In 2001, Gladys Mensing began taking metoproclamide, a generic version of Reglan, to treat a stomach disorder. No branded versions of the drug had been available since the mid 1980s. After taking metoproclamide for four years, Mensing experienced early symptoms of tardive dyskinesia, an untreatable neurological disease. She no longer can live independently or control the muscles in her tongue, face, arms, and legs.

When Mensing began taking metoproclamide, the generic drug’s label matched that of the branded manufacturer. In 2009, FDA required generic manufacturers to include a warning that long-term use of the drug carried a 20% risk of causing tardive dyskinesia. Mensing’s lawyers argue that medical studies had identified this risk well before 2001, when she began taking the drug, but that generic manufacturers had shirked their duty to alert FDA about it.

Attorney Jay Lefkowitz told the Court that if makers of generic drugs complied with strict state consumer laws by labeling their products different from the way innovator companies do, they would be violating federal law. Unmoved by this argument, Justice Ruth Bader Ginsburg observed that state laws are not at odds with federal law, they complement it.

Justice Samuel Alito wondered about the financial consequences of requiring generic-drug manufacturers to monitor for adverse events and inform FDA of them. “I don’t know whether this is a good idea or not, but it does seem to me that it may significantly increase the costs for generic drug manufacturers, and therefore counteract one of the objectives of the statute, which was to provide generic drugs at a low cost,” he said during arguments.

Justice Alito may have a point, but surely we should not overlook another objective of the law, which is to ensure that drugs are safe. The idea that the manufacturer of a generic drug can create and distribute a product without any responsibility for understanding it or ensuring that it does not harm its users is quite hard to swallow, in my opinion.

More than 70% of prescriptions filled in the US are generic drugs. The Court’s decision is expected in June, and it will surely affect a large section of the industry, one way or the other.

The Justice Department charged that AstraZeneca improperly influenced the content of continuing medical-education programs that it sponsored so that it could promote unapproved uses of Seroquel. The US also alleged that, in an attempt to influence physicians’ prescribing habits, AstraZeneca paid doctors to give promotional lectures to other healthcare professionals about unapproved uses of Seroquel. Such payments violated the federal Anti-Kickback Statute, according to Justice.

In addition, Justice alleged that AstraZeneca paid to use doctors’ names as authors of articles that were ghostwritten by medical-literature companies. The articles described studies that the doctors had not conducted, and they formed the basis for promotional messages about unapproved uses of Seroquel.

In a press statement, AstraZeneca denied these allegations but noted that it had entered into a five-year corporate integrity agreement with the US Department of Health and Human Services’s Office of the Inspector General.

The alleged AstraZeneca payments are quite similar to the kinds of payments that drugmakers would have to report under a transparency bill in Connecticut. As I noted last week, Pfizer (New York) is fighting the Connecticut bill, but similar provisions are already part of federal law.

The public does not appear to be on Pfizer’s side. According to an analysis of previous studies that the Journal of the American Medical Association published last week, a majority of patients and research participants believe that financial relationships between medicine and industry should be disclosed because they may influence research and clinical care. “In clinical care, patients believed financial ties decreased the quality and increased the cost of care,” according to the authors of the analysis. “In research, financial ties affected perceptions of study quality. In two studies, readers’ perceptions of journal article quality decreased after disclosure of financial ties,” said the authors.

Bills like Connecticut’s seem to enjoy broad support, and news of AstraZeneca’s settlement might strengthen it. I think that companies such as Pfizer should overcome any reservations they might have about reporting payments to physicians. They stand to gain the public’s trust, which is a valuable commodity in a competitive market.

The bill, SB-270, would require drugmakers to adopt a marketing code of compliance that, among other things, forbids them from buying meals for doctors at continuing-education events and from compensating doctors for attending such events. The bill also would require transparency in pharmaceutical companies’ interactions with healthcare providers. The General Assembly’s Public Health Committee has approved SB-270, and the bill awaits approval by the full Assembly.

In an interview with Connecticut newspaper The Day, Liz Power, a Pfizer spokeswoman, said the bill would hinder the relationship between doctors and the company’s field representatives, who provide “critical information about prescription medicines” to busy doctors. I don’t see how the bill would reduce sales representatives’ ability to convey information about their drugs. Surely they can do that without giving doctors gifts.

