Friday, February 28, 2014

Hospitals still facing medication shortages

DES MOINES, Iowa —U.S. hospitals are coping better with ongoing shortages of hundreds of medications, but a new survey indicates obtaining those drugs from alternate sources is costing them hundreds of millions of dollars

Premier Inc., the hospital group that did the survey, conservatively estimates that cost at $230 million a year over three years per hospital.

That doesn't include costs for additional workers or overtime hours for staff searching for scarce drugs, as well as some other extra costs, which come out of hospitals' already razor-thin profit margins.

Shortages of drugs, particularly generic injectable drugs that had been cheap, have escalated since 2005.

While the number of new shortages has declined recently, the total of new and prolonged shortages keeps climbing. Causes include quality problems, recalls and the small number of manufacturers.

Read more:

Thursday, February 27, 2014

Ritalin shortage prompts call for Health Canada changes

Pharmacists say the impact of a current Canada-wide Ritalin drug shortage could have been reduced if Health Canada took a tougher stance on pharmaceutical companies.

The current shortage affects 10 milligram doses of the brand name medication Ritalin, which is made by Novartis Pharmaceuticals, as well as the generic form of methylphenidate hydrochloride.

Ritalin, a stimulant, is commonly prescribed to help treat attention deficit hyperactivity disorder (ADHD).

The shortage is listed on, a website backed by Health Canada, where drug makers can voluntarily post shortage information.
According to the online database, the shortage is expected to last 37 days. The shortage is blamed on an "unexpected increase in demand caused by Gx [generic drug] back order."

Could have been imported

According to Diane Lamarre, the president of the Quebec Order of Pharmacists, Health Canada needs to change its policies to prevent something like this from happening again.

Health Canada does not currently require pharmaceutical companies to report drug shortages, although drug makers may opt to voluntarily alert doctors and pharmacists.

Lamarre said that makes it difficult for pharmacists to deal with shortages.
“It’s a problem. It’s difficult to evaluate clearly," she said.

"When there are drug shortages we may have time to import it from other countries … but each week, each day is important in terms of having time to import this medication.”

For now, Lamarre says patients who use Ritalin will have to rely on alternatives by doubling smaller doses or using long-acting versions of their medication.

Lamarre adds that while using alternative medication might not be ideal, patients have few options.
“It might not suit a child perfectly. Medication choice should be tailored.”

She said patients can ask for a doubled 5-milligram dose, although she warns that supplies could soon run out for that as well.

FDA's plan to ease drug shortages needs work

According to a just-released analysis by the Government Accountability Office, the Food and Drug Administration is doing a better job at preventing drug shortages.

As Center for Drug Evaluation and Research Deputy Director Doug Throckmorton recently told Congress, new shortages declined in 2012 for the first time in a number of years and 2013 data indicated a similar downward trend. He said the agency's new authorities (granted under a 2012 law) have allowed the FDA to manage shortages more aggressively.

In 2010, 178 drug shortages were reported to the FDA. Thirty-eight shortages were prevented by companies voluntarily notifying the agency of potential issues that could lead to shortages; the agency was able to work with the companies to avoid shortages.

Inside CDER resides the agency’s Drug Shortage Program. The program was established to address potential or actual shortages of drugs that have a significant impact on public health. Through communication, facilitation and negotiation, the program works with pharmaceutical manufacturers and components of FDA to manage product shortages.

For example, when the drug shortage involves a generic product, the FDA works with other firms making the drug to help them ramp up production if they are willing to do so. Often they need new production lines or raw-material sources approved to help increase supplies. The FDA can and does expedite review to help resolve shortages of medically necessary drugs.

But the FDA can’t require the other firms to increase or commence production.

The agency tries to do the best it can with limited authority, spare resources and shared staff. In addition to direct communication with industry, the Drug Shortage Program also gets reports from health care professionals, patients and professional organizations using the email address">

But, as you can imagine, there is not a lot of email traffic. And there is no social media effort to promote the program’s purpose or existence.

The FDA’s Drug Shortage Program is a good start, but it’s not getting the job done. The problem is getting worse. The agency needs more authority and greater resources. In short, more needs to happen.

The Institute for Safe Medication Practices reports that in a survey of 1,800 health care practitioners, more than half said they frequently or always encounter difficulties associated with drug shortages.
The top three problems fall squarely within the zone of appropriate FDA attention and action:
-- Little or no information available about the duration of a drug shortage (85 percent).

-- Lack of advanced warning from manufacturers or the FDA to alert practitioners of an impending drug shortage and suggested alternatives (84 percent).

-- Little or no information about the cause of the drug shortage (83 percent).

Survey respondents felt “unsupported by the FDA and are perplexed regarding why the U.S. is experiencing drug shortages of epic proportion that are often associated with third-world countries.”
Should the issues of both authority and funding for the FDA’s efforts to mitigate drug shortages be hung on the Prescription Drug User Fee Act Christmas tree, which authorizes the agency to collect fees from companies that produce certain drug or biological products, or addressed in separate legislation? Either way, it’s an issue that must be addressed with alacrity before it becomes a question of American lives.

