Clonazepam, a type of benzodiazepine drug commonly prescribed for anxiety and insomnia, is produced in facilities on multiple continents, according to a new study.Joe O'Connal/The Canadian Press
The global trade war has put a spotlight on the complicated supply chains of consumer goods such as cars and cellphones.
But even a tiny pill of a commonly prescribed generic drug travels tens of thousands of kilometres and through multiple factories in different continents to get to a Canadian patient, a new study shows.
The paper, “Journey of a pill,” was published last month in the Canadian Family Physician journal and pulls back the curtain on one of the most secretive parts of the pharmaceutical industry: how a drug is made.
Initiated by family doctor Myles Sergeant, the study was produced by a team of physicians and graduate students led by McMaster University engineering graduate Harjas Kaur. It traced the production journey of clonazepam, a type of benzodiazepine drug commonly prescribed for anxiety and insomnia.
U.S. puts drug tariffs on the table, threatening entire supply chains
The complex supply chain of such a simple drug illustrates how prescription drug supplies can be vulnerable to external shocks. The study was initiated three years ago, as the industry was coming out of drug shortages caused by COVID-19 supply-chain hiccups, but was published as a new threat was emerging: tariffs.
U.S. President Donald Trump has threatened tariffs on pharmaceuticals in what he said is a bid to increase domestic drug manufacturing. However, tariffs could instead lead to supply-chain bottlenecks and drug shortages because of how many key ingredients come from other markets.
There are two core ingredients for any drug: the active pharmaceutical ingredients (APIs) and the excipients, which are substances added to stabilize APIs and help patients’ bodies absorb them.
Most APIs for generic drugs are made in China and India, and clonazepam is no exception. According to the study, ingredients for its APIs are first extracted and chemically processed in Guangzhou and Hangzhou, then sent to Shanghai to be shipped to Mumbai, and on to Bangalore.
Ms. Kaur said the API is in the form of a powder comprised of tiny white crystals. Each individual shipment of an API would be in a small box and often transported by ship or truck, although planes could be used sometimes.
Excipients are produced separately in China and shipped to facilities in India or Germany, where they are combined with the APIs to make tablets.
Those tablets are then sent to the United States, where they are tested in New Jersey and repacked into smaller bottles in Tennessee.
For distribution in Canada, the bottles are then shipped to a centre in the Greater Toronto Area for redirecting where needed in the country.
The whole journey can be about 52,000 kilometres long, the researchers estimated.
From China and India to Vancouver: The great journey of clonazepam
One likely example route for the production and distribution of clonazepam, which can vary depending on factors such as which mode of transportation is used in a particular trip
Product transported:
API resources
Excipients
Active Pharmaceutical Ingredient (API)
Tablets
Transportation method:
Ship
Truck
1
API RESOURCES (12,220 KM)
AND EXCIPIENTS (11,220 KM)
In China, the API resources (intermediates) are extracted and chemically processed in Guangzhou and Hangzhou, while the excipients are extracted and chemically produced in Guangzhou and Shanghai. Both products are shipped to Mumbai from Shanghai. The intermediates are trucked to Bangalore, where they are chemically processed to create the final product, the API.
Shanghai
CHINA
CHINA
Hangzhou
Mumbai
Guangzhou
INDIA
INDIA
Bangalore
1,000 km
2
API (980 KM) AND TABLETS (20,500 KM)
The API is trucked back to Mumbai, where it is mixed with the excipients to make tablets. The tablets are sent directly to the U.S. via Cape of Good Hope, South Africa. Alternatively, tablets can be sent to U.S. via Europe, after API and tablets are sent to Germany via Rotterdam for tableting and redistribution respectively.
Mumbai
INDIA
INDIA
Bangalore
2,000 km
3
REDISTRIBUTION IN
NORTH AMERICA (7,600 KM)
The final product arrives in New Jersey, where it’s tested for safety and quality. It is then sent to Tennessee for repackaging and then to Vancouver via the Greater Toronto Area. By the time it arrives in a local store and is made available for purchase, the clonazepam may have travelled over 50,000 kilometres.
CANADA
CANADA
Vancouver
Toronto
U.S.
U.S.
New Jersey
Tennessee
1,000 km
MURAT YÜKSELIR / THE GLOBE AND MAIL, SOURCE: HARJAS KAUR AND MYLES SERGEANT, McMASTER UNIVERSITY; OPENSTREETMAP
From China and India to Vancouver: The great journey of clonazepam
One likely example route for the production and distribution of clonazepam, which can vary depending on factors such as which mode of transportation is used in a particular trip
Product transported:
API resources
Excipients
Tablets
Active Pharmaceutical Ingredient (API)
Transportation method:
Ship
Truck
1
API RESOURCES (12,220 KM)
AND EXCIPIENTS (11,220 KM)
In China, the API resources (intermediates) are extracted and chemically processed in Guangzhou and Hangzhou, while the excipients are extracted and chemically produced in Guangzhou and Shanghai. Both products are shipped to Mumbai from Shanghai. The intermediates are trucked to Bangalore, where they are chemically processed to create the final product, the API.
