A few weeks ago, we hosted a webcast which addressed questions surrounding the relatively slow uptake of single-use technologies for biopharma measurement and control. Speakers Michael Kowolenko (formerly Sr. VP with Wyeth Biotech and Biogen Idec), Kit Erlebach (Merck) and Paul Priebe (Sartorius Stedim) offered a range of perspectives on what has been holding back single-use in biopharma. (A partial transcript is below.

Also at the SAP World Tour (see previous post), Merck’s IT Account Manager for Vaccine Manufacturing, Dermot McCaul, spoke about his company’s ongoing implementation of SAP’s Manufacturing Integration and Intelligence (SAP MII) application.

Susan Boyle apparently suffered an anxiety attack after the final installment of "U.K.'s Got Talent," so if anyone needs another inspiring story of someone who is following the beat of his or her own drummer, and who seems to be enjoying it....here's former Merck marketing manager and now full-time viral video comedian, Nalts, who has left the corporate world to pursue his true calling.  Click here for more.

There has been some discussion recently about Merck's recent continuing medical education publishing venture with Elsevier: a technically detailed corporate publication with a peer-reviewed look and the weighty name: Australasian Journal of Bone and Joint Medicine.  More on this from the Bioethics Blog.

If you put credence in Swiss firm Covalence's annual ethics rankings, yes, GSK, BMS, and J&J are the most ethical companies in the Pharmaceuticals and Biotech sector. The list looks like this:

1. GSK

2. BMS

3. J&J

4. Abbott

5. Novartis

6. Roche

7. Boehringer Ingelheim

8. Astra Zeneca

9. Pfizer

The news today that DSM Biologics and Crucell N.V. had again scaled up production of the PER.C6 cell line was another sign that biopharma cell culture capacity concerns are (probably) a thing of the past, and that PER.C6 represents a breakthrough. Who better to consult with than Eric Langer of BioPlan Associates, whose annual biopharma capacity and production report is a key industrywide gauge. Langer was gracious enough to respond to our emailed questions:

This week, the Second International Symposium on Green Processing in the Pharmaceutical and Fine Chemical Industries was held at Yale University in New Haven. The event brought together some of the finest minds working in green chemistry today, from industry, academia and government.  Several speakers came from Japan and Europe, while an expert from Dr. Reddy's (based in the U.S.) discussed using green chemistry to develop generic drug products.  Lunch keynote speaker was Connecticut DEP Commissioner Gina McCarthy.

The next few posts today will talk about Day 1 of the conference.

But wrapping up the first day was a panel discussion on "Greening the Pharmaceutical Lifecycle: Turning Challenges into Opportunities."   A fairly vague title, it wound up focusing on exactly what I'd hoped it would:  the issue of pharmaceuticals in the drinking water (touched on in previous posts here and there), and what that means to the public, industry and regulators. Moderating the session was none other than Berkeley Cue, Jr, who was so instrumental to Pfizer's Green Chemistry program.

Discussing the problem were Peterson Myers, CEO at Environmental Health Sciences and coauthor of "Our Stolen Future," Nicholas Anastas, a scientist from Massachusetts DEP, and Duane Huggett from the University of North Texas' Institute of Applied Sciences.

Several attendees noted that some drug companies, notably Pfizer, AstraZeneca and Merck,  have already come up with detailed databases and that this work is ongoing.  (Yes, but it's also voluntary...and we cynics know what can happen with voluntary industry programs that aren't universally embraced) Concerns were aired that this may ultimately prove to be a "non-issue," and wouldn't it be a shame if overly prescriptive measures were taken. Panelists also discussed new ways of analyzing impacts that could form the basis of future regulations. 

One audience member concluded that the greatest need was to optimize bioavailability and to develop new delivery systems, but potential end-of-pipe treatments were also discussed.

