Ranbaxy’s troubles stretch back at least to 2006, when FDA found significant deviations from CGMP at the company’s Dewas and Paonta Sahib, India, plants. The agency sent a Warning Letter that year and two more in 2008. In September 2008, FDA decided to deny any new drug applications or abbreviated new drug applications that listed either of the two plants as a manufacturer. It also issued an Import Alert that allowed US border officials to detain imported products manufactured at those facilities.

As if the manufacturing problems were not serious enough, federal officials, reportedly including FDA employees, searched Ranbaxy’s New Jersey offices in 2007. The US Department of Justice (DOJ) later launched an investigation into allegations of conspiracy, false statements, and healthcare fraud at the company. DOJ suspected Ranbaxy of fabricating bioequivalence and stability data to support abbreviated new drug applications, and of attempting to conceal CGMP violations.

The situation worsened in 2009, when FDA charged Ranbaxy Laboratories’s Paonta Sahib facility with falsifying data and test results in approved and pending drug applications. The agency stopped all substantive scientific review of new and pending drug-approval applications containing data generated by the facility. A few months later, Malvinder Mohan Singh stepped down as the company’s chairman, CEO, and managing director.

Last week, Ranbaxy signed the consent decree in hopes of resuming US sales of drugs manufactured at the two banned plants. In a press statement, Ranbaxy pledged to ensure the integrity of its data and to comply with CGMP. Indicating that DOJ’s suspicions had some foundation, the company also set aside $500 million to resolve civil and criminal liability arising from the department’s investigation.

Ranbaxy has taken unspecified “systematic corrective steps” to straighten itself out, according to the statement. Although we might be skeptical about these measures, the company’s new owner Daiichi Sankyo might bring the rigor and discipline that Ranbaxy seems to need. Let’s hope on behalf of patients everywhere that Ranbaxy can turn over a new leaf in 2012.

Last Thursday, FDA issued an interim final rule requiring manufacturers that are the only producer of certain drug products to report all manufacturing interruptions to the agency. Early notification will help FDA work with drug manufacturers and doctors to make sure that patients have access to life-supporting products. The interim rule was spurred by President Obama’s Oct. 31, 2011, executive order, which directed FDA to reduce and prevent drug shortages.

But the agency is not relying on just one tactic. In addition to the interim final rule, FDA is developing a tracking database to monitor drug shortages. The database will record the numbers of shortages, the reasons for shortages, and what steps FDA is taking to address and prevent them. The database is a high priority for the agency, which hopes to complete it in 2012.

Also, several observers have expressed concern that unscrupulous organizations could attempt to reap large profits from drug shortages. In response, FDA has begun analyzing reports about drug stockpiling and exorbitant pricing. The agency plans to provide the Department of Justice with information about these reported activities, and the Department will determine whether they are consistent with the law. This issue is on Congress’s radar, too: Senator Charles E. Schumer (D-NY) recently introduced a bill to make price gouging on scarce drugs a federal crime.

As any supply-chain professional knows, having one source of a crucial item is far from an ideal situation. If a drug is crucial but not profitable, we may not see new sources spring up to provide additional supply-chain security. But FDA’s initiatives promise to ease the threat of drug shortages and reduce patients’ suffering.

After reviewing the data, obstetricians, gynecologists, and pediatricians at the Center for Drug Evaluation and Research (CDER) determined that Plan B One-Step “was safe and effective in adolescent females, that adolescent females understood the product was not for routine use, and that the product would not protect them against sexually transmitted diseases,” according to a statement by FDA Commissioner Margaret Hamburg. CDER also concluded “that adolescent females could use Plan B One-Step properly without the intervention of a healthcare provider,” according to the statement. And FDA is not alone—the American Academy of Pediatrics also supports over-the-counter access to emergency contraception.

Sebelius’s concern about the ostensible lack of studies including 11-year-olds seems unusual when one considers that many over-the-counter drugs have not been studied in preadolescents—and some are far more dangerous than Plan B One-Step. “Acetaminophen can be fatal, but it’s available to everyone,” Susan Wood, a former FDA assistant commissioner, told The New York Times. “So why are contraceptives singled out every single time when they’re actually far safer than what’s already out there?”

FDA places great emphasis on scientific data, as any manufacturer contemplating a process change well knows. In this instance, FDA’s informed decision seems to have been overruled for reasons other than scientific ones.

Also see Christopher Allen and Angie Drakulich’s sidebar “Behind the Counter.”

Drug companies, including Pfizer, are wooing insured consumers by offering copay coupons, which reduce the amount of money that the latter must spend for a branded drug. These coupons are intended to discourage a patient from switching to a generic therapy. To redeem the coupons, consumers often must submit personal information that allows the firms to promote products to individual patients.

