Michelle Hoffman, editorial director of Pharmaceutical Technology.

Michelle Hoffman

Several years ago, I asked my doctor to give me a genetic test to see whether I carried a mutation predisposing me to develop a particular disease. My concern stemmed from the fact that I belong to a demographic with a higher incidence of predisposing genes than the general population. Because I had no other risk factors for the disease, he advised me not to take the test. The reason? He was concerned that if I tested positive for the mutation and then later developed the disease, I could be refused health insurance because I had a "pre-existing condition."  

I thought he was joking at first. Yes, yes, I replied, very funny. Obviously the mutation pre-existed the condition. But the same could be said of diabetes, certain heart conditions, cancers, Parkinson's, and so on. Were the insurance companies really going to deny insurance to everyone whose illness arose from some genetic mistake? Ultimately, science was going to decipher the gene or genes that predisposed all of us to some condition or another. And in that case, who could get insurance?  

It turns out my doctor was not the only one concerned about preventing genetic discrimination by insurers and employers. For the past five years, Congress has been trying to pass some form of a genetic information nondiscrimination act. Most recently, the 2007 version passed in the House this April by a vote of 420 to 3. But the need for such legislation is not apparent to everybody, it seems. 

On March 8, in a hearing before the US House Energy and Commerce Committee's Subcommittee on Health, Burton J. Fishman of Fortney & Scott, LLC, speaking on behalf of the Genetic Information Nondiscrimination in Employment Coalition, an employer group, called the bill a "remedy in search of a problem," according to a press release issued by the Genetics & Public Policy Center (GPPC). Burton went on to argue against a law "that imposes real burdens and actual costs based on distant, contingent eventualities...." 

Not so hypothetical, countered Karen Pollitz, who conducted a study as a research professor at the Georgetown University Health Policy Institute. In her study, Pollitz asked insurance providers to evaluate the insurability and premiums for hypothetical applicants. Of the 23 companies surveyed, said the GPPC release, 5 indicated they would take an adverse action (denying coverage, charging more for premiums, or excluding certain conditions from coverage) on the basis of genetic test results.  

The bill is now in the Senate, where it is expected to pass—if it ever comes up for a vote. Senator Tom Coburn (R–OK) has put a "hold" on the bill, which can delay the vote indefinitely. According to a report published on Aug. 8, 2007, at 

 the Senator wrote in an Aug. 1 letter to his constituents that he believes the bill, as drafted, "contains unintended consequences." The Senator's letter went on to say that it was lack of precision and not the overall purpose of the bill that he found objectionable. We emailed the Senator asking him to enumerate his specific concerns, but at press time, we had not yet received an answer. 

Without further elaboration, we can't know what unintended consequences the Senator fears. But we can imagine the grave consequences that a failure to pass the bill might have for the pharmaceutical industry. The industry is now moving toward targeted therapies; therapies aimed to treat specific subsets of individuals in a disease population. And more often than not, the likelihood of an individual benefiting from a particular therapy, where others afflicted with the disease will not, will be determined by a genetic test. How ironic then, that the very genetic test that suggests an individual would respond favorably to a certain course of therapy might also preclude that individual from taking the drug, because it shows that the individual has a pre-existing condition.  

I took my doctor's advice, by the way, and declined to take the test. But if the Genetic Information Nondiscrimination Act is passed, I certainly will.  

Articles

In an age of "pre-existing conditions," can a new bill help patients get the treatment they need?

It's in the Genes

 announced today that a consent decree filed against the company in May 2002, had been dissolved by the US District Court for the District of New Jersey in Newark. The 

   enjoined the company from manufacturing, packaging, or distributing some 42 products in its Kenilworth and Union, New Jersey, plants and another 13 products in its plants in Manati and Las Piedras, Puerto Rico, because of violations of 

’s good manufacturing practices. The company, then under the direction of CEO Richard J. Kogan, was also directed to recall and destroy all lots of Theophylline and Proventil Repetabs in the United States that were still within their labeled expiration periods. Finally, the government levied stiff fines against the company totaling $500 million.

On January 3, 2006, the company announced it had completed all of the 212 significant steps and the 30 validation actions set out by the decree. At the time, the company petitioned the government to dissolve the decree and allow them to reopen the plants.  

statement issued through a company press release

, Fred Hassan, Schering-Plough’s chairman and CEO responded to the dissolution by saying, “This is an important milestone for Schering-Plough as we continue to put issues of the past behind us and make further progress on our Action Agenda. Schering-Plough colleagues have worked hard to establish continuous quality improvement and compliance as part of our culture. In turn, we have been working diligently to earn the trust of our stakeholders. Ensuring quality in our products and systems underpins everything we do.”

