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.

Concern about pharmaceuticals in our water supply has been in the public consciousness for a few years now. In 2009, the Environmental Protection Agency found traces of various drugs in fish caught in rivers that receive effluent from wastewater-treatment plants. The drugs were believed to come from doses that people had excreted or flushed down the toilet. In response, FDA updated its guidelines for disposing of drugs. New research, however, shows another potential source of drugs in our waterways.

French scientists investigated fish called wild gudgeon that lived upstream and downstream of a steroid-manufacturing facility owned by sanofi. About 60% of the fish downstream of the facility had both male and female sexual characteristics, as opposed to 5% of the population upstream. Researchers identified pollutants such as diuretics and anti-inflammatory agents in the river. The fish’s abnormalities could prevent them from breeding and also signal problems in other species.

“People think drug release is regulated, but it’s not,” said Joakim Larsson, a pharmacologist at the University of Gothenburg in Sweden, to Nature. But this lack of oversight may end: the European Commission is now considering whether to set limits on common drugs (e.g., ibuprofen and the contraceptive ethinylestradiol) in waterways.

Setting limits might prove difficult, however. Scientists have not yet determined safe limits for many pharmaceuticals in the aquatic environment, or how widespread the problem is, according to Susan Jobling, an aquatic ecotoxicologist at Brunel University in London who spoke to Nature.

The French researchers’ findings certainly are alarming, but regulators won’t have a solid basis for any decisions until more information comes to light. I’m encouraged that sanofi is cooperating with regulatory agencies, researchers, and ecological associations to investigate the scope and root of the problem. In the meantime, the pharmaceutical industry would do well to keep this story in mind, and perhaps review whether it can reduce the potential risks of its waste-disposal procedures.

Also see my previous posts about pharmaceuticals in water:

“Water without Side Effects”

“Hope for Bipolar Fish”

The manufacturing plant was closed in April following massive recalls of more than 40 types, and 135 million bottles, of infants’ and children’s medicines on April 30, 2010, due to contamination and substandard quality. The April 30th recall was also the subject of a hearing by the House Committee on Oversight and Government Reform in May. J&J responded by presenting an action plan to FDA in July outlining how to improve product quality. The company also appointed a corporate head of quality in August that reports directly to the CEO.

The company has issued numerous additional recalls related to product quality in the past year, the most recent was the last week’s voluntary recall of Rolaids products after consumer reports found wood and metal particles in the tablets.

McNeil has also had problems with quality in Puerto Rico. In January 2010, FDA issued a Warning Letter to McNeil for “significant violations of the Current Good Manufacturing Practice (CGMP) regulations” at its facility in Sector Montones, Las Piedras.

Executive Appointments
J&J expanded the office of the chairman Wednesday by adding two new positions. The company appointed Alex Gorsky, currently worldwide chairman of medical devices and diagnostics, and Sheri McCoy, currently worldwide chairman of pharmaceuticals, to the positions of vice-chairmen of the executive committee, effective Jan. 3, 2011. Gorsky will have the added responsibilities of the medical device and diagnostics group, global supply chain, and government affairs and policy. McCoy will oversee the pharmaceuticals group, consumer group, the corporate office of science and technology, and corporate affairs.

“These appointments will ensure we are well-positioned for sustainable growth into the future,” said William C. Weldon, chairman and CEO. “The changes are an appropriate step in furthering our long-term succession plans, and assuring talented, experienced leaders at all levels of the organization.”

The move appears to indicate that the beginnings of a succession plan is in place—the New York Times and other news outlets are calling the two promotions a “horse race” to determine who will take over as CEO. Although Weldon has faced criticism for his handling of the company’s recent quality problems and pressure to step down from his position, a company spokeswoman told NYT that Weldon “has no plans to retire.”

Click here to view a list of previous PharmTech blog posts about J&J.

Half of the respondents said the biggest area of risk is raw materials sourced outside of the US. Sixty-one percent said contaminated or nonconforming raw materials was the top threat in the next five years.

Drug counterfeiting and diversion were seen by executives as major threats to their global supply chains in the next five years, with 44% and 35% of respondents, respectively, citing them as risks. Forty percent of all respondents that produce life science products reported that their company’s products have been counterfeited or illegally diverted. The report says that these threats were “virtually non-existent” as little as 10 years ago, which underscores the rapid growth of the problem of counterfeit drugs.

The growth of globalization presents challenges to industry that the report grouped into three broad categories: on-demand visibility, control over the supply network, and the need for collaboration.

In terms of visibility of their supply chains, 77% of executives said that their primary means of gaining visibility into suppliers’ practices is a periodic audit, 25% said they share common practices and 3% have access to real-time data. The report states that the lack of on-demand visibility is due to the slow speed of gathering information about a company’s supply chain. Regarding the ability to merge data from multiple locations to provide a global view of the supply chain, 66% said they could do it, but they must manually aggregate the data; 15% said that it was not possible; and only 19% said they could do it in real time.

