The inspection report in question contains disturbing observations about J&J’s Lancaster, Pennsylvania, facility, which manufactures over-the-counter products such as Pepcid and Mylanta. If the inspectors’ observations are to be believed, plant managers have been taking a laissez faire approach to the facility’s manufacturing operations. For example, inspectors noted that the plant’s instructions for cleaning and maintaining equipment omitted crucial details about the materials and methods required. Nor did the instructions explain how to disassemble and reassemble equipment to ensure proper cleaning. Inspectors also claimed that the plant’s equipment was not inspected routinely according to written procedures.

This state of affairs opens the door to malfunctions, and FDA officials apparently had a chance to witness several of them. During one packaging operation, a capper machine crashed, a cooling loop failed, and operators observed leaky bottles of product. Yet inspectors said that staff did not conduct quality reviews of products that had been manufactured during equipment failures.

Inspectors did not give the plant’s analytical-testing operations high marks, either. FDA officials said the plant’s laboratory controls did not establish scientifically sound test procedures to ensure that products meet standards of identity, strength, purity, and quality. Inspectors observed as analysts strayed from written test procedures without justification. And when employees took samples of drug products to determine their conformance with specifications, they did not properly identify the samples, according to FDA.

The well-publicized quality problems at its Fort Washington, Pennsylvania, plant apparently haven’t spurred J&J to confirm that its other US manufacturing operations are up to snuff. But the new problems in Lancaster also affect Merck & Co. (Whitehouse Station, NJ), which operates the plant as a joint venture with J&J. I’m sure that Merck does not want its reputation to suffer by association with J&J. If it hasn’t already, Merck will probably lean on its partner to help improve the Lancaster facility. It might take this extra pressure to get J&J to seek and address systemic problems at its manufacturing operations. In the meantime, the public will eye both companies with suspicion.

First, Novartis agreed to pay as much as $152.5 million to eligible class members, including current and former sales representatives and entry-level managers. The plaintiffs apparently are satisfied with the settlement, which allows “full compensation” for the women, thus “ensuring that every woman who worked at Novartis over the past eight years has been compensated fairly,” according to David Sanford, the plaintiffs’ lead lawyer, in a press statement.

Even better, Novartis agreed to spend $22.5 million on programs designed to ensure fair treatment of all members of the company’s sales force. For example, Novartis will revise its sexual-harassment policy and training to stress that it will not tolerate inappropriate behavior or comments. The company also will work to ensure that employees can raise concerns safely and that the complaints are addressed promptly. Novartis also will revise its performance-management process, which could help prevent raises and promotions from being withheld on the basis of sex.

Perhaps the most important part of the agreement is the company’s pledge to retain an external specialist who will identify and remedy, with recommendations from the plantiffs’ lawyers, unjustified gender disparities. If the specialist is sufficiently motivated and perceptive, his work could go a long way toward closing the gender gap that apparently exists at the company. This arrangement could be a model for the pharmaceutical industry, which, like other industries, still suffers from discrepancies in pay and opportunity that fall along gender lines.

I suggest that Novartis’s new specialist investigate whether women are equally represented in the company’s management positions. It still seems to me that too few women are promoted to these types of jobs, and companies would reap various benefits from having more women managers.

The settlement between Novartis and the plaintiffs promises to help reduce gender inequality at the company. The outside specialist’s oversight in particular gives me hope that Novartis will be held to account if its policies result in discrimination. The pharmaceutical industry as a whole should take note of this settlement and remember the still unresolved problem of gender-based inequality.

Late 2008: The so-called “phantom recall” took place, in which J&J allegedly hired contractors to pose as customers and buy a certain type of adult Motrin in order to remove the product from store shelves. The House Committee on Oversight and Government Reform is currently investigating J&J’s actions in regards to the removal of the product from stores.

November 2009: McNeil recalled five lots of Tylenol Arthritis Pain Caplet 100 count bottles because of an unusual smell or taste. Nausea and related symptoms were reported by consumers.

