxes can raise these costs even higher.

More importantly, denaturing agents are scarce. In a Twitter thread on March 25, Tognetti noted the difficulty of obtaining them:

To be clear, if I didn’t have to track down denaturing agents (there are several, but isopropyl alcohol is the most common), I could turn out 200 gallons of finished hand sanitizer TODAY.

(As an additional concern, the Distilled Spirits Council notes that the extremely bitter or toxic nature of denaturing agents may impose additional costs on distillers given the need to thoroughly cleanse them from their equipment.)

Congress attempted to address these concerns in the CARES Act, the coronavirus relief package. Section 2308 explicitly waives the federal excise tax on distilled spirits used for the production of sanitizer, however it leaves the formula specification in the hands of the FDA. Unless the agency revises its guidance, production in the US will be constrained by the requirement to add denaturing agents to the plentiful supply of ethanol, or distilleries will risk being targeted with enforcement actions if they produce perfectly usable sanitizer without denaturing their alcohol.

Local distilleries provide agile production capacity

In recent days, larger spirits producers including Pernod-Ricard, Diageo, and Bacardi have announced plans to produce sanitizer. Given their resources and economies of scale, they may end up taking over a significant part of the market. Yet small, local distilleries have displayed the agility necessary to rapidly shift production. It’s worth noting that many of these distilleries did not exist until fairly recently. According to the American Craft Spirits Association, there were fewer than 100 craft distilleries operating in the United States in 2005. By 2018, there were more than 1,800. This growth is the result of changing consumer interests, but also the liberalization of state and local laws to permit distilleries and tasting rooms. That many of these distilleries have the capacity to produce sanitizer in a time of emergency is a welcome, if unintended, consequence of this liberalization.

[TOTM: The following is part of a blog series by TOTM guests and authors on the law, economics, and policy of the ongoing COVID-19 pandemic. The entire series of posts is available here.

This post is authored by Julian Morris, (Director of Innovation Policy, ICLE).]

SARS-CoV2, the virus that causes COVID-19, is now widespread in the population in many countries, including the US, UK, Australia, Iran, and many European countries. Its prevalence in other regions, such as South Asia, much of South America, and Africa, is relatively unknown. The failure to contain the virus early on has meant that more aggressive measures are now necessary in order to avoid overwhelming healthcare systems, which would cause unacceptable levels of mortality. (Sadly, Italy’s health system has already been overwhelmed, forcing medical practitioners to engage in the most awful triage decisions.) Many jurisdictions, ranging from cities to entire countries, have chosen to implement mandatory lockdowns. These will likely have the desired effect of slowing transmission in the short term, but they cannot be maintained indefinitely. The challenge going forward is how to contain the spread of the virus without destroying the economy. 

In this post I will outline the elements of a proposal that I hope might do that. (I’ve been working on this for about a week and in the meantime some of the ideas have been advanced by others. E.g. this and this. Great minds clearly think alike.)

1. Identify those who have had COVID-19 and have recovered — and allow them to go back to work

While there are some reports of people who have had COVID-19 becoming reinfected, this seems to be very rare (a recent primate study implies reinfection is impossible) and the alleged cases may have been a result of false negative tests followed by relapse by patients. The general presumption is that having the disease is likely to confer immunity for several months at least. Moreover, people with immunity who no longer show symptoms of the disease are very unlikely to transmit the disease. Allowing those people to go back to work will lessen the burden of the lockdown without appreciably increasing the risk of infection

One group of such people is readily identifiable, though small: Those who tested positive for COVID-19 and subsequently recovered. Those people should be permitted to go back to work immediately.

2. Where possible, test, trace, treat, isolate

The town of Vo in Northern Italy, the site of the first death in the country from COVID-19, appears to have stopped the disease from spreading in about three weeks. It did so through a combination of universal testing, two weeks of strict lockdown, and quarantine of cases.  Could this be replicated elsewhere? 

Vo has a population of 3,300, so universal testing was not the gargantuan exercise it would be in, say, the continental US. Some larger jurisdictions have had similar success without resorting to universal testing and lockdown. South Korea managed to contain the spread of SARS-CoV2 relatively quickly through a combination of: social distancing (including closing schools and restricting large gatherings), testing anyone who had COVID-19 symptoms (and increasingly those without symptoms), tracing and testing of those who had contact with those symptomatic individuals, treating those with severe symptoms, quarantining those who tested positive but had no or only mild symptoms (the quarantine was monitored using a phone app and strictly enforced), and publicly sharing detailed information about the known incidence of the virus. 

A study of 181 cases in China published in the Annals of Internal Medicine found that the mean incubation period for COVID-19 is just over 5 days and only about 1 in 100 cases take longer than 14 days. By implication, if people have been strictly following the guidelines on avoiding contact with others, washing/sanitizing hands, sanitizing other objects, and avoiding hand-to-face contact, it should be possible, after two weeks of lockdown, to identify the vast majority of people who are not infected by testing everyone for the presence of SARS-CoV2 itself.

But that’s a series of big ifs. Since it takes a few days for the virus to replicate in the body to the point at which it is detectable, people who have recently been infected might test negative. Also, it is unlikely to be feasible logistically to test a significant proportion of the population for SARS-CoV2 in a short period of time. Existing tests require the use of RT-PCR, which is expensive and time consuming, not least because it can only be done at a lab, and while the capacity for such tests is increasing, it is likely around 50,000 per day in the entire US. 

Test, trace, treat, and isolate may be a feasible option for towns and even cities that currently have relatively low incidence of SARS-CoV2. However, given the lethargic progress of testing in places such as the US, UK and India, and hence poor existing knowledge of the extent of infection, it will not be a universal panacea.

3. Test as many people as possible for the presence of antibodies to SARS-CoV2

Outside those few places that have dramatically ramped up testing, it is likely that many more people have had COVID-19 than have been tested, either because they were asymptomatic or because they did not require clinical attention. Many, perhaps most of those people will no longer have the virus in their system but they should still have antibodies (indicating immunity). In order to identify those people, there should be widespread testing for antibodies to SARS-CoV2. 

Antibody tests are inexpensive, quick, and some can be done at home with minimal assistance. Numerous such tests have already been produced or are in development (see the list here). For example, Chinese manufacturer Innovita has produced a test that appears to be effective; in a clinical trial of 447 patients, it identified the presence of antibodies to SARS-CoV2 in 87.3 % of clinically confirmed cases of COVID-19 (i.e. there were approximately 13% false negatives) but zero false positives. Innovita’s test was approved by China’s equivalent of the FDA and has been used widely there. 