When asked about track-and-trace and serialization technologies, which can help industry gain control over the supply chain, survey respondents said the hurdles to implementing such technology are cost; difficulty of implementation; lack of industry standards; and lack of regulatory requirements and guidance. In terms of specific technologies in use or planned by the executives, 79% said their company uses barcodes, 57% use 2D barcodes, 34% use RFID, 17% use GPS tags, and 8% use none of these measures. Most executives said they could track manufacturing location (84%) and genealogy such as raw material, ingredient, etc., (73%), but 50% or less were able to track elements such as transaction history, chain of custody, record of ownership, environmental storage conditions, and ePedigree.

Industry executives identified the need for collaboration, and said their preferred method for creating best practices around standards is through industry consortium such as the Pharmaceutical Supply Chain Initiative, the Experimental Physics and Industrial Control System, and the Rx-360 consortium.

Weldon will also be asked to explain the circumstances surrounding what the committee dubbed the “phantom recall” of Motrin in 2008, 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 phantom recall came to light in documents produced during the committee’s first hearing on May 27, 2010.

Weldon was not present for the May hearing because of a scheduling conflict. Colleen Goggins, worldwide chairman of J&J’s consumer group, spoke to the committee in May in Weldon’s place. She is also expected to testify today.

Committee Chairman Edolphus “Ed” Towns also invited Joshua Sharfstein, principal deputy commissioner at the US Food and Drug Administration, to discuss the phantom recall at the hearing. Towns requested copies of all FDA documents regarding J&J’s 2008 Motrin recall, including all communication between employees of the agency and J&J from January 2009 to June 2009.

The hearing will begin at 10:00 a.m. ET and can be seen via webcast at http://oversight.house.gov.

J&J issued a recall of millions of its daily disposable contact lenses, 1 Day Acuvue, sold in Japan and more than two dozen other Asian and European countries, according to a report from the Associated Press. Consumers complained that they experienced a stinging sensation when inserting the lenses. The company estimates that the recall includes roughly 100,000 boxes of contact lenses. The recalled lenses were not sold in the US or Canada, and J&J did not announce the recall in the US.

According to a company spokesperson interviewed by AP, the problem arose because a piece of equipment failed during manufacture and the lenses were not properly rinsed, and the recalled lenses contain a substance that was used in the manufacturing process. The company has identified and corrected the problem, which affected only one manufacturing line in the Ireland-based manufacturing facility, according to the AP report.

In related J&J news, this week the US Food and Drug Administration posted on its website an Aug. 19 Warning Letter to DePuy Orthopaedics, a business unit of J&J that makes joint replacements, issued for marketing violations for two of its products. FDA says it never approved the sale of DePuy’s TruMatch Personalized Solution System, a device that features proprietary software and a CT scanner that produces a three-dimensional model of a patient’s knee prior to knee replacement surgery. FDA’s letter also states that DePuy marketed its Corail Hip System for two uses that were not approved by the agency. The agency asked DePuy to stop marketing the products and correct the violations detailed in the letter.

According to WSJ’s report, J&J appointed company veteran Ajit Shetty to head the quality group, which will oversee the company’s three major business segments: pharmaceuticals, medical device, and consumer. Chief quality officers for each of these business units will report to Shetty’s group. Weldon also told WSJ that the managers of J&J’s 120 global manufacturing facilities will report to the new quality group.

Weldon told WSJ that he understands that the recalls “have sapped trust and confidence in J&J,” saying that the company has “a lot to do to earn that back,” echoing his sentiments in his May 7 open letter posted on J&J’s blog. A company-wide emphasis on manufacturing quality is a step in the right direction.

See related posts:

J&J and Guilt by Association

A Timeline of J&J/McNeil’s Recent Recall Troubles

J&J CEO Invited to Second Congressional Hearing

Five More Lots Added to January 2010 Tylenol and Benadryl Recall

More Trouble for J&J: Blacksmith Brands’ PediaCare Recall and J&J’s “Phantom Recall”

Tylenol Hearing to Take Place Today

Some Recalled Infants’ Tylenol Had Too Much Acetaminophen

NeoProfen is a nonsteroidal, anti-inflammatory therapy administered to premature infants with a heart condition known as a patent ductus arteriosus (PDA), in which a blood vessel in the heart that normally closes at birth instead remains open, causing too much blood to flow to the lungs. NeoProfen is to treat premature babies with a PDA who weigh between 500 and 1500 g, who are no more than 32 weeks gestational age when usual medical management (e.g., fluid restriction, diuretics, respiratory support, etc.) is ineffective, according to Lundbeck’s recall notice.

The recall was issued as a precautionary measure, and Lundbeck said it had not received reports of adverse events due to the particulates in the affected lots. “The potential adverse events resulting from the use of a sterile injectable product with particulates can be very serious and potentially fatal,” said the company in its recall notice. Risks of particulate matter in the medication include the potential to obstruct blood vessels (which could induce pulmonary emboli or activate platelets and/or neutrophils to induce anaphylactic reactions) and particulates in an intravenous injection could cause foreign body granulomas and local irritation of blood vessels, according to the notice.

Lundbeck stated that it advised the US Food and Drug Administration of the recall and notified wholesalers, hospital pharmacies, and prescribing neonatologists of the recall and product shortage. Given the vulnerable heath of the population treated with a drug such as NeoProfen, it is vital that a drug manufacturer communicate quickly and effectively about a recall—especially in the event of a suspected quality issue.

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 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.