Looming Water Shortages and the "Tamoxifen Effect"
Mr. Myers sees the issue becoming "a perfect storm" for the industry, driven by global water shortages and the fact that "21st century endocrinology is beginning to replace 16th-century toxicology" as the method for gauging impact.  "It won't go away," ne noted.  As Nicholas Anastas later asked, channeling Rumi, "Do you [industry] want to be the moth or the flame?"  (He was asking the wrong crowd, though.  These were scientists, who generally pursue the truth, however unpalatable it may be. Perhaps the question should be directed to the C-level at top executive meetings. )

He then mentioned non-monotonic dose response curves, and what some studies have seen with Tamoxifen, the breast cancer drug.  At the right concentration levels, the drug can destroy cancer cells, but at lower concentrations, some studies have found that it may stimulate the growth of tumors!  "The regulatory system is blind to this type of effect," he said. "And we may find that some pharmaceuticals in our drinking water follow these same curves."

Mr. Hugget from Texas noted the strains on Dallas' water system, and the Trinity River which, at one point is 90% effluent.  Given that the local population  is expected to double by 2050, people will eventually have to use recycled water. He also mentioned a recent Warsaw meeting in which 89 presentations focused on pharmaceuticals in the environment, as well as the data from India, published in Chemical Week and C&EN, which found extremely high levels of drugs in manufacturing effluents.

EMEA in Europe is far more involved in this issue than FDA, Hugget said, singling out Sweden for its work in assessing and addressing the problem.  In the U.S., he said, FDA and EPA are planning to partner to look at "mode of action" guidelines

(Great---two resource-strapped agencies, one of which (FDA) is now somewhat in crisis, working together without top level government or industry support or funding on an extremely complex, challenging and important issue. How much progress can be made?  What kind of time-line are we looking at, and how much money would be involved....wanted to ask that question, but why ruin the party, especially since it's pretty much unanswerable...Data are already being collected by industry, Mr. Hugget noted, but are they the right type of data?

Environmental Pharmacy Needed in Curricula
Once data on drugs' persistence, bioaccumulation and toxicity are available, and made available to physicians, nurses and the public (and these groups educated to make better prescription choices----he suggested that courses in Environmental Pharmacy be included in curricula), it will be necessary to look into applying newer techniques such as molecular modeling, added Mr. Anastas from Massachusetts DEP (brother of the Yale professor Paul, director for the Center for Green Chemistry and Green Engineering). 

He noted the "Nocebo" effect, and the fact that, when told there may be a contaminant in the water, some people suddenly develop symptoms <ribshot----this was a serious crowd> He also mentioned end of pipe treatment options, some of which are being developed by Terry Collins at the University of Massachusetts (formerly of Carnegie-Mellon), which include UV and other forms of biofiltration.

Audience members brought up the fact that drug metabolites in the environment can be far more toxic than the drugs themselves, a fact that all panelists and Mr. Cue agreed was very important. They also mentioned the fact that the drug industry already possesses vast amounts of clinical data on each of its drugs.  "We know what the knowns are. What worries me are the unknown unknowns," one attendee asked.  Panelists agreed that mixtures of drugs topped the list.

In general, Europe  is ahead of the U.S. in examining these issues and requiring industry to provide more data.

Clearly this issue will take many years, much science and $ to assess and mitigate.  I was pleased to see it being openly debated, and hope that the discussion is advanced, and facts shared by experts, at industry management meetings. 

As DEP Commissioner McCarthy noted, we're in an age where the market is driving political decisions and the market is clearly demanding safe, environmentally sound solutions.  That same market can also drive policies that are based on bad science, if industry fails to take the public's concerns seriously.

An industry that's already lost favor with the public doesn't need to lose any more good will.

AMS

Unfortunately, there is a "Jekyll and Hyde" aspect to many pharma companies today as they struggle with the dictates of shareholders and the whole blockbuster model.  Nowhere was that more evident today than in two articles received within hours of each other. First, from Forbes, a piece on "How Merck Healed Itself" and got it's mojo back. Click here to read.

Mojo wasn't evident, however, in news (far from its labs) of the  $400-million settlement of  a qui tam suit brought forth by sales manager Dean Steinke. More from the release that his legal team issued today....