The employees who visited Hartford asserted that the bill would discourage drugmakers from doing business in the state. This claim might be grounded in Power’s statement to The Day that the bill would be expensive to implement. But the bill echoes the rules laid out in the Physician Payments Sunshine Act of 2009, which was signed into law in March 2010 as part of Congress’s healthcare-reform legislation. Indeed, Power told The Day that many of SB-270’s proposed regulations overlap with new federal requirements. As long as the reporting requirements and restrictions on gifts to doctors are part of federal law, it’s hard to see what Pfizer would gain by moving from Connecticut to, say, Utah.

By fighting what seems like a reasonable attempt to ensure transparency in relationships between doctors and drug companies, Pfizer ends up looking like it wants to use questionable techniques to persuade physicians to prescribe its drugs. I don’t see how the bill would cost the company a significant amount of money, especially if Pfizer will have to comply with similar federal rules anyway. For the same reason, I’m equally puzzled about how the bill could influence Pfizer to transfer jobs out of Connecticut.

So far, the company has not given clear explanations about how SB-270 would interfere unfairly with its operations or harm its bottom line. Unless the company makes a more convincing case, its resistance to the bill will seem like much ado about nothing.

Last month, US Food and Drug Administration Commissioner Margaret Hamburg announced the agency’s six-point plan for tougher enforcement of its policies and regulations as means of protecting public health. The plan, which includes actions like setting postinspection deadlines, speeding the Warning Letter process, and working more closely with FDA’s regulatory partners, was designed to “to prevent harm to the American people,” as Hamburg said in an FDA release. 

The agency has been actively involved in several recent cases involving instances of illegal importation and sales, drug diversion, and misbranding of drug products. FDA’s Office of Criminal Investigations has conducted investigations and partnered with other government offices when necessary.

From the United States Attorney’s Office, District of New Hampshire
On July 27, 2009, Christopher Chase, of Lynn, Massachusetts, was sentenced to three and a half years imprisonment and three years of supervised release for his involvement in an Internet prescription drug scheme that distributed anabolic steroids, human growth hormone (HGH), insulin-like growth factor (IGF-1), and clenbuterol throughout the United States. A two-count indictment charged Chase and two codefendants with conspiracy and money laundering. 

According to the indictment, Chase and his team illegally imported the drugs from overseas, primarily China, marketed them as body-building substances, and sold them without a prescription on various websites. Of course, FDA has not approved anabolic steroids, HGH, or IGF-1 for use in body-building activities, and clenbuterol is not approved for use in humans by FDA. Although some countries have approved it as a prescription-only bronchodilator, clenbuterol is known to be abused by bodybuilders for its weight-loss properties, according the the Department of Justice. The money from the sales of these drugs was sent to various merchant bank accounts that Chase had set up, and then laundered through foreign countries such as China and Moldova.  

FDA’s Office of Criminal Investigations worked with US Immigration and Customs Enforcement, the US Postal Inspection Service, and the Internal Revenue Service, Criminal Investigations office on the case.

From the United States Attorney’s Office, Southern District of Florida
Last month, Arnesto Segredo was convicted of conspiring to divert the prescription HIV drug Serostim (somatropin [rDNA origin] for injection, EMD Serono, Rockland, MA) and Nutropin AQ (somatropin [rDNA origin] injection, Genentech, South San Francisco, CA), which is approved for the treatment of growth hormone deficiency, and one count of causing the diversion of these drugs in interstate commerce.

Segredo used unlicensed California-based suppliers to ship hundreds of boxes of Serostim, and some Nutropin AQ, to him in Miami from 2000–2002. He operated a prescription drug wholesaler that was not licensed to engage in the distribution of prescription drugs in Florida from 2000–2001. Segredo later ran his scheme through Genendo Purchasing Organization, a Miami-based prescription drug wholesaler that became licensed in Florida in July 2001. According to a press release from the US Attorney’s Office, a significant portion of the Serostim originated from California-based AIDS patients who sold their Serostim supplies secured from the Medi-Cal Medicaid program. The drugs were shipped from the California-based unlicensed suppliers to Segredo in Florida.

