OTC, Rx Drug Risk Equation May Be Altered In Upcoming GMP Plan

FDA is considering applying different levels of scrutiny to OTC and Rx drugs as part of its new risk-based approach to pharmaceutical Good Manufacturing Practices.

Addressing whether the risk-based approach could lead FDA to change its current policy of equally weighing OTC and Rx GMP violations due to the view that OTCs are less risky, Center for Drug Evaluation & Research Director Janet Woodcock, MD, said the agency is "definitely thinking about it."

FDA's field staff "are really committed to looking into these questions," she added.

"As regulators we have the obligation to have the lowest burden system that will accomplish societal objectives," Woodcock said at the Consumer Healthcare Products Association's Manufacturing Controls Seminar in Parsippany, N.J. Oct. 11.

FDA publicly announced its plans to update pharmaceutical cGMPs in August and expects the initiative to take about two years to fully implement (¹ (Also see "FDA GMP Plan Stresses Consistency; Systems Approach Ratified By Crawford" - Pink Sheet, 26 Aug, 2002.), p. 8).

Elaborating on Woodcock's comments, FDA New Jersey District Director Douglas Ellsworth noted "there is product risk, but that is not all of it. There is also process risk."

"Most of the things we are talking about...[are] not really new concepts, but ways of thinking about things in the pharmaceutical industry," he said. "We will look at what are the critical control points and...what is the public health risk associated with" a product.

For example, "a dandruff shampoo maybe has public health risks not so much associated with [side effects], but maybe there are risks associated with contamination," he noted. "What are the critical control points to reduce contamination? So this is a process risk."

Ellsworth cited guaifenesin as another example, stating: "I have heard that people can almost drink a bottle of that and not get sick. But what are some of the risks? What are the control points in that manufacturing process? Maybe it is raw material control. Maybe it is cross-contamination control."

Ellsworth summed up FDA's new approach to GMP enforcement as having "a better ability to identify the critical points in a manufacturing process, assess the risk associated with those critical points and then adopt optimal control technologies to control risk associated with those control points."

"So we will be looking at ways to focus on process points that create the greatest health risk. That will be the future," he concluded.

The agency could implement a tiered approach, designating certain product classes or delivery forms as higher inspection concerns than others. In response to a question on the viability of such a model, Woodcock conceded she did not have an "answer to that, [but]...I think it is a good thing for us to consider."

Speaking during a separate session Oct. 10, Ellsworth was more definitive on the possibility. FDA does follow a "tiered approach to GMP inspections" overseas, "with certain types of product classes a higher priority than others, and we are going to be putting that out in the domestic arena this year," he stated.

As an example of how a tiered system might work, Ellsworth noted since "sterile products pose a greater risk than other products...we may look at sterile facilities more often."

The different processes by which consumers obtain OTC and Rx drugs will not factor into FDA's assessment of product risk. Woodcock stated physicians' involvement in Rx drug distribution, as opposed to the self-selection of most OTCs, does not impact how the agency conducts inspections.

"Most physicians...never see or touch the drug product, so the physician is actually very removed" from the risk equation, Woodcock said. As a result, there are "not...a lot of differences here in quality issues based on the fact that" Rx drugs are distributed through a learned intermediary while OTCs are not, she stated.

Overall, the concept of risk has many different aspects, Woodcock said. She pointed out that FDA "might deem something high risk because the manufacturer repeatedly had problems. That is one element."

Another risk factor is whether a product "has a lower tolerance...for problems," she added. "We need better data, and we are in the process of trying to gather those data so that when we actually determine risk we have some algorithms that we can [use to] put together a number of factors," Woodcock said.

One of the factors FDA likely will consider is the location of the plant being inspected. Woodcock agreed that a facility based in a Third World country would probably be approached as presenting a higher potential for risk than a plant found in the U.S.

"That is a good example" of what the risk-based approach needs to address, Woodcock continued, noting FDA has "a lower rate of GMP inspections in Third World countries than we...do in the U.S."

Manufacturing controls and product risk sometimes might not even be the issue. Ellsworth noted several recent GMP violations have not been due to manufacturing problems, but to poor or faulty management oversight (² (Also see "GMP Violations Usually Due To Poor Management Controls – FDA’s Ellsworth" - Pink Sheet, 14 Oct, 2002.), p. 12).

The district director said FDA also is open to the idea of employing third parties to help implement its risk-based GMP program.

The agency is looking for "the most efficient, best way to do this, and if we find that there are some good third-party models out there, obviously we are going to evaluate that and see if we can apply them to the FDA system," Ellsworth said.

Although FDA still is piecing together its new GMP program, Woodcock reiterated the agency may use consultants to help create its quality initiatives.

"We are planning to, and we have money that we can use to get consultants," the CDER director said. She noted FDA has assembled working groups to address different issues affecting the GMP initiative, and that "if they determine they need the help of consultants then we...would help them get a contract."

Woodcock added that while the arrival of a new commissioner could alter the focus of some of the agency's efforts, the initiative likely will remain relatively unchanged. White House economic advisor Mark McClellan, MD/PhD, was confirmed by the Senate Oct. 17.

"You never know what new things may come along with a change in leadership, but certainly I think he is in full support of this and this will continue," she said.

[Editor's note: Extensive coverage of FDA's risk-based GMP initiative may be found in the October issue of "The Gold Sheet." For a trial subscription, contact Marianne Macholtz at 301-664-7182].