Today's Shortages

ASHP/FDA
Adenosine Inj.
Atorvastatin Tablets
Bupivacaine nj
Cefotetan Disodium Inj.
Cisatracurium Inj.
Erythromycin Lactobionate Inj.
Mannitol Inhalation Capsules
Octreotide Inj.
Sincalide Inj.
Sodium Cvhloride 0.45% Inj. Bags

State legislation would tighten controls on compounding pharmacies

Compounding pharmacies in Michigan may soon operate under a system of tighter controls and regulations, and employees could face felony charges and prison sentences if patients are injured or die because the new rules are not followed.

The aim behind Senate bills 704 and 904, sponsored by Sen. Joe Hune, R-Hamburg, is to prevent the kind of injuries and deaths suffered in the state two years ago when the Framingham, Mass.-based New England Compounding Center allegedly sent tainted medicine to clinics around the country.

Michigan was the hardest hit when the tainted steroids were delivered to clinics in the state, resulting in 264 infections and 19 deaths. Nationwide, the death count hit 64 with 751 cases of fungal infections or meningitis, according to the Centers for Disease Control and Prevention.

"Hearing from constituents that have been so adversely impacted by these tainted steroids, it's the least we can do," Hune said.

Compounding pharmacies mix and assemble pharmaceuticals to create a drug or form of medicine needed by a patient.

Hune's bills would add a series of requirements for these businesses, including that accurate records of its procedures are maintained, that the pharmacies are subject to a physical state inspection once every two years and that all compounding pharmacies designate a "pharmacist-in-charge" responsible for making sure the business follows the state regulations.

The criminal penalties for violating the rules that result in personal injury include a maximum of a four-year prison sentence. A violation that resulted in a patient death would carry a maximum 15-year sentence.

The legislation would also give the state the ability to immediately suspend the pharmacy license of the business if notice was received by the CDC or the Food and Drug Administration of imminent risk to public health or safety.

Attorney General Bill Schuette's office has been working with Hune on the bill, and supports the legislation he says will protect patients and hold pharmacists accountable.

"We can never undo the damage experienced by the victims of this meningitis tragedy, but we have a responsibility to find justice and ensure this never happens again," Schuette said in a statement to Crain's. "There is nothing more important than patient safety, and our laws should reflect that commitment."

The bill received its first hearing Thursday before the Senate Health Policy committee, and several organizations testified in support of it. No one voiced opposition.

Kelly Elizondo, state assistant attorney general, said she has handled a half-dozen licensing actions involving compounding pharmacies, and the legislation could save lives.

Compounding pharmacies currently do not have to create or keep records of the calculations or formula used to fill a prescription, she said. A recent case she worked on involved a pharmacist at a compounding pharmacy who made an error when mixing components of the medication.

The pharmacist was supposed to include 0.6 grams of the active ingredient of the drug, and instead included 6 grams of the ingredient, resulting in great harm to the patient, who had to be hospitalized, she said.

The record-keeping requirements in Hune's bills would have made a difference, she said, because it would require the pharmacist to record the strength, quantity and dosage of the compounded pharmaceutical, the formula used and the mixing instructions, all ingredients, the date of preparation and the name of the person who conducted the compounding.

"If that pharmacist had the formula and had been writing down what he was doing, I firmly believe he would have caught his error, and this gentleman would have been spared hospitalization," Elizondo said. "This is a very good bill that could save patient lives."

The record keeping also would assist investigators if there was an outbreak of illness, so that it could be traced back easily to the source. Part of the problem with the tainted steroid case in 2012 was that the company in Massachusetts was allegedly acting as a manufacturer of compounded pharmaceuticals -- making batches of steroids and selling them to clinics across the country -- rather than making a specific drug linked to a prescription for a specific patient.

That practice was also found to be going on in Michigan after the Department of Licensing and Regulatory Affairs inspected every compounding facility in the state after the news came out about the tainted steroids.

Those pharmacies changed their practices, and many compounding facilities updated their facilities to make sure they were compliant with state and federal laws following the inspections, according to LARA, which supports Hune's bill.

Larry Wagenknecht, chief executive officer of the Michigan Pharmacists Association, whose organization includes those working in compounding pharmacies, said he supports the bill as do the vast majority of compounding pharmacies.