In addition to new actions, the FDA has been more willing to demonstrate regulatory flexibility.
For example, in some cases where particles were found to be contaminating a drug that was in short supply, the agency allowed the company to filter the drug to avoid disrupting supplies instead of shutting down the production line altogether.

While the FDA’s new authorities are both timely and important, there are many pieces to the drug shortages problem – not the least of which is that 30 percent of manufacturing capacity of hospital injectables is off-line due to FDA inspection issues.

That’s a lot of capacity. In fact, according to the agency, 43 percent of reported potential shortages were due to manufacturing problems. Safety is non-negotiable and alleviating a shortage by shorting good manufacturing practices is a bad and dangerous pathway. Expediency causes as many problems as it solves.

That being said, regulatory discretion must be part of the solution – and per Throckmorton, it is. With 30 percent of production capacity off-line because of FDA issues, the agency must continue to work with manufacturers to find creative, science-based solutions. If you create a "science- and risk-based action plan," industry can often address quality issues without disrupting supplies of essential drugs.
But who inspects the inspectors? Perhaps the FDA should undertake an agency audit to see why there’s been such a jump in manufacturing issues. It’s hard to believe that year-over-year, production quality control has suffered such a significant lapse. Is there something wrong in the way FDA inspectors (many of them still wet behind the ears and eager to please) are doing their jobs? It’s a question worth asking – and answering.

But the real headline is that artificially low prices are the major cause of drug shortages.
Most of the drug shortages that occur in the U.S. arise in the generics market, where profitability is fairly low. For many of these drugs the market can only sustain a handful of manufacturers -- sometimes just one or two. So, when supply disruptions occur -- caused by manufacturing violations, production delays, shipping problems or ingredient issues -- there aren't a lot (or in many cases any) additional producers in the market to pick up the slack.

In plain English: Artificially low prices caused the manufacturing decline of the drugs that are in short supply, and a variety of perverse government regulations (ranging from Medicaid reimbursement rates to the benighted 340B Drug Pricing Program) contribute to the causes.
Where there is still a profit left, you rarely see shortages.

Congrats to the FDA for a job well begun. But the issue of drug shortages -- and particularly the economic issues that must be addressed -- must not be left half done.

Clinicians Look for Ways To Ease Effects of Saline Shortage

A shortage of IV sodium chloride solution has struck hospitals across the United States, forcing some clinicians to adopt conservative saline measures or to turn to alternative products.

To ascertain the effect of the shortage, the American Society of Heath-System Pharmacists (ASHP) surveyed U.S. pharmacy directors earlier this month. Of the pharmacists who responded, 76% reported that the shortage has affected their institutions. Among the pharmacists affected by the shortage, slightly more than half said conservation efforts have been sufficient to preserve supplies. Pharmacists who indicated their supply of saline was inadequate to fulfill patient needs, on the other hand, represented 29% of respondents.

“While the survey does not point to patients being harmed as a result of the shortage, such a severe shortage of this widely used intravenous solution is extremely concerning,” said Paul W. Abramowitz, PharmD, ScD (Hon.), the chief executive officer of ASHP, in a Feb. 11 statement.

The ASHP survey revealed that the shortage has had a wider influence among certain areas of care than others. An impact on surgery and perioperative care was reported by 64% of pharmacists, whereas 10% of respondents cited an impact on pediatric care.

At St. Jude Children’s Research Hospital, in Memphis, Tenn., clinicians are “weathering the storm,” said William L. Greene, PharmD, St. Jude’s chief pharmaceutical officer. “Conservation efforts have focused on minimizing waste, especially at the bedside, where allowing longer hang times [up to 48 hours] of simple solutions reduces the need for replacement,” Dr. Greene said. Although changing IV bags at 24 hours is a common infection control method due to the perceived increase in risk of contamination over time, a 2009 study found no relationship between length of infusate use and bacterial colonization (J Clin Nurs 2009;18:3022-3028).

Lactated Ringer’s solution, dextrose and other fluids may provide health care systems with alternatives to saline, which 64% of the ASHP survey population report using. But these are not always good substitutions for sodium chloride solution, Dr. Greene noted; certain medications compatible with saline are incompatible with dextrose, for example, including the antifungal agent caspofungin, as well as the antibiotics daptomycin and meropenem. 

The lack of saline has also started to put pressure supply of substitute options. “We’re beginning to see that it’s more difficult to obtain some of the alternative fluids,” Dr. Green said, “but it’s not elevated to the point where anyone would call it a shortage.”

The FDA, meanwhile, is pursuing the importation of sodium chloride, and other forms of saline may be available. Compounded saline or 0.45% sodium chloride solution, for example, could be used as alternatives to 0.9% saline, said Bona E. Benjamin, BS Pharm, the director of Medication-Use Quality Improvement at ASHP. For health care systems that choose to use compounded sodium chloride, purchasers should “make sure [saline] is compounded by an ethical, licensed pharmacy that observes sterile standards,” she said.

