Where are my drugs made?

is a General Practitioner, and Founder and Principal Investigator at PrimeHealth Clinical Research in Toronto, Ontario.

 

On July 10, 2018 Health Canada issued a recall of several products containing the blood pressure lowering drug, valsartan. This came in response to a disclosure from its Chinese manufacturer that the drug had been contaminated with a known carcinogen. A massive effort to contact patients to stop the affected drug lots, and to replace it with an alternative, ensued. Few clinicians had been even remotely aware that valsartan is mostly manufactured in China.

Valsartan is far from unique in this regard. China has become the world’s dominant supplier of essential ingredients needed to make most of the world’s other medicines as well.

When I purchase a head of lettuce in Canada, I can see a clear disclosure of its origin. Most other consumer items are held to the same standard. However, when it comes to vital medicines such disclosure rules do not apply. Instead, trust is placed primarily in Health Canada’s oversight. The quality of a drug’s manufacturing process rarely makes the radar when clinicians assess unexpected adverse events. The ongoing failure to disclose where drugs are made reduces the vital consideration of potential quality issues in drug manufacturing.

How is it that most of the active pharmaceutical ingredients (APIs) in Canadian drugs originate in China? In the 1980s the U.S., Europe and Japan had been the world’s manufacturer of most APIs. This changed in 1984 when the U.S. mandated the birth of generic drugs. This new demand for cheaper drugs pushed demand for cheaper ingredients. In 2000 the U.S. effectively removed tariffs on goods, including those on pharmaceuticals imported from China.

Soon thereafter, China was able to out-compete American manufacturers by flooding the market with cheap drugs. One example of this is penicillin. The over abundance of penicillin coming from China exported to the U.S. made manufacturing penicillin in the U.S. uncompetitive. The last penicillin manufacturer in the U.S. stopped producing the drug by 2004. China has since repeated this practice with most other drugs, too, and has thereby successfully out-competed most of its global competitors in manufacturing APIs.

To compound this effect, goods manufactured abroad remained subject to tariffs when importing to China. Such tariffs compounded the impact of higher costs of manufacturing APIs outside of China, further stifling competition. China’s domination in the manufacturing of APIs was thereby ensured. Once China had a stronghold on a particular API, what generally followed was a price increase of that API.

Most clinicians are unaware that active ingredients are currently manufactured in China.

Such heavy reliance on any one country is concerning. Improving the transparency of where drugs are made may help in reversing this dependency.

While simple in concept, the real-life application of such transparency is surprisingly complex. While most APIs originate in China, pharmaceutical companies often purchase and package the final product elsewhere utilizing components from other countries. This confounds a simplistic definition of “where a drug is made”.  Still, at a minimum, Canadians need to be informed of the origin of the API.

The introduction of such transparency in Canada would carry with it far-reaching implications. In addition to an  increased awareness among Canadian physicians that APIs have mostly been outsourced to China, physicians might consider more carefully the quality of manufacturing when assessing unexpected adverse events.

What the introduction of such transparency is not likely to do is to significantly impact the quality of APIs manufactured in China. This is because of the world’s pharmaceutics, even though we pay very high prices for drugs compared to most other countries.

Nor could such transparency be expected to improve Health Canada’s true level of oversight in foreign drug manufacturing. Health Canada lacks sufficient resources to travel to foreign countries to inspect even a fraction of the numerous outsourced manufacturers. Financial constraints force Health Canada to rely on pharmaceutical companies themselves to ensure that Canadian standards are met.

Ultimately, foreign drug manufacturers are under no direct obligation to adhere to Canadian standards. The check and balance in the commerce of pharmaceuticals rests with the drug manufacturers’ willingness to comply with our standards in order to optimize their sales. Manufacturing standards in China have improved substantially as western drug companies continue pouring billions of dollars into research facilities in China in the ongoing quest to manufacture cheaper drugs. Yet, our dependency on one country manufacturing the majority of our drugs raises serious concerns.

Transparency about drug ingredients' origins is at least as important as transparency of ingredients in foods and other goods. Knowing where drugs come from empowers Canadians and their clinicians to question manufacturing practices when a drug stops working or when faced with an unexplained adverse event. The manufacturing process of drugs is highly complex. Errors that are naturally inherent to this process need to be considered as part of the differential diagnosis when faced with a drug failure.  It also needs to be reported when suspected.