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.

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.

A few weeks ago, Representative Michele Bachmann (R-MN) made waves by claiming that the vaccine for human papillomavirus could have dangerous side effects. She retreated from her remarks after the American Academy of Pediatrics said that they had no scientific validity. Makers of biopharmaceuticals might feel vindicated, but a recent poll emphasizes that Bachmann is not alone in her views.

About 21% of respondents to an NPR–Thomson Reuters Health Poll believed that autism was linked to vaccines, and 7% believed that diabetes was linked to vaccines. Nearly half of the respondents worried about the side effects of vaccines, and about the same portion were concerned about their long-term effects on health. About a quarter of respondents said that their opinions about vaccines had changed during the past five years.

Patients’ concerns about vaccines’ safety are not supported by the evidence. Federal officials have studied vaccines’ links to side effects 12 times in the past 25 years, and the most recent report from the Institute of Medicine (IOM) found inadequate evidence to accept a causal relationship in the vast majority of cases. IOM did, however, find evidence to reject relationships between the measles–mumps–rubella (MMR) vaccine and autism, and between that vaccine and diabetes.

IOM did find links between vaccines and some adverse events, but the events were either rare or transient. For example, patients vaccinated against chicken pox can develop pneumonia, hepatitis, or meningitis late in life if an unrelated illness (e.g., cancer) compromises their immune system. In addition, the MMR vaccine was linked to temporary joint pain in children and female adults.

Biopharmaceutical manufacturers that are confident of their products’ safety could still benefit by launching a public-education program. Publicizing the many federal studies that have found vaccines to be safe and, as I wrote a few weeks ago, disclosing safety information gained during trials of approved vaccines could help to assuage patients’ fears.

Understanding critical quality attributes will help Pfizer develop robust design spaces and, ultimately, achieve real-time release, said Gerry Migliaccio, senior vice-president of network performance for Pfizer Global Supply, according to In-Pharma Technologist. Migliaccio made his remarks at a meeting of FDA’s Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. Using QbD as a basis, and process analytical technology to establish manufacturing controls, Pfizer believes it will be able to reduce quality-control costs, achieve real-time release, and quickly get a return on its investment.

But not all companies are rushing to adopt QbD. Manufacturers of small-molecule generic drugs fear that spending the extra initial time and effort to adopt QbD could prevent them from being the first to file an application for their products. “If you’re not first to file, you may as well be last,” said Yatindra Joshi, vice-president of generics R&D for Teva, at the same FDA meeting. Consequently, some generic-drug manufacturers aren’t willing to gamble that the benefits of QbD will outweigh the profits lost by not being first to file.

If Pfizer and other heavyweights adopt QbD, it could boost patients’ confidence in the safety and efficacy of marketed drugs. But patients would benefit even more if generic-drug manufacturers felt freer to pursue this initiative. By making some elements of QbD mandatory in filings, FDA could “level the playing field,” said Joshi. This idea seems like one plausible solution that could be of advantage to the industry and consumers alike.

For FDA’s evaluation of the QbD program so far, please watch for Pharmaceutical Technology’s September issue, in which CDER’s Helen Winkle and Moheb Nasr analyze the initiative’s present and future.

The case began after several patients took a generic version of metoclopramide for stomach ailments and ultimately developed tardive dyskinesia, a serious neurological disease. As required under federal law, the label for the generic product was the same as that for the branded drug, which was no longer available. But the plaintiffs alleged that the manufacturer of the generic drug had evidence about the product’s potential side effects and failed to alert FDA about them as state law required.

In his majority opinion, Justice Thomas ruled that federal law pre-empts the plaintiffs’ suit. A company cannot comply both with federal law, which requires manufacturers to use the same warning label as that for the branded product, and with a state law that requires them to change the warning label when evidence supports it, he held. In such an instance, federal law prevails over state law. Yet Thomas conceded that if the generic-drug manufacturers had asked FDA for help in changing the corresponding brand-name label, they might have been able to accomplish under federal law what state law required.

