Taking Your Drug From Rx-to-OTC: Working with the FDA

The push is on to switch prescription drugs to over-the-counter medications. But pharmaceutical companies must tread carefully on the path to an Rx-to-OTC switch.

In the first of a two-part series, a regulatory expert and the head of OTC at the FDA talk candidly about how to increase your chances of winning with the FDA.

In the final hours before the 2002 U.S. Food & Drug Administration’s (FDA) Non-Prescription Drugs Advisory Committee (NDAC) hearing on whether the heartburn medication Prilosec should be switched from a prescription medicine to an over-the-counter one, Procter & Gamble’s Regulatory Chief for Personal Healthcare Products, Dr. Doug Bierer, was nervous. As the team leader on the joint project with Astra-Zeneca and one of the main presenters before the ad-com, Dr. Bierer couldn’t help wondering: would ad-com members find the arguments compelling? Was the proposed labeling clear? Would they support approval?

“I was elated when we got the ad-com’s recommendation, and doubly elated when the FDA approved the switch last year,” said Dr. Bierer, who currently serves as Vice President, Regulatory and Scientific Affairs, at the Consumer Healthcare Products Association (CHPA). “We’d been working on this for nearly a decade.”

Ten years for any drug approval is not uncommon, but Rx-to-OTC switches come with additional hurdles to jump, and a unique process to understand.

Understand the system

There is an “OTC Manual of Policies and Procedures” on the FDA website that explains the process of applying for an Rx- to-OTC switch.

It’s a complicated one, because sponsors must deal with two separate FDA divisions – the Review Division, which oversees the prescription uses for a specific drug, and the OTC Division, which reviews all switches. These two divisions may have different issues that need to be resolved when considering the switch.

“With a prescription drug, everything goes in the package insert,” said Dr. Bierer. “But when a drug is OTC, instructions about dosage, safety warnings, contraindications, and other relevant information has to fit on the OTC package label. That’s where the OTC division is coming from – they’re thinking about the consumer, how a drug can be labeled and used over-the-counter.”

The OTC Division may require additional consumer behavior studies, if no similar drugs are on the OTC market. 

“If we’re talking about an antihistamine for example, we know people know how to take those,” said Dr. Charles Ganley, Director of the Division of OTC Drugs at the FDA. “But in Prilosec’s case, there were no other drugs with the same indication OTC, so we had to be sure it would be taken correctly and by the right population.”

Talk to the FDA – early and often

Dr. Bierer advises opening a dialogue with the FDA before you even submit the Investigational New Drug application (IND). At the very first meeting pre-IND, the sponsor should ask the FDA the following three questions:

1. Is our proposed clinical program adequate to provide the data you would need to decide whether to approve this Rx-to-OTC switch?

2. Have we identified all the potential safety issues that need to be addressed?

3. Does our program accurately identify the right OTC target population?

“One of the biggest mistakes companies commonly make is not bringing the FDA into their decision-making process soon or often enough,” said Dr. Bierer. “If you talk and more importantly, listen to the FDA, you’ll have the information you need to address their issues.”

“Up until and even after the advisory committee meeting, you should continue to request regular meetings with the FDA, outlining your evolving rationale for the switch, asking them a series of questions, and always asking, ‘do you agree?’”

“If they don’t agree,” said Dr. Bierer, “Ask them what additional information they need?”

Dr. Ganley agrees.

“Not only should they talk to us early and often, but if they don’t understand our position or don’t agree, they should ask for further discussions,” said Dr. Ganley. “I think sometimes companies are hesitant do that, thinking maybe it would upset or bother us.

“Speeding access to safe and affordable medicines is one of the FDA’s stated priorities, and FDA Commissioner Mark McClellan frequently talks about the agency’s mandate to speed up the approval process,” said Dr. Ganley. “If companies do get that impression (that they are bothering us), I’d like to know about it, because we’re not here to be an obstacle. We’re charged with getting safe and affordable medicines out there, and we have an obligation to help companies figure out a way to do that.”

Don’t get mad, keep talking

Dr. Bierer said a lot of companies shoot themselves in the foot with the FDA by allowing emotions to take over if there is disagreement. 

“There is no point in getting upset with the FDA.

You have a job to do, they have a job to do,” said Dr. Bierer.

“It’s important to look at the issue from the FDA perspective and figure out a way to move forward.

At the end of the day you’re really looking to negotiate a win-win for both the company and the FDA.”

The other issue is full disclosure.

“It’s also important to be upfront with the FDA on issues surrounding your data,” said Dr. Bierer. “Better to identify the issues and what you plan to do about them, rather than waiting for the FDA to ask.”

Know the FDA’s real concerns

According to Dr. Bierer, FDA reviewers may be talking about one issue but have an underlying concern that they are not articulating. The sponsor needs to ferret that out.

“For example, at one point with Prilosec, the FDA said they weren’t sure they could switch the drug to OTC because of a safety issue, but it turned out they were really concerned about having to make a policy change in order to approve the switch," said Dr Bierer. "We dealt with that by giving them the data that would help them work through such a policy decision. That sort of thing happens a lot.”

CHPA is currently working with the FDA to try and make the entire Rx-to-OTC approval process more transparent and predictable for companies.

“If the process is more clearly defined, with guidelines for studies and more standardized procedures, it would help decrease development time and costs for industry,” said Dr. Bierer. “This could help FDA reviewers, and hopefully translate into faster approvals, lower prices and greater access to OTC drugs for consumers.”

Dr. Ganley is also a strong advocate within the FDA of avoiding “negative messages” – that is, not saying a drug simply can’t be switched from Rx-to-OTC.

“I do see that attitude occasionally within the agency, and it’s frustrating,” said Dr. Ganley. “It’s too easy to just say no, we can’t allow that drug to go over-the-counter. It’s much more scientifically challenging to have to explain your specific objections and then figure out what data might be necessary to overcome them.”

As with any drug approval, with an Rx-to-OTC switch application, the FDA looks to the NDAC Advisory Committee for guidance.

In our next issue of The Edge: How to prepare for the advisory committee meeting, to ensure success.

Consumer Healthcare Products Association (CHPA) www.chpa-info.org
Federal Drug Administration (FDA) www.fda.gov OTC Division: 301-827-2241

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