5/14/2010 [Essay by John Scharmann and Jim Dickinson*] “Change” was what drove Barack Obama into office, and his inability to materially change agencies like FDA may be what drives him from it in 2012. The key and talented people he sent there, like most of their counterparts from prior administrations of both parties, lacked the raw, brutish determination to avoid being captured by an agency bureaucracy that has seen so many would-be reformers come and go.

 

Take, for instance, the issue of regulatory enforcement. After 30 years of a relaxed, industry-enabling and “get government off the backs of the people” Reaganesque policy that infused the regulatory enforcement culture in Washington, where is FDA? Behind the 8-ball, say many. Apart from raising the rhetoric and a 50% jump in Warning Letters, Obama’s team at FDA has in 18 months introduced nothing of a true “reforming” nature for the front-line troops in the field.

 

The team’s doubtless sincere intentions amount, in the end, to so much smoke and mirrors, in our opinion. Eighteen months may be too short a time to develop comparative statistics, but although we have seen aggressive pronouncements from commissioner Margaret Hamburg, little of change-making substance has emerged where “the rubber meets the road.” Might the unseen truth be that a politically modulated FDA can’t be allowed to upset its politically modulated patrons — the companies whose user fees fuel agency programs and whose donations will empower candidates seeking office in November?

 

Thus, Hamburg’s office could not even define the term “regulatory science” as applied to enforcement when we asked her to do it. “Regulatory science,” in case you have forgotten, is Hamburg’s cause célèbre in bringing Obama-era change to FDA. The trouble seems to be that its meaning is hard to absorb — especially in the context of enforcement.

 

Seeking her definition and allowing six days for her to provide it, we followed the prescribed procedure of submitting it through the Press Office, addressed to assistant commissioner for public affairs George Strait, expressed as follows: 

“How would Dr. Hamburg define the term ‘regulatory science’ with respect to (a) Interpretation of GMP requirements at the point of routine everyday regulatory investigations in-the-plant by FDA field personnel, and (b) FDA decision-making at the executive level on whether to launch a federal court prosecution based on recommendations from the field?”

After 24 hours with no acknowledgment that he’d received it, Strait responded to an email prod, saying he’d referred it to Meghan Scott in Hamburg’s office and she in turn advised that she was working toward our deadline five days hence. The due time passed, and after further prodding, several hours later Scott supplied the following, attributable to Hamburg: 

“Advances in regulatory science — the science needed to evaluate, ensure and monitor a product’s safety, effectiveness, potency, quality and performance — can promote quality and lower costs of production development and manufacturing. In order to harness regulatory science to update the manufacturing process, FDA is supporting work on ‘quality by design.’ Areas of investigation include new statistical approaches to detect changes in process or product quality, continuous processing — in which materials continuously cycle through equipment to reduce overall manufacturing time and costs —and Process Analytical Technology to monitor and control, rather than just test, manufacturing processes.

 

“By better controlling complex manufacturing processes, and enhancing their efficiency, these approaches can use regulatory science to provide quality products for patients who need them. In addition, new technologies, including flexible manufacturing facilities and modular and disposable equipment, can speed production of products in both routine and emergency situations.”

Huh? How did that answer our enforcement-context questions? What Hamburg came up with sounded more like a sales pitch for a nebulous concept than a rubber-meets-the-road definition for agency investigators and industry alike. Did someone lose our question and try to fudge an answer on Hamburg’s unknowing behalf? And where did the idea come from that inserting an intermediary between a question and its answer would improve anything?

 

Whatever the explanation, the incident revealed a shining beacon of regulatory and managerial detachment, of a “buck stops here” agency head whose work is done for her by others below who can themselves be lost by their own detachment.

 

In other words, as to the matter at hand, this incident invites the assumption that Hamburg doesn’t have a clue as to how her cause célèbre translates into an enforcement context. But does she? Might the problem really be that she is being treated like an “empty suit” in the hands of her managers, and that she could give a convincing accounting of herself on this and any other matter if left to fend for herself?

 

We remember DBB — “Days Before Bush” — when if we wanted to ask (say, for example) former commissioner David Kessler a question, all we had to do was ask his secretary, Kay Hamric (whom we knew and shared mutual respect) was he in? If he was free, she connected us, and Kessler would answer us as fully as he could or ask someone else to do so. If he wasn’t free, we asked her to tell him we’d call him at home that night. As a lawyer (JD) as well as a pediatrician (MD), Kessler knew what today’s Obama appointees apparently do not know: His conversations with us and other reporters were protected and even required by the First Amendment; he once evicted associate commissioner for public affairs Jeff Nesbit from an interview with us on this basis — “Jim must be able to do his job,” he told Nesbit.

 

Those days and their forerunners now stand windswept and barren, like the statues on Easter Island. Furthermore, the examples we describe here, when extrapolated through hundreds of other permutations throughout the agency, show the hopelessness of the Obama “change” agenda.

 

Welcome to the new “smoke and mirrors” world of distrust in government. Far from making government more transparent as Obama vowed, FDA is much less transparent than it was in DBB.