However, he said there could be unintended consequences, if some of the compounders feel the penalties are not worth the risk of operating in the state, and may get out of the business.

Sen. James Marleau, R-Lake Orion, chairman of the Health Policy Committee, said the legislation could be approved and sent to the full Senate at next week's hearing.

http://www.crainsdetroit.com/article/20140427/NEWS/304279971/state-legislation-would-tighten-controls-on-compounding-pharmacies#

Rationing Salt Water — Disaster Planning and Daily Care Delivery

Over the past several years, drug shortages have continued to complicate the routine delivery of health care in the United States. The Food and Drug Administration (FDA) is currently tracking nearly 100 shortages resulting from a host of causes, such as the consolidation of markets and manufacturers, limited availability of raw materials, and quality problems resulting in product recalls and delivery interruptions (see Examples of Drug Shortages Listed on the FDA Website for examples).1

Clinicians have become accustomed to these deficiencies, and they troubleshoot accordingly. Yet there are important implications for the quality and safety of patient care, since clinicians must regularly negotiate unfamiliar drug alternatives, concentrations, or dosing strategies. Shortages also have significant budgetary implications. For example, according to some of our colleagues, in 2012 doxycycline sold for a penny a tablet, yet because of a cascade of manufacturer shutdowns and discontinuations, the current price is at least $1.59 per tablet.

Current critical shortages of vecuronium, intravenous nitroglycerin, and lorazepam have required the hospitals where two of us work to adopt contingency measures, including, in one case, providing explicit, written direction about substitutions for intravenous nitroglycerin. Complicating the ability to substitute, however, are further shortages of potential replacement medications. Nicardipine and a component of nitroprusside drips, thiosulfate, are both in short supply.

The national shortage of normal saline, however, represents a new chapter in supply shortages.2The administration of normal saline (and other crystalloids) is a basic underpinning of patient care. In many ways, it is more the lifeblood of hospital care than blood itself. As supply-chain disruptions have caused a shortage of saline, demand for alternatives has spiked, causing a ripple effect. As hospitals increase their product orders to compensate for the shortage, the backlog of orders awaiting delivery grows. The fact that health care facilities would have to ration the use of such a fundamental resource is perhaps the most significant demonstration yet of the importance of addressing these vulnerabilities.

So what should we do? Drug shortages provide the opportunity, if not the imperative, to apply emergency-management methods to the daily delivery of care. Using these “disaster-response” tools on a day-to-day basis offers a systematic, coordinated approach and also prepares institutions to deploy them more effectively during a large-scale disaster.

Four foundational elements of emergency management — mitigation, preparedness, response, and recovery — provide a framework that health care institutions can use to grapple with the everyday challenge of drug and other product shortages. Mitigation involves preventing the incident from occurring or blunting its impact through design or system changes. The FDA has taken proactive steps, in partnership with manufacturers and others, to prevent or reduce the effects of shortages. Through a range of approaches, such as early notification, expedited inspections, and regulatory flexibility, the FDA helped prevent 282 shortages in 2012 and 170 shortages in 2013. These successful efforts provide strong groundwork on which to build greater transparency and supply-chain monitoring into our daily systems, although a recent report of the Government Accountability Office suggests that there is still room for strengthening responses to drug shortages.3

Preparedness activities involve making plans and obtaining adequate supplies. Health care institutions can take these steps by determining who has what authority (e.g., for purchasing or new vendor agreements), roles, and responsibilities for incident management during supply shortages; stockpiling vital supplies during times of no shortage; identifying backup vendors; and finding partners, such as other health care institutions, that can collaborate and share information and resources during a shortage.

During an active drug shortage or other crisis, the plans and partnerships developed during preparedness activities can be put to use. Primarily, the response can be managed through an incident-management system, a framework widely used by hospitals and emergency services that establishes leadership, clear roles, responsibilities, procedures, and communication channels for addressing the incident. Incident management is scalable and responsive to the size of the event. In the case of a shortage of normal saline, a hospital system could designate a pharmacy or administrative leader who would coordinate and be responsible for activities to address the shortage.

