Some of those in favor of relaxed reimportation often argue that the drug industry is fear mongering when it points to potential safety problems with drugs or ingredients sourced from abroad. "Be afraid, be very afraid. "  Well, recent events have shown that there is reason for fear....or at least for extreme caution when ensuring the pedigree of any raw materials  sourced from abroad. 

Busy and eventful week.  Michele's on her way to Ireland to visit biotech and pharma labs, and Paul had nice interviews with AstraZeneca's CEO David Brennan and former House majority leader Dick Gephardt. 

Any crime covered by the press inspires a wave of copycats.  So, it seems, the global heparin supply chain will have to be closely monitored for some time.  Both 2-D NMR and capillary electrophoresis have been recognized as the best ways to assess the purity of heparin. Both are beautiful techniques, and yield a lot of information, but they also require highly experienced analysts and expensive equipment. 

On Monday afternoon, a manufacturing and operations discussion group focused on the topic of global competition.  Session chair Julian Wilkins, Vice President of PharmaConsult US, Inc. and a part-time professor of Pharmaceutical Manufacturing at Stevens Institute set the stage with an introduction spelling out the issues and challenges.

The prospect of California's e-pedigree and drug serialization legislation being pushed back to 2015 (from 2009, then 2011) has the industry breathing a sigh of relief, or is it a sigh of frustration? Drug Channel's Adam Fein, back from his self-imposed blog-cation, weighs in. Perhaps most relevant, says Fein, is the fact that California seems deferential to a national track-and-trace system.

But is that national system likely to materialize, driven by FDA? Probably not, says Fein in his Sept. 3 blog entry.

--PWT

The California state assembly has passed SB 1307, a measure that sponsor Sen. Mark-Ridley Thomas says is designed to ensure patient safety, but will in actuality yet again push back the proposed compliance date for drug manufacturers and distributors to meet electronic pedigree requirements to 2015--rather than the 2011 (and 2009) previously designated.

California's inability to nail down a firm compliance date and hold manufacturers' feet to the fire will certainly heighten calls for federal pedigree legislation. More to come . . .

--PWT

At the American Chemical Society national conference last weekend, Rensselaer Polytechnic researcher Dr. Robert Linhart announced that his team may have built the first fully synthetic heparin. Whether or not you believe that the possibility of another contamination crisis of natural raw heparin exists, the potential for a heparin supply independent of the whims and worries of the global supply chain, not to mention the global pig population, is certainly welcome news.

Is synthetic heparin feasible on a large scale? Yes and no, says one of Linhart's collaborators, professor Jian Liu at the University of North Carolina. The science is there to produce synthetic heparin at the milligram level, and almost there to produce it at the kilo level, Liu told me this morning. But a lack of investment and low market incentive may collude to limit the short-term outlook for engineered heparin.

"We need someone who's willing to serve as partner to expedite production," Liu says. Right now, the researchers are talking with several smaller biotech firms about development for clinical trials. They have not yet been approached by larger pharma companies.

Synthesizing heparin involves introducing sulfa groups into polysaccharides derived from E. Coli bacteria, Liu says, in order to produce an key enzyme for heparin production. The cost of this process is 10 to 100 times less than making heparin from human enzyme, Liu says.

There are a couple technical issues to be worked out before synthetic heparin could be produced at greater rates, much less at a rate to satisfy the current market demand of 30 to 40 tons per year. The first, says Liu, would be improving the yield of the starting materials. The second would be scaling up the current lab procedures to an industrial level--an "engineering problem," says Liu.

And there are financial issues. Even though heparin prices have risen this year to more than $5,000 per kilo, the cost is not prohibitive to warrant a major push towards an alternative. The incentive is not there.

Unless another crisis occurred. While Liu and colleagues certainly don't wish for this, the impetus for their research, which began in 2005, was that the heparin supply is vulnerable. Three main factors are involved in control of the supply, Liu notes: the global pig supply, the heparin harvesting and purification process, and the analytical control. While measures by FDA, other regulatory bodies, and heparin suppliers and manufacturers to establish greater control have been "pretty impressive," according to Liu, the current way of making heparin will always be vulnerable to environmental (e.g., porcine disease) and human (e.g., purposeful adulteration) factors.

Liu likens maintaining control of the heparin supply to maintaining antidoping procedures for Olympic athletes. "You have to know what you're looking for," he says. But just as athletes find ways to circumvent drug tests, there may always be heparin contaminants that will fall outside of materials inspection parameters.

Synthetic heparin created in a GMP environment from fermentation to packaging would certainly eliminate these concerns. The best-case scenario, however, is that synthetic heparin could be ready for patient use within 4-5 years, Liu says. But this is only if there are investment dollars for development and production scale-up.

Pharmaceutical Manufacturing, PharmaManufacturing.com, and On Pharma have been covering, and analyzing, the heparin case since it began. In September, we'll take a closer look at the lessons learned from the heparin crisis, and what all manufacturers must do to ensure safe and efficient supply lines.

--Paul Thomas

At a meeting at DIA in Boston yesterday, Mike Svinte, President of Global Life Sciences at IBM provided a sneak peek and insights into a new report probing CEO challenges and concerns and their implications. The report, which is due to be released next month, will distill interviews with more than 1,100 CEOs from around the world, 40 of them heading life sciences companies, including mid-sized companies, in North America, Europe and Asia. Not that their individual names can or will be disclosed, but the CEO’s appeared very willing to engage in open dialogue and creative discussion of issues. "The interviews were a bit like therapy for some,” Svinte said.