In her dissent, Justice Sotomayor wrote that FDA requires generic-drug firms to propose label changes when they believe that a label is inadequate. But the defendants (Actavis and Pliva) made no such proposals. Generic-drug manufacturers might sometimes be able to prove that it would be impossible for them to comply with federal and state laws regarding labeling, wrote Sotomayor. But the defendants showed “only that they might have been unable to comply with both federal law and their state-law duties to warn” the plaintiffs about side effects [emphasis mine].

“As a result of today’s decision, whether a consumer harmed by inadequate warnings can obtain relief turns solely on the happenstance of whether her pharmacist filled her prescription with a brand-name or generic drug,” wrote Sotomayor. Given that more and more prescriptions are being filled with generic drugs, this conclusion is distinctly troubling.

In light of the Court’s decision, we may need to re-evaluate the process for changing drug labels to ensure that it is sound and reasoned without being onerous. Most importantly, we need to protect patients’ right to seek redress if any manufacturer has failed in its obligation to provide adequate warnings about potential side effects.

But when Committee Chair Representative Darrell Issa (R-CA) recently visited Maridalia Torres, FDA’s Puerto Rico district director, he learned that neither she nor her staff had visited the McNeil facilities since the time of the hearings. What’s more, Torres had not evaluated McNeil’s corrective actions, but had relied on a third-party compliance officer—hired by McNeil—for information. In a letter to FDA Commissioner Margaret Hamburg, Rep. Issa asked whether FDA had taken any disciplinary actions against its Puerto Rico employees.

Last week, Senators Charles Grassley (R-IA) and Max Baucus (D-MT) expressed concerns about the way FDA oversees the citizen-petition process. As the agency was considering the approval of generic alternatives to Sanofi’s Lovenox blood thinner, it reviewed letters from a professor and two medical groups requesting that approval be delayed. At Congress’s request, Sanofi produced documents revealing that it had encouraged the groups to write to FDA. The company paid the two groups more than two million dollars each, and paid the doctor more than $200,000. None of these three parties revealed their financial relationship with Sanofi to FDA in their letters. And FDA apparently did not ask.

In their letter, the senators warned that abuse of the citizen-petition process could delay patient access to “potentially affordable, safe, and effective generic alternatives.” The lawmakers asked what steps FDA had taken to ensure that the process was transparent.

No government agency is perfect, and FDA does suffer from a chronic shortage of resources. But if FDA is at fault in these two incidents, it is because of a lack of diligence rather than a lack of funds. Patients, whose lives are at stake, need the agency’s protection. I hope FDA rises to the challenge of Congress’s tough questions.

Many drugmakers have taken their investors’ advice to heart. One salient example is Pfizer, whose CEO Ian Read plans to slash R&D budgets by about 25% over the next two years. Chris Viehbacher, CEO of Sanofi, told Reuters that R&D cost cutting would increase throughout the industry this year and next. Companies are likely to focus their discovery efforts on the most lucrative areas in an attempt to get more bang for their R&D buck.

But, profitable or not, don’t patients need new and better drugs? Where will they come from? Drugmakers may well outsource innovation by partnering with entities such as universities and contract research organizations, Tim van Biesen, head of Bain and Company’s healthcare practice, told Reuters. They’d be following Hollywood’s strategy of sourcing “movies and scripts from all over the place,” he said. Shire already seems to have started along this path.

Big Pharma also might take advantage of its scientific expertise and marketing muscle by creating follow-on biologics. Cheaper versions of biopharmaceutical treatments for rheumatoid arthritis and cancer are in big demand, said David Snow, CEO of Medco Health Solutions, to Reuters. Making follow-on biologics could be a way for Big Pharma to boost sales. In addition, the discount for these medicines likely will be less than that for small-molecule drugs because they’re tougher to copy—and fewer competitors will manufacture them.

While these strategies might eventually improve Big Pharma’s bottom line, they also represent a shift away from the traditional model of what a drug company is. And even if it helps the drug industry, will the emerging model serve patients’ interests?

The first story is a Federal Trade Commission (FTC) staff report that was published last Tuesday. According to the agency’s research, the number of pay-to-delay deals between branded and generic-drug manufacturers increased more than 60% between fiscal 2009 and 2010. By keeping generic drugs off the market, these arrangements cost taxpayers $3.5 billion a year in higher drug prices, said FTC Chairman Jon Leibowitz in a press release.