Many hospitals and health care coalitions are already taking this approach to respond to drug shortages. Pharmacy supervisors are often designated as incident managers. They maintain situational awareness by comparing any shortfalls in orders against current stock levels and expected monthly consumption levels, optimally providing early warning of a shortage situation. They can communicate these shortages to providers in terms of “red, yellow, green” triage categories denoting the degree of severity, taking into account factors such as the urgency of the shortfall and its probable effect on clinical practice. They can also build safeguards into the ordering of unfamiliar agents (through alerts incorporated into the electronic health record system) and their preparation (for instance, preparing them in the pharmacy rather than on the patient's hospital floor).

The collaboration involved in the incident-management process and the clarity that ideally results from it mean that clinicians are not forced to make ad hoc decisions that may be inconsistent with ethical frameworks or preferred strategies. Instead, uniform stewardship actions taken throughout the whole institution — or the whole community — such as sharing, conserving, substituting, adapting, reusing, and reallocating, can be used to address shortages.

These key stewardship actions are components of the Institute of Medicine's standards-of-care guidelines for catastrophic emergencies. Developed initially for planning for an H1N1 influenza pandemic, these guidelines provide foundational ethical and procedural guidance for the allocation of scarce resources during disasters. This guidance was recently adapted by the Association of State and Territorial Health Officials for use in drug-shortage events.4,5

Incident management also promotes coordination of decision making with other health care facilities, systems, and partners in the community (including emergency medical services and public health agencies) by designating liaisons as the points of contact and coordination. During the recent saline shortages, for example, the Northern Virginia Hospital Alliance released a coalition-purchased disaster cache of intravenous fluids to member hospitals for their immediate use, stemming the need for restrictive conservation measures. Many hospitals offered guidance to providers on using alternative crystalloids or smaller bags, emphasizing oral hydration, enteral feeding, and reduced preoperative fasting times whenever possible. These policies are often shared with other facilities and through health care networks and response coalitions, resulting in consistent, community-wide practices.

Recovery should begin even during an organization's response to a shortage, through replenishment of consumed “emergency” supplies, with the goal of returning the facility to usual practices, if not better ones. For example, a retrospective review might lead to decisions to increase the backup for critical supplies when they are not in short supply or to revise plans for similar events in the future.

The shortage of normal saline highlights the way in which breaking even a single link in our fickle supply chain can have profound effects on routine health care delivery. Application of stewardship strategies for resource allocation tailored to the degree of deficit, coupled with the use of an incident-management system, will ensure a fair, informed, and structured response across this delivery continuum.

Finally, an added benefit to “practicing” these strategies during day-to-day incidents is that personnel will then be more comfortable with them when a full-scale disaster occurs. In other words, preparedness rests on the back of strong day-to-day systems. Daily use translates to disaster utility.

EXAMPLES OF DRUG SHORTAGES LISTED ON THE FDA WEBSITE.*

Atropine sulfate injection

Bupivacaine hydrochloride (Marcaine, Sensorcaine) injection

Calcium chloride injection

Calcium gluconate injection

Dobutamine hydrochloride injection

Epinephrine injection

Epinephrine (1 mg/ml, preservative-free)

Fentanyl

Heparin sodium injection

Lidocaine hydrochloride (Xylocaine) injection

Magnesium sulfate injection

Nitroglycerin in 5% dextrose injection

Sodium chloride (0.9%) injection bags

http://www.nejm.org/doi/full/10.1056/NEJMp1401833

Prescription drug shortages compromising patient care

Pharmacists warn a worsening drug shortage is making it increasingly difficult to supply medications for patients and that's compromising their medical care.

Canada's online drug availability reporting system lists 350 products in short supply. That means at least once a day pharmacist Victor Chu sees patients looking for medication they can't find elsewhere.

"We also have pharmacies calling us asking us to — we're a compounding pharmacy — to make up medications. We can actually mimic the commercial product that's not currently available."

Patient Nicholas Read was surprised by when his pharmacist told him she did not have the inhaler he has been using for years.                

"I was told that there was none available and that it wouldn't be available until July," said Read. "She said shortages were typical in pharmacies, but this year they are seeing more shortages than ever before."

Jeff Morrison of the Canadian Pharmacists Association says one reason for shortages is a lack of ingredients. 

