Wednesday, October 2, 2013

CDER's Sklamberg on Criminals, Pleasing FDA Inspectors and Evolving Enforcement Approach Latest News; FDA in process of forming Office of Pharmaceutical Quality (OPQ),| Posted: 1 October 2013

By Alexander Gaffney, RF News Editor 

In remarks made on 30 September 2013 at the 2013 RAPS Regulatory Convergence conference, Howard Sklamberg, director of the Center for Drug Evaluation and Research's (CDER) Office of Compliance, provided a number of glimpses into what his office has in store over the coming months.

The Case for Quality (for Drugs, too)

The first should be of little surprise to anyone who has kept tabs on the US Food and Drug Administration (FDA) in recent years: Quality. As with its medical device center, the Center for Devices and Radiological Health (CDRH), FDA is seeking to make a similar "case for quality" within the pharmaceutical sector.
"CDER is focusing on ways of improving its assessment of quality," Sklamberg said. "We're in the process of forming an Office of Pharmaceutical Quality (OPQ)," which would combine many review functions--good manufacturing practices and chemistry, manufacturing and controls, for example--that are currently spread throughout various CDER offices into one office.
The goal, Skalmberg said, is to adopt a "lifecycle approach to reviewing products," much in the same way that regulators within industry often work.

From Lagging to Leading

Sklamberg also spoke at length about product surveillance, both for traditional and compounded pharmaceutical products. The key, he said, was to move away from traditionally lagging indicators and toward a better surveillance function.
He said current efforts within this space are focused on trying to find uniform metrics across the industry that could facilitate better overall compliance.
This also applied to various geographic regions, Sklamberg added. "We want to be able to see where the leading indicators are, regardless of where they are located."
But like most other divisions of FDA, a major focus of the Office of Compliance remains the Food and Drug Administration Safety and Innovation Act (FDASIA), he said. These activities vary widely, including reducing a backlog of applications, clearing new applications, ensuring the security of the supply chain, leveraging its new authorities in constructive ways and obtaining metrics from industry.

Struggles at Home and Abroad

The center has also been at the epicenter of a debate about whether the agency at large has sufficient authority to regulate pharmaceutical compounders. Sklamberg refused to comment on current efforts to alter FDA's enforcement paradigm by the House and Senate, but noted the legal difficulties the agency continues to face--various legal setbacks, a general lack of information, and a difficult time defining where a compounding pharmacy becomes a pharmaceutical manufacturer in practice.

"Because these firms had not registered with us, we sometimes had to go on the Internet to do research on these firms," revealed Sklamberg.
The director also weighed in on the agency's increasingly global focus, saying he is seeking "parity" between foreign and domestic inspections. While refusing to comment on any specific countries, he said that the "lengthening supply chain is a reality and one FDA very much has the responsibility to grapple with, and is."
"FDA has to be able to do its job," he continued. "We have to be able to inspect a foreign firm, either for an application or postmarket activity. When a firm interferes with or prevents us from inspecting, those actions are now violations of FDASIA. This provides an incentive for firms to allow us to do our job."
"Our inspections must match where the inventory is, and identify where the greatest risk is," Sklamberg added.

On Coming Guidance and Enforcement Discretion

Finally, Sklamberg provided one piece of news likely to be of interest to any regulatory professionals dealing with contract manufacturers: Additional guidance is on the way. The agency has been sending out many Warning Letters in recent months referencing deficient contracting arrangements in which the primary company is exercising insufficient oversight over the contractor.
And with respect to guidance documents, Sklamberg said he's also looking to be more specific in the future when declaring how and under which circumstances FDA might plan to exercise its enforcement discretion--the general term for when FDA maintains its authority to regulate a particular activity or product, but chooses not to for a variety of reasons.

Everyone Here is a Criminal--and Why That Matters

Why the reason for clarity? Simple: You--yes you, the person reading this--are probably a criminal. Don't worry, as there's (hopefully) little need to shave your head and change your name. The real issue, Sklamberg said, is that even seemingly innocuous actions in the incorrect circumstances are violations of US federal law. And if you're a regulatory professional dealing with federal programs under the Federal Food, Drug and Cosmetic Act, the possibility of violating a law are myriad.
"Many people in this room have committed a federal crime," Sklamberg exclaimed to the room before him, receiving a chorus of nervous chuckles in reply. The key differentiator, he said, is in how FDA exercises its enforcement discretion--who deserves the feel the long arm of FDA's legal authority? Making that approach abundantly clear in its guidance documents is important.
"If we locked every one up, there would be no drugs," mused Sklamberg.

How to Get out of--and Stay out of--FDA's Compliance Dog House

The final topic touched on by Sklamberg had to do with what happens when FDA does come knocking, and finds something wrong. An audience member inquired as to FDA's approach. What, he asked, would placate FDA investigators that a person had made an earnest error, and was not acting out of willful ignorance or malice?
Sklamberg said the key differentiator is having a robust quality system in place that ensures there "is a system in place to prevent this problem from happening again."
The director said he recognized that "even if your objective is to produce a quality product, you can't reduce the risk of failure to zero percent." The key, he said, was to exhibit a commitment to quality and embed it into every part of your operational structure.
The key question manufactures need to ask themselves, according to Sklamberg: "What systems do I have in place to convince FDA that this problem won't happen again?"
"The right incentives have to be in place, and improvements must be embedded into future changes," he added. Which isn't to say FDA will always like what it hears from a company.
"We have a job to do, which is partly an oversight one," Sklamberg explained. "That's going to, at least in some situations, be adversarial. Hopefully it won't be unnecessarily so."
quoted from here

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