CMAJ News
For the record
Published at www.cmaj.ca between Apr. The new warning letter regards in persistent or significant disability or 20 and May 18 breaches uncovered during a July– incapacity, be life-threatening or result August 2009 FDA inspection of an in death. Apotex receives second FDA Apotex facility located at 150 Signet The report indicates that there has Drive in Toronto, during which “sev- been a steady increase of adverse reac- warning eral violations that are identical” to tion reports since 2001, when roughly those found during the inspection of the 11 000 incidents were reported (www.hc he United States Food and Drug Etobicoke facility were discovered. -sc.gc.ca/dhp-mps/alt_formats/pdf/med Administration (FDA) has “These identical CGMP violations eff/bulletin/carn-bcei_v20n2-eng.pdf). T issued a second warning letter demonstrated a lack of adequate Roughly 70% (18 301) of 2009 inci- in a year to Toronto, Ontario-based process controls and raised serious dents involved pharamaceuticals, while generic drug manufacturer Apotex Inc. questions regarding your corporation’s 23% (5998) involved biotechnology for lapses in good manufacturing prac- quality and production systems,” the products. There were 833 adverse reac- tices. warning letter states. tion reports involving biologics, 516 The violations cause Apotex drug The violations included contamina- involving natural health products, 379 products to be considered “adulterated” tion of a diabetes drug with an “active involving radiopharmaceuticals and 34 within US regulations “in that the meth- pharmaceutical ingredient” and unspec- involving cells, tissues and organs. ods used in, or the facilities or controls ified “charred materials.” Other viola- Health Canada says that 8428 of the used for, their manufacture, processing, tions included contamination found adverse reaction reports were made by packing, or holding do not comform to, within an antihistamine, as well as fail- consumers and patients, while 6064 are not operated or administered in con- ure “to have an adequate equipment came from physicians, 4364 from other formity” with Current Good Manufac- cleaning and maintenance procedure or health professionals, 3853 from phar- turing Practice (CGMP), states the program to prevent contamination that macists, 2906 from nurses, 6 from den- FDA’s Mar. 29 letter to Apotex Inc. would alter the safety, identity, tists, 3 from naturopaths and 437 from President Jack M. Kay (http://www.fda strength, quality, or purity of the drug other unspecified persons. .gov/ICECI/EnforcementActions/Warn product beyond other established The report indicates that market ingLetters/ucm207508.htm). requirements.” authorization holders submitted 305 847 As a consequence, the FDA informed The FDA letter also states that the foreign adverse reaction reports in 2009, Kay that it would “recommend with- numerous violations cited “are not as compared with roughly 80 000 in holding approval of any new applica- intended to be an all-inclusive state- 2001. — Wayne Kondro, CMAJ tions or supplements listing your firm as ment of violations that exist at your a drug product manufacturer” until such facility.” AIDS funding promises time as corrective action is taken. Apotex did not respond to telephone “In addition, failure to correct these inquiries about the FDA warning letter. broken violations will result in FDA continuing — Wayne Kondro, CMAJ to deny entry of articles manufactured at ealthy nations are using the Apotex Inc., Toronto, Canada, into the Adverse reaction reports recent economic crisis to United States,” the warning letter added. W renege on promised AIDS The FDA had issued a similar warn- soaring relief, reports the International Treat- ing letter on June 25, 2009, with ment Preparedness Coalition, a world- respect to manufacturing breaches here was a 35% increase in wide advocacy group for people living uncovered at a Dec. 10–19 inspection domestic adverse reaction with HIV. of an Apotex facility in Etobicoke, T reports to the Canada Vigi- In the report Rationing Funds, Risk- Ontario. lance Program in 2009, Health Canada ing Lives: World Backtracks on HIV The latest FDA letter adds that while says in its annual report on the inci- Treatment, the coalition documents Apotex recalled about 659 batches of dence of adverse reactions. early warning signs resulting from the different products as a result of the Eto- The department received 27 496 global pull back on AIDS commitment bicoke inspection, there was evidence reports in 2009, of which 74.9% were and blasts major donors, such as the of “serious and repeat violations” and deemed to be serious enough as to Global Fund to Fight AIDS, Tuberculo- Apotex’s response to the manufacturing require in-patient hospitalization or sis and Malaria and the United States problems has been “inadequate and prolongation of existing hospitalization, President’s Emergency Plan for AIDS lacks sufficient corrective actions.” cause congenital malformation, result Relief (PEPFAR), for stalling or flat-