December 2009: McNeil expanded the November recall to include all lots of Tylenol Arthritis Pain 100 count because of the unusual, moldy odor.

Jan. 15, 2010: McNeil recalled certain products, including Benadryl, Motrin, Rolaids, Simply Sleep, St. Joseph Aspirin, and Tylenol, because of the same musty, moldy smell identified in the November and December recall. The company determined that the odor was caused by the presence of a chemical called 2,4,6-tribromoanisole (TBA), which originated from the breakdown of a chemical used on the wooden pallets that stored and transported packaging materials for the medications. According to the company’s press release, the health effects of TBA have not been well studied, but no serious adverse events have been reported in the medical literature. McNeil said it would stop shipment of products that came in contact with packaging materials stored on the pallets and would also require suppliers to stop using the pallets.

April 30, 2010: McNeil announced that more than 40 types of children’s and infants’ products were voluntarily recalled because the products may not have met quality standards. McNeil advised that the medications not be given to children and infants, as a precautionary measure. Quality issues included the possibility of the medication containing too much of the active ingredient, containing substandard inactive ingredients, or containing tiny particles. The recall included more than 135 million bottles of children’s medication.

May 5: 2010: The House Committee on Oversight and Government Reform announced an investigation into McNeil’s April 30 recall.

May 6, 2010: McNeil closed its Fort Washington, Pennsylvania, facility in connection with the April 30 recall.

May 14, 2010: The Committee announced a hearing scheduled for May 27 to examine the circumstances of the April 30 recall.

May 25, 2010: JNJBTW.com, J&J’s blog, outlined an action plan that was developed with the help of a consultant designed to improve quality and manufacturing conditions at McNeil Consumer Healthcare. The announcement of the outline stated that a detailed version of the plan will be submitted to FDA by July 15.

May 27, 2010: The House Committee on Oversight and Government Reform held a hearing on the April 30 recall. Joshua Sharfstein, FDA’s principal deputy commissioner, testified on behalf of FDA. Colleen Goggins, worldwide chairman of Johnson & Johnson’s Consumer Group testified in place of CEO Bill Weldon, who was unable to attend because he was recovering from back surgery.

Documents produced at the hearing revealed what Committee Chairman Edolphus Towns dubbed a “phantom recall,” in which it appeared McNeil hired contractors to buy certain adult Motrin products. Towns later accused McNeil of initiating a formal recall only after FDA “discovered this covert activity” in a June 3, 2010, press release.

May 28, 2010: Blacksmith Brands, a provider of over-the-counter drug and healthcare products, voluntarily recalled four types of pediatric medications that were manufactured at the Johnson & Johnson/McNeil Consumer Healthcare plant at Fort Washington, Pennsylvania.

June 2, 2010: Towns requested information from J&J about its “phantom recall” of Motrin in 2008. Also, Towns requested information from Blacksmith Brands about its May 28 recall of products manufactured by J&J.

June 3, 2010: Towns requested information from the contractor allegedly hired by J&J in the so-called “phantom recall.”

June 15, 2010: McNeil expanded its Jan. 15, 2010, recall to include five more lots of Benadryl and Tylenol that were “inadvertently omitted from the initial recall action,” according to a company release. The additional lots were recalled for the same unusual odor that caused the January recall.

June 22, 2010: CEO Bill Weldon was asked by the Committee to testify at a second hearing about the company’s recalls. A date was not set for the second hearing.

July 8, 2010: McNeil issued another recall related to the moldy, musty odor of the Jan. 15 recall. Twenty-one lots of certain Benadryl, Children’s Tylenol Meltaways, Motrin, and Tylenol were recalled as a precautionary measure. McNeil says that an ongoing internal review showed that these products could have come in contact with the pallets that contained TBA, and therefore could have the foul odor.

Also, five complaints filed in the U.S. District Court for Northern Illinois against McNeil are seeking class-action status. Consumers accused McNeil of fraud and racketeering for not recalling all of its children’s products and for not adequately reimbursing consumers for their out-of-pocket expenses.