Sentencing is scheduled for October 23, 2009 in Miami. FDA’s Office of Criminal Investigations conducted the investigation.

From the United States Attorney’s Office, Northern District of New York
In a case involving the misbranding of drugs by physicians, The Plastic Surgery Group (TPSG, Albany, NY) pleaded guilty in early August to one felony count of misbranding drugs, and five physicians, the practice administrator, and the supervisory nurse of TPSG also pleaded guilty to strict-liability misdemeanor misbranding violations. In 2004, TPSG misled patients by injecting them with the unapproved product TRI-toxin (botulinum toxin type A) manufactured by Toxin Research International (Tuscon, AZ) instead of the FDA-approved brand Botox Cosmetic (botulinum toxin type A) manufactured by Allergan (Irvine, CA) patients believed they received. Patients not only believed they were getting Botox injections, but paid Botox prices for the cheaper and more dangerous unapproved drug TRI-toxin that TPSG administered.

TPSG faces a fine of up to $500,000 and an order to pay restitution to about 150 patients, who paid approximately $100,000 for the phony Botox injections. The individual defendants face up to one year in prison and fines of up to $100,000. Sentencing is scheduled to take place on Dec. 10, 2009. FDA’s Office of Criminal Investigations conducted the investigation of this case.

These cases are examples of FDA’s efforts to protect consumers by stemming the flow of illegal or adulterated substances. Increased enforcement of FDA’s regulations, especially in the face of rising of illegal activity concerning prescription drugs online, will help to protect public health. As Hamburg said, “The FDA must be vigilant, the FDA must be strategic, the FDA must be quick, and the FDA must be visible.”

UnitedHealth Group, a Minneapolis-based healthcare company, recently announced that it would soon provide a price break to members who correctly use certain asthma and antidepressant drugs. The news was reported in a Wall Street Journal article by Peter Loftus of Dow Jones Newswires.  

To get the $20 copay discount, members must refill their prescriptions within about 30 days after their last prescription runs out. Eligible drugs include GlaxoSmithKline’s Advair, AstraZeneca’s Symbicort, Eli Lilly’s Cymbalta, Wyeth’s Effexor XR, and Wyeth’s Pristiq. The discount applies to members who have a normal copay of $50 on these drugs, meaning the new copay would be $30, according to Loftus’ article.

The idea of rewarding patients who adhere to their prescribed medications is a win-win situation. The patient is able to continue his drug regimen and get the treatment he needs—while saving some money. In the current economy where some patients are discontinuing their prescriptions because of cost, this financial motivation is especially important. The insurance company is able promote the patient’s health and, theoretically, save money in the long run by preventing the patient from becoming more sick and then requiring additional medical care or medication.

Asthma and antidepressant drugs make perfect sense for this type of plan because a lack of necessary medication or a gap in a medication regimen can negatively affect the patient’s health. If this plan works, UnitedHealth and other health insurance companies may consider expanding the program to those individuals on medication for diabetes and other long-term conditions that need to be controlled in order to reduce the risk of complications. 

Strong opposition can block legislation quite effectively, as Sen. John McCain (R-AZ) recently discovered. A Senate Committee defeated his amendment to allow the reimportation of prescription drugs when McCain tried to append it to the “Affordable Health Choices Act.” And the amendment was withdrawn from the “Family Smoking Prevention and Tobacco Control Act” before that.

Likewise, an approval pathway for follow-on biologics that does not contain 12 years of data exclusivity will face stiff opposition from BIO. Rep. Henry Waxman’s (D-CA) “Promoting Innovation and Access to Life-Saving Medicine Act” has faced criticism from Congress and industry alike. At first blush, you might predict its fate to be similar to that of McCain’s drug-reimportation amendment.

But, as Senior Editor Patricia Van Arnum noted, the White House has signaled its preference for an approach similar to Waxman’s. BIO called the approach a “risky short cut to biosimilars” and will undoubtedly be bending lawmakers’ ears about its preference. Nevertheless, the Presidential imprimatur could make a great difference. President Obama remains widely popular and might have enough political strength to draw the Congressional support he needs to codify his vision for follow-on biologics.