Schering-Plough announced today that a consent decree filed against the company in May, 2002, had been dissolved by the US District Court for the District of New Jersey in Newark.

Court Dissolves Schering-Plough Consent Decree

There he goes again. On June 20, 2007, President Bush vetoed a bill that would provide government funds for embryonic stem cell research. This is the second time (and only his third veto) the president has vetoed such a bill. The first time was less than a year ago, in fall 2006. 

The president's position has been consistent. "Destroying human life in the hopes of saving human life is not ethical," he said at a press conference on the day of the second veto. This has been his reasoning all along, and it reflects a religious belief that human life starts at the moment of conception—with the creation of the embryo—and that destroying an embryo is tantamount to taking a human life.  

Much of the debate around stem cell research has focused on the validity of that assertion. But that approach is unproductive. It is clear that the president and others are quite sincere in their belief of the humanity of the embryo, and that no amount of debate will change that. One might also mount an argument about whether a leader of a religiously pluralistic and democratic nation has the right to make decisions on personally held religious beliefs. But those who voted for George W. Bush elected a president who made it clear he'd be guided in public policies by personal religious principles—so it's disingenuous to express surprise and a bit late to express voter's remorse. 

Many of the president's followers argue that embryonic stem cell research has to date provided no therapies. Well, is that really surprising when the research has received no government funding for the past seven years? True, there is private funding for this research. But what most people don't know is that the ban on federally funded embryonic stem cell research also bans researchers from using laboratory facilities that receive any federal funds—even if the research itself is privately funded. And that means that a good deal of private money must be spent on building research facilities—facilities that duplicate ones already in existence—in which to perform embryonic stem cell research. Such facilities, and the equipment that goes into them, are extremely expensive and soak up a good deal of that private funding before they can house even a single embryo. 

The president himself is persuaded that there exist ethical alternatives to embryonic stem cell research. Indeed, at the same time he vetoed the embryonic stem cell bill, he signed an executive order, which, in his words, "strengthen our nation's commitment to research on pluripotent stem cells."  The order, he says, "directs the Department of Health and Human Services and the NIH to ensure that any human pluripotent stem cell lines produced in ways that do not create, destroy, or harm human embryos will be eligible for federal funding." In other words, the president is encouraging (but not providing additional funding for) the use of technologies that derive cells with the same capacity for growth and differentiation as embryonic stem cells. The problem is that without research on embryonic stem cells, how do we judge the biological or therapeutic equivalence of the "ethically derived" pluripotent cells?  

Maybe the only way to fight the veto is to assail the logic of the president's argument—that destroying human life in the hope of saving human life is not ethical. But the president is presenting a false dichotomy. Failing to fund embryonic stem cell research is not the moral equivalent of saving embryos—or, to use the president's rhetoric—human lives. But it does fail to alleviate suffering of other human lives. The embryos targeted for research purposes would otherwise be destroyed—thrown out—whether or not the research is federally funded.  

So the choice comes down to this: Either break apart the embryos and culture the individual cells into ones that may someday be the basis for medical therapies, or simply destroy the embryos—to no one's benefit. In other words, do we destroy human life to save human life? Or do we destroy human life for no good reason at all? 

By vetoing stem cell research funding, the President is vetoing potentially life-saving treatments.

A Moral Decision, A Vital Consequence

I was in business school for the peak of the Internet frenzy, so the effect of the Internet on business practices and the economy was a frequent topic for classroom discussion. At the time, every retailer on earth it seemed was scrambling to develop an online purchasing option. But it didn't take long for many of those early online retailing attempts to fail.  

One of my professors suggested that retailers who were just slapping up online interface were neglecting to develop the sales and distribution infrastructure to support online retailing. So, while orders might have poured in over the Internet, retailers hadn't put in place the extra personnel required to fill the orders. Missing were the personnel to package and ship merchandise. Retailers had also failed to make the necessary arrangements with their shippers to accommodate all of the extra outgoing mail. The net effect was that orders arrived late (or were inaccurately filled, or both). This was particularly devastating during the Christmas holiday season, when holiday presents ordered over the Internet arrived at their destinations long after the holiday was over. Both consumers and sellers felt burned and retreated for a while from online retailing.  

Participate in the annual Pharmaceutical Technology Employment Survey.			

Looking back, the lesson seems so obvious but apparently wasn't at the time, or more retailers would have planned appropriately. 

This story may serve as a cautionary tale for the outsourcing industry. This year's survey indicates that drugmakers large and small expect to increase their use of contracted services—a substantial boon for contractors. About a quarter of service providers who responded expect their revenues to grow by 20% or more. But as Jim Miller notes in his cover story, this rapid growth may be straining contractors' resources.  

