The federal agency that President Biden has tasked with implementing a national vaccine mandate has struggled to respond to the coronavirus pandemic, drawing fire for failing to issue broad safety rules specifically aimed at keeping workers safe from workplace transmission.

But with the vaccine mandate announced Thursday, Biden has finally given the Occupational Safety and Health Administration (OSHA) the green light to take aggressive action.

The new rule compels private companies with more than 100 workers to require employees to get vaccinated or submit to regular testing for the virus. Agency officials, who only learned about the mandate last week, must now move quickly to draft a plan for implementing and enforcing the mandate, a complex undertaking that represents one of the biggest challenges in the agency’s 50-year history.

“This is certainly the most controversial thing OSHA has ever done,” said Jordan Barab, a former OSHA deputy and workplace safety expert with the House Committee on Education and Labor. “It’s very big and very significant.”

Politically, the effort is already drawing fire. Prominent Republicans have condemned the mandate, blasting it as an unconstitutional infringement on personal liberties. Republican governors in multiple states have threatened to sue, with Georgia Gov. Brian Kemp (R) pledging to “pursue every legal option available to the state of Georgia to stop this blatantly unlawful overreach by the Biden administration.”

But many business groups have been more receptive. Even the U.S. Chamber of Commerce, which opposed previous efforts to create emergency rules to combat the coronavirus in workplaces, said it would wait to review the details of the new vaccine mandate before commenting.

On Friday, officials at the Department of Labor, which oversees OSHA, declined to comment on how they plan to implement the vaccine mandate. Many questions about the process ahead remain unanswered.

Among the most pressing: How long will businesses have to comply with the mandate, and how will OSHA enforce it? Should the mandate include other workplace safety requirements — such as masking and social distancing — to prevent workplace transmission? Should businesses be required to communicate any exposures or outbreaks to their workers? And will OSHA provide federal funding to cover the cost of Biden’s requirement that workers be compensated for time off to get the vaccine and recover from any side effects? Or will those costs fall on employers?

OSHA officials will proceed under broad authorities granted the agency by the Occupational Safety and Health Act, adopted in the 1970s. The act gives the Labor secretary authority to create a rule in times of duress — called an emergency temporary standard or ETS — to protect employees from “grave danger from exposure to substances or agents determined to be toxic or physically harmful or from new hazards.” The ETS process allows the agency to circumvent months of hearings and public comment normally required to implement a new safety rule.

Many previous efforts — to regulate exposure to Benzene, a toxic chemical found in plastic, detergents and pesticides in 1977 and the carcinogen asbestos in 1983 — were squashed after successful challenges in the courts.

Analysts predicted that an ETS for the vaccine mandate may also have a tough road ahead.

“An emergency temporary standard is an extraordinarily difficult route to go for OSHA,” said Baruch Fellner, an occupational safety lawyer at the firm Gibson Dunn. “OSHA has never succeeded in promulgating an emergency temporary standard. Not only has it never succeeded in promulgating emergency temporary standards, in most instances, when confronted normally by unions asking for or otherwise filing a lawsuit to obtain an ETS, it has declined to pursue that, recognizing the legal hurdles.”

Labor advocates and workplace safety experts have been clamoring for OSHA to create an ETS for workplace safety since the beginning of the pandemic. As outbreaks coursed through meatpacking plants, hospitals, grocery stores, warehouses and prisons, advocates hoped the agency would create a set of unified safety rules that would mandate social distancing, mask-wearing and sanitation procedures to help prevent workplace transmission.

But the Trump administration, with its close alliances in the business community, declined to act.

At the outset of his presidency, Biden directed the agency to study the feasibility of such a standard. But he shied away from it this spring as vaccination rates soared and hopes rose that the end of the pandemic was near.

Instead, the White House opted for a limited rule that required medical facilities where coronavirus patients are treated to implement mandatory mask-wearing, social distancing, and cleaning and disinfecting procedures, and to notify workers when they are exposed to infections. It also required employers to provide paid time off for workers to get vaccinated. That rule has so far escaped legal challenge.

Among the most pressing questions is how OSHA plans to enforce the coronavirus vaccine mandate. The agency already has a hotline for workers to report safety issues. Those calls typically kick off a process that includes phone interviews and inspections.

OSHA could require businesses to certify in writing that they are in compliance, potentially targeting such a requirement to high-risk industries, former officials said.

Enforcing the mandate through inspections could prove difficult. The number of OSHA inspectors atrophied during the Trump administration. Under Biden, the agency has begun staffing back up. But currently just 1,850 inspectors are in charge of enforcing safety regulations among more than 8 million employers representing 130 million workers.

Still, research shows that much of OSHA’s power comes from the mere threat of enforcement. A study released last summer by a Duke University researcher found that a single OSHA news release about a company found to be in violation of federal law can push nearby companies to improve compliance by as much as 73 percent.

“The power of OSHA regulation is not enforcement. It’s that most employers want to follow the law,” said David Michaels, who headed the agency under former president Barack Obama. “When you have an OSHA standard, most employers will try to meet it. The inspection side backs that up: Some employers need some additional encouragement. But most employers will do what OSHA requires.”

Vaccine mandates have long proved particularly controversial for the agency, former officials said. During the early 1990s, as concerns grew about bloodborne pathogens such as HIV and hepatitis B, the agency avoided issuing a full-fledged hepatitis B vaccine mandate for workers who regularly come into contact with blood, such as medical personnel and police and corrections officers, Barab said.

Instead the agency issued a requirement that companies simply make the vaccines available to those workers, he said.