CMAJ•JUNE 15, 2010 • 182(9) E421 © 2010 Canadian Medical Association or its licensors News lining promised funding (www.itpc 2007, only Botswana, Djibouti, and tml?id=/include/mpr_ndc_finder.inc), global.org/images/stories/doc/ITPC_M Rwanda had met that target. are distributed in Canada, the United TT8_FINAL.pdf). Private donations in the US and States, Dominican Republic, Dubai The report points to increasing caps Europe have also declined. Between (UAE), Fiji, Guam, Guatemala, on the number of people enrolled in 2007 and 2008, US-based philan- Jamaica, Puerto Rico, Panama, treatment programs, drug stock outs thropies decreased spending by about Trinidad & Tobago and Kuwait. and the frequency with which govern- 3%, while funding for European All of the products have been volun- ment-run antiretroviral treatment pro- HIV/AIDS charities dropped by 7%. tarily recalled by McNeil Consumer grams turn patients away at the door as The report tracks the fallout in six Healthcare “in consultation” with the the fallout of domestic and external nations: India, Kenya, Latvia, Malawi, FDA. funding cuts in the wake of the global Swaziland and Venezuela. It says con- “The FDA recommends that con- economic crisis. sequences include severely limited sumers stop using these products,” the “Providing access to AIDS treatment access to antiretroviral treatments, agency stated in announcing the recall for 4 million people has been the most shortages in physicians and nurses to (www.fda.gov/NewsEvents/Newsroom ambitious public health effort in his- provide treatment, and government /PressAnnouncements/ucm210441.htm). tory,” says the coalition board member reliance on outdated AIDS plans, as “As a precautionary measure, par- Gregg Gonsalves. “And after all this well as unreliable data on treatment ents and caregivers should not adminis- effort, we’ve got a few men in Wash- needs. ter these products to their children,” the ington [DC], in London [United King- “Nations with middle-sized FDA states. “Some of the products dom] and in Ottawa [Ontario] saying economies and considerable epidemics included in the recall may contain a maybe it’s time to do something else.” will be able to hold back the flood, but higher concentration of active ingredi- That’s the same as “saying to mil- the poorest countries are already being ent than specified; others contain inac- lions of people: drop dead. Without hit hard by this backtracking,” says tive ingredients that may not meet treatment that is certainly their fate,” Gonsalves. internal testing requirements; and oth- Gonsalves earlier stated in a media “If we don’t pay now, we’ll be pay- ers may contain tiny particles. While release. ing soon,” he adds. “Before the number the potential for serious medical events Created in 2001, the Global Fund of people in hospital beds goes up, is remote, FDA advises consumers who was intended to provide US$10 billion before we see a rise in funerals, the have purchased these recalled products per year to fight AIDS, tuberculosis damage will already be done.” to discontinue use.” and malaria. According to the report, Canada can play a major role in McNeil Consumer Healthcare stated that bold promise was not met; by shifting the trend if Stephen Harper can in a press release that the recall was a 2008, donations topped out at only $3 be convinced to make universal access “precautionary” measure (www.jnj billion per year (www.theglobalfund to treatment a priority at the next G8 .com/connect/news/all/McNeil-Consum .org/en/pressreleases/?pr=pr_100308). meeting, Gonsalves says. “Living south er-Healthcare-announces-voluntary-re The report criticizes US President of the border, we look to Canada for call-of-certain-OTC-infants-and-childrens Barack Obama and UK Prime Minister more progressive policies.” -products). Gordon Brown for failing to honor The report estimated that while “McNeil