There are few details regarding why saline is in short supply. “Apparently, one manufacturer had some production problems, and that shifted demand to other providers,” Dr. Greene said. “This strain on supplies was accentuated when another manufacturer had a scheduled shutdown … for maintenance purposes.  Production levels simply have not returned to levels which meet demand.”

Lookout List

Hospital pharmacy buyers....things to keep your eye on....

Infuvite ADLT
Lactated Ringer 1000ml
Sodium Chloride 1000ml
Vecuronium 10ml

Today's Shortages

Ammonium Molybdate Injection
Ascorbic Acid Injection
Calcium Chloride Injection
Levocarnitine Injection
Neostigmine Methylsulfate Injection
Nitroglycerin Injection
Papaverine Injection
Potassium Acetate Injection
Sodium Phosphate Injection

Wednesday, February 26, 2014

Weekly FDA Enforcement Report For Drugs And Biologics

The Food and Drug Administration (FDA) has released its Drug and Biological product Enforcement Report for February 19, 2014. The agency publicizes recalls in its weekly report as press releases are not issued for all recalls. Manufacturers issue recalls voluntarily or the FDA initiates the action.
Classification I Recall
A Classification I recall signifies a reasonable probability of serious adverse health consequences or death.
  • Biologics: No biologics recalled this week.
  • Drugs: No drugs recalled this week.
Classification II Recall
A Classification II recall signifies that the product may cause temporary or medically reversible adverse health consequences.
  • Biologics: Life Technologies Corporation voluntarily issued a recall for Allset Plus and Invitrogen HLA Typing Assay due to false negative results. Inland Northwest Blood Center recalled Cryoprecipitated AHF and Frozen Plasma due to collection from a donor with a history of Hepatitis after age eleven. Several other blood centers issued Class II recalls this week.
  • Drugs: Watson Laboratories, Inc. from Davies, FL recalled Diclofenac Sodium and Misoprostol Delayed-Release Tablets, 75 mg/0.2 mg in a 60-count bottle for prescription only, due to split tablets in stability samples. Activis, Inc. recalled Relstar (triptorelin pamoate) Injectable Suspension due to a labeling error. Mylan Pharmaceuticals Inc. recalled Levothyroxine Sodium Tablets, USP, 200 mcg in a 100-count bottle, available by prescription due to subpotency during stability testing. Caraco Pharmaceutical Laboratories Ltd. recalled Oxcarbazepine Tablets, 300 mg in 100 tablet bottles due to broken tablets.
Classification III Recall
A Classification III recall signifies that the product is not likely to cause adverse health consequences.
  • Biologics: Blood Centers of the Pacific - Irwin Center recalled Red Blood Cells Deglycerolized Leukocytes Reduced. Antigen Laboratories Inc. recalled Bermuda Grass Pollen Allergenic Extract due to subpotency. 
  • Drugs: Bracco Diagnostics Inc. issued a recall nationwide and to Puerto Rico for VoLumen Barium Sulfate Suspension (0.1 % w/v, 0.1 ww/w) in a 450 mL bottle, available by prescription only. The recall was due to failed stability testing.

Tennessee gets new rules on compounding pharmacies

More than six months after they were first approved, new rules governing the operation of compounding pharmacies in Tennessee have passed legal muster and gone into effect.
The rules, issued by the state Board of Pharmacy, were drawn up in reaction to a nationwide outbreak of fungal meningitis that hit particularly hard in Tennessee. Sixteen Tennessee patients died after being injected with fungus-tainted spinal steroids shipped from a Massachusetts drug compounding firm.
Reginald Dillard, executive director of the pharmacy board, said the final version of the rules won approval from the state attorney general and went into effect late last month.
The panel was forced to drop from the lengthy package provisions that would have empowered the board or the state health commissioner to order the immediate shutdown of a pharmacy without first holding a hearing.
“There is no provision for an immediate cease-and-desist order,” Dillard said. “We can’t just shut someone down.”
The rules do, however, set in place new requirements for pharmacies that compound drugs.
Drug compounders are now required to disclose to state regulators what sterile drugs they are compounding and maintain records of the patients or health facilities to which those drugs were shipped.
The rules also require that compounding pharmacies submit quarterly reports to the state board and establish quality assurance programs. Training programs for those compounding the drugs are also mandatory.
Other requirements include special labeling, including specific warnings of possible adverse effects.
Dillard said the rules do allow the board to issue a summary suspension order, but an actual shutdown cannot be ordered until a hearing is held.
The rules also require that drug compounders comply with federal sterility standards, Dillard said.
The board and its staff are still reviewing a new federal law on drug compounders to see whether it will require any changes at the state level. The panel must also come up with a permanent version of the compounding regulations.
“We hope to have that done by May,” Dillard said.
The fungal meningitis outbreak has been blamed on the now-defunct New England Compounding Center, which shipped thousands of vials of fungus-tainted methylprednisolone acetate to Tennessee and 19 other states.
Overall, 64 patients died and 751 were sickened, 153 of them in Tennessee.