Scanwell Health, a San Francisco-based startup, has an exclusive license to produce Innovita’s test in the U.S. and has already begun the process for obtaining approval from the US FDA under its Emergency Use Authorization. Scanwell estimates that the total cost of the test, including overnight shipping of the kit and support from a doctor or nurse practitioner from Lemonaid Health, will be around $70. One downside to Scanwell Health’s offering, however, is that it expects it to take 6-8 weeks to begin shipping testing kits once it receives authorization from the FDA

So far, the FDA has approved at least one SARS-CoV2 antibody test, produced by Aytu Bioscience in Colorado. But Aytu’s test is designed for use by physicians, not at home. In Europe, at least one antibody test, produced by German company PharmACT, is already available. (That test has similar characteristics to Innovita’s.) Another has been approved by the MHRA in the UK for physician use and is awaiting approval for home use; the UK government has ordered 3.5 million of these tests, with the aim of distributing 250,000 per day by the end of April. 

Unfortunately, some people who have antibodies to SARS-CoV2 will also still be infectious. However, because different antibodies develop at different times during the course of infection, it may be possible to distinguish those who are still infectious from those who are no longer infectious. Specifically, immunoglobulin (Ig) M is present in larger amounts while the viral load is still present, while IgG is present in larger amounts later on (see e.g. this and the figure below). So, by testing for the presence of both IgM and IgG it should be possible to identify a large proportion of those who have had COVID-19 but are no longer infectious. (The currently available antibody tests result in about 13 percent false negatives, making them inappropriate as a means of screening out those who do not have COVID-19. But they produce zero false positives, making them ideal for identifying those who definitely have or have had COVID-19). In essence, people whose IgG test is positive but IgM test is negative can then go back to work. In addition, people who have had COVID-19 symptoms, are now symptom-free, and test positive for antibodies, should be allowed to go back to work.

4. Test for SARS-Cov2 among those who test negative for antibodies — and ensure that everyone who tests positive remains in isolation

Those people who test negative for SARS-CoV2 using the quick antibody immunoassay, as well as those who are positive for both IgG and IgM (indicating that they may still be infectious) should then be tested for SARS-CoV2 using the RT-PCR test described above. And those who test negative for SARS-CoV2 should then be permitted to go back to work. But those who test positive should be required to remain in isolation— and seek treatment if necessary.

5. Repeat steps 3 and 4 until nobody tests positive for COVID-19

By repeating steps 3 and 4, it should be possible gradually to enable the vast majority of the population to return to work, and thence to a life of greater normalcy, within a matter of weeks.

6. Some (possibly rather large) caveats

All of this relies on: (a) the ability rapidly to expand testing and (b) widespread compliance with isolation requirements. Neither of these conditions is by any means guaranteed, not least because the rules effectively discriminate in favor of people who have had COVID-19, which may create a perverse incentive to violate not only the isolation requirements but all the recommended hygiene practices — and thereby intentionally become infected with SARS-CoV2 on the presumption that they will then be able to go back to work sooner than otherwise. So, before this is rolled out, it is important to ensure that there will be widespread testing for COVID-19 in a timeframe shorter than the likely total time for contracting and recovering from COVID-19.

In addition, if test results are to be used as a means of establishing a person’s ability to travel and work while others are still under lockdown, it is important that there  be a means of verifying the status of individuals. That might be possible through the use of an app, for example; such an app might also provide policymakers to make better resources allocation decisions too. 

Also, at-risk individuals should be strongly advised to remain in isolation until there is no further evidence of community transmission. 

7. The Mechanics of Testing

Given that there are not currently sufficient tests available for everyone to be tested in most locations, one obvious question is: who should be tested? As noted above, it makes sense initially to target those who have had COVID-19 symptoms and have recovered. Since only those people who have had such symptoms—and possibly their physician if they presented with their symptoms—will know who they are, this will rely largely on trust. (It’s possible that self-reporting apps could help.) 

But it may make sense initially to target tests more narrowly. The UK is initially targeting the antibody detection kits to healthcare and other key workers—people who are essential to the continued functioning of the country. That makes sense and could easily be applied in other places. 

Assuming that key workers can be supplied with antibody detection kits quickly, distribution should then be opened up more widely. No doubt insurance companies will be making decisions about the purchase of testing kits. Ideally, however, individuals should be able to buy kits such as Scanwell’s without going through a bureaucratic process, whether that be their insurance company or the NHS. And vendors should be free to price kits as they see fit, without worrying about the prospect of being subject to price caps such as those imposed by Medicaid or the VA, which have the perverse effect of incentivising vendors to increase the list price. Finally, in order to increase the supply of tests as rapidly as possible, regulatory agencies should be encouraged to issue emergency approvals as quickly as possible. Having more manufacturers with a diverse array of tests available will increase access to testing more quickly and likely lead to more accurate testing too. Agencies such as the FDA should see this as their absolute priority right now. If the Mayo clinic can compress 6 months’ product development into a month, the FDA can surely do its review far more quickly too. Lives—and the economy—depend upon it.

We don’t yet know how bad the coronavirus outbreak will be in America.  But we do know that the virus is likely to have a major impact on Americans’ access to medication.  Currently, 80% of the active ingredients found in the drugs Americans take are made in China, and the virus has disrupted China’s ability to manufacture and supply those ingredients.  Generic drugs, which comprise 90% of America’s drugs, are likely to be particularly impacted because most generics are made in India, and Indian drug makers rely heavily on Chinese-made ingredients.  Indeed, on Tuesday, March 3, India decided to restrict exports of 26 drugs and drug ingredients because of reductions in China’s supply.  This disruption to the generic supply chain could mean that millions of Americans will not get the drugs they need to stay alive and healthy.

Coronavirus-related shortages are only the latest in a series of problems recently afflicting the generic drug industry.  In the last few years, there have been many reports of safety issues affecting generic drug quality at both domestic and overseas manufacturing facilities.  Numerous studies have uncovered shady practices and quality defects, including generics contaminated with carcinogens, drugs in which the active ingredients were switched for ineffective or unsafe alternatives, and manufacturing facilities that falsify or destroy documents to conceal their misdeeds.

We’ve also been inundated with stories of generic drug makers hiking prices for their products.  Although, as a whole, generic drugs are much cheaper than innovative brand products, the prices for many generic drugs are on the increase.  For some generics – Martin Shkreli’s Daraprim, heart medication Digoxin, antibiotic Doxycycline, insulin, and many others – prices have increased by several hundred percent. It turns out that many of the price increases are the result of anticompetitive behavior in the generic market. For others, the price increases are due to the increasing difficulty of generic drug makers to earn profits selling low-priced drugs.