"The raw materials used to make the drugs are being sourced from countries like China and India and there's quality assurance problems."

http://www.cbc.ca/news/canada/british-columbia/prescription-drug-shortages-compromising-patient-care-1.2621826

Today's Shortages

ASHP/FDA
Adenosine Inj.
Amikacin Inj.
Azithromycin Inj.
Calcitriol Inj.
Cefpodoxime Inj.
Cytarabine Inj.
Dfexamethasone Sodium Phosphate
Dexmethylphenidate Hydrochloride
Dimercaprol Inj.
Doxorubicin Inj.
Doxycycline Capsules and Tablets
Ephedrine Inj.
Haloperidol Decanoate Inj.
Heparin Sodium Inj.
Indigo Carmine Inj.
Leuco Inj.
Methotrexate Tablets

April 24, 1943: U of A prof grows belladonna to help meet drug shortage

EDMONTON - A University of Alberta pharmacology professor was credited for “doing the impossible” with the first large-scale production of the medicinal plant belladonna in Canada.

Alberta’s soil and climate, combined with the ingenuity and hard work of Dr. A.W. Matthews, resulted in a drug of excellent quality, and with a better appearance than the prewar drug previously imported from Central Europe, said officials of the company in Eastern Canada where the crop was sent.

Matthews took matters into his own hands a year earlier when drug companies were forced to start rationing belladonna.

The plant was used to increase secretions of the body, as well as by eye specialists to dilate the pupil.

Though widely regarded as unsafe, belladonna is used today as a sedative, to stop bronchial spasms in asthma and whooping cough, and as a cold and hay fever remedy. It is also used for Parkinson’s disease, colic, motion sickness and as a painkiller.

Matthews had been cultivating drug plants on a small scale when he heard of the shortage and planted some seeds in a greenhouse. He then leased a vacant lot and planted 5,000 young plants early in June.

Four months of back-breaking work followed as Matthews and his assistant, Mervyn J. Huston, mothered the slow-growing plants through a wet summer, which further delayed their growth.

At the end of the process, Matthews found the harvest yielded 750 pounds per acre, a yield comparable to that obtained under ideal conditions in a large research project being carried out in the eastern United States. But the professor cautioned Alberta farmers about starting to grow belladonna.

“The basis of growing the crop depends entirely upon hand labour and very special care,” Matthews said. “The plant is definitely not adaptable to mass production methods, and with the shortage of labour growing worse every day (because of the war), the planters’ difficulties are bound to increase. “

Matthews and his assistant hoped some of the drug made from the plants they had grown would fill the empty spaces on shelves of western pharmacies.

“Then we will feel that our work has been of some consequence,” he said.

http://www.edmontonjournal.com/April+1943+prof+grows+belladonna+help+meet+drug+shortage/9768577/story.html

Hospira, another recall, not surprising anymore

Hospira Recalls Drugs Due to Visible Particulates

The FDA announces that Hospira Inc. will initiate a voluntary nationwide recall to the user level for one lot of 0.25% Marcaine (Bupivacaine HCl Injection, USP), 10 mL, Single-dose Vial – Preservative Free (NDC 0409-1559-10), Lot 34-440-DD. The recall is due to a confirmed customer report of discolored solution with visible particles embedded in the glass as well as discolored solution. 

To date, Hospira has not received reports of any adverse events associated with this issue for this lot. Hospira has attributed the embedded particulate to a supplier’s glass defect. As a result of this issue, Hospira is working with its supplier on implementing corrective and preventive actions.

If the particulate goes undetected and solution is administered - depending on the particle size and number - it could block administration of the drug to the patient, causing a delay in therapy. However, this is an unlikely outcome due to the size of the subvisible particulates identified. It is more likely that particulates are able to pass through the catheter and may result in local inflammation, mechanical disruption of tissue, or immune response to the particulate.

While extremely rare, particulate exposed to strong magnetic fields (e.g. MRI), could potentially dislodge and cause tissue damage. However, the particulate size identified is considered too small. Therefore, an adverse outcome is extremely unlikely. Marcaine is packaged 10 units per carton/100 units per case in glass fliptop vials. The impacted lot of Marcaine was distributed December 2013 through January 2014 to wholesalers/distributors, hospitals and clinics nationwide.

This recall is being conducted with the knowledge of the U.S. Food and Drug Administration.
Hospira is headquartered in Lake Forest, Ill.

http://www.cemag.us/news/2014/04/hospira-recalls-drugs-due-visible-particulates