"Heparin Was an Industry Wake-Up Call": A Star Turn by CDER's Janet Woodcock

Janet Woodcock, head of FDA’s CDER, strikes me as the type of person you’d want in charge during a crisis.  And that’s exactly where FDA, and CDER, have found themselves this year, so I’m not surprised that Dr. W. was reassigned from her post of Chief Medical Officer and Deputy Commissioner to head up CDER.  Using the triage imagery of the Emergency Room, running the Critical Path initiative is important, but maintaining control of CDER, drug review and inspections, is urgent.

Woodcock opened her keynote with her usual call for global harmonization, science based manufacturing and control, emphasizing the point that it is the industry’s job to understand and control its processes, even as its supply chains become more complex.

The recent heparin contamination case, she said, was a wakeup call for the industry, and emphasized the need for vigilance throughout the supply chain.  Globalization has made this vigilance difficult, she said, especially since the number of drug products made at foreign sites has more than doubled since 2001, while the site inspection rate has declined by 41%.  Adding more inspectors and inspections as the Agency plans to do, using increases in funding, FDA still won’t be able to catch up with the global outsourcing trend.

Generic drugs, now most widely subscribed in the U.S. pose a particular problem, since distant facilities are increasingly named in ANDA’s. 

FDA has also been hampered by a fragmented global regulatory framework.  “In many ways, [global regulation is]  back in the 1950’s.”  Even though nations are rallying around ICH, there is still variability and fragmentation.  For a U.S. government agency, there has been an erosion of FDA’s ability to “mind the store,” when that store is global.

Dr. Woodcock's use of understatement brought chuckles to the audience. At one point, she mentioned that she had spoken to Congress about these issues several times and “expects to make further appearances.”  “We need to deal with today’s global realities,” she said, “and how we maintain quality in this new environment.”

Dr. Woodcock went on to discuss the issue of counterfeit and substandard drugs in the emerging drug manufacturing centers (or, rather, as Dr. Rosling, described them, the mid and low-income nations).  Local training programs will be critical, she said.  (We’ll be writing about one such program, in Madagascar, that was established by USP and has become a model and template for others of this type). 

Inspection's No Panacea; No Buck-Passing, Please
Dr. Woodcock emphasized that inspection is only one component of regulation.  “Congress is very focused on this, but it won’t be the way to guarantee [safety and quality].”

Instead, she said, manufacturers, brokers, importers and distributors need to take primary responsibility for quality.  Regulators can work more closely with local law enforcement agencies, but it is the duty of manufacturers and suppliers.  “Ours in an audit function.  We need to enable continuous improvement and we cannot impede innovation.”

Role of Professional and Technical Societies
Professional technical societies and standard setting organizations need to set standards, Dr. Woodcock said, mentioning the work that ISPE is doing with the PQLI.  Meanwhile, she said, technical societies need to widen the circle and develop global professional communities.

A critical step for harmonization, she said, will be increasing the presence and effectiveness of local inspectorates, to establish standards for ICH and non ICH regions.

There may be a need to extend cGMP’s to excipients, she noted, to modernize manufacturing and harmonize pharmacopeial standards. “Every time we have fragmentation, we create more barriers for global product quality.”

She mentioned the need for more effective methods for supply chain management and integration as well as better automization of globalinventory management.

Dr. Woodcock touched on the FDA Beyond Our Borders program, and the fact that the Agency will be recruiting new people.

She asked the audience to comment on proposed registration and listing system using structured product labeling.  “We need to prevent any train wrecks, errors on the IT side.”

Tracking and Tracing
FDA is also working to develop unique product identifiers, and evaluating the use of DUNS (Dun and Bradstreet) numbers, and moving to electronic verification of listings.  The Agency, she said, will continue to encourage RFID and technologies like it.

Defining the Design Space, Controlling Excipient and API Quality
Finally, the Agency will release a “regulatory agreement guidance” on QbD and the Design Space and related guidances for filing status on related supplements.  This is at the top of the Center’s priority list, she said.  (This should be welcome for the many people out there who still don't really understand the idea of the Design Space or other key terminology of QbD.  An informal poll during a Webcast we aired this month (click here to view) found that this was a major obstacle for most people contemplating this new model for drug development)

Recent events have highlighted the importance of the quality of excipients and APIs, and the need to identify sources of variability in these components, which is the key to ensuring final product quality.

She mentioned the public’s and regulators concerns about food and drug adulteration and food-borne illnesses, and the fact that a number of draft bills would establish controls for manufacturers and increase FDA’s authority.  “We will expect to see legislation move in late Winter, early Spring” she says.

She mentioned that Critical Path was quietly progressing, but that pharmacovigilance initiatives have moved forward at a faster pace, especially in the area of genomic data submission.  “Some drug labels are even starting to contain genomic data,” she said.  An example of Stevens Johnson syndrome, which has been linked to specific alleles….testing is being required.

The Biomarker Consortium at FNIH is also making progress, she said, as well as the Clinical Trial Improvement initiative with Duke University.

Getting a Handle on Unsuspected Adverse Events
Dr. Woodcock also said that the FDAA has led to improvements in pharmacovigilance, especially the REMS risk management process, as well as a major pediatric drug safety program.  However, she said there is a need for systems to be able to detect unsuspected adverse events more efficiently.  The Agency is now developing IT systems that would be able to use medical claims and other data to better link prescription and purchase data with clinical outcomes.

Also on the IT front, the Agency’s Sentinel system is being shored up, and pilot projects are now ongoing.

The science base, she said, has invigorated drug manufacturing and complementary efforts will be needed in drug development and postmarket surveillance, and all these efforts will need to be much more tightly linked to quality.



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