Even before the coronavirus outbreak, there were numerous instances of shortages for critical generic drugs.  These shortages often result from drug makers’ lack of incentive to manufacture low-priced drugs that don’t earn much profit. The shortages have been growing in frequency and duration in recent years.  As a result of the shortages, 90 percent of U.S. hospitals report having to find alternative drug therapies, costing patients and hospitals over $400 million last year.  In other unfortunate situations, reasonable alternatives simply are not available and patients suffer.

With generic drug makers’ growing list of problems, many policy makers have called for significant changes to America’s approach to the generic drug industry. Perhaps the FDA needs to increase its inspection of overseas facilities?  Perhaps the FTC and state and federal prosecutors should step up their investigations and enforcement actions against anticompetitive behavior in the industry? Perhaps FDA should do even more to promote generic competition by expediting generic approvals

While these actions and other proposals could certainly help, none are aimed at resolving more than one or two of the significant problems vexing the industry. Senator Elizabeth Warren has proposed a more substantial overhaul that would bring the U.S. government into the generic-drug-making business. Under Warren’s plan, the Department of Health and Human Services (HHS) would manufacture or contract for the manufacture of drugs to be sold at lower prices.  Nationalizing the generic drug industry in this way would make the inspection of manufacturing facilities much easier and could ideally eliminate drug shortages.  In January, California’s governor proposed a similar system under which the state would begin manufacturing or contracting to manufacture generic drugs.

However, critics of public manufacturing argue that manufacturing and distribution infrastructure would be extremely costly to set up, with taxpayers footing the bill.  And even after the initial set-up, market dynamics that affect costs, such as increasing raw material costs or supply chain disruptions, would also mean greater costs for taxpayers.  Moreover, by removing the profit incentive created under the Hatch-Waxman Act to develop and manufacture generic drugs, it’s not clear that governments could develop or manufacture a sufficient supply of generics (consider the difference in efficiency between the U.S. Postal Service and either UPS or FedEx).

Another approach might be to treat the generic drug industry as a regulated industry. This model has been applied to utilities in the past when unregulated private ownership of utility infrastructure could not provide sufficient supply to meet consumer need, address market failures, or prevent the abuse of monopoly power.  Similarly, consumers’ need for safe and affordable medicines, market failures inherent throughout the industry, and industry consolidation that could give rise to market power suggest the regulated model might work well for generic drugs.   

Under this approach, Hatch-Waxman incentives could remain in place, granting the first generic drug an exclusivity period during which it could earn significant profits for the generic drug maker.  But when the exclusivity period ends, an agency like HHS would assign manufacturing responsibility for a particular drug to a handful of generic drug makers wishing to market in the U.S.  These companies would be guaranteed a profit based on a set rate of return on the costs of high-quality domestic manufacturing.  In order to maintain their manufacturing rights, facilities would have to meet strict FDA guidelines to ensure high quality drugs. 

Like the Warren and California proposals, this approach would tackle several problems at once.  Prices would be kept under control and facilities would face frequent inspections to ensure quality.  A guaranteed profit would eliminate generic companies’ financial risk, reducing their incentive to use cheap (and often unsafe) drug ingredients or to engage in illegal anticompetitive behavior.  It would also encourage steady production to reduce instances of drug shortages.  Unlike the Warren and California proposals, this approach would build on the existing generic infrastructure so that taxpayers don’t have to foot the bill to set up public manufacturing.  It would also continue to incentivize the development of generic alternatives by maintaining the Hatch-Waxman exclusivity period, and it would motivate the manufacture of generic drugs by companies seeking a reliable rate of return.

Several issues would need to be worked out with a regulated generic industry approach to prevent manipulation of rates of return, regulatory capture, and political appointees without the incentives or knowledge to regulate the drug makers. However, the recurring crises affecting generic drugs indicate the industry is rife with market failures.  Perhaps only a radical new approach will achieve lasting and necessary change.

Last week the Senate Judiciary Committee held a hearing, Intellectual Property and the Price of Prescription Drugs: Balancing Innovation and Competition, that explored whether changes to the pharmaceutical patent process could help lower drug prices.  The committee’s goal was to evaluate various legislative proposals that might facilitate the entry of cheaper generic drugs, while also recognizing that strong patent rights for branded drugs are essential to incentivize drug innovation.  As Committee Chairman Lindsey Graham explained:

One thing you don’t want to do is kill the goose who laid the golden egg, which is pharmaceutical development. But you also don’t want to have a system that extends unnecessarily beyond the ability to get your money back and make a profit, a patent system that drives up costs for the average consumer.

Several proposals that were discussed at the hearing have the potential to encourage competition in the pharmaceutical industry and help rein in drug prices. Below, I discuss these proposals, plus a few additional reforms. I also point out some of the language in the current draft proposals that goes a bit too far and threatens the ability of drug makers to remain innovative.  

1. Prevent brand drug makers from blocking generic companies’ access to drug samples. Some brand drug makers have attempted to delay generic entry by restricting generics’ access to the drug samples necessary to conduct FDA-required bioequivalence studies.  Some brand drug manufacturers have limited the ability of pharmacies or wholesalers to sell samples to generic companies or abused the REMS (Risk Evaluation Mitigation Strategy) program to refuse samples to generics under the auspices of REMS safety requirements.  The Creating and Restoring Equal Access To Equivalent Samples (CREATES) Act of 2019 would allow potential generic competitors to bring an action in federal court for both injunctive relief and damages when brand companies block access to drug samples.  It also gives the FDA discretion to approve alternative REMS safety protocols for generic competitors that have been denied samples under the brand companies’ REMS protocol.  Although the vast majority of brand drug companies do not engage in the delay tactics addressed by CREATES, the Act would prevent the handful that do from thwarting generic competition.  Increased generic competition should, in turn, reduce drug prices.

2. Restrict abuses of FDA Citizen Petitions.  The citizen petition process was created as a way for individuals and community groups to flag legitimate concerns about drugs awaiting FDA approval.  However, critics claim that the process has been misused by some brand drug makers who file petitions about specific generic drugs in the hopes of delaying their approval and market entry.  Although FDA has indicated that citizens petitions rarely delay the approval of generic drugs, there have been a few drug makers, such as Shire ViroPharma, that have clearly abused the process and put unnecessary strain on FDA resources. The Stop The Overuse of Petitions and Get Affordable Medicines to Enter Soon (STOP GAMES) Act is intended to prevent such abuses.  The Act reinforces the FDA and FTC’s ability to crack down on petitions meant to lengthen the approval process of a generic competitor, which should deter abuses of the system that can occasionally delay generic entry.  However, lawmakers should make sure that adopted legislation doesn’t limit the ability of stakeholders (including drug makers that often know more about the safety of drugs than ordinary citizens) to raise serious concerns with the FDA. 