Shanghai
CHINA
CHINA
Hangzhou
Mumbai
Guangzhou
INDIA
INDIA
Bangalore
1,000 km
2
API (980 KM) AND TABLETS (20,500 KM)
The API is trucked back to Mumbai, where it is mixed with the excipients to make tablets. The tablets are sent directly to the U.S. via Cape of Good Hope, South Africa. Alternatively, tablets can be sent to U.S. via Europe, after API and tablets are sent to Germany via Rotterdam for tableting and redistribution respectively.
Mumbai
INDIA
INDIA
Bangalore
2,000 km
3
REDISTRIBUTION IN NORTH AMERICA (7,600 KM)
The final product arrives in New Jersey, where it’s tested for safety and quality. It is then sent to Tennessee for repackaging and then to Vancouver via the Greater Toronto Area. By the time it arrives in a local store and is made available for purchase, the clonazepam may have travelled over 50,000 kilometres.
CANADA
CANADA
Vancouver
Toronto
U.S.
U.S.
New Jersey
Tennessee
1,000 km
MURAT YÜKSELIR / THE GLOBE AND MAIL, SOURCE: HARJAS KAUR AND MYLES SERGEANT, McMASTER UNIVERSITY; OPENSTREETMAP
From China and India to Vancouver: The great journey of clonazepam
One likely example route for the production and distribution of clonazepam, which can vary depending on factors such as which mode of transportation is used in a particular trip
Product transported:
Transportation method:
API resources
Excipients
Ship
Tablets
Truck
Active Pharmaceutical Ingredient (API)
1
API RESOURCES (12,220 KM)
AND EXCIPIENTS (11,220 KM)
In China, the API resources (intermediates) are extracted and chemically processed in Guangzhou and Hangzhou, while the excipients are extracted and chemically produced in Guangzhou and Shanghai. Both products are shipped to Mumbai from Shanghai. The intermediates are trucked to Bangalore, where they are chemically processed to create the final product, the API.
Shanghai
CHINA
CHINA
Hangzhou
Mumbai
Guangzhou
INDIA
INDIA
Bangalore
1,000 km
2
API (980 KM) AND TABLETS (20,500 KM)
The API is trucked back to Mumbai, where it is mixed with the excipients to make tablets. The tablets are sent directly to the U.S. via Cape of Good Hope, South Africa. Alternatively, tablets can be sent to U.S. via Europe, after API and tablets are sent to Germany via Rotterdam for tableting and redistribution respectively.
Mumbai
INDIA
INDIA
Bangalore
2,000 km
3
REDISTRIBUTION IN
NORTH AMERICA (7,600 KM)
The final product arrives in New Jersey, where it’s tested for safety and quality. It is then sent to Tennessee for repackaging and then to Vancouver via the Greater Toronto Area. By the time it arrives in a local store and is made available for purchase, the clonazepam may have travelled over 50,000 kilometres.
CANADA
CANADA
Vancouver
Toronto
U.S.
U.S.
New Jersey
Tennessee
1,000 km
MURAT YÜKSELIR / THE GLOBE AND MAIL, SOURCE: HARJAS KAUR AND MYLES SERGEANT, McMASTER UNIVERSITY; OPENSTREETMAP
Dr. Sergeant said they picked clonazepam because it is a common generic drug that has been on the market for a long time and has many suppliers, which the team hoped would make it easier to find information.
Research was still a challenge. They searched industry reports, pharmaceutical databases and export records; spoke to pharmacies about shipment origins; and contacted individuals and companies in the industry, who were often reluctant to talk.
“I couldn’t believe how secret it was,” Dr. Sergeant said.
(In fact, more sources came to them after publication; the information in this article is based on their most up-to-date research and may differ slightly from the journal article.)
Ms. Kaur and Dr. Sergeant stressed that the journey mapped out in their study is a representative route backed up by their research, but that it can vary depending on the manufacturer or transportation method (such as whether a boat or plane is used).
Dr. Sergeant said he drew a few lessons from the research. One is how vulnerable this long supply chain is to any number of shocks, whether it be a fire at a factory or a tariff. A disruption could cause harmful delays in patients receiving their medication.
“We need a more compact, resilient supply chain,” he said.
Another lesson is the large amount of greenhouse-gas emissions created by all this travelling. He said 4.6 per cent of Canada’s emissions are estimated to come from the health sector, of which one-quarter are likely from medication.
One possible solution is to bring more of the supply chain into North America.
But Dr. Sergeant said in the case of clonazepam in particular, one solution is to just prescribe less of it and reduce patients’ need for it.
“It’s a habituating med that we overprescribe,” he said. “There are better things to do for sleep and anxiety than prescribe a benzodiazepine.”