How Sick is Our Generic Drug Supply?

After my post on the availability of a generic alternative to Bystolic, several readers expressed concern about the quality of generic medications in general.

The skeptical cardiologist has posted quite a bit on generic quality issues, including two posts in 2018 (see here and here) which asked if readers knew where their medications were made.

These posts were triggered by the recall of valsartan and similar BP meds due to the identification of carcinogenic compounds in batches made in India and China. I extended the discussion to generic rosuvastatin, a drug I took (and still do) in generic form and my cholesterol-lowering drug of choice for many patients.

I noted then that brand-name drugs could be made off-shore and that some generics are made in the US.

The development of a generic version of rosuvastatin (Crestor) has been very helpful for many of my patients. Looking online, generic rosuvastatin goes for about $10 per month compared to $260 for Crestor.

Is it worth paying an extra $250 per month to get brand-name Crestor if, let’s say, it was manufactured in the U.S.? For most people it isn’t. For one thing, there is no guarantee of where your brand-name drug is manufactured.

Crestor used to be made in a factory in Bristol, England, but this was shut down in 2017 and now I can’t tell where AstraZeneca makes the stuff. Frankly, I’m surprised that they are selling any of the drug, which used to account for $5 billion of their annual sales.

So my cholesterol drug is made in India by an Indian company and my blood pressure drug is made in Columbus, Ohio, by a Jordanian company.

I never realized how globalized the pharmaceutical industry has become. Hopefully, the FDA is doing a good job of monitoring the safety and quality of products we rely on for our well-being that are manufactured all over the globe.

After hearing of the generic nebivolol availability I tried, unsuccessfully, to find where Bystolic was made but whether made in the US or India may not be the main problem.

The Promise and The Peril of the Generic

In September of this year, Farah Stockman wrote an excellent long work of investigative journalism on this topic in the New York Times entitled “Our Generic Drug Supply is Sick“

She starts off stating the promise of the generic drug which now represent 90% of prescriptions filled in the US:

The American health care system is built on the idea that a pill is a pill. Generic drugs are considered equal to and interchangeable with one another — and also with the name brand. This gospel has existed since 1984, when a law known as Hatch-Waxman was passed, allowing companies to make drugs that had gone off patent without having to replicate the same expensive clinical trials. For the most part, all they had to do was prove that the generic was manufactured using good practices and worked in the body in a similar way, within an acceptable range.Hatch-Waxman has been a stunning success. Americans have grown increasingly comfortable with generic medications, which now represent 90 percent of the prescriptions that are filled in this country. Their widespread use has translated into trillions of dollars in savings. Politicians and experts agree that any hope we have for affordable, universal health care rests on generic drugs.But in recent years, the generic drug supply has been plagued by problems. Whereas name-brand drugs can be so expensive that people can’t afford them, generics are often so cheap that companies stop making them or cut corners to turn a profit.

and summarizes the perils:

Competition for market share at rock-bottom price points has led to chronic shortages, unpredictable price-spikes, allegations of illegal price-fixing, and substandard and even dangerous practices. Production of generics has shifted overseas, where it’s harder for the Food and Drug Administration to inspect factories. Major companies have been caught faking and manipulating the data that is supposed to prove that drugs are effective and safe. Probable carcinogens have been discovered in the drug supply. During the pandemic, which caused several countries to ban the export of medical supplies, a new fear has arisen: that faraway factories might one day cut Americans off from their drugs. Dozens of lifesaving medications are made with ingredients no longer manufactured in the United States.

Opinion | Our Generic Drug Supply Is Sick – The New York Times

Stockman examines the origins, growth, and demise of Mylan, initially an American generic maker. In 2016 I described in detail one aspect of Mylan’s story which resulted in public furor over EpiPen prices quadrupling, concluding:

Perhaps it would be better if the US, instead of having Congress rush into action and investigations when certain drug costs become worthy of news articles and public shaming, had a system in place like most other industrialized nations, that monitored and regulated drug costs.
Under such a system, life-saving medications like the EpiPen would not arbitrarily quadruple in price.

Americans subsidize drug costs for the rest of the world to the point that many of my patients obtain cheaper brand name drugs from online Canadian pharmacies.

One part of the problem is that the US has long spent more on prescription medication than other countries. In 2013 per capita US spending on rx drugs was $858 compared to $400 for 19 industrialized nations. Examples of markedly higher prices in the US are the statin drug crestor (216$/month for 10 mg in US versus $46 in France) and the asthma inhaler Advair ($216 US versus $20 in France.)

A 2018 article in JAMA analyzed the sources of the high prices in the US and concluded it is due to the fact that “unlike nearly every other advanced nation, the US health care system allows manufacturers to set their own price for a given product.

Are All Generics Created Equal: Checking Generic Quality and Consistency

I’ve been meaning to write about Valisure, a unique online pharmacy, for several years. The Valisure website describes its creation as a direct response to batch variability of a generic seizure medication with a narrow therapeutic window:

Founders Adam Clark-Joseph and David Light reconnected after Adam suffered serious complications caused by batch variability of his anticonvulsant medication. Upon further research, they began to grasp the magnitude and pervasiveness of the problem throughout the pharmaceutical industry. Adam and David brought together a team of like-minded scientists and pharmacy experts to develop and deploy a solution. The result was Valisure, a company dedicated to preventing anyone from suffering adverse effects from low quality medications.

Valisure has done excellent work proving that generics are not all equivalent by checking the chemical makeup of medications before they reach consumers. “Every medication or supplement Valisure analyzes comes with a certificate of analysis listing important chemical properties of the samples analyzed at Valisure’s lab.

For those patients who want to know exactly what is going on each batch of pills they get, Valisure is an option.

Light At The Tunnel’s End?

Stockman ends her article on the sick US generic system with a ray of sunshine:

The realization that the free market isn’t working for generic drugs has led some to turn to nonprofits as a solution. In 2018, Dan Liljenquist, a Utah health care executive fed up with drug shortages and price spikes, brought together a group of hospital administrators and philanthropists to create a buyers club. Members agree on the drugs they want, and then the organization, Civica Rx, enters into long-term contracts with licensed manufacturers to produce them. Since the collective is funded by its members, not investors, it can prioritize need and quality over profit.

Civica doesn’t pretend that all drugs are equal. It sources drugs from the United States and Europe so it has more visibility into the supply chain. It stockpiles several months of supply, bucking the trend of just-in-time manufacturing. And it supplies drugs that the market has failed to reliably produce. Today, it counts more than 50 health systems as members — over a third of all licensed hospital beds in the United States.

In January, a month after the announcement that the old Mylan plant would shut down, Civica unveiled plans to build a 120,000-square-foot factory in Virginia to make sterile injectable drugs, which have been particularly hard to source. The nonprofit has begun to supply hospitals with vancomycin, an antibiotic used to treat severe pneumonia, which had been scarce and expensive for years prior. Civica’s prices are competitive, but not rock-bottom.

The American generic drug supply is quite ill as a full read of Stockman’s article reveals.

To cure this illness, Americans need to pay careful attention to how generic substitutions are working, consider utilizing pharmacies like Valisure which validate the purity of medications, and elect local and federal officials who will work toward a comprehensive system of both drug prices and quality control.

If you are a health care administrator/executive or businessman get behind organizations like Civica Rx or create one of your own.

Generously Yours,

-ACP