3. Curtail Anticompetitive Pay-for-Delay Settlements.  The Hatch-Waxman Act incentivizes generic companies to challenge brand drug patents by granting the first successful generic challenger a period of marketing exclusivity. Like all litigation, many of these patent challenges result in settlements instead of trials.  The FTC and some courts have concluded that these settlements can be anticompetitive when the brand companies agree to pay the generic challenger in exchange for the generic company agreeing to forestall the launch of their lower-priced drug. Settlements that result in a cash payment are a red flag for anti-competitive behavior, so pay-for-delay settlements have evolved to involve other forms of consideration instead.  As a result, the Preserve Access to Affordable Generics and Biosimilars Act aims to make an exchange of anything of value presumptively anticompetitive if the terms include a delay in research, development, manufacturing, or marketing of a generic drug. Deterring obvious pay-for-delay settlements will prevent delays to generic entry, making cheaper drugs available as quickly as possible to patients. 

However, the Act’s rigid presumption that an exchange of anything of value is presumptively anticompetitive may also prevent legitimate settlements that ultimately benefit consumers.  Brand drug makers should be allowed to compensate generic challengers to eliminate litigation risk and escape litigation expenses, and many settlements result in the generic drug coming to market before the expiration of the brand patent and possibly earlier than if there was prolonged litigation between the generic and brand company.  A rigid presumption of anticompetitive behavior will deter these settlements, thereby increasing expenses for all parties that choose to litigate and possibly dissuading generics from bringing patent challenges in the first place.  Indeed, the U.S. Supreme Court has declined to define these settlements as per se anticompetitive, and the FTC’s most recent agreement involving such settlements exempts several forms of exchanges of value.  Any adopted legislation should follow the FTC’s lead and recognize that some exchanges of value are pro-consumer and pro-competitive.

4. Restore the balance established by Hatch-Waxman between branded drug innovators and generic drug challengers.  I have previously discussed how an unbalanced inter partes review (IPR) process for challenging patents threatens to stifle drug innovation.  Moreover, current law allows generic challengers to file duplicative claims in both federal court and through the IPR process.  And because IPR proceedings do not have a standing requirement, the process has been exploited  by entities that would never be granted standing in traditional patent litigation—hedge funds betting against a company by filing an IPR challenge in hopes of crashing the stock and profiting from the bet. The added expense to drug makers of defending both duplicative claims and claims against challengers that are exploiting the system increases litigation costs, which may be passed on to consumers in the form of higher prices. 

The Hatch-Waxman Integrity Act (HWIA) is designed to return the balance established by Hatch-Waxman between branded drug innovators and generic drug challengers. It requires generic challengers to choose between either Hatch-Waxman litigation (which saves considerable costs by allowing generics to rely on the brand company’s safety and efficacy studies for FDA approval) or an IPR proceeding (which is faster and provides certain pro-challenger provisions). The HWIA would also eliminate the ability of hedge funds and similar entities to file IPR claims while shorting the stock.  By reducing duplicative litigation and the exploitation of the IPR process, the HWIA will reduce costs and strengthen innovation incentives for drug makers.  This will ensure that patent owners achieve clarity on the validity of their patents, which will spur new drug innovation and make sure that consumers continue to have access to life-improving drugs.

5. Curb illegal product hopping and patent thickets.  Two drug maker tactics currently garnering a lot of attention are so-called “product hopping” and “patent thickets.”  At its worst, product hopping involves brand drug makers making minor changes to a drug nearing the end of its patent so that they gets a new patent on the slightly-tweaked drug, and then withdrawing the original drug from the market so that patients shift to the newly patented drug and pharmacists can’t substitute a generic version of the original drug.  Similarly, at their worst, patent thickets involve brand drug makers obtaining a web of patents on a single drug to extend the life of their exclusivity and make it too costly for other drug makers to challenge all of the patents associated with a drug.  The proposed Affordable Prescriptions for Patients Act of 2019 is meant to stop these abuses of the patent system, which would facilitate generic entry and help to lower drug prices.

However, the Act goes too far by also capturing many legitimate activities in its definitions. For example, the bill defines as anticompetitive product-hopping the selling of any improved version of a drug during a window which extends to a year after the launch of the first generic competitor.  Presently, to acquire a patent and FDA approval, the improved version of the drug must be different and innovative enough from the original drug, yet the Act would prevent the drug maker from selling such a product without satisfying a demanding three-pronged test before the FTC or a district court.  Similarly, the Act defines as anticompetitive patent thickets any new patents filed on a drug in the same general family as the original patent, and this presumption can only be rebutted by providing extensive evidence and satisfying demanding standards to the FTC or a district court.  As a result, the Act deters innovation activity that is at all related to an initial patent and, in doing so, ignores the fact that most important drug innovation is incremental innovation based on previous inventions.  Thus, the proposal should be redrafted to capture truly anticompetitive product hopping and patent thicket activity, while exempting behavior this is critical for drug innovation. 

Reforms that close loopholes in the current patent process should facilitate competition in the pharmaceutical industry and help to lower drug prices.  However, lawmakers need to be sure that they don’t restrict patent rights to the extent that they deter innovation because a significant body of research predicts that patients’ health outcomes will suffer as a result.

In January a Food and Drug Administration advisory panel, the Tobacco Products Scientific Advisory Committee (TPSAC), voted 8-1 that the weight of scientific evidence shows that switching from cigarettes to an innovative, non-combustible tobacco product such as Philip Morris International’s (PMI’s) IQOS system significantly reduces a user’s exposure to harmful or potentially harmful chemicals.

This finding should encourage the FDA to allow manufacturers to market smoke-free products as safer alternatives to cigarettes. But, perhaps predictably, the panel’s vote has incited a regulatory furor among certain politicians.

Last month, several United States senators, including Richard Blumenthal, Dick Durbin, and Elizabeth Warren, sent a letter to FDA Commissioner Scott Gottlieb urging the agency to

avoid rushing through new products, such as IQOS, … without requiring strong evidence that any such product will reduce the risk of disease, result in a large number of smokers quitting, and not increase youth tobacco use.

At the TPSAC meeting, nine members answered five multi-part questions about proposed marketing claims for the device. Taken as a whole, the panel’s votes indicate considerable agreement that non-combustible tobacco products like IQOS should, in fact, allay the senators’ concerns. And a closer look at the results reveals a much more nuanced outcome than either the letter or much of the media coverage has suggested.