Tuesday, February 25, 2014

Despite New Pharmacy, Federal Judge Denies Stay Of Execution For Missouri Inmate

A federal judge has said Wednesday's execution may proceed.
District Judge Beth Phillips denied Missouri inmate Michael Taylor's requests for stays of execution early Monday morning. Her ruling has been appealed to a higher court.
Taylor asked for his execution to be delayed for three reasons.
1. Missouri changed its drug supplier at the last minute.
For the past three executions, the Missouri Department of Corrections bought its supply of pentobarbital from an Oklahoma compounding pharmacy called the Apothecary Shoppe.
Compounding pharmacies aren't like drug manufacturers. Drug manufacturers are regulated by the Food and Drug Administration, while compounding pharmacies are not. Manufactured drugs have a high assurance that the drugs are of a certain quality, while compounding pharmacies' products have a much higher failure rate.
Compounding pharmacy's drugs are made for specific prescriptions so they vary from batch to batch. Taylor argued that the new pharmacy hasn't been investigated to see if the business is reputable or has been cited in the past for shoddy practices.
Phillips was not swayed.
"By selecting an unknown pharmacy, [the state] may have changed the members of the execution team, but they have not altered the protocol in any way," Phillips wrote. "Here, the pharmacy is yet again unknown," as was the case for last November's execution. Taylor has "not presented new evidence to the court."
2. The Supreme Court has been asked to intervene.
In a previous ruling, the Eighth Circuit Court of Appeals said that for an inmate to prove the execution method is cruel and unusual punishment, he has to propose an available alternative.
Taylor's attorneys appealed that ruling to the U.S. Supreme Court, arguing that they cannot find out the necessary information to propose an alternative. The state has made it illegal to name the pharmacy supplying Missouri with its execution drug and has gone to great lengths to keep the identity hidden.
After asking the Supreme Court to intervene, the high court requested further filings from the state. Taylor said the Supreme Court's interest should pause his execution.
"Even then, after requesting a further response, the probability that the Supreme Court would [listen to arguments in this case] is only 8.6 percent," Phillips ruled. "A-less-than-10-percent chance is not a reasonable probability," she said.
3. The attorney general has shown disregard for the courts.
Missouri's drug source isn't the only point of controversy in the state's execution methods. It's also the state's timeline.
For the past three executions, Missouri carried it out while the inmates still had appeals pending. It's a tactic that legal experts say only Missouri employs.
The attorney general's office has been criticized for this action by two federal judges. But ultimately, Phillips thought this, too, did not warrant a stay.
Missouri's execution procedure states the inmate "may be escorted to the execution room if no stay is in place and no legal activity is in process to prevent the execution."
"Taylor has not established that the alleged violation of the written procedure is a core aspect of the procedure," Phillips wrote.
The judge says the state's failure to follow this procedure doesn't necessarily mean a violation of the Eighth Amendment, which prohibits cruel and unusual punishment.
Taylor is facing the death penalty for abducting, raping and killing a 15-year-old girl in 1989.
Monday's rulings have been appealed to the Eighth Circuit Court of Appeals, the conservative court that previously ruled the inmates have to propose an alternative method of execution. However that court rules this time, the decision is likely to be appealed again to the Supreme Court.

Drug Shortages Continue to Vex Doctors

Despite efforts by the Obama administration to ease shortages of critical drugs, shortfalls have persisted, forcing doctors to resort to rationing in some cases or to scramble for alternatives, a government watchdog agency said on Monday. The number of annual drug shortages — both new and continuing ones — nearly tripled from 2007 to 2012.
In recent years, drug shortages have become an all but permanent part of the American medical landscape. The most common ones are for generic versions of sterile injectable drugs, partly because factories that make them are aging and prone to quality problems, causing temporary closings of production lines or even entire factories.
The analysis by the United States Government Accountability Office, released Monday, was required by a 2012 law that gave the Food and Drug Administration more power to manage shortages. The watchdog agency was designated to evaluate whether the F.D.A. had improved its response to the problem, among other things.
The accountability office concluded that the F.D.A. was preventing many more shortages now than in the past — 154 potential shortages in 2012 compared with just 35 in 2010 — but that the total number of shortages has continued to grow. In 2012, the number of drugs in short supply, both new and long-term, was 456, the report said, up from 154 in 2007. Such drugs now include the heart medicine nitroglycerin, and cisatracurium, which is used to paralyze muscles during surgery and for patients on ventilators.
“We are at a public health crisis when we don’t have the medicines to treat acutely ill patients and we don’t have the basics like intravenous fluids,” said Erin Fox, a drug expert at the University of Utah whose data was used in the analysis. The most acute shortage now is that of basic IV fluids, she said.
Dr. Douglas C. Throckmorton, a senior F.D.A. official who deals with shortages, pointed out in testimony on Monday at a Congressional hearing on the matter that the number of new shortages declined in 2012 for the first time in a number of years, and that 2013 data indicated a similar downward trend. He said the agency, endowed with new powers under the 2012 law, has been able to manage shortages more aggressively.
Manufacturers are now required to alert the agency of potential shortages before they happen. And agency officials have been careful when using their regulatory muscle.
For example, in some cases where particles were found to be contaminating a drug that was in short supply, the agency allowed the company to filter the drug to avoid disrupting supplies instead of shutting down the production line altogether.
What drives shortages is often a mystery. The drug industry rarely spells out the precise reason for a shortage, citing its need to protect competitive trade information.
The 2012 law required that companies provide the F.D.A. with a general reason, but Ms. Fox said that it was often not specific enough to understand the particular causes of a shortage. Dr. Throckmorton said that two-thirds of the production disruptions that led to shortages were caused by quality problems and efforts to fix them.
Economic factors are also a contributing factor. Narrow profit margins are making some drug companies reluctant to invest in fixing old production facilities. Changes in Medicare reimbursement and the role of group purchasing organizations, which buy drugs on behalf of hospitals, could also be contributing, by further reducing prices that producers get for the drugs.
And in a peculiarity of the generic drug industry, a drug is often made by only a few producers, making it difficult to mitigate the effects of a shortage when it happens. The accountability agency’s report cited a study that found just three manufacturers produced 71 percent of the country’s sterile injectable cancer drugs in 2008.
What is more, generic drug producers have significantly ramped up the number of drugs they are producing, pumping out many different drugs on a single production line, which stretches already limited factory capacity and creates a situation ripe for quality problems, the report said.
One study it cited found that production in the sterile injectable market had increased by half between 2006 and 2010, without a similar rise in manufacturing capability. Manufacturers, motivated by profit, will often choose to increase production of higher profit drugs on their busy factory floors, even if that means risking a shortage of less profitable drugs.
The accountability office praised the F.D.A. for increased nimbleness, and acknowledged that it could not ultimately force drug companies to produce. But it said the agency needs to use its drug databases, not just to track which drugs are running low, but also to identify patterns that can help prevent shortages.