Consumer Healthcare is their country’s promises to donate a fair some 4 million people have access to initiating this voluntary recall because share toward the Global Fund. Obama HIV treatment, another 6 million peo- some of these products may not meet is also criticized for pledging US$50 ple still need it. — Lauren Vogel, required quality standards,” the com- billion to PEPFAR during his election Ottawa, Ont. pany stated in a press release. “This campaign, but then flat-lining funding recall is not being undertaken on the increases in 2010. basis of adverse medical events.” “I’m deeply disappointed in the Children’s health products The firm added that it is “conducting president, because the US has found recalled a comprehensive quality assessment money for bailouts and huge stimulus across its manufacturing operations and bills over the past 12 months, and what he United States Food and has identified corrective actions that we’re asking comes down to promises Drug Administration (FDA) is will be implemented before new manu- made and promises kept,” says Gon- T advising consumers to stop facturing is initiated at the plant where salves. “A 2.2% increase isn’t keeping using certain over-the-counter infant’s the recalled products were made.” that promise, because it’s effectively and children’s liquid health products The firm’s Canadian branch stated making it impossible to put new people manufactured by McNeil Consumer in a release that the recall in Canada is on treatment.” Healthcare as there may have been “limited to Children’s MOTRIN® and The report also singles out leaders of flaws in their manufacture. Infant’s MOTRIN® liquid suspension 46 African nations for failing to allo- The 40 products, which include products and Children’s TYLENOL® cate 15% of their annual budgets infant and children’s Tylenol®, Cough & Runny Nose liquid suspen- toward health spending, as agreed in Motrin®, Zyrtec® and Benadryl® sion only. No other Canadian product is the Abuja Declaration of 2001. As of (www.mcneilproductrecall.com/page.jh impacted.”
E422 CMAJ•JUNE 15, 2010 • 182(9) News
(www.mcneilcanada.com/en/downloads But many other countries — such as The RCMP said the policy revisions /JJ_Release_on_April30.pdf). — Emily the United States and England — have were made in to recommendations from Panetta, Ottawa, Ont. implemented funding systems in which the Commission for Public Complaints hospitals are rewarded on the basis of Against the RCMP, the province of Ontario introduces health patient outcomes (called payment by Alberta’s guidelines on CEW use and results or pay for performance) or the Braidwood Inquiry into the Oct. 14, care accountability legislation activity-based funding (CMAJ 2008; 2007 death of Polish citizen Robert 178:1207-8). Dziekanski at Vancouver International inking hospital chief executive The provincial government indi- Airport after being shot by a taser officer salaries to patient satis- cated it will be consulting with hospi- (www.rcmp-grc.gc.ca/news-nouvelles L faction and emergency wait tals, local health networks and others in /2010/05-03-cew-ai-eng .htm). times, the adoption of patient-based refining the precise payment system Ian McPhail, interim chair of the funding for larger hospitals and a that will be used. “Among the issues to Commission for Public Complaints requirement that hospitals “develop be considered is how to recognize hos- Against the RCMP called the moves and post annual quality improvement pitals with unique roles, such as acade- “prudent” (www.cpc-cpp.gc.ca/nrm/nr plans” are among measures included mic health centres, as well as those /2010/20100504-eng.aspx ). The com- in proposed Ontario legislation to bol- serving small and rural communities.” mission added in a news release that ster accountability in the province’s The Ontario Hospital Association discussions are ongoing in regard to health care system. called the legislative proposals “an RCMP adoption of other recommenda- “We want our health care system to important next step in continuous qual- tions, “including the need for manda- be focused on patient needs with health ity improvement” (www.newswire .ca tory medical attention after every Taser services supported by the best evidence /en/releases/archive/May2010/03/c808 use, as injuries may not be visible or and highest standards,” said Ontario 0.html). — Emily Panetta, Ottawa, Ont. apparent to the RCMP member, nor Minister of Health and Long-Term will the member