Merck & Co., Inc. ("Merck"), has agreed to pay more than $400 million to the U.S., 49 states and the District of Columbia to settle qui tam whistleblower-led allegations that the pharmaceutical giant illegally defrauded Medicaid and other public healthcare programs across the U.S., according to a federal Settlement Agreement unsealed today. Merck employed four schemes to grab or maintain market share for drugs including Vioxx(R), Zocor(R), Cozaar(R), Fosamax(R), Maxalt(R), and Singulair(R), according to qui tam whistleblower lawyers Steven H. Cohen, Mark Kleiman and BethAnne Yeager, who represent the whistleblower, a former Merck district sales manager. Capping a marathon, seven-plus-year investigation among federal and state authorities and the qui tam whistleblower's legal team, the Merck case presents several major legal milestones, according to Cohen, Kleiman and Yeager, including:

-- The first Government recovery from investigation into marketing of Zocor and Vioxx;

-- The first fully-coordinated whistleblower-federal-state Medicaid fraud investigation;

-- The first Medicaid fraud enforcement in which the States, led by Nevada, tested an innovative -- and successful -- prosecution theory;

-- The first federal and state nominal price Medicaid fraud settlement; and

-- The second largest civil False Claims Act ("FCA") recovery to federal and state Medicaid programs.

Although Merck did not admit to wrongdoing, in addition to returning  $400 million to taxpayers, the Whitehouse Station, New Jersey-based drug manufacturer has agreed to be bound by a Corporate Integrity Agreement, according to Cohen, who, along with Yeager is associated with the Whistleblower Action Network in Chicago. "Our relator, a former Merck sales manager, blew the whistle on Merck which resulted in a nationwide investigation by federal and state prosecutors that returned hundreds of millions of taxpayer dollars to the Medicaid program," Cohen said.

"When we realized the extent of the fraud, we took the evidence straight to the Government. Taking on Merck required close coordination and cooperation between us and the state and federal prosecutors. This taskforce approach and unrelenting commitment won a huge victory for the taxpayers." Kleiman said.

"This landmark case exposed abuses of Medicaid's Best Price nominal price exception, and strengthened the Medicaid Rebate program to reduce the states' drug costs," Yeager said.

Aside from the huge settlement, the second largest FCA civil fraud Medicaid recovery, the case marked new ground with a collaborative investigation model that saw the relator and his lawyers work closely with state and federal Government investigators to press the case. This new investigative model, Cohen said, "will become the basis for future qui tam whistleblower investigations, especially in an age of shrinking government budgets."

The FCA, initially sponsored by President Abraham Lincoln to stop military fraud during the Civil War, allows private citizens with knowledge of fraud to help the Government recover ill-gotten gains and additional civil penalties. The FCA allows the Government to collect up to three times the amount it was defrauded, in addition to civil penalties of $5,500 to $11,000 per false claim. Whistleblowers whose cases settle or are won in court usually receive rewards representing 15 to 25 percent of qui tam recoveries.

The federal investigation was conducted by the U.S. Attorney's Office for the Eastern District of Pennsylvania, under the direction of Patrick L. Meehan, U.S. Attorney, Assistant U.S. Attorney Virginia Gibson, Chief of the Civil Division, and Assistant U.S. Attorney Viveca Parker. Parker led the broad investigation, including the review of more than 400 boxes of Merck documents, and fostered the coordinated work of her office, the states, the whistleblower and his attorneys.

At the state level, Nevada Chief Deputy Attorney General Tim Terry, head of the state's Medicaid Fraud Control Unit, worked with the whistleblower legal team on the groundbreaking companion case brought by the State of Nevada and the whistleblower. The Nevada case is part of the of the $400 million global settlement announced today.

Terry and Patrick Keenan, Deputy Attorney General for Illinois, along with representatives from Attorneys' General Offices in Delaware, Massachusetts and Illinois made up the investigation team on behalf of the States' Medicaid fraud units that brought about today's global settlement.

Cohen, Kleiman and Yeager praised the work of the investigation team. "The federal and state prosecutors on this case represent the highest calling of public service, Cohen said. "If it had not been for Tim Terry, Viveca Parker and the rest of the Government team we would not be announcing today's global settlement against Merck."

....reportedly due to sterilization issues at the manufacturing plant.  Is this deja vu all over again? (Think: Chiron 2004) More from the Associated Press.  FDA and CDC will issue more information later this afternoon.  Stay tuned.