US drug regulator trying out collegial approach

Getting it wrong with pharmaceutical drugs can be critical - at least from the patients' point of view. And adverse reactions can quickly impact the companies producing the drugs.

Regulators, too, are not immune and that is why quality control is a critical part of the evaluation of new drugs.

That is where Moheb Nasr enters the picture. The Cairo University pharmacy graduate leads the Office of New Drug Chemistry at the US Food and Drug Administration's Center for Drug Evaluation and Research.

His main job is quality control of new drugs looking for approval to enter the market - both in terms of assessing the chemistry behind the drug and the large scale manufacturing process.

"My responsibility is in determining that the drug was discovered correctly, that the product and dosage form was developed correctly and that manufacturing facilities are capable of producing the drug consistently and to high quality," he says.

"We conduct a thorough scientific review of the product design and manufacturing process. Then there are site inspections to ensure that the design specification that we approve could be implemented. Working these two elements together, we decide whether to approve or not approve the drug."

He notes that, at the end of the day, the FDA operates on a risk-benefit analysis - examining the medical needs, the risks associated with approving the drug and possible manufacturing difficulties. "We look at all these things and decide whether it is worth approving the drug, weighing the benefits and the risks."

While public perception can be of a bewildering array of new treatments coming on to the market, Dr Nasr says the volume of new drug applications has levelled off in the past five years, although the number of drugs coming back through the system in new forms is increasing.

His office also has to deal with drugs, such as Tysabri, the radical treatment for multiple sclerosis developed by Irish company Elan in association with Biogen Idec, which are back in the regulatory system. Tysabri was originally approved by the FDA on a fast-track system but was suspended soon after its launch when significant health problems emerged in a number of patients.

While Dr Nasr's office won't have to re-examine the quality issue as the drug is not being reformulated, it will be responsible for overseeing any necessary changes in its labelling.

Dr Nasr agrees that many of the easy targets for drug companies have now been hit, meaning that new drugs are increasingly tackling more complex diseases, which carries greater risks.

"I think drugs coming to the FDA for new therapies will come in two areas - totally new drugs, essentially on the biotech side, and existing drugs which can now be delivered in different and more focused ways," he says.

He points to the imminent approval for an insulin drug that can be inhaled, like asthma treatments, rather than injected. "That's a case of a treatment that has been around a long time and now, because of convenience and challenges with injecting insulin to diabetic patients, having a different mode like a dry powder inhaler offers opportunities for insulin."

Dr Nasr was in Dublin this week to talk about the changing face of drug regulation. The FDA is keen to encourage a more collegial approach to the business of drug approval.

"The quality of drugs in the market now is high, so it is not that we have a problem with quality of what is out there," he says. "The reason we are changing the way we review drugs is that we want to use more science and take advantage of scientific advances, while taking advantage of limited resources.

"We also want to find a way to facilitate drug development. When we have a high regulatory hurdle, there is less incentive and it is more expensive to develop new drugs. We are a public health agency and we have a responsibility to try to facilitate drug development."

He said the current regime militated against using new technologies to improve drug delivery - with supplementmental applications required that carry significant cost issues and are seen by the industry as risky.

"We want to put in place a system that rewards people who have done a better job in developing their products - carrying out proper scientific development which you can share with the agency. That gives us more confidence that the manufacturer has the ability not only to manufacture the drug but also to make minor changes without reverting to us."

He sees this as promoting a partnership approach compared to the more adversarial regime that drug manufacturers often perceive with the FDA system.

"It will be good for industry and good for us," says Dr Nasr, "reducing the agency's workflow and streamlining the regulatory process."