Lookout List

Buyers....keep your eyes on..

Cefazolin 2 Gm Duplex 50ml 
Sodium Chloride 1000ml 
Solu-Medrol 125

Today's Shortages

Calcium Acetate Capsules
Ceftazidime Injection
Chorionic Gonadotropin (Human) Injection
Cisatracurium Injection
Dihydroergotamine Mesylate Injection
Doxorubicin Liposomal Injection
Ezetimibe and Atorvastatin Tablets
Gentamicin injection
Haloperidol Decanoate Injection
Heparin Sodium Injection
Iron Sucrose Injection
Lomustine Capsules

Monday, February 24, 2014

Lookout List

Hospital buyers...things to keep your eyes on...

Adenosine 2ml 
Bumetanide 4mL 
Cefazolin 1GM 
Lac Ringer 1000ml 
Neostigmine 1:1000 
Sod Chl 500ml 
Sodium Chloride 1000ml 

Today's Shortages

Adenosine Injection
Bumetanide Injection
Clindamycin Injection
Cytarabine Injection
Dexamethasone Sodium Phosphate
Diltiazem Injection
Empty Evacuated Containers
etomidate Injection
Fluorouracil Injection
Haloperidol Lactate Injection
Lactated Ringer’s Injection Bags
Nicardipine Hydrochloride Injection
Vancomycin Hydrochloride Injection

Sunday, February 23, 2014

Europe’s hostility to capital punishment at root of U.S. execution drug shortage

Brussels • There’s one big reason the United States has a dearth of execution drugs so acute that some states are considering solutions such as firing squads and gas chambers: Europe won’t allow the drugs to be exported because of its fierce hostility to capital punishment.

The phenomenon started nine years ago when the EU banned the export of products used for execution, citing its goal to be the "leading institutional actor and largest donor to the fight against the death penalty." But beefed up European rules mean the results are being most strongly felt in the United States now, with shortages becoming chronic and gruesome executions making headlines.

In Ohio last month, Dennis McGuire took 26 minutes to die after a previously untested mix of chemicals began flowing into his body, gasping repeatedly as he lay on a gurney. On Jan. 9, Oklahoma inmate Michael Lee Wilson’s last words were: "I feel my whole body burning."

The dilemma again grabbed national attention this week when an Oklahoma pharmacy agreed Monday to refrain from supplying an execution drug to the Missouri Department of Corrections for an upcoming lethal injection. Death row inmate Michael Taylor’s had argued in a lawsuit that recent executions involving the drug pentobarbital would likely cause "inhumane pain" — and, ahead of a hearing set for Tuesday, The Apothecary Shoppe said it would not provide the drug.

EU nations are notorious for disagreeing on just about everything when it comes to common policy, but they all strongly — and proudly — agree on one thing: abolishing capital punishment.

Europe saw totalitarian regimes abuse the death penalty as recently as the 20th century, and public opinion across the bloc is therefore staunchly opposed to it.

The EU’s uncompromising stance has set off a cat-and-mouse game, with U.S. corrections departments devising new ways to carry out lethal injections only to hit updated export restrictions within months.

"Our political task is to push for an abolition of the death penalty, not facilitate its procedure," said Barba Lochbihler, chairwoman of the European Parliament’s subcommittee on human rights.

Europe’s tough stance has caused U.S. states to start experimenting with new drug mixtures, even though convicts’ lawyers and activists argue they increase the risk of painful prolonged death and may violate the constitutional ban on cruel and unusual punishment.