necessarily be aware Care Deb Matthews in a press release of any underlying medical conditions (www.news.ontario.ca/mohltc/en/2010/ RCMP restricts use of tasers of the subject. There also remains the 05/improving-health-care-for-ontarians recommendation to generally limit the .html). “Improving quality of care not he Royal Canadian Mounted CEW to members with five years or only means better patient care, it Police has moved to restrict the more of experience (except those on improves the value of our health care T use of conducted energy specialized teams).” — Emily Panetta, investment.” weapons (CEWs) — more commonly Ottawa, Ont. The Excellent Care for All Act, known as tasers — by unveiling a pol- 2010 proposes that hospital CEOS — icy that prohibits the use of the hand- Better a hospital than a 14 of whom earned salaries higher than held weapons except in cases involv- $500 000 in 2009 — would have their ing bodily harm or the clear threat of dumpster compensation and bonuses linked to harm. their facility’s ability to achieve perfor- The policy limits the use of tasers “to reating a drop-off zone for mance targets that are established as situations where a subject is causing unwanted babies is preferable part of their “quality improvement bodily harm, or the police officer C to them being “left in a dump- plans” (www.ontla.on.ca/bills/bills-files believes, on reasonable grounds, that ster,” says the developer of a Vancou- /39_Parliament/Session2/b046.pdf). the subject will imminently cause bod- ver, British Columbia-based initiative Each hospital would be obliged to ily harm” (www.rcmp-grc.gc.ca/ccaps-s that will allow troubled women to establish a quality committee that pcca/cew-ai/operations-17-7-eng.htm). anonymously abandon their newborn would craft the plan and deliver an Other revisions to the policy babies. annual accountability report. As part of include: “It’s not ideal. The ideal would be to the process, hospitals would have to • requiring officers to give a verbal know a little bit about the medical his- regularly conduct patient and employee warning, where tactically feasible, tory for placement of the baby. But it’s satisfaction surveys, as well as ensure so the subject is aware of the immi- preferable to be in a safe place without that a process is in place for handling nent deployment of the CEW, that information then to be left in a patient complaints. • requiring officers to request medical dumpster,” says Dr. Geoffrey Cundiff, The patient-based funding system assistance, when feasible, prior to head of the obstetrics and gynecology for larger hospitals, which will be intro- using the CEW in medically high- department at St. Paul’s Hospital. duced on Apr. 1, 2011, will see facili- risk situations. The “angel’s cradle” initiative ties reimbursed according to the num- • adding further CEW-related record allows a mother to put a baby in a ber and type of patients that they see. keeping requirements, and bassinet in a private area of the hospi- Canadian hospitals have traditionally revising CEW testing procedures to tal, press an alarm with a 30-second received money via a block-funding determine if CEWs are operating delay and then leave. Hospital staff model, which grants annual lump sums. within manufacturer specifications.” would recover and treat the infant and
CMAJ•JUNE 15, 2010 • 182(9) E423 News then hand it over to the Ministry of then we want them to do it in a safe needed to protect the health spending of Children and Family Development to place.” — Emily Panetta, Ottawa, Ont. governments and donors alike.” long-term care and likely, adoption. With regard to the millennium Should a mother want to reclaim her Progress being made on development goal of halving the pro- maternal rights and responsibilities, she Millennium Development portion of people who suffer from would have to negotiate with the min- hunger, for example, the WHO notes istry, Cundiff says. “The ministry is Goals that undernutrition remains “an under- going to pursue what’s best for the baby lying cause in about one-third of all and the mother. If the mother’s circum- lthough progress is being child deaths. Over the past year, rising stances change and she’s healthy, that made in many nations toward food prices coupled with falling could be the best situation for the baby.” A achieving the World Health incomes have increased the risk of mal- Cundiff says he borrowed the notion Organization’s eight health-related