Two men imprisoned in Canada are accused of playing a leadership role from behind bars in what American authorities are calling one of the world's most prolific fentanyl-trafficking and money-laundering operations.

The charges in the case, which come as North America grapples with an increasingly deadly opioid crisis, are said to the first in the United States against designated Chinese manufacturers of fentanyl and other opiates.

The U.S. Justice Department says customers bought pure fentanyl and other dangerous drugs online directly from Chinese factories, and inexperienced users would overdose because they didn't realize the potency of the opioids.

According to the indictments, Jason Berry and Daniel Ceron ran the Canadian end of the alleged criminal enterprise while imprisoned in the Drummond Institution in Drummondville, Que.

Further details about them were not immediately available, but they are accused of arranging shipments of fentanyl and other drugs from Canada to Florida and Portland Ore., in 2014, according to documents filed with an American court.

The duo are among five Canadians facing charges, U.S. authorities said.

In all, more than a dozen accused from around the world were involved in the manufacture and distribution of tonnes of fentanyl and other powerful narcotics sold in the United States, Deputy Attorney General Rod Rosenstein announced Tuesday.

Two Chinese nationals, Xiaobang Yan, 40, and Jian Zhang, 38, were indicted as overall leaders of the group that operated from January 2013 through August 2016.

"The investigations of Yan and Zhang revealed a new and disturbing facet of the opioid crisis in America: Fentanyl and fentanyl analogues are coming into the United States in numerous ways, including highly pure shipments of fentanyl from factories in China directly to U.S. customers who purchase it on the internet," the U.S. Justice Dept. said in a statement.

"Unwary or inexperienced users often have no idea that they are ingesting fentanyl until it is too late."

Fentanyl and related opiates are blamed for 20,000 deaths in the U.S. last year and nearly 3,000 more in Canada. Several deaths and serious illness have been tied directly to the alleged ring, U.S. authorities said.

Federal agents were able to identify more than 100 distributors of synthetic opioids involved with Yan's networks, they said.

"Xiaobing Yan, Jian Zhang and their respective associates represent one of the most significant drug threats facing the country -- overseas organized crime groups capable of producing nearly any synthetic drug imaginable, including fentanyl, and who attempt to hide their tracks with web-based sales, international shipments and cryptocurrency transactions," said Robert Patterson, acting administrator of the U.S. Drug Enforcement Administration.

U.S. officials said Yan kept tabs on legislation and law-enforcement activities in the United States and China, and modified the chemical structures of the fentanyl analogues he made to evade prosecution in the United States.

Assistant Commissioner Joanne Crampton with the RCMP, one of several agencies involved in the investigation, said the force has implemented a national strategy aimed at tackling fentanyl importers, distributors and traffickers.

"Synthetic drugs, in particular fentanyl, are a major threat to both our countries," Crampton said in Washington. "It is our duty to combat it in every possible way."

Court documents from the District Court eastern division in North Dakota allege the accused used American, Canadian and virtual currency for their transactions in which they ordered and sold the drugs online via secretive web sites.

"To hide their financial transactions, co-conspirators used off-shore accounts, anonymous virtual currency transactions, and third parties to move money, as well as using encrypted communication applications to discuss financial transactions," the indictment states.