“Reduce the risk of disease”: Despite the finding that IQOS reduces exposure to harmful chemicals, the panel nominally rejected a claim that it would reduce the risk of tobacco-related diseases. The panel’s objection, however, centered on the claim’s wording that IQOS “can reduce” risk, rather than “may reduce” risk. And, in the panel’s closest poll, it rejected by just a single vote the claim that “switching completely to IQOS presents less risk of harm than continuing to smoke cigarettes.”

“Result in large number of smokers quitting”: The panel unanimously concluded that PMI demonstrated a “low” likelihood that former smokers would re-initiate tobacco use with the IQOS system. The only options were “low,” “medium,” and “high.” This doesn’t mean it will necessarily help non-users quit in the first place, of course, but for smokers who do switch, it means the device helps them stay away from cigarettes.

“Not increase youth tobacco use”: A majority of the voting panel members agreed that PMI demonstrated a “low” likelihood that youth “never smokers” would become established IQOS users.

By definition, the long-term health benefits of innovative new products like IQOS are uncertain. But the cost of waiting for perfect information may be substantial.

It’s worth noting that the American Cancer Society recently shifted its position on electronic cigarettes, recommending that individuals who do not quit smoking

should be encouraged to switch to the least harmful form of tobacco product possible; switching to the exclusive use of e-cigarettes is preferable to continuing to smoke combustible products.

Dr. Nancy Rigotti agrees. A professor of medicine at Harvard and Director of the Tobacco Research and Treatment Center at Massachusetts General Hospital, Dr. Rigotti is a prominent tobacco-cessation researcher and the author of a February 2018 National Academies of Science, Engineering, and Medicine Report that examined over 800 peer-reviewed scientific studies on the health effects of e-cigarettes. As she has said:

The field of tobacco control recognizes cessation is the goal, but if the patient can’t quit then I think we should look at harm reduction.

About her recent research, Dr. Rigotti noted:

I think the major takeaway is that although there’s a lot we don’t know, and although they have some health risks, [e-cigarettes] are clearly better than cigarettes….

Unlike the senators pushing the FDA to prohibit sales of non-combustible tobacco products, experts recognize that there is enormous value in these products: the reduction of imminent harm relative to the alternative.

Such harm-reduction strategies are commonplace, even when the benefits aren’t perfectly quantifiable. Bike helmet use is encouraged (or mandated) to reduce the risk and harm associated with bicycling. Schools distribute condoms to reduce teen pregnancy and sexually transmitted diseases. Local jurisdictions offer needle exchange programs to reduce the spread of AIDS and other infectious diseases; some offer supervised injection facilities to reduce the risk of overdose. Methadone and Suboxone are less-addictive opioids used to treat opioid use disorder.

In each of these instances, it is understood that the underlying, harmful behaviors will continue. But it is also understood that the welfare benefits from reducing the harmful effects of such behavior outweigh any gain that might be had from futile prohibition efforts.

By the same token — and seemingly missed by the senators urging an FDA ban on non-combustible tobacco technologies — constraints placed on healthier alternatives induce people, on the margin, to stick with the less-healthy option. Thus, many countries that have adopted age restrictions on their needle exchange programs and supervised injection facilities have seen predictably higher rates of infection and overdose among substance-using youth.

Under the Food, Drug & Cosmetic Act, in order to market “safer” tobacco products manufacturers must demonstrate that they would (1) significantly reduce harm and the risk of tobacco-related disease to individual tobacco users, and (2) benefit the health of the population as a whole. In addition, the Act limits the labeling and advertising claims that manufacturers can make on their products’ behalf.

These may be well-intentioned restraints, but overly strict interpretation of the rules can do far more harm than good.

In 2015, for example, the TPSAC expressed concerns about consumer confusion in an application to market “snus” (a smokeless tobacco product placed between the lip and gum) as a safer alternative to cigarettes. The manufacturer sought to replace the statement on snus packaging, “WARNING: This product is not a safe alternative to cigarettes,” with one reading, “WARNING: No tobacco product is safe, but this product presents substantially lower risks to health than cigarettes.”

The FDA denied the request, stating that the amended warning label “asserts a substantial reduction in risks, which may not accurately convey the risks of [snus] to consumers” — even though it agreed that snus “substantially reduce the risks of some, but not all, tobacco-related diseases.”

But under this line of reasoning, virtually no amount of net health benefits would merit approval of marketing language designed to encourage the use of less-harmful products as long as any risk remains. And yet consumers who refrain from using snus after reading the stronger warning might instead — and wrongly — view cigarettes as equally healthy (or healthier), precisely because of the warning. That can’t be sound policy if the aim is actually to reduce harm overall.

To be sure, there is a place for government to try to ensure accuracy in marketing based on health claims. But it is impossible for regulators to fine-tune marketing materials to convey the full range of truly relevant information for all consumers. And pressuring the FDA to limit the sale and marketing of smoke-free products as safer alternatives to cigarettes — in the face of scientific evidence that they would likely achieve significant harm-reduction goals — could do far more harm than good.

In the wake of the recent OIO decision, separation of powers issues should be at the forefront of everyone’s mind. In reaching its decision, the DC Circuit relied upon Chevron to justify its extreme deference to the FCC. The court held, for instance, that

Our job is to ensure that an agency has acted “within the limits of [Congress’s] delegation” of authority… and that its action is not “arbitrary, capricious, an abuse of discretion, or otherwise not in accordance with law.”… Critically, we do not “inquire as to whether the agency’s decision is wise as a policy matter; indeed, we are forbidden from substituting our judgment for that of the agency.”… Nor do we inquire whether “some or many economists would disapprove of the [agency’s] approach” because “we do not sit as a panel of referees on a professional economics journal, but as a panel of generalist judges obliged to defer to a reasonable judgment by an agency acting pursuant to congressionally delegated authority.

The DC Circuit’s decision takes a broad view of Chevron deference and, in so doing, ignores or dismisses some of the limits placed upon the doctrine by cases like Michigan v. EPA and UARG v. EPA (though Judge Williams does bring up UARG in dissent).

Whatever one thinks of the validity of the FCC’s approach to regulating the Internet, there is no question that it has, at best, a weak statutory foothold. Without prejudging the merits of the OIO, or the question of deference to agencies that find “[regulatory] elephants in [statutory] mouseholes,”  such broad claims of authority, based on such limited statutory language, should give one pause. That the court upheld the FCC’s interpretation of the Act without expressing reservations, suggesting any limits, or admitting of any concrete basis for challenging the agency’s authority beyond circular references to “abuse of discretion” is deeply troubling.