In an upcoming execution in Louisiana, the state is set to follow Ohio’s example in using the untested drug cocktail used in McGuire’s execution. It changed its execution protocol last week to use Ohio’s two-drug combination because it could no longer procure pentobarbital, a powerful sedative.

The execution was scheduled for February, but was stayed pending a federal judge’s examination in April regarding whether the state can proceed with the plan to execute Christopher Sepulvado, convicted in the 1992 killing of his 6-year-old stepson.

In 2010, Louisiana switched from the established three-drug protocol to a one-drug pentobarbital lethal injection, but eventually that drug also became unavailable because of European pressure.

"The lethal injection that they are using now in certain states has never been tested, verified, let alone been approved for executions," said Maya Foa of Reprieve, a London-based charity fighting the death penalty. "This amounts to using humans as guinea pigs. No doctor would ever do that."

Ohio prosecutors counter that condemned inmates are not entitled to a pain-free execution under the Constitution.

Even if the effect of the two drugs used by Ohio "presents some inherent risk of discomfort, that does not amount to cruel and unusual punishment," Christopher Conomy, an assistant Ohio attorney general, argued in court documents last month.

The U.S. execution dilemma goes back to 2005, when the EU restricted exports of goods "for the purpose of capital punishment or for the purpose of torture." That ban includes items such as electric chairs and lethal injection systems.

The drug shortage then started biting in 2010 when Hospira Inc., the sole U.S. manufacturer of sodium thiopental, a sedative that is part of the normal three-drug mixture, stopped production. A few months later, Hospira dropped plans to produce it in Italy because the government there asked for guarantees that it would never be used in executions.

States in 2011 switched to pentobarbital, but Denmark-based Lundbeck Inc., the drug’s only U.S.-licensed maker, faced a public backlash and quickly said it would put the medication off-limits for capital punishment through a tightly controlled distribution system.

Fearing for their reputation, the companies never wanted to see their drugs used in executions.

As U.S. authorities started looking for other sources, Britain went ahead and restricted exports of sodium thiopental and other drugs at the end of 2010.

"This move underlines this government’s ... moral opposition to the death penalty in all circumstances," Business Secretary Vince Cable said then.

Germany’s government also urged pharmaceutical companies to stop exports, and the country’s three firms selling sodium thiopental promised not to sell to U.S. prison authorities.

The EU then updated its export regulation in late 2011 to ban the sale of eight drugs — including pentobarbital and sodium thiopental — if the purpose is to use them in lethal injections.

That produced a flurry of action in the United States. In May 2012 Missouri announced it would switch to using the anesthetic propofol, infamous for its role in Michael Jackson’s overdose death. But propofol, too, was manufactured in Europe, by Germany’s Fresenius Kabi.

Missouri’s plan prompted an outcry across Europe and the EU threatened to restrict propofol exports. That in turn provoked a medical outcry in the U.S. because propofol is used in about 95 percent of surgical procedures requiring an anesthetic, according to the American Society of Anesthesiologists.

Fresenius Kabi, whose slogan is "caring for life," swiftly moved amid a blitz of bad PR and EU threats to introduce a stringent distribution control to prevent sales to U.S. prisons. Another manufacturer, Germany’s B. Braun, immediately followed suit.

In October 2012 Missouri Governor Jay Nixon expressed indignation, saying state and federal court systems, not European politicians, should decide death penalty policy. Still, a month later he backtracked and halted what was to have been the first U.S. execution using propofol.

Missouri and other states have since also resorted to custom-made batches of drugs, while refusing to divulge which pharmacy produced them — as in the case being heard Tuesday.

The secrecy has led to new lawsuits, not least after safety concerns over such drugs arose in 2012 after contaminated injections from a Massachusetts facility caused a meningitis outbreak that killed 64 people and sickened hundreds.

An attorney for McGuire’s family supported the European position.

"I think it’s right for the (pharmaceutical) companies to draw a line when people are using the drugs for the wrong purposes," said Jon Paul Rion.

Drug Shortages Exacerbated by Supply Chain Woes

Assigning responsibility for the costs linked to maintaining adequate supplies of medications is at the heart of the medication shortage issue, says one pharmaceutical economist.

New rules and greater cooperation between major players appear to be leveling off a spike in medication shortages that began nearly a decade ago. But with at least 38 new drug shortfalls last year, providers are continuing to scramble to make sure the best treatments are available to their patients.

"We, on a routine basis, have to deal with shortages of medication that require mitigation," said Dan Johnson, director of pharmacy services at St. Anthony's Medical Center in St. Louis. When shortages occur, the hospital's pharmacists coordinate with the medical staff, wholesalers, and manufacturers to find alternate therapies or new sources for scarce medications.

In some cases, Johnson says the only option is to "restrict the drug to the patients who really need it."
Erin Fox, director of the Drug Information Service at the University of Utah in Salt Lake City, says a recent shortage of oncology drugs demonstrates the potentially severe consequences for patients.
"When you have a limited supply, you have to decide which patients will get a medication and which might not," Fox said, noting "there is no other effective alternative" for several cancer medication regimens.