"This is especially true for basic infrastructure capabilities like customer service and project management," writes Miller. Is this starting to sound familiar? Of particular (and particularly ominous) note for service providers, the survey uncovers a  gap between customer and service provider definitions of service excellence," Miller notes.  

So, sellers beware! All evidence indicates that the outsourcing industry will continue to grow—unless, of course, it gets trapped in a bubble.  

Infrastructure must be in place before jumping into outsourcing.

From Boon to Bubble?

 earlier this month advises companies on how to treat polymorphic drug compounds-those that exhibit multiple structural forms-in filing abbreviated new drug applications (ANDAs). The bottom line, according to the guidance, is that generic drug products containing the polymorphs be the “same” as the reference listed drug (RLD) in active ingredients, bioavailability, and bioequivalence. The guidance pertains to orally available drugs that are either solid- or suspension-dosage products.

Polymorphisms arise when compounds are identical chemically, but not structurally. This can happen when two solids take on different crystalline forms-such as graphite and diamond; when molecules are disordered and fail to produce a repeatable crystal lattice, as is the case for the molecules in glass; or when solvent is trapped inside the crystal structure-as in hydrates, where water molecules are found within crystals. The guidance notes that different polymorphisms may alter physical properties of compounds and affect their solubility, which in turn can alter their bioavailability or bioequivalence. In addition, polymorphic forms of a compound may alter the way the compound behaves during production, which again, may alter the finished drug’s biological activities. On this latter point, the guidance specifically states, “Since an ANDA applicant should demonstrate that the generic drug product can be manufactured reliably using a validated process, we recommend that you pay close attention to polymorphism as it relates to pharmaceutical processing.”

The guidance also emphasizes the effect polymorphisms may have on drug stability, which again, may alter the drug’s biological activity.  But the guidance goes on to say that “it is the stability of the drug product and not stability of the drug substance polymorphic form that should be the most relevant measure of drug equality.” Otherwise, a generic drug can be considered the “same” as the active ingredient in an RLD if the generic compound conforms to the standards set out in a United States Pharmacopeia (USP) monograph, if one exists for that particular drug substance. These standards generally include the chemical name, empirical formula, and molecular structure of the compound. However, the “FDA may prescribe additional standards that are material to the 

 of a drug substance.” But as concerns polymorphisms, the guidance goes on to say “…differences in drug substance polymorphic forms do not render drug substances different active ingredients for the purposes of ANDA approvals….” Finally, the guidance reminds ANDA applicants that the biological performance characteristics of a drug are also dependent on the drug’s formulation and advises applicants to consider the properties of both the drug substance and formulation excipients, when assessing “sameness.” For the full guidance, click 

A new guidance issued by the US Food and Drug Administration earlier this month advises companies on how to treat polymorphic drug compounds?those that exhibit multiple structural forms?in filing abbreviated new drug applications.

New FDA Guidance on Polymorphic Compounds in Generic Drugs

More than  five million US adults import prescription drugs from other countries, according to a survey conducted by the 

Pharmaceutical Research and Manufacturers of America

 (PhRMA). Concerned over the number of counterfeit drugs entering the US, PhRMA launched the survey to determine who was importing prescription drugs and why.

The survey shows that importers tend to be under 35, a bit younger than nonimporters, and they are more likely to be Hispanic and come from southern border states than are non-importers. Contrary to popular wisdom, adults purchasing drugs from other countries do carry health insurance. Approximately 85% of the importers have policies with prescription drug insurance. However, importers typically spend more money out of pocket on prescription drugs during a 12-month period than do their non-importing counterparts. Seventy-one percent of importers with medical coverage said their prescription-drug beneift was insufficient to cover their needs. In spite of these statistics, and quite unexpectedly, the survey also demonstrated that one in five importers has an annual income of $100,000 or more.

The top reason for drug importation was, not surprisingly, price, a motivator for more than 85% of the importers. More surprising, about half the importers lacked prescriptions for the drugs they wanted. The prescription drugs most often imported include drugs for infections requiring antibiotics, pain, allergies, hypertension, digestive problems and high cholesterol.  

While Canada is the single leading country exporting drugs to the US, Canadian drugs account for less than half of all drugs coming from overseas. The majority of drugs came from other countries, or the importers were uncertain as to the country of origin of their imports. 

In a statement published on the PhRMA website, the organization’s President and CEO, Billy Tauzin said, “This study further confirms what the Food and Drug Administration has been saying all along – millions of Americans are circumventing the system and going to other sources to buy their medicine because they do not have a doctor’s prescription for the medicine they want. Alarmingly, this behavior increases an individual’s risk to being exposed to dangerous counterfeit medicines.”

More than five million US adults import prescription drugs from other countries, according to a survey conducted by the Pharmaceutical Research and Manufacturers of America.