Separation of powers is a fundamental feature of our democracy, and one that has undoubtedly contributed to the longevity of our system of self-governance. Not least among the important features of separation of powers is the ability of courts to review the lawfulness of legislation and executive action.

The founders presciently realized the dangers of allowing one part of the government to centralize power in itself. In Federalist 47, James Madison observed that

The accumulation of all powers, legislative, executive, and judiciary, in the same hands, whether of one, a few, or many, and whether hereditary, selfappointed, or elective, may justly be pronounced the very definition of tyranny. Were the federal Constitution, therefore, really chargeable with the accumulation of power, or with a mixture of powers, having a dangerous tendency to such an accumulation, no further arguments would be necessary to inspire a universal reprobation of the system. (emphasis added)

The modern administrative apparatus has become the sort of governmental body that the founders feared and that we have somehow grown to accept. The FCC is not alone in this: any member of the alphabet soup that constitutes our administrative state, whether “independent” or otherwise, is typically vested with great, essentially unreviewable authority over the economy and our daily lives.

As Justice Thomas so aptly put it in his must-read concurrence in Michigan v. EPA:

Perhaps there is some unique historical justification for deferring to federal agencies, but these cases reveal how paltry an effort we have made to understand it or to confine ourselves to its boundaries. Although we hold today that EPA exceeded even the extremely permissive limits on agency power set by our precedents, we should be alarmed that it felt sufficiently emboldened by those precedents to make the bid for deference that it did here. As in other areas of our jurisprudence concerning administrative agencies, we seem to be straying further and further from the Constitution without so much as pausing to ask why. We should stop to consider that document before blithely giving the force of law to any other agency “interpretations” of federal statutes.

Administrative discretion is fantastic — until it isn’t. If your party is the one in power, unlimited discretion gives your side the ability to run down a wish list, checking off controversial items that could never make it past a deliberative body like Congress. That same discretion, however, becomes a nightmare under extreme deference as political opponents, newly in power, roll back preferred policies. In the end, regulation tends toward the extremes, on both sides, and ultimately consumers and companies pay the price in the form of excessive regulatory burdens and extreme uncertainty.

In theory, it is (or should be) left to the courts to rein in agency overreach. Unfortunately, courts have been relatively unwilling to push back on the administrative state, leaving the task up to Congress. And Congress, too, has, over the years, found too much it likes in agency power to seriously take on the structural problems that give agencies effectively free reign. At least, until recently.

In March of this year, Representative Ratcliffe (R-TX) proposed HR 4768: the Separation of Powers Restoration Act (“SOPRA”). Arguably this is first real effort to fix the underlying problem since the 1995 “Comprehensive Regulatory Reform Act” (although, it should be noted, SOPRA is far more targeted than was the CRRA). Under SOPRA, 5 U.S.C. § 706 — the enacted portion of the APA that deals with judicial review of agency actions —  would be amended to read as follows (with the new language highlighted):

(a) To the extent necessary to decision and when presented, the reviewing court shall determine the meaning or applicability of the terms of an agency action and decide de novo all relevant questions of law, including the interpretation of constitutional and statutory provisions, and rules made by agencies. Notwithstanding any other provision of law, this subsection shall apply in any action for judicial review of agency action authorized under any provision of law. No law may exempt any such civil action from the application of this section except by specific reference to this section.

These changes to the scope of review would operate as a much-needed check on the unlimited discretion that agencies currently enjoy. They give courts the ability to review “de novo all relevant questions of law,” which includes agencies’ interpretations of their own rules.

The status quo has created a negative feedback cycle. The Chevron doctrine, as it has played out, gives outsized incentives to both the federal agencies, as well as courts, to essentially disregard Congress’s intended meaning for particular statutes. Today an agency can write rules and make decisions safe in the knowledge that Chevron will likely insulate it from any truly serious probing by a district court with regards to how well the agency’s action actually matches up with congressional intent or with even rudimentary cost-benefit analysis.

Defenders of the administrative state may balk at changing this state of affairs, of course. But defending an institution that is almost entirely immune from judicial and legal review seems to be a particularly hard row to hoe.

Public Knowledge, for instance, claims that

Judicial deference to agency decision-making is critical in instances where Congress’ intent is unclear because it balances each branch of government’s appropriate role and acknowledges the realities of the modern regulatory state.

To quote Justice Scalia, an unfortunate champion of the Chevron doctrine, this is “pure applesauce.”

The very core of the problem that SOPRA addresses is that the administrative state is not a proper branch of government — it’s a shadow system of quasi-legislation and quasi-legal review. Congress can be chastened by popular vote. Judges who abuse discretion can be overturned (or impeached). The administrative agencies, on the other hand, are insulated through doctrines like Chevron and Auer, and their personnel subject more or less to the political whims of the executive branch.

Even agencies directly under the control of the executive branch  — let alone independent agencies — become petrified caricatures of their original design as layers of bureaucratic rule and custom accrue over years, eventually turning the organization into an entity that serves, more or less, to perpetuate its own existence.

Other supporters of the status quo actually identify the unreviewable see-saw of agency discretion as a feature, not a bug:

Even people who agree with the anti-government premises of the sponsors [of SOPRA] should recognize that a change in the APA standard of review is an inapt tool for advancing that agenda. It is shortsighted, because it ignores the fact that, over time, political administrations change. Sometimes the administration in office will generally be in favor of deregulation, and in these circumstances a more intrusive standard of judicial review would tend to undercut that administration’s policies just as surely as it may tend to undercut a more progressive administration’s policies when the latter holds power. The APA applies equally to affirmative regulation and to deregulation.

But presidential elections — far from justifying this extreme administrative deference — actually make the case for trimming the sails of the administrative state. Presidential elections have become an important part about how candidates will wield the immense regulatory power vested in the executive branch.

Thus, for example, as part of his presidential bid, Jeb Bush indicated he would use the EPA to roll back every policy that Obama had put into place. One of Donald Trump’s allies suggested that Trump “should turn off [CNN’s] FCC license” in order to punish the news agency. And VP hopeful Elizabeth Warren has suggested using the FDIC to limit the growth of financial institutions, and using the FCC and FTC to tilt the markets to make it easier for the small companies to get an advantage over the “big guys.”

Far from being neutral, technocratic administrators of complex social and economic matters, administrative agencies have become one more political weapon of majority parties as they make the case for how their candidates will use all the power at their disposal — and more — to work their will.