Generic drugs could help ease our budgetary woes by reducing costs for taxpayer-funded health programs such as Medicare and Medicaid. The public shows little enthusiasm for Rep. Paul Ryan’s (R-WI) plan to turn Medicaid into a voucher system. I’d imagine that support for a solution that entailed generic drugs would be much greater.

The other story is the joint effort by FTC and FDA to remove products that make fraudulent claims about treating sexually transmitted diseases (STDs) from the market. Most of these products are sold on the Internet, which can be a “toxic wasteland for consumers,” said Richard Cleland, assistant director of FTC’s Division of Advertising Practices, in a conference call with reporters last Tuesday. By raising awareness about these products and providing information about the proper way to diagnose and treat STDs, the FTC–FDA effort will protect public health. I’d argue that well informed patients who seek proper treatment sooner are less likely to need federal assistance for expensive treatments later.

It’s understandable that lawmakers would want to take a hard look at federal spending, but cost cutting should not be undertaken recklessly. These efforts on the part of FTC and FDA could save the government money in the long run, besides safeguarding our well being. I’m sure that our government could find funds for valuable initiatives like these.

After their daughter suffered seizures following the administration of a diphtheria–pertussis–tetanus vaccine, Russell and Robalee Bruesewitz went before the “Vaccine Court” that Congress established in 1986 to adjudicate such claims. The tribunal, which has decided against two out of every three plaintiffs, found that the Bruesewitzes had failed to prove that the vaccine had harmed their daughter.

Seeking compensation, the family filed a product-liability lawsuit. Their lawyer argued that Wyeth-Lederle, the vaccine’s manufacturer, had the technology to produce a less reactive, purified pertussis vaccine, but declined to do so. The case was moved to federal court at the company’s request, and a series of judges ruled that federal law prohibited the case from proceeding.

The case hinged on the 1986 law that created the Vaccine Court. It states that vaccine manufacturers cannot be held liable for damages arising from a vaccine-related injury or death “if the injury or death resulted from side effects that were unavoidable even though the vaccine was properly prepared and was accompanied by proper directions and warnings.”

The Court’s decision sets out an interpretation of this language, which Justice Ginsburg found confusing. “If a manufacturer could be held liable for failure to use a different design, the word ‘unavoidable’ would do no work,” wrote Justice Scalia in the Court’s opinion.

But Justice Sotomayor’s interpretation of the clause was exactly the opposite of Scalia’s, showing that the confusion has not been dispelled. The “text, structure, and legislative history compel the conclusion that Congress intended to leave the courthouse doors open for children who have suffered severe injuries from defectively designed vaccines,” she wrote in her dissent.

The Court’s decision means that patients can only seek redress from the Vaccine Court, and not through civil lawsuits. Since the Vaccine Court’s compensation fund comes from an excise tax on vaccines, drug companies will not have to pay any damages resulting from claims of harmful vaccines. The Supreme Court’s decision protects manufacturers from having to pay ruinous amounts in damages, but making patients pay compensation when drugmakers’ products cause harm strikes me as distinctly unfair. I think we need legislation that restores patients’ rights to seek damages, re-establishes accountability for drugmakers, and helps ensure an adequate supply of vaccines for the country.

Nanomedicine manufacturer Midatech Group (Oxford, England) and drug-delivery company MonoSol Rx (Warren, NJ) recently filed a provisional US patent application for “Nanoparticle Film Delivery Systems” that could transmit proteins and peptides through buccal or sublingual administration. The delivery system bypasses the gastrointestinal (GI) tract and sends medicine directly into the bloodstream. This mechanism could reduce side effects and prevent the GI tract from destroying the therapy.

About two weeks ago, the Georgia Institute of Technology gave Vyteris (Fair Lawn, NJ) the option to exclusively license its patented thermal-ablation and microdevice-fabrication technologies for transdermal drug delivery. The technology was developed to enhance skin permeation to the point where drugs with high molecular weight could be administered without injections or infusions.

These and other new technologies could one day challenge the dominance of injections as a method for administering vaccines. Considering how rapidly the market for vaccines is growing, drugmakers would do well to take notice of these exciting developments. Vaccinations might soon become as painless as freshening the breath with an oral strip. Maybe needles’ days are numbered.