When a patient chews, crushes, or dissolves immediate-release opioid formulations, it exposes the entire active-ingredient dose and enables the drug to be injected or snorted. Taking oxycodone this way produces a high concentration of the drug in the blood quickly and increases the chance that the patient will abuse the drug or become addicted.

Atlantic Pharmaceuticals (Atlanta, GA) wants to use its Smart/Script oral delivery technology to deter oxycodone abuse. Loading a drug into the Smart/Script technology renders it noncrushable and nonextractable in common injectable solutions, according to the company’s website. Smart/Script protects the drug until it reaches the gastrointestinal system, where it is released.

I think Atlantic is on the right track. Tracking drug shipments, restricting medicines’ availability, and other regulatory approaches could certainly help reduce drug abuse. But using formulation or drug-delivery techniques seems like a way of nipping drug abuse in the bud. A problem of this magnitude calls for a multipronged approach, and it encourages me to see that pharmaceutical companies are using ingenuity to develop creative solutions.

What’s Big Pharma to do?

“Put its shoulder to the wheel and develop new drugs,” some innovator companies might answer. Take Pfizer (New York), for example. The company said it achieved its goal of advancing 12 new molecular entities (NMEs) into late-stage development by March 2009. The heavyweight hopes to increase its Phase III pipeline to 24–28 NMEs by December 2009 and file 15–20 regulatory submissions from 2010 to 2012. Pfizer’s absorption of Wyeth’s (Madison, NJ) research and development (R&D) department might give the company an advantage.

But other data in the Wolters Kluwer Health analysis raise the suspicion that a supercharged R&D effort won’t necessarily save innovators’ bacon. Last year, the rate of prescription abandonment jumped 34% over the 2006 level (a prescription is abandoned when a patient fails to pick it up from the pharmacy). The greater the copay, the greater the likelihood that a prescription will be abandoned, says the report.

The data suggest that the battered economy is a major factor behind increased sales of generic drugs. And the economy is one problem that innovator companies are probably not equipped to solve. Might Big Pharma become more and more involved in manufacturing generics?

Last Tuesday, lawmakers in the state of Washington considered a bill that bans drug companies from buying patients’ prescription records for marketing purposes. A woman testified before the state House’s Health Care Committee about being contacted by pharmaceutical marketers. After she switched from a branded drug to a cheap generic alternative, marketers attempted to persuade her to use a new version of the branded drug (for which there was no generic equivalent) instead.

The bill would prohibit this kind of contact, ostensibly making it easier for the state to save money on prescription-drug reimbursement. But an equally important effect would be to maintain patients’ privacy by keeping medical information away from pharmaceutical companies.

The bill seems to have momentum. One Washington legislator opposed a similar bill aimed at protecting doctors’ privacy, but supports the new patient-oriented bill.

As I said in regard to a similar New Hampshire law, I believe drug companies are entitled to perform market research to stay competitive and innovative. Yet I think few of us would want our personal information open to public scrutiny. I think the Washington bill and the New Hampshire law strike the right balance between promoting pharmaceutical industry and protecting individual rights.

Two new studies highlight the steps-some of them too risky-that patients are taking to protect their pockets from totally emptying.

One study from the Center for Studying Health System Change reports that one in seven children and working-age Americans went without a prescription drug in 2007 because of cost concerns. That number was one in 10 in the year 2003. The same study found that one in four working-age adults (19-64) with a chronic condition reported unmet prescription drug needs in 2007. And those with low incomes or uninsured, points out the report, were even more vulnerable.

The second study, a newly released Harris Poll , reports that as of December 2008, 81% of adults surveyed would choose a generic drug over a brand name drug. That percentage was 68% in October 2006. Other Harris Poll findings show that consumers have been turning to discount stores such as Wal-Mart and online companies to purchase their drugs. The use of local independent pharmacies decreased from 12% to 8% between October 2006 and December 2008.

As a consumer, I can understand changing one’s shopping habits to find lower-priced drug options or selecting a generic drug over a brand name drug when one is available. But it doesn’t make sense to me that anyone should go without a medication they need because of cost. It is often asked whether healthcare is a right or a privilege-and everyone is entitled to his or her own opinion. But if a person is sick and there is a drug that can help, I don’t think the thickness of one’s wallet should determine whether the person can access the needed drug.