FDA's Woodcock Expresses Concern Not All Generics Are Equivalent, But OGD May Have Solution

It didn't seem like deliberate choice to play good cop-bad cop, but Acting Office of Generic Drugs Director Keith Webber and Center for Drug Evaluation and Research Director Janet Woodcock offered a near textbook version of it at the recent Generic Pharmaceutical Association Fall Technical Conference.

Both Webber and Woodcock focused on charges that generics may sometimes not be truly bioequivalent to the brand versions, but while Woodcock sounded just scary, Webber offered industry a way to get the handcuffs off and maybe have a soda.

Generics industry has made “kind of an enemy” of frustrated customers who are being forced in many cases to take generic medications," Woodcock said.

Woodcock said that generic industry officials have told her some products are not equivalent to their brand-name counterparts. Typically the individuals are part of the manufacturing or product development processes and they generally cite quality issues as the reasons for the problems, she said.

It only feeds the public’s skepticism of generic quality and is a serious issue, Woodcock said.

“So some of this may just be worrying, but I’ve heard it enough times from enough people to think that there is a feeling out there amongst some parties that there are a few products that are not meeting quality standards,” she said Sept. 20.

The remarks left many in the audience scratching their heads. There's been one prominent whistleblower case in the generics industry, but it did not result in any FDA enforcement action.

Following a newspaper article accusing Mylan of covering up manufacturing errors at a plant in Morgantown, W.Va., the company asked FDA to investigate and an agency inspection later found no significant problems (Also see "Mylan Has Strong Quarter But Huge GMP Overhang" - Pink Sheet, 30 Jul, 2009.).

A Third Arm Could Come In Handy

Speaking at the conference the next day, Webber, who has been acting OGD director for about six months, noted that FDA already has several efforts underway to counter generic skepticism, including working with sponsors on a study of anti-depressants and collaborating with the National Institutes of Health on a study of anti-convulsants.

Webber said the agency also is conducting more media interviews to communicate its confidence in generics. His message seemed similar in tone to one given by then-OGD Director Gary Buehler last fall.

Buehler, who is now Teva's VP of regulatory strategic operations, had defended the quality of generic drugs but noted that industry could do more to bolster it (Also see "FDA Aims To Bolster Generics' Image With Research, Regulatory Changes" - Pink Sheet, 16 Nov, 2009.).

Webber said in an interview following his address, “Manufacturers should look at the design of the product and try as best they can to mimic or improve the presentation of the product. … We need a drive on industry’s part to a more equivalent presentation of the product.”

OGD Acting Director Webber suggested expanding bioequivalence studies to include a second arm comparing the reference-listed drug to itself.

Generic companies could sponsor research to refute negative equivalence claims as well as publish data demonstrating therapeutic equivalence, Webber said, and he also suggested expanding bioequivalence studies to include another arm comparing the reference-listed drug to itself.

That additional arm would be a way to show the variability of the branded drug in patients, which could fight claims that only the generic drug has a variable effect.

The skepticism problem is not a new one for FDA. The agency now is pushing generic manufacturers to adopt the Quality by Design manufacturing approach to improve applications and promote better understanding of formulations (Also see "FDA Officials Urge Generic Drug Industry to Adopt QbD to Improve Submissions" - Pink Sheet, 1 Jul, 2010.).

Woodcock said she was surprised the generic industry has not accepted QbD more enthusiastically, because it can save it money through a more efficient manufacturing process. She said generic manufacturers, who operate in a business with a small profit margin, should be interested in lowering costs.

“I would think manufacturing for the generic industry ought to be your core competency,” she said.

Extreme Generic Make-Over

Woodcock also recommended a kind of brand make-over for the generic industry because, as she put it, the industry has made “kind of an enemy” of frustrated customers who are being forced in many cases to take generic medications.

Manufacturers should not stop at achieving equivalence, she said. The industry must deal with “intangibles” like product presentation and patient perception. Problems with tablets having a foul odor or bad taste must be fixed. Rougher tablet coatings and larger sizes compared to branded products also must be changed, she said.

“People have to take some responsibility and recognize, I think, that therapeutic equivalence isn’t everything,” Woodcock said. “Can’t you really think about meeting or exceeding patient expectations? Can’t you have a product that’s more acceptable to a consumer than an innovator product …? That would help a lot.”

[Editor's note: This story has been revised to indicate that FDA itself has stated that it found no problems at Mylan's Morgantown facility.]

By Derrick Gingery