"That's a really hard position for providers to be in," she said.

FDA Drug Shortage Report

 In July 2012, the Food and Drug Administration Safety and Innovation Act became law. In addition to requiring drug manufacturers to provide timely notice of impending or unexpected medication shortages, FDASIA required the FDA to issue annual reports on pharmaceutical shortfalls.

The federal agency released its first "Annual Report on Drug Shortages" this month, with the research focusing on the first three months of 2013. The report notes a slowing in the rate of new medication shortages.

"While the number of new shortages… quadrupled from approximately 61 shortages in 2005 to more than 250 in 2011, after actions by the FDA working with stakeholders, that number significantly decreased in 2012 to 117 shortages. However, shortages continue to pose a real challenge to public health," the report states.

The FDA report indicates reforms in recent years such as FDASIA are having an impact.

"As a result of recent actions by the President, Congress, and FDA, manufacturers are notifying FDA about potential shortages earlier than in the past. Early notification of potential shortages gives FDA additional time to work with sponsors and other groups to identify ways to maintain treatment options and prevent a shortage," the report states.

"Using a range of available tools, including regulatory flexibility when appropriate, FDA's Center for Drug Evaluation and Research (CDER) worked with manufacturers to successfully prevent 140 shortages from January 1 to September 30, 2013. In addition, the number of new shortages tracked by CDER for this same time period is 38, compared to the 117 new shortages during calendar year 2012."

The federal agency can choose from a suite of responses when a drug shortage is reported, including:
  • Determining whether other manufacturers are willing and able to increase production.
  • Expediting FDA inspections of manufacturers attempting to restore production.
  • Working with affected manufacturers to investigate the root cause of a shortage.
Bearing the Cost

 "It's a very complex problem. If we could fix it tomorrow, it would be great, but that's unlikely," said Cynthia Reilly, director of the medication safety and quality division at the American Society of Health-System Pharmacists.

"We really can't hold one party responsible for drug supply," she said. "Realistically, part of the reason we have great drugs to treat patients is we have a free market."

Enrique Seoane-Vazquez, PhD, an associate professor at the Massachusetts College of Pharmacy and Health Sciences University in Boston, said assigning responsibility for the costs linked to maintaining adequate supplies of medications is at the heart of the drug shortage issue.

"If a hospital doesn't have a medication, nobody is responsible even if you die," said Seoane-Vazquez, who serves as director of MCPHSU's International Center for Pharmaceutical Economics. "This is the main problem… the lack of responsibility."

He said the players at the opposite extremes of the supply chain—manufacturers and healthcare providers—would face significant costs if they were compelled to bear the burden of avoiding drug shortages alone.

"They don't produce an extra amount in case there is a shortage," Seoane-Vazquez said of pharmaceutical companies. "They produce enough to satisfy the needs of their clients."

For hospitals, stockpiling supplies of medications presents a financial drain, he said. "Hospitals could be required to have the medications to meet the needs of their patients, but it will cost you more," Seoane-Vazquez said.

Transparency Needed

 In addition to sorting out the economic imperatives of operating a robust medication supply chain, Fox said boosting transparency in the pharmaceutical industry is needed to ensure a steady supply of quality medications. The University of Utah College of Pharmacy faculty member said the common practice of drug companies contracting out medication lines is problematic.

"Just like our food, we need to know where our drugs are coming from," Fox said. "Some companies are forthcoming with that information and some companies are not… I want to know: is that product quality, or is it going to be recalled? I want to know those medicines are safe."

Fox said the shortage of medications is particularly acute for injectable drugs, noting there are fewer than 10 manufacturers worldwide.

In a prepared statement earlier this month, Ralph Neas, president and CEO of the Generic Pharmaceutical Association, said his group's members are playing a key role in providing a supply of affordable medications to patients around the world.

"Generic pharmaceuticals play a critical role in any strategy to hold down health costs," Neas said. "We will continue to work with policymakers to ensure any proposed laws and regulations do not undo the framework responsible for decades of more affordable generics and trillions of dollars in savings."

Neas describes 2013 as "a year of milestone achievements" for the generic drugs industry. "Generic utilization hit an all-time high as 84 percent of prescriptions dispensed are now generic," he said.
"Congress passed the Drug Quality and Security Act to establish a nationwide, reliable system for tracking prescription medicine that further safeguards our nation's prescription drug supply and protects patients. The law also enhances the ability of regulators to limit risks posed by counterfeit or adulterated products and reassures patients that the generic medicines they receive are secure from the manufacturer all the way to the pharmacy."

Embracing Shared Responsibility

 St. Anthony's pharmacy director says the best way to achieve a permanent solution to the nation's drug shortage problem is through teamwork among the players in the supply chain. "We're all part of the problem," Johnson said. "We all need to work together."

The new FDA shortage reporting rules are seen as a significant step toward greater cooperation. "That gives us a chance to allocate drugs before we run out," he said.

"It really is a situation that we are all in it together," Johnson said. "If we don't work together… sometimes we make these situations worse."

