Recent Health Policy Briefs: Regulating Compounding Pharmacies and Basic Health Program Update

The latest Health Policy Brief from Health Affairs and the Robert Wood Johnson Foundation examines the Compounding Quality Act, a law signed by President Obama in November 2013, which seeks to fill the gaps in the Food and Drug Administration’s (FDA’s) inspection and enforcement oversight of compounding pharmacies.

This law was enacted in the wake of a 2012 fungal meningitis outbreak, linked to a Massachusetts drug compounding company. The outbreak caused more than 700 people to become ill and left sixty-four dead. Before the new law was passed, compounding pharmacies were primarily regulated by states, not the FDA.

The compounding pharmacy industry initially catered to patients with specialized needs. Since the 1990s, many compounding pharmacies have also begun engaging in what is now called nontraditional compounding: manufacturing certain drugs in large quantities for sale to doctors’ offices and hospitals. This health policy brief traces the evolution of compounding pharmacies and the changes brought to this industry by the new law.

In April Health Affairs also posted an update to an earlier brief that provides more information on the issues surrounding the Basic Health Program and outlines options for states.

Health Policy Briefs are aimed at policy makers, congressional staffers, and others needing short, jargon-free explanations of health policy basics. Sign up for an e-mail alert about upcoming briefs. The briefs are also available from the Robert Wood Johnson Foundation’s website. Please feel free to forward the briefs to any of your colleagues who are tracking health issues. And after you’ve taken a look, we welcome your feedback at: hpbrief@healthaffairs.org.

Regulating Compounding Pharmacies. Topics covered in this brief include:

• What’s the background? As the brief explains, compounding pharmacists, like almost all licensed medical professions, are regulated by states, not the federal government. However, the FDA has historically maintained that compounded drugs are “new drugs” under the Federal Food, Drug, and Cosmetic (FD&C) Act, which has always allowed the agency to loosely retain compounding pharmacies under its scrutiny. As the brief points out, the FDA has for many years known about serious illnesses and deaths associated with improperly compounded medicine, but little was done to punish offending pharmacies. According to the brief, Congress made its first effort in 1997 to bring compounding into a federal regulatory framework. A wave of court cases followed, leaving the legal landscape a patchwork of different standards. As the brief suggests, the events that transpired during the fall of 2012 was a crisis waiting to happen.
• What’s in the law? “It is Congress’ job to fix the law when it is inadequate,” declared Rep. Henry Waxman (D-CA) during a 2013 House Energy and Commerce subcommittee hearing. “We must do more than blame the FDA but give it the clear authority it needs.” The brief explains that the Compounding Quality Act provides two major changes: It sets up a voluntary category known as “outsourcing facilities,” (section 503B of FD&C Act) that allows compounders to sell unlimited quantities of drugs on the FDA’s drug shortage list, provided that the companies follow a set of new procedures and pay a $15,000 annual fee to the FDA. The brief also explains how the new law makes it possible for the FDA to distinguish between traditional compounders and companies that produce large quantities of compounded drugs.
• What’s next? With the new rules in place, implementation lies ahead. The drug compounding community is waiting for more detailed guidance later this year from the FDA on several questions the law has left unresolved, which the brief details. How well the new law is working will be assessed by a mandatory report, to be published within the next three years by the Government Accountability Office. The real tests, however, will be how many large companies register under section 503B—and whether New England Compounding Center–like catastrophes are prevented.

Today's Shortages

ASHP/FDA
Clarithromycin Immediate Release Tablets
Granisetron Hydrochloride Inj.
Intraveneous Fat Emulsion
Labetalol Inj.
Lido w/ Epi Inj
Nicardipine Hydrochloride
Rocuronium Inj.
Sodium Phosphate Inj.
Succinylcholine Chloride Inj.
Vancomycin Hydrochloride Inj.
Cvecuronium Bromide Inj.

There's a Massive Shortage of One Critical Drug in American Hospitals

The news: Saline is essentially a fancy word for salt and water, albeit in a sterile condition. It is used in all manners of crucial, intravenous procedures, from dialysis to hydration. Still, it sounds like a rather no-frills product — how hard can it be to mix salt and water together?

Apparently, pretty hard.

Since January hospitals across the country have been struggling to cope with a saline shortage. In fact, it got so bad that last month the Food and Drug Administration (FDA) started to import shipments of 0.9% saline solution from a manufacturing facility in Norway. A bag of saline solution, which used to go for a $1, can now fetch five or six times that.

It seems ludicrous to imagine bags of salt water being flown across the Atlantic when we have facilities that could easily manufacture it at home, but it's hardly that simple.

Why do we have a saline shortage? Despite the huge market and demand, the production of saline is concentrated among a few companies, which means that if even one of them has a problem — like, say, a recall — there can be huge consequences for the entire country.

Image Credit: Vox

It also doesn't help that there was a spike in flu cases earlier this year. Dehydrated flu patients need intravenous saline injections, and this pressing need has exacerbated an already dwindling supply.

And there's no reason why there should be more saline manufacturers. The solution is hardly a high-profit product, and it's a costly challenge to produce the solution in a completely sterile environment to make it safe for injection directly into a patient's veins.

What will happen next? The FDA is working with manufacturers to kick saline production into a higher gear. The agency is also easing regulations so that foreign plants, such as the Norwegian company and the Spanish branch of a company called Baxter, can send some much-needed reinforcements in the meantime.

Hospitals have also had to tackle the challenge of rationing their remaining supply. Some are using smaller-sized bags or diluting the solution with non-saline ingredients. It's a strange and unexpected predicament, but it's a potentially dangerous reality that pharmacists and doctors across the country must face.

Today's Shortages

ASHP/FDA
Ondansetron Inj
Pantoprazole Tablets
Propofol Inj
Rabies Immune Globulin
Tdap

Today's Shortages

ASHP/FDA
Pantoprazole Tablets
Propofol Inj.
Rabies Immune Globulin
Tdap

FDA Attempting to Ease Drug Shortages

The FDA is assuring healthcare executives that it "will take every action within its authority" to address shortages of saline and other drugs, but reminding them that it doesn't have the authority to direct manufacturers' business decisions.

Responding to a letter from American Hospital Association Executive Vice President Rick Pollock, FDA Commissioner Margaret Hamburg says what the agency can do, among other measures