The coupons may help consumers, but they oblige plan sponsors, such as employers or state governments, to pay high prices for branded drugs when generic alternatives are available. Drug companies can prevent plan sponsors from knowing when enrollees have redeemed the coupons by processing them through a “shadow claims system,” according to a statement from the Pharmaceutical Care Management Association. Copay coupons will increase costs for these sponsors by $32 billion over the next decade, according to research from Visante.

At a time when state governments and private companies are pinching pennies, it’s hard to believe that they will allow drug companies to use these tactics for very long. Arrangements such as Pfizer’s agreement to manufacture generic Lipitor for Watson, in exchange for a share of net sales, seem comparatively more benign. Deals like this don’t appear to constrain patients’ choice or force payors to spend more than necessary for a given drug. They might be the “least bad” option for drugmakers without new blockbusters on the horizon.

Citing interviews with stakeholders, GAO recommended creating an information clearinghouse, through which companies could share information anonymously on adulterated ingredients with FDA and other companies. A clearinghouse could help FDA disseminate information about adulterated products quickly and enable the agency and industry to respond to adulteration rapidly. If the clearinghouse were managed by a neutral third party, it could ensure that the information did not identify specific companies.

This strategy could help allay industry’s concerns about sharing information when an adulterated ingredient has not entered into commerce. Companies are afraid that they may be sued if they reported that a supplier intentionally adulterated a product and the accusation is later found to be baseless. A wrongful accusation “can have serious consequences, such as compromising the integrity of the company’s brands and products if certain information became public,” according to the report.

Because potential adulterants often are unknown or unidentified, it can be hard for FDA to detect them. “For example, during the heparin incident, the available test methods for heparin were not able to detect the contaminant oversulfated chondroitin sulfate,” said the report. “Industry may be the best source of tests to detect adulteration because companies develop such tests to monitor the products they receive from their suppliers; however, industry officials indicated that they are often reluctant to share such information because it is proprietary.”

By eliminating details that could identify specific pharmaceutical companies, an information clearinghouse could allay industry’s concerns, help FDA dedicate its resources efficiently in the event of potential adulteration, and protect citizens from ingesting harmful drugs. It sounds like a win for all involved. GAO has done us a service in writing this report, and I hope FDA takes its recommendations seriously.

After reviewing its documentation, the company concluded that routine preventive maintenance and requalification of manufacturing equipment at the site was overdue. Ben Venue suspended manufacturing so that it could assess the entire site and take appropriate corrective actions to ensure the safety of its products. The suspension will affect Johnson & Johnson, which markets Doxil, as well as Pfizer, Hospira, and Teva.

Last month, President Obama ordered FDA to take various steps intended to prevent and reduce drug shortages. The agency will require advance notice from manufacturers likely to face manufacturing disruptions, and it will expedite reviews of new drug suppliers, production sites, and manufacturing changes.

These steps, while helpful, do not address an important factor that contributes to drug shortages: manufacturing deficiencies. Even before Ben Venue conducted its own review, FDA found 48 quality concerns during an inspection of the Bedford site in May 2011. FDA likely needs a larger pool of inspectors to oversee drug manufacturing sites more thoroughly. But the government’s current desire for austerity will probably preclude the budget increase that would make hiring possible.

Maybe FDA should prioritize manufacturing sites for inspection if they are among a few that produce a medically necessary drug such as Doxil. Greater attention to crucial sites could identify problems earlier and, ideally, resolve them without disrupting drug supply.

The National Institutes of Health recently administered cancer vaccine PANVAC to 26 women with breast or ovarian cancer. PANVAC, a recombinant poxviral vaccine, produces two proteins associated with tumor cells to stimulate the body’s immune system to attack the cancer. During the trial, the median time it took for the breast-cancer patients’ condition to progress was 2.5 months, and the patients’ median survival time was 13.7 months. One breast cancer patient was still alive 37 months later. Median survival for the 14 ovarian-cancer patients was 15 months, and one woman went 38 months before her disease progressed. Although the trial was small and did not include a control group, these results seem encouraging.

Researchers from Oxford University also have attempted to fight cancer with the immune system. A team led by Paul Fairchild, codirector of the Oxford Stem Cell Institute, used stem-cell technology to create new dendritic cells from a patient’s skin. The dendritic cells, which organize part of the body’s immune response, carried the marker Melan A so that they would trigger an attack on melanomas. In the study, the team’s dendritic cells activated immune cells that produce antibodies and those that kill other cells. Previous studies using other dendritic cells had stimulated only part of the immune system.

Both of these techniques are still in their early phases. It will be some time before the studies lead to therapies from which patients can benefit, but they add to our knowledge of cancer and underscore the importance of oncology research. I take encouragement from these early steps, which I hope will inspire other drugmakers to take up the challenge of battling cancer.