July 15, 2010: J&J intends to share its detailed action plan for improving quality with FDA.

The suit was brought by Novartis employees whose primary responsibility is to visit physicians’ offices, drop off drug samples, and deliver scripted messages about the company’s products. Echoing the opinion of much of the pharmaceutical industry, Novartis argued that these workers are outside salespersons and therefore exempt from overtime pay under federal and state law.

The case finally reached the US Court of Appeals for the Second Circuit, which rejected Novartis’s reasoning. The decision might have been influenced by the US Department of Labor, which took the unusual step of filing an amicus appeal brief in support of the sales reps. This decision likely will affect the entire pharmaceutical industry, which faces several similar lawsuits filed by sales reps seeking overtime pay.

At first glance, the decision seems like good news for pharmaceutical sales reps. But the obligation to pay overtime might become another excuse for drug companies to cut their sales forces. In response to the recession, pharmaceutical manufacturers have laid off thousands of reps as a cost-cutting measure. Even without the recession, reps have been on shaky ground as physicians become increasingly unwilling to meet with them. As a result, companies have sought alternative ways of reaching doctors such as e-detailing.

I’m happy to see the Department of Labor and the Second Circuit protect sales reps’ right to fair compensation. On the other hand, I still fear for the reps’ jobs under the current market conditions. Maybe new blockbusters would be the best cure for these workers’ job insecurity.

The committee’s letter to Weldon on Tuesday said the second hearing was scheduled for June 30, but the committee later said that the date would be rescheduled, according to reports. Weldon will be expected to discuss J&J’s recent manufacturing and quality-control woes, including the April 30 recall of more than 135 million units of children’s and infants’ products and what the committee’s chairman calls the “phantom recall” of 2008, in which contractors were hired to remove products from store shelves, according to documents produced during and after the May 27 hearing.

Reports could not confirm whether Weldon would attend the upcoming hearing. Also, JNJBTW, the company’s blog, has been silent on the issue since the May 27 posting of the prepared statement made by Colleen Goggins, J&J’s consumer group chairman, to the oversight committee. Goggins attended the hearing in place of the recovering Weldon.

With regard to melamine contamination specifically, FDA jumped to issue a new guidance in August 2009 on Pharmaceutical Components at Risk for Melamine Contamination, which addresses the use of methods such as LC-MS/MS and GS-MS. The new guidance asks manufacturers to test at-risk components (i.e., ingredients or raw materials that rely on a test for nitrogen content for identity, purity or strength). Also in 2009, FDA issued a Draft Guidance for Industry: Incorporation of Physical Chemical Identifiers (PCIDs) into Solid Oral Dosage Form Drug Products for Anticounterfeiting. 

The International Pharmaceutical Excipients Council (IPEC), along with PhRMA, GPhA, CHPA, and SOCMA, launched a coalition to monitor melamine adulteration and is working closely with the US Pharmacopeia to look at monographs and testing. Meanwhile, USP has been meeting with industry and regulators regarding the use of infrared spectroscopy in tandem with gel permeation chromatograph for excipient analysis, which should help check for melamine contamination. There are still some differences, however, among regional pharmacopeias when it comes to testing requirements.

To discuss these updates and what they mean for industry, Pharmaceutical Technology is hosting and SGS Life Science Services is sponsoring a free webinar on the subject on June 29. On the panel will be FDA’s Dr. Steven Wolfgang from the Recall and Shortages Branch, FDA’s Brian Hasselbalch from the Division of Manufacturing and Product Quality, and Dave Schoneker, representing IPEC and global regulatory affairs for Colorcon.

McNeil’s January 2010 recall affected several of its over-the-counter products, including Benadryl, Motrin, Rolaids, Simply Sleep, St. Joseph Aspirin, and Tylenol. The company also recalled lots of Tylenol Arthritis Pain 100 count with EZ-Open Cap in December 2009 because of the same odor. After an investigation following the Jan. 15 recall, the unusual odor was attributed to the presence of a chemical called 2,4,6-tribromoanisole (TBA). McNeil concluded that the TBA came from a chemical used on the wooden pallets that stored and transported packaging materials for the medications.

