With jury selection in a landmark opioid trial just three weeks away, lawyers for two Ohio counties said Wednesday they would prove that opioid manufacturers and distributors harmed public health and safety, and demanded they be held accountable.

In new legal papers, Cuyahoga and Summit counties said that “the opioid epidemic . . . constitutes an unreasonable interference with public health, public safety, public peace or public comfort” that should be laid at the feet of the drug industry.

Seeking billions of dollars, the two counties have sued the drug companies, demanding they pay damages and help clean up the crisis by subsidizing addiction treatment, emergency services, health care and other measures. The counties are part of a mammoth federal case brought by more than 2,500 cities, counties, Native American tribes and others.

The long-awaited showdown pits the counties against seven drug companies: manufacturers Johnson & Johnson and Teva Pharmaceuticals; distributors McKesson Corp., Cardinal Health, AmerisourceBergen and Henry Schein; and retailer Walgreens. Walgreens has been sued only over the conduct of its internal system of warehousing and distributing opioids to its retail stores — not for the way its pharmacists dispensed them.

The new arguments reveal little that has not emerged during nearly two years of pretrial jousting, but they help define the outlines of the upcoming trial. The parties were required to file the legal papers by Wednesday.

Janssen Pharmaceuticals, a subsidiary of health conglomerate Johnson & Johnson, argued in its filing that it could not be held responsible for sparking the worst drug crisis in the nation’s history.

“Janssen’s medications did not cause or contribute to that crisis,” wrote lawyers for the subsidiary. “Janssen’s medications had among the lowest rates of abuse and diversion of any [potentially abused] prescription opioid on the market. Nor can plaintiffs blame the crisis on Janssen’s marketing.”

Similarly, Walgreens asserted the counties “cannot show that any conduct by Walgreens resulted in the diversion of prescription opioid medications that could have caused the harms that plaintiffs allege.”

The two counties are test cases in the consolidated lawsuit that accuses the drug companies of responsibility for overdose deaths and addiction that allegedly resulted from their handling of prescription painkillers.

They have accused the companies of creating a “public nuisance” that harmed the health of residents of the two counties, and allege some of them operated in concert, in much the same way as an illegal drug gang would. Other charges include civil conspiracy and violation of Ohio’s corrupt practices law.

More than 200,000 people have died of overdoses from prescription narcotics since 1999, according to government data.

All the local trials have been placed before a federal judge in Ohio, who chose the two counties as “bellwether” plaintiffs in an effort to determine how other lawsuits might fare.

Other drug companies have settled with the counties, or been dropped from the first trial by mutual agreement. Most notably, Purdue Pharma, the manufacturer of OxyContin that is widely blamed for fueling the crisis, is attempting to fashion a $10 billion to $12 billion settlement with the federal plaintiffs and attorneys general from nearly every state that has sued the company and its owners, the Sackler family.

As it did in a recent case in Oklahoma, Johnson & Johnson contends that its two opioid products, Duragesic and Nucynta ER, made up less than 1 percent of the prescription opioid market in Summit and Cuyahoga counties.

The company also noted that Duragesic, a fentanyl painkiller delivered over 72 hours via a skin patch, is much more difficult to abuse than pills. “The Duragesic patch and Nucynta ER consistently ranked among the least abused and diverted opioid products — in Ohio or anywhere else,” the company wrote.

Johnson & Johnson lost the Oklahoma case in August, when a judge ordered it to contribute $572 million toward the costs of addressing the drug crisis. Judge Thad Balkman said that sum covers a single year of what the company is responsible for.

Walgreens said it will show at trial that “its distribution centers always followed appropriate protocols for monitoring suspicious orders, reporting them to [the Drug Enforcement Administration] and evaluating whether they should be shipped.” Under federal law and regulations, distributors — the wholesalers who move painkillers from manufacturers to dispensers — are responsible for flagging orders that indicate possible diversion of drugs to the streets and notifying the DEA.

McKesson, the nation’s largest drug distributor, said in its filing that it would “introduce evidence establishing that it complied with DEA’s shifting guidance regarding suspicious orders.”

Teva said the counties cannot prove a causal link between drug sales by the company or its subsidiaries and any harms to Cuyahoga or Summit residents. “At trial, the counties will not be able to present testimony showing a single false statement that any Teva or Actavis Generic defendant made to a single prescriber in the counties; a single county doctor who was misled by anything that they said or did; or a single patient who was harmed because of a false statement,” company lawyers wrote.