As Justice Thomas, again, noted in Michigan v. EPA:

In reality…, agencies “interpreting” ambiguous statutes typically are not engaged in acts of interpretation at all. Instead, as Chevron itself acknowledged, they are engaged in the “formulation of policy.” Statutory ambiguity thus becomes an implicit delegation of rulemaking authority, and that authority is used not to find the best meaning of the text, but to formulate legally binding rules to fill in gaps based on policy judgments made by the agency rather than Congress.

And this is just the thing: SOPRA would bring far-more-valuable predictability and longevity to our legal system by imposing a system of accountability on the agencies. Currently, commissions often believe they can act with impunity (until the next election at least), and even the intended constraints of the APA frequently won’t do much to tether their whims to statute or law if they’re intent on deviating. Having a known constraint (or, at least, a reliable process by which judicial constraint may be imposed) on their behavior will make them think twice about exactly how legally and economically sound proposed rules and other actions are.

The administrative state isn’t going away, even if SOPRA were passed; it will continue to be the source of the majority of the rules under which our economy operates. We have long believed that a benefit of our judicial system is its consistency and relative lack of politicization. If this is a benefit for interpreting laws when agencies aren’t involved, it should also be a benefit when they are involved. Particularly as more and more law emanates from agencies rather than Congress, the oversight of largely neutral judicial arbiters is an essential check on the administrative apparatus’ “accumulation of all powers.”

The interest of judges tends to include a respect for the development of precedent that yields consistent and transparent rules for all future litigants and, more broadly, for economic actors and consumers making decisions in the shadow of the law. This is markedly distinct from agencies which, more often than not, promote the particular, shifting, and often-narrow political sentiments of the day.

Whether a Republican- or a Democrat— appointed district judge reviews an agency action, that judge will be bound (more or less) by the precedent that came before, regardless of the judge’s individual political preferences. Contrast this with the FCC’s decision to reclassify broadband as a Title II service, for example, where previously it had been committed to the idea that broadband was an information service, subject to an entirely different — and far less onerous — regulatory regime.  Of course, the next FCC Chairman may feel differently, and nothing would stop another regulatory shift back to the pre-OIO status quo. Perhaps more troublingly, the enormous discretion afforded by courts under current standards of review would permit the agency to endlessly tweak its rules — forbearing from some regulations but not others, un-forbearing, re-interpreting, etc., with precious few judicial standards available to bring certainty to the rules or to ensure their fealty to the statute or the sound economics that is supposed to undergird administrative decisionmaking.

SOPRA, or a bill like it, would have required the Commission to actually be accountable for its historical regulations, and would force it to undergo at least rudimentary economic analysis to justify its actions. This form of accountability can only be to the good.

The genius of our system is its (potential) respect for the rule of law. This is an issue that both sides of the aisle should be able to get behind: minority status is always just one election cycle away. We should all hope to see SOPRA — or some bill like it — gain traction, rooted in long-overdue reflection on just how comfortable we are as a polity with a bureaucratic system increasingly driven by unaccountable discretion.

Yesterday the Heritage Foundation published a Legal Memorandum, in which I explain the need for the reform of U.S. Food and Drug Administration (FDA) regulation, in order to promote path-breaking biopharmaceutical innovation.  Highlights of this Legal Memorandum are set forth below.

In recent decades, U.S. and foreign biopharmaceutical companies (makers of drugs that are based on chemical compounds or biological materials, such as vaccines) and medical device manufacturers have been responsible for many cures and advances in treatment that have benefited patients’ lives.  New cancer treatments, medical devices, and other medical discoveries are being made at a rapid pace.

The biopharmaceutical industry is also a major generator of American economic growth and a high-technology leader.  The U.S. biopharmaceutical sector directly employs over 810,000 workers, supports 3.4 million American jobs across the country, contributed almost one-fourth of all domestic research and development (R&D) funded by U.S. businesses in 2013—more than any other single sector—and contributes roughly $790 billion a year to the American economy, according to one study.   American biopharmaceutical firms collaborate with hospitals, universities, and research institutions around the country to provide clinical trials and treatments and to create new jobs.  Their products also boost workplace productivity by treating medical conditions, thereby reducing absenteeism and disability leave.

Properly tailored and limited regulation of biopharmaceutical products and medical devices helps to promote public safety, but FDA regulations as currently designed hinder and slow the innovation process and retard the diffusion of medical improvements.  Specifically, research indicates that current regulatory norms and the delays they engender unnecessarily bloat costs, discourage research and development, slow the pace of health improvements for millions of Americans, and harm the American economy.  These factors should be kept in mind by Congress and the Administration as they study how best to reform (and, where appropriate, eliminate) FDA regulation of drugs and medical devices.  (One particular reform that appears to be unequivocally beneficial and thus worthy of immediate consideration is the prohibition of any FDA restrictions on truthful speech concerning off-label drug uses—speech that benefits consumers and enjoys First Amendment protection.)  Reducing the burdens imposed on inventors by the FDA would allow more drugs to get to the market more quickly so that patients could pursue new and potentially lifesaving treatments.

Thanks to Geoff for the introduction. I look forward to posting a few things over the summer.

I’d like to begin by discussing Geoff’s post on the pending legislative proposals designed to combat strategic abuse of drug safety regulations to prevent generic competition. Specifically, I’d like to address the economic incentive structure that is in effect in this highly regulated market.

Like many others, I first noticed the abuse of drug safety regulations to prevent competition when Turing Pharmaceuticals—then led by now infamous CEO Martin Shkreli—acquired the manufacturing rights for the anti-parasitic drug Daraprim, and raised the price of the drug by over 5,000%. The result was a drug that cost $750 per tablet. Daraprim (pyrimethamine) is used to combat malaria and toxoplasma gondii infections in immune-compromised patients, especially those with HIV. The World Health Organization includes Daraprim on its “List of Essential Medicines” as a medicine important to basic health systems. After the huge price hike, the drug was effectively out of reach for many insurance plans and uninsured patients who needed it for the six to eight week course of treatment for toxoplasma gondii infections.

It’s not unusual for drugs to sell at huge multiples above their manufacturing cost. Indeed, a primary purpose of patent law is to allow drug companies to earn sufficient profits to engage in the expensive and risky business of developing new drugs. But Daraprim was first sold in 1953 and thus has been off patent for decades. With no intellectual property protection Daraprim should, theoretically, now be available from generic drug manufactures for only a little above cost. Indeed, this is what we see in the rest of the world. Daraprim is available all over the world for very cheap prices. The per tablet price is 3 rupees (US$0.04) in India, R$0.07 (US$0.02) in Brazil, US$0.18 in Australia, and US$0.66 in the UK.