nutrition, especially among children” of an angel’s cradle from the so-called Millennium Development Goals, some (www.who.int/whosis/whostat/EN_W “foundling wheels” of 12th-century nations are “falling behind,” the WHO HS10_Part1.pdf ). Europe, which saw the installation of says in an update on efforts to tackle Moreover, “in some countries, the wooden cribs or baby hatches in ill-health by 2015. prevalence of undernutrition has churches and convents for mothers to “Often the countries making the increased, and worldwide stunted growth safely abandon their infants. “I like to least progress are those affected by still affected about 186 million children read history and I had been reading high levels of HIV/AIDS, economic under five years of age in 2005.” about foundling wheels. I thought that’s hardship or conflict,” the WHO says in Similarly, there are regional and actually a good idea,” he says. a fact sheet, Progress towards the national variations in achieving the mil- The proposal was rapidly supported health-related Millennium Develop- lennium development goal of a 67% by the hospital’s senior board. “We ment Goals (www.who.int/mediacen- reduction in child mortality from 1990 spent a lot of time trying to think about tre/factsheets/fs290/en/index.html). levels. “In 2008, the total annual number the ethical and legal ramifications,” Evidence of progress toward achiev- of deaths in children under five years old Cundiff says. “A lot of the work ing the goals includes indicators that fell to 8.8 million — down by 30% from focused on taking the concept to fewer children are dying and fewer are the 12.4 million estimated in 1990. Mor- authorities, Child and Family Develop- underweight. As well, fewer people are tality in children under five years old in ment, and also internally within our contracting HIV, more people have 2008 was estimated at 65 per 1000 live institution — speaking to physicians in access to safe drinking water and more births, which is a 27% reduction from 90 the emergency department, the nursery women have access to help during per 1000 live births in 1990.” care unit and [hospital] security.” childbirth. But the greatest reductions occurred Cundiff adds that using the angel’s Although five years remain to the in the wealthiest households and in urban cradle might be the best option for an 2015 deadline for achieving the targets, areas. The progress has not been unfit mother in desperate circum- improvements in some areas have matched “in countries facing economic stances. “There are women who will already been “striking,” the WHO says. crises or conflicts. Low-income countries abandon their babies out in the commu- “The percentage of underweight chil- would need to increase their annual aver- nity. There’s a reason they’re not using dren [under the age of five] is estimated age rate of decline from 1.9% to 10.9% their resources — maybe they don’t to have declined from 25% in 1990 to in order to achieve the target. Reducing know about them, or maybe they don’t 16% in 2010, HIV infections dropped child mortality increasingly depends want to come forward,” he says. 16% between 2001 and 2008 and the upon tackling neonatal mortality; glob- “There’s a need for anonymity, and we percentage of the world’s population ally about 40% of deaths.” felt this was an approach to reach those with access to safe water has increased The report also suggests there have women and make them aware of the from 77% to 87%, enough to reach the been improvements in child health other options.” MDG target.” interventions, including “the use of Cundiff stresses that the program Nevertheless, challenges remain, insecticide-treated nets to prevent seeks to inform mothers of their options WHO adds. In some countries, malaria; efforts to prevent mother-to- — providing contact information for “progress has been limited because of child transmission of HIV; and vacci- adoption agencies and government ser- conflict, poor governance, economic or nation against hepatitis B and vices — before leaving a child. “All of humanitarian crises, and lack of Haemophilus influenzae type B pneu- our literature, even the sign on the door, resources. The effects of the global food, monia.” — Emily Panetta, Ottawa, Ont. provides other options,” he says. “But if energy, financial and economic crises on they’re going to abandon their baby, health are still unfolding, and action is DOI:10.1503/cmaj.109-3258
E424 CMAJ•JUNE 15, 2010 • 182(9)