Specifically, the five newly recalled lots include: four lots of Benadryl Allergy Ultratab tablets, 100 count, sold in the US; and one lot of Extra Strength Tylenol Rapid Release Gels, 50 count, sold in the US, Trinidad and Tobago, Bermuda, and Puerto Rico, according to Tuesday’s press release.

The company’s latest announcement comes in the wake of a Congressional hearing and investigation about its April 30, 2010, of more than 40 infants’ and children’s products. The US House Oversight and Government Reform Committee also uncovered what Chairman Edolphus Towns called a “phantom recall” in which it appears Johnson & Johnson hired contractors to systematically remove certain Motrin products from store shelves in late 2008. Towns asserted that J&J initiated a recall only after FDA was made aware of the company’s actions, and earlier this month asked the contractors to provide details of their activity in the situation.

The New York Times reported last week that the committee and J&J disagree about their interpretations of the events of the “phantom recall.” J&J says nothing was wrong with the way it removed the products from stores and that there was no safety risk in the products. By not issuing a recall, the company wanted to take the product out of stores “with as little disruption and consumer confusion as possible,” said a McNeil spokesperson quoted in the NYT article. NYT obtained a July 2009 email from an FDA official to a McNeil executive that said, “It seems that your company is doing a recall even though you are calling it a ‘retrieval.’ The agency’s position is that your company should do a voluntary recall of the product since it appears to be that you are already doing a recall of the product.”

In his closing statement at the May 27 hearing, Towns said he would introduce legislation that would give FDA mandatory recall authority and the power to halt drug production. Do you think FDA should have this authority? The the results of PharmTech’s poll on the topic, available here.

Scientists previously have observed active pharmaceutical ingredients (APIs) in our water supply, thus spurring calls for an investigation. The US Geological Survey (USGS) now has conducted the first study in the United States that assesses pharmaceutical manufacturing facilities as a potential source of pharmaceuticals in the environment.

The group discovered that effluent from two wastewater-treatment plants in New York that receive more than 20% of their wastewater from pharmaceutical facilities had concentrations of pharmaceuticals that were 10 to 1000 times higher than outflows from 24 plants nationwide that do not receive wastewater from pharmaceutical manufacturers. Among other APIs, USGS found 3800 ppb of the muscle relaxant metaxalone and 1700 ppb of the analgesic oxycodone in wastewater-treatment plants’ effluent.

One goal of the study was to help officials develop effective water-management practices. Indeed, current practices may be insufficient. A recent European study found that treatment failed to remove the majority of pharmaceuticals from incoming wastewater, and these drugs were still present in the river waters receiving the treated water. On the positive side, European researchers found that single pharmaceuticals in river waters posed no significant risks, probably because they were highly diluted. But pharmaceuticals often are present as mixtures that could have greater, unknown toxic effects on ecosystems.

USGS has done us all a favor by quantifying the levels of APIs in the effluent from treatment plants, but this should be the first step in a longer process. We need to gain a clearer understanding of APIs’ potential effects on ecosystems so that we can set limits on these chemicals. Ultimately, we must use data from USGS and future studies to find better ways of removing APIs from wastewater. I think that these steps are crucial to safeguarding our health and to protecting our environment.

WHO Director-General Margaret Chan noted in the June 2009 announcement that, “No previous pandemic has been detected so early or watched so closely, in real-time, right at the very beginning. The world can now reap the benefits of investments, over the last five years, in pandemic preparedness.”