 

And in the “rubber meets the road” world of FDA enforcement policy, over the past 10 to 15 years many of our major firms — Abbott Laboratories, Schering Plough, Steris Laboratories, Eli Lilly, McNeil Consumer Healthcare — to name several who have had major CGMP problems that caused great expense to their stockholders, have fallen from grace at FDA’s hands. Their costs came about by the companies agreeing to remove products from the market or pay fines associated with consent decrees. There were no criminal penalties addressed to the managers of these firms, only civil penalties.

 

In the case of McNeil, a major firm with significant CGMP problems, while commissioner Hamburg states that the likelihood of serious problems for the consumer is remote, this is not something that should be considered in the equation of regulatory follow-up.

 

The facts include the use of microbiological contaminated raw material that caused McNeil’s products to be adulterated under the FD&C Act under section 402(a)(4) of the Act. The firm was operating without adequate laboratory facilities called for in their Quality Assurance plan. Other deficiencies included a lack of adequate employee training, and poorly maintained manufacturing equipment. Examples included dust on equipment and some equipment patched with duct tape.

 

Apparently unguided by “regulatory science,” the FDA-483 that was presented to McNeil consisted of 20 items crafted in the time-honored FDA way.

 

Hyattsville, MD-based industry consultant and former FDA enforcement official Carl R. Nielsen thinks there are multiple factors that “go way beyond corporate management going lax” in cases like this. He told us the whole current OTC regulatory paradigm is not set up or designed to mitigate risks in global trade and manufacturing. “FDA wants to say industry just needs to have a robust quarantine/release program, but FDA does not have a robust OTC surveillance program that covers the complete supply chain from the manufacturers of the APIs and excipients to finished dose,” Nielsen said.

 

Perhaps that is something Hamburg’s “regulatory science” in an enforcement context could energize, if we knew its parameters and meaning?

 

The McNeil FDA-483 demonstrates that there is what Nielsen calls “a real quality and safety problem with the ingredients in the international trade and further confirms non-adherence to good CGMPs resulting in drugs that are not safe and don’t do what they are supposed to do. The ingredient supply chain issue is not a new issue, just a quiet FDA issue. The OTC industry needs to have robust and practical QC/QA measures in place for their supply chains that can quickly and effectively be verified on a frequent/routine basis. It simply is not good enough for FDA to say who has the responsibility to ensure product safety.

 

“Every person I have known in my life at some point took or takes OTC drugs,” Nielsen said. “Public exposure to potential risks from unsafe OTCs is, in my opinion, at least equivalent to risks presented by Rx drugs, and perhaps present greater risks. Right now it is probably a quiet unknown.”

 

Meanwhile, in a Bnet online blog, commentator Jim Edwards critiqued what he acknowledged was a courageous blog on the McNeil matter by J&J CEO William Weldon, suggesting that it revealed that “J&J’s jumbled archipelago of 250 companies in 57 countries, with separate names and management trees, may be to blame: There’s not enough hands-on accountability from the top. Important information doesn’t appear to be moving quickly enough up the chain of command.”

 

The same might be said in spades for the movement of regulatory and public information through FDA’s stove-piped chain of command and its “archipelago.”

 

When you consider the breadth of the CGMP deficiencies at McNeil and similarly CGMP-relaxed companies, what should be the approach of FDA in an enforcement action? From the questionable success of consent decrees and the civil penalties connected with these agreements, it appears that you cannot fine these companies enough to cause them to change their methods of operation and cause other firms to be concerned with these remedies.

 

The agency has stated that criminal prosecution is up for consideration. If it applies this sanction, individuals will have to be named. Even with this type of action we’re not sure that the normal type of penalties given upon conviction will raise much concern. Maybe jail time is called for?

 

Extremely harsh penalties do not seem to deter, however, in the context of the worldwide responsibilities of FDA-regulated industries. On 7/7/07, China executed Zheng Xiaoyu, its former top food and drug regulator, after his conviction for taking bribes and approving untested drugs. This all resulted from adulterated raw materials used by American manufacturers to produce certain types of pet foods that reportedly killed a number of pets.

 

Even given this, we are still receiving adulterated products from Chinese drug manufacturers because of CGMP violations — so even the possibility of death appears to not to cause the survivors to change their ways.

 

While the death penalty is out of the question for failure to maintain company compliance with the FD&C Act, we wonder what it will take to bring accountability and credibility back to regulated industry — and to its allies in a user fee-dependent FDA?

 

As recently as last month, FDA’s chief saber-rattler Eric Blumberg, deputy chief counsel for litigation, told the Food & Drug Law Institute that unidentified industry heads will roll in a new FDA crack-down using the Park (“knew or should have known”) strict liability doctrine. We’ve heard this before from Blumberg, without much obvious effect — but in that old rubber-meets-the-road reality, truth is increasingly hostage to the prevailing political philosophy. Do we really want to hurt our campaign contributors, or don’t we?

 

Meanwhile, untransparent FDA Press Office boiler-plate language still smokes and mirrors us: “FDA can neither confirm nor deny that an investigation exists.” Nor, apparently, can it even tell us what “regulatory science” in an enforcement context means.

 

Any suggestions on what it will take to get both industry and FDA managers to do the difficult but right thing in their administration of their official duties?

 

* Jim Dickinson is editor of FDA Webview, and John Scharmann is consulting editor and a former FDA Denver District director.

 

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