Cancer patients given contaminated drugs

The health of 17 Queensland cancer patients had been put at risk after they were given a contaminated batch of cancer drugs.

Doctors are closely monitoring the health of the patients, amid fears the drugs could post a major risk to their weakened immune systems, the ABC reports.

Acting Deputy Director General of Queensland Health Jeannette Young says the patients were given the drug as part of their chemotherapy regimes at public and private hospitals across the state.
Affected stocks have since been recalled.

The Therapeutic Goods Administration (TGA) last week issued a recall notice in relation to the drugs, the ABC said.

Dr Young said as soon as the advice was issued, doctors across the state were alerted.

None of the affected patients have so far shown any adverse reactions but they will continue to be watched closely, she said.

Demand for compounded drugs grows as awareness increases

Michael Stringer mixed powders in a bowl Friday, grinding and stirring with mortar and pestle like a druggist from an earlier time.

Stringer, who owns Doctors Center Pharmacy on West Main Street, is one of a growing number of pharmacists practicing the old-school craft of compounding drugs.

Compounding is used when ready-made pharmaceuticals won’t work. Whether a patient is unable to swallow pills or needs a nausea medication made into a cream, compounding pharmacists can usually tailor the product to the patient.

“It can be as simple as flavoring (a drug for a child),” said Stringer, who has been compounding drugs since he started practicing pharmacy 22 years ago.

While the bulk of Stringer’s business continues to be in ready-made drugs, his compounding work has boomed in recent years.

Since 2005, he’s seen an increase in the number of people seeking individualized drugs for everything from hormone replacement therapy to topical pain creams to a cat’s behind-the-ear thyroid medication gel.

So, what’s changed?

“Patients are more informed,” he said. “If I have to come up with one thing, that would probably be it. Patients are more informed about what they want and need as far as their healthcare.”

On average, Stringer said he fills about 500 to 600 compounding prescriptions a month. While it doesn’t sound like much compared to the 7,000 to 8,000 regular prescriptions filled, the compounding work is far more time-consuming and meticulous.

Regular prescriptions are often filled in a matter of minutes, but compounded drugs are specially-made on site. Because of that, they usually have at least a 24-hour turnaround, Stringer said.
Compounded drugs can be slightly pricier, as well, he said. That’s partly because of the time it takes to mix them and partly because of the expensive equipment involved. The price of the drug also is important, he said.

Stringer’s compounding lab cost about $50,000, but other labs can be more or less depending on the needs of a pharmacist’s patients.

While most of the news on compounding drugs has been positive, the Food and Drug Administration recently got involved after several people died from drugs that were made in a compounding pharmacy, then shipped all over the country.

The result was a federal act requiring all compounding pharmacists to submit to FDA inspections, as well as other regulations.

Pfizer Resumes Levoxyl Shipping

Pfizer Inc. will resume shipping a thyroid-disorder drug that was in short supply for the past year after a manufacturing-quality lapse prompted a recall, one of many drug shortages that have dogged the industry in recent years.

Pfizer said in a letter to doctors this month it expected the drug, Levoxyl, to be available in U.S. retail pharmacies around March 3. The company said in its letter it is offering eligible patients a 30-day free trial of Levoxyl, in an apparent effort to win back market share lost during the shortage. Pfizer didn't immediately provide further comment.

The Levoxyl shortage was disruptive because it forced patients and doctors to switch to alternative drugs. Some patients said they experienced new side effects with other drugs, such as hair loss, or had to pay higher out-of-pocket costs for alternatives.

Levoxyl is approved to treat hypothyroidism, a deficiency in the body's production of certain hormones, and to treat and prevent goiter. Patients typically take the drug every day on a continuing basis.

Pfizer stopped shipping the drug in February 2013 after receiving complaints of uncharacteristic, plasticlike odors in the product. Pfizer attributed the odor problem to an oxygen-absorbing canister packaged in certain bottles to enhance product stability. The company recalled about 52,000 bottles of the product because of the odor.

When Pfizer suspended shipments last year, it said Levoxyl may not become available again until mid-2014 because it would take time to evaluate and implement changes to the product.

Pfizer has corrected the problem with the oxygen-absorbing canister and has resumed manufacturing of the product, it said in its letter to doctors this month.

Pfizer acquired Levoxyl with its $3.6 billion purchase of King Pharmaceuticals in 2011. The company doesn't disclose sales of the product.

Some alternatives for patients include AbbVie's Synthroid and generic drugs that contain the same active ingredient as Levoxyl.

Jeffrey Garber, an endocrinologist with Harvard Vanguard Medical Associates in Boston, said his practice had to switch about 1,000 Levoxyl users to alternative drugs including Synthroid and a generic drug made by Mylan Inc. The practice hired a part-time staffer to help notify patients they needed to switch and then undergo blood tests to ensure the new drug was working properly.

Dr. Garber said some patients complained of not feeling right after switching to alternatives, with some experiencing side effects such as hives. But many have adjusted to new medications, he said.
Citing the cumbersome process of switching, Dr. Garber said he is unlikely to proactively switch patients back to Levoxyl unless they specifically ask for it. "What would possess anyone to switch again?" he said.