Previous pandemics were declared in 1968 when about 1 million died of influenza, and in 1918, when the Spanish flu killed tens of millions. As for the definition of “pandemic,” the public, politicians, advocacy groups, and the media are currently debating what it means and whether WHO changed its definition of the word before declaring the 2009 H1N1 swine flu disease as such. As of June 11, 2009, when WHO made the Phase 6 announcement, 74 countries had officially reported 28,774 cases of influenza A (H1N1) infection, including 144 deaths. The US Centers for Disease Control and Prevention (CDC) estimated  that between 14 million and 34 million cases of 2009 H1N1 had occurred between April 2009 and Oct. 17, 2009, including between 63,000 and 153,000 2009 H1N1-related hospitalizations, and between 2,500 and 6,000 2009 H1N1-related deaths. Ultimately, a pandemic declaration means that countries should implement their national pandemic plans.

About a year after the declaration, groups on both sides of the Atlantic are claiming that WHO falsely led the public to believe there was a pandemic based on influence and input from the pharmaceutical industry. A Council of Europe report said that WHO “vastly overrated” the seriousness of the situation. Another report, published in the British Medical Journal, claims that some experts advising WHO were paid consultants of drug companies that manufacture influenza treatments and vaccines. 

On the Pan American Health Organization (PAHO, the US office of WHO) website’s myths and facts page, the organization counters that it did not exaggerate the pandemic. “We have always known that pandemics can range in severity from mild to severe and can even undergo a change in severity as they run their course. WHO and other responsible health authorities have adopted a preventive approach-that is, preparing for the worst-case scenario in order to save lives. Better to prevent than regret…. In making this decision, WHO consulted independent world experts through Advisory Committees. WHO is constantly verifying that the experts who sit on its Advisory Committees have no conflicts of interest that could influence their technical opinion. So far, the health impact of this pandemic, compared to that of past pandemics, has been moderate. Countries have found means and have taken actions that were critical to reducing the severity of the pandemic.”

Because the H1N1 swine-flu was relatively new, more stringent precautions were taken, says the website.

Of note, WHO commissioned its own 29-member external panel to examine how it addressed and managed the H1N1 swine-flu pandemic in April 2010. The panel’s report is expected to be presented to the 2011 World Health Assembly. And the US Government Accountability Office (GAO) produced a report in November 2009 about how the US government handles pandemics. GAO recommended that the Homeland Security Council instruct the White House National Security Staff to help develop a monitoring and reporting process for action items at the nonfederal level.

The irony of the situation is that if WHO had not declared a pandemic and lives were lost as a result of swine flu (indeed, CDC estimates that as many as 18,300 deaths occurred between April 2009 and April 2010 as a result of the 2009 H1N1 virus) , the world would be harping on the organization for not doing its job and not declaring a pandemic. At the end of the day, WHO was unlikely to receive full public and political support no matter what action it took. As citizens, we depend on governments and governmental bodies to protect us. It seems WHO and its 193 member states—including the US—were trying to do just that.

See related blog post, “In the Name of Accountability”

Unfortunately, hope did not seem to be forthcoming. Although 431,000 jobs were added in May 2010, 411,000 of them were temporary positions with the US Census. Total private employment rose by 41,000 jobs, a small increase over the April level.

The picture becomes more positive if we examine the number of planned job cuts. So far this year, the pharmaceutical industry has shed 34,157 jobs, according to a new report by Challenger, Gray, and Christmas. That figure is only about 67% of the 51,034 jobs the industry cut during the same period in 2009.

Taken together with similar declines in other sectors, the drug industry’s decrease in job cuts is further evidence that job cuts have returned to prerecession levels, said John A. Challenger, chief executive officer of Challenger, Gray, and Christmas, in a statement accompanying the report. Challenger noted that the economy is still fragile, despite the nascent recovery, but indicated that job cuts could decrease further during the summer, which traditionally is the slowest period for downsizing.

I think the industry has reason for optimism. The slowed pace of pharmaceutical job cuts may indicate that the industry is finding its footing again. Let’s hope that drugmakers’ prospects continue to brighten throughout the summer months. By year’s end, it would be satisfying to point to this period as the beginning of the industry’s comeback.

[orig. published June 7, 2010]