At least six drug companies have received subpoenas from federal prosecutors, a development that indicates a broad criminal investigation is probably underway of the industry’s role in the opioid epidemic that has claimed hundreds of thousands of lives.

A criminal probe would add to the woes of drug companies, many of which already face lawsuits from about 2,500 cities and counties in federal courts, and scores of others filed by state attorneys general and others in state courts, according to legal documents.

In financial disclosures in the past several weeks, opioid manufacturers Mallinckrodt Pharmaceuticals, Teva Pharmaceutical, Johnson & Johnson and Amneal Pharmaceuticals and wholesale drug distributors McKesson and AmerisourceBergen have acknowledged receiving subpoenas for information. Most of them came from the U.S. attorney’s office in Brooklyn, but AmerisourceBergen said it received the requests from several different U.S. attorneys, including one in New Jersey.

Teva, for example, reported that it received an April subpoena from the Justice Department for “documents relating to the manufacture, marketing and sale of opioids.” In August 2019, the company received a grand jury subpoena from Brooklyn prosecutors for material on how it distributes opioid medications and prevents narcotics from being diverted for illegal use.

Teva said it understands the requests are “part of a broader investigation into manufacturers’ and distributors’ monitoring programs and reporting under the Controlled Substances Act,” the federal law that spells out drug companies’ responsibility to police the billions of prescription narcotics in circulation.

Similarly, McKesson, the largest wholesale distributor of drugs in the United States, reported that it received grand jury subpoenas in April and June from the same prosecutors “seeking documents related to the company’s anti-diversion policies and procedures and its distribution” of prescription opioids. It, too, described the demands as “part of a broader investigation by that office into pharmaceutical manufacturers’ and distributors’ compliance with the Controlled Substances Act and related statutes.”

McKesson also disclosed being served an administrative warrant by the Drug Enforcement Administration in July to inspect a company warehouse in West Sacramento, Calif., for information on compliance with those laws.

The Wall Street Journal first reported the subpoenas on Tuesday.

A spokesman for U.S. Attorney Richard P. Donoghue in Brooklyn declined to comment Wednesday. A Teva spokeswoman said in an email that “Teva is cooperating with the subpoena. We are confident in our order monitoring practices and policies, which are designed to ensure that medicines are delivered appropriately and in compliance with all applicable laws and regulations.”

A McKesson spokesman referred to the company’s late October filing, which said that “we generally respond to such subpoenas and requests in a cooperative, thorough and timely manner.”

AmerisourceBergen said in its most recent disclosure filed with the Securities and Exchange Commission that it “has received subpoenas from several U.S. Attorney’s Offices” since July 2017 regarding “distribution of controlled substances and diversion control programs.”

The company said it has been “engaged in discussions” with those prosecutors, including the U.S. attorney’s office in New Jersey, and has been producing documents. A spokesman declined to discuss the filing Wednesday.

More than 400,000 people have died of opioid overdoses since 1999, about half of them as a result of prescription narcotics and half from illicit drugs such as heroin and fentanyl.

For more than a decade, the DEA has attacked diversion of opioids through civil and administrative actions against companies — occasionally over the objections of the agency’s own investigators, who have pressed for criminal charges in what they considered egregious cases. The DEA’s efforts led to hundreds of millions of dollars in fines, mainly against wholesale drug distributors, which, under the Controlled Substances Act, are the primary gatekeepers of the legal flow of narcotics.

But the government began using more aggressive tactics this year. In May, a Boston jury convicted five Insys Therapeutics executives of a racketeering conspiracy for paying bribes and kickbacks to persuade doctors to prescribe its highly addictive fentanyl spray. The company later declared bankruptcy.

In April, a federal prosecutor in New York filed criminal conspiracy charges against a drug distributor, Rochester Drug Cooperative, and two of its executives — the first time criminal charges were brought against a wholesaler.

In July, a U.S. attorney in Ohio filed similar charges against the defunct distributor Miami-Luken and two of its former executives, and a McKesson compliance officer was indicted by a Kentucky grand jury in March.

Separately, Purdue Pharma, the manufacturer of OxyContin, the powerful painkiller widely blamed for fueling the opioid epidemic, has acknowledged in bankruptcy papers that it is working with the Justice Department to resolve a criminal matter. A person familiar with those negotiations, who spoke on the condition of anonymity because the talks are ongoing, said they stem from investigations by federal prosecutors in Connecticut, Vermont and New Jersey.

It would be unusual for a federal grand jury to issue a subpoena in anything other than a criminal investigation. Johnson & Johnson reported receiving one from the Brooklyn prosecutor in August. A spokesman said the company “believes that at all times, its anti-diversion policies and procedures for distribution of its opioid medications complied with the law.”

Amneal said received it a subpoena from an assistant U.S. attorney in southern Florida relating to the “marketing, sale and distribution of oxymorphone.” The company did not respond to a request for comment.