Nearly a quarter of the life sciences CEOs interviewed admit that they have had no, or only minimal success at managing change within their organizations.  At the same time, IBM analysts found, they are hungry for change.  The study suggests that CEOs need to “seed” their organizations with challenges and to gain inspiration by examples from other industries that have already undergone transformation. They will then need to convince their companies that change is necessary, and cultivate enthusiasm for it

IBM’s research shows that life sciences companies’ financial performance tends to be better when CEOs encourage change and invest in new areas, Svinte said. The questions are where to invest and why, and how will pharma’s industry model and business model need to change for the future. Will pharma companies be the "dinosaurs" predicted years ago---holding companies that outsource all key functions?

Not enough CEO’s have actively wrestled with these questions, the survey suggests.

Talent shortages top the list of their concerns---63% of pharma CEOs named this the major problem (compared with 48% in other industries. Regulatory issues, as one might expect, came in second (53% vs. 45% for other industries).

One factor driving change, CEO respondents say, is a better informed consumer, who demands more as he or she pays more."We’re experiencing increased pressure related to environmental initiatives,” wrote one anonymous CEO from
North America.“Transparency is being driven by the government as well as by consumers. There is great risk in not focusing on rising consumer expectations."

As pharma moves from the old multinational model to a globally integrated one, Svinte said, issues of global regulation, intellectual property protection and talent shortages in India, China and other regions of the world may pose risk but more CEO's say they are investing there.

Three quarters of pharma CEOs are pursuing innovations in business models. More than half are focused on enterprise model innovation or reconfiguring the breakdown between what work is done inhouse and what is outsourced. Only 17% were focused on new industry model innovations, including those that will involve diagnostics and targeted or personalized medicine, and will require new revenue and enterprise models.  Among blue sky possibilities discussed was the concept of consumers paying for a therapy only if it worked.  (Ha! Don’t hold your breath waiting for this to happen – brief editorial interjection)

62% of the life sciences CEOs surveyed also see rising expectations of corporate social responsibility as a positive, rather than a negative one. But nearly a quarter of respondents don’t expect such work to have any impact on their corporate bottom lines. IBM analysts suspect that new dimensions of corporate responsibility may not yet have reached pharma CEOs’ radar screens.Pharma CEO’s may recognize the drug industry’s duty to “do no harm,” but they may not be able to measure the footprint that pharma has on society, analysts suggest, pointing to the issue of drug residues in the world’s municipal water supplies.

Knowledge management and the drive to turn data into information are becoming more important to a growing number of CEOs, the study found, since these establish a framework for more collaboration and cross-functional product development.

Manufacturing and supply chain management are becoming a priority for more CEO’s, Svinte said, although they were not probed in depth, by themselves, in this survey.

Among other subjects that came up at this discussion was IBM’s patient-centered healthcare project,

Also talked about was the MidEast Consortium on Infectious Diseases, a program underway in the
Middle East that is using supercomputers to predict future pandemics and the potential impact of changes within patient population.

Look for more detailed reporting on the research and trends in future issues of our magazine and online.

And now for something completely different (for any opera fans or Italophiles out there).

AMS

Ever see the old Abbott and Costello "who's on first" baseball routine?  "I don't know" was on third base.

Pharma is not the only industry that suffers from less-than-perfect supply chain risk management, as Juran Institute CEO Joe De Feo pointed out in a recent audio interview. 

As the heparin tragedy has pointed out, many companies may not be aware of who their second- and third-tier suppliers are, especially when there are shortages of raw materials and a first-tier supplier opts to buy material on a spot basis or to work, temporarily,  with a new source. 

How well does your company know its business partners---all of them?  Drug industry professionals, please take a few minutes to respond to a new survey we've developed with experts from Marsh Consulting Group, to benchmark drug company supply chain risk management.  Results will be kept strictly confidential---and, besides, you can also use an alias and your hotmail address for an additional layer of security.

Marsh will interpret results in September's issue.

Established compendial tests are inadequate (topic for an upcoming article) for assessing intentionally adulterated material ---just as we never factored in the potential for suicide bombers in national security plans, we may never have suspected that so many people would intentionally profit from counterfeit drugs.  USP and FDA have been meeting for the past few months to change that, and to specify the use of advanced analytical techniques---USP is also developing standards for  process analytical technologies (PAT) and incorporating PAT into its framework.

(Recent news reports find that drug counterfeiting is dramatically on the rise, and Nigeria's brave Dr. Dora Akunyili , head of FDA-equivalent NAFDAC has reportedly asked for life prison terms for offenders (read on for more).  Stiff penalties are allegedly on the books in India.  Even Peru has reportedly instituted 10-year prison sentences for offenders---more here.) .

AMS

Greetings from Las Vegas, all, where PackExpo is in full swing.  I haven't been able to see many booths yet, but I've heard presentations from David Ray at Parsec Automation and Bob Naegle at Videojet, each of which was exciting in its own way.

Ray gave a thorough explanation of how Parsec's real-time process management software can help manufacturers determine Overall Equipment Effectiveness (OEE). He provided enlightening examples of how seemingly minor problems in efficiency or availability can quickly lead to significant production losses, and conversely, how much extra money a small gain in OEE can generate over a one-year period. Ray is a Six Sigma Black Belt, so he isn't just selling a product.

Naegle detailed Videojet's new line of track-and-trace solutions, developed through the company's recent acquisition of Prism, a data management software provider. The Prism software leverages Videojet's marking and coding capabilities to create sets of unique codes with parent-child relationships between codes used at the package, case and pallet level for ultimate traceability. The flexible system allows pharma manufacturers to specify their preferences for alphanumeric code, serial 2-D codes or complex 2-D codes, to upload the software to their own or Videojet-provided computers, and to use internet-based programs to track when and where those codes are scanned. This system seems promising both for anti-counterfeiting and anti-diversion as well as for product recalls.

More to come; time to head to another meeting. 

-HP