One technique was accelerated approval for drugs to treat serious diseases. This authority allows the agency to approve a drug based on clinical data showing that it is reasonably likely to have a clinical benefit, even if data do not demonstrate that the drug has this benefit. Almost half of the newly approved drugs received Priority Review because they had the potential to offer major advances in treatment, or because no adequate therapy existed. FDA sets a six-month target date to review such drugs.

Although these changes in procedure are well-intentioned, we may legitimately ask how they will affect patients’ safety. After all, GSK’s diabetes drug Avandia received fast-track approval, but an article published in The New England Journal of Medicine later linked the drug to an increased risk of heart attacks. The Wall Street Journal notes that a Senate Finance Committee report last year accused the company of hiding data showing Avandia’s cardiovascular risks, and GSK has just agreed to pay the US government $3 billion to settle this and other claims.

Creating a short timeline for drug approval could hurt the agency’s reviews of clinical data. FDA approved Pfizer’s smoking-cessation drug Chantix after an accelerated priority-review process. The agency concluded that the drug did not increase the risk of psychiatric problems such as depression. But researchers from Wake Forest Baptist Medical Center found that Chantix was eight times more likely to result in suicidal behavior or depression than nicotine-replacement products. One reason for the discrepancy could be that, unlike FDA, the researchers performed disproportionality analysis on the data—a technique that is increasingly being used to find links in side-effect data that normally escape detection in clinical trials.

FDA’s staff includes well-vetted and experienced scientists, but they need sufficient time to work thoughtfully and thoroughly. Even though the agency’s initiative has increased the number of new-drug approvals, it may also be increasing the risk that a company can hide negative data from regulators, or that the agency’s own analyses will not be as complete as they could be. In light of the problems with Avandia and the conflicting studies about Chantix, I think FDA should review its efforts to promote innovation to be sure that the agency maintains high standards for drug safety.

Last week, the World Intellectual Property Organization (WIPO), an agency of the United Nations, founded WIPO Re:Search, a forum for public and private organizations to share intellectual property (IP) and expertise with global-health researchers. By establishing a public database of IP, WIPO Re:Search aims to help develop new drugs and vaccines to treat neglected tropical diseases, malaria, and tuberculosis. The National Institutes of Health and companies such as AstraZeneca, Eisai, GlaxoSmithKline, Novartis, Pfizer, and Sanofi have agreed to work with the group.

To join WIPO Re:Search, member organizations agree to let the group license their IP to researchers on a royalty-free basis in many cases. But some observers say that these terms will not make information accessible enough. “Instead of allowing all countries where neglected diseases are prevalent to access the products, the initiative restricts royalty-free licenses to least-developed countries only, with access for other developing countries negotiable,” said Doctors without Borders in a press statement. Many patients that suffer from neglected tropical diseases do not live in least-developed countries. “In the Americas, for example, Chagas disease affects 21 countries, but the consortium will only provide royalty-free licenses for Haiti, where Chagas is not endemic,” according to the statement.

I think that WIPO’s initiative has great potential to help ease suffering and save lives. It’s encouraging to see the pharmaceutical industry dedicate resources to treating diseases that do not necessarily represent lucrative markets. And, by pooling a large amount of expertise, collaborations such as this one promise to solve stubborn problems more quickly than might otherwise be the case. But Doctors without Borders seems to be raising legitimate concerns. Considering its overall profitability, does the pharmaceutical industry have an obligation to help countries in need?

As the unemployment rate hovers around 9.1%, the federal government needs to find ways to create jobs. Congress is debating whether a tax break on repatriated money would prompt companies to hire more workers, as I mentioned last week. Meanwhile, the Obama administration is eyeing another potential means of stimulating job growth: investing in biological research.

When he signed the America Invents Act in September, President Obama committed to developing a National Bioeconomy Blueprint by January 2012. The blueprint will describe ways to manage investment in biological research to improve the nation’s health and create the “jobs of the future.” Aside from identifying potentially productive investments in R&D, the blueprint will also describe regulatory reforms to reduce burdens on biopharmaceutical manufacturers.

Illustrating the maxim that great minds think alike, FDA is already seeking to identify and reform burdensome and inefficient regulations as part of its own initiative to stimulate biomedical innovation. At the same time, the agency plans to establish a common understanding among stakeholders to clear the approval pathway for exceptionally promising therapies. These goals are included in the agency’s recent report titled Driving Biomedical Innovation: Initiatives to Improve Products for Patients.

Biological research is the foundation of a significant portion of the American economy, as the White House website notes. The combined efforts of the president and FDA could help discover and develop new therapies. If they also encourage biopharmaceutical companies to hire new employees, they will help mitigate an urgent problem that has not yet been addressed sufficiently.