So what gives in the U.S.? Or rather, what does not give? What in our system of drug distribution has gotten stuck and is preventing generic competition from swooping in to compete down the high price of off-patent drugs like Daraprim? The answer is not market failure, but rather regulatory failure, as Geoff noted in his post. While generics would love to enter a market where a drug is currently selling for high profits, they cannot do so without getting FDA approval for their generic version of the drug at issue. To get approval, a generic simply has to file an Abbreviated New Drug Application (“ANDA”) that shows that its drug is equivalent to the branded drug with which it wants to compete. There’s no need for the generic to repeat the safety and efficacy tests that the brand manufacturer originally conducted. To test for equivalence, the generic needs samples of the brand drug. Without those samples, the generic cannot meet its burden of showing equivalence. This is where the strategic use of regulation can come into play.

Geoff’s post explains the potential abuse of Risk Evaluation and Mitigation Strategies (“REMS”). REMS are put in place to require certain safety steps (like testing a woman for pregnancy before prescribing a drug that can cause birth defects) or to restrict the distribution channels for dangerous or addictive drugs. As Geoff points out, there is evidence that a few brand name manufacturers have engaged in bad-faith refusals to provide samples using the excuse of REMS or restricted distribution programs to (1) deny requests for samples, (2) prevent generic manufacturers from buying samples from resellers, and (3) deny generics whose drugs have won approval access to the REMS system that is required for generics to distribute their drugs. Once the FDA has certified that a generic manufacturer can safely handle the drug at issue, there is no legitimate basis for the owners of brand name drugs to deny samples to the generic maker. Expressed worries about liability from entering joint REMS programs with generics also ring hollow, for the most part, and would be ameliorated by the pending legislation.

It’s important to note that this pricing situation is unique to drugs because of the regulatory framework surrounding drug manufacture and distribution. If a manufacturer of, say, an off-patent vacuum cleaner wants to prevent competitors from copying its vacuum cleaner design, it is unlikely to be successful. Even if the original manufacturer refuses to sell any vacuum cleaners to a competitor, and instructs its retailers not to sell either, this will be very difficult to monitor and enforce. Moreover, because of an unrestricted resale market, a competitor would inevitably be able to obtain samples of the vacuum cleaner it wishes to copy. Only patent law can successfully protect against the copying of a product sold to the general public, and when the patent expires, so too will the ability to prevent copying.

Drugs are different. The only way a consumer can resell prescription drugs is by breaking the law. Pills bought from an illegal secondary market would be useless to generics for purposes of FDA approval anyway, because the chain of custody would not exist to prove that the samples are the real thing. This means generics need to get samples from the authorized manufacturer or distribution company. When a drug is subject to a REMS-required restricted distribution program, it is even more difficult, if not impossible, for a generic maker to get samples of the drugs for which it wants to make generic versions. Restricted distribution programs, which are used for dangerous or addictive drugs, by design very tightly control the chain of distribution so that the drugs go only to patients with proper prescriptions from authorized doctors.

A troubling trend has arisen recently in which drug owners put their branded drugs into restricted distribution programs not because of any FDA REMS requirement, but instead as a method to prevent generics from obtaining samples and making generic versions of the drugs. This is the strategy that Turing used before it raised prices over 5,000% on Daraprim. And Turing isn’t the only company to use this strategy. It is being emulated by others, although perhaps not so conspicuously. For instance, in 2015, Valeant Pharmaceuticals completed a hostile takeover of Allergan Pharmaceuticals, with the help of the hedge fund, Pershing Square. Once Valeant obtained ownership of Allergan and its drug portfolio, it adopted restricted distribution programs and raised the prices on its off-patent drugs substantially. It raised the price of two life-saving heart drugs by 212% and 525% respectively. Others have followed suit.

A key component of the strategy to profit from hiking prices on off-patent drugs while avoiding competition from generics is to select drugs that do not currently have generic competitors. Sometimes this is because a drug has recently come off patent, and sometimes it is because the drug is for a small patient population, and thus generics haven’t bothered to enter the market given that brand name manufacturers generally drop their prices to close to cost after the drug comes off patent. But with the strategic control of samples and refusals to allow generics to enter REMS programs, the (often new) owners of the brand name drugs seek to prevent the generic competition that we count on to make products cheap and plentiful once their patent protection expires.

Most brand name drug makers do not engage in withholding samples from generics and abusing restricted distribution and REMS programs. But the few that do cost patients and insurers dearly for important medicines that should be much cheaper once they go off patent. More troubling still is the recent strategy of taking drugs that have been off patent and cheap for years, and abusing the regulatory regime to raise prices and block competition. This growing trend of abusing restricted distribution and REMS to facilitate rent extraction from drug purchasers needs to be corrected.

Two bills addressing this issue are pending in Congress. Both bills (1) require drug companies to provide samples to generics after the FDA has certified the generic, (2) require drug companies to enter into shared REMS programs with generics, (3) allow generics to set up their own REMS compliant systems, and (4) exempt drug companies from liability for sharing products and REMS-compliant systems with generic companies in accordance with the steps set out in the bills. When it comes to remedies, however, the Senate version is significantly better. The penalties provided in the House bill are both vague and overly broad. The bill provides for treble damages and costs against the drug company “of the kind described in section 4(a) of the Clayton Act.” Not only is the application of the Clayton Act unclear in the context of the heavily regulated market for drugs (see Trinko), but treble damages may over-deter reasonably restrictive behavior by drug companies when it comes to distributing dangerous drugs.

The remedies in the Senate version are very well crafted to deter rent seeking behavior while not overly deterring reasonable behavior. The remedial scheme is particularly good, because it punishes most those companies that attempt to make exorbitant profits on drugs by denying generic entry. The Senate version provides as a remedy for unreasonable delay that the plaintiff shall be awarded attorneys’ fees, costs, and the defending drug company’s profits on the drug at issue during the time of the unreasonable delay. This means that a brand name drug company that sells an old drug for a low price and delays sharing only because of honest concern about the safety standards of a particular generic company will not face terribly high damages if it is found unreasonable. On the other hand, a company that sends the price of an off-patent drug soaring and then attempts to block generic entry will know that it can lose all of its rent-seeking profits, plus the cost of the victorious generic company’s attorneys fees. This vastly reduces the incentive for the company owning the brand name drug to raise prices and keep competitors out. It likewise greatly increases the incentive of a generic company to enter the market and–if it is unreasonably blocked–to file a civil action the result of which would be to transfer the excess profits to the generic. This provides a rather elegant fix to the regulatory gaming in this area that has become an increasing problem. The balancing of interests and incentives in the Senate bill should leave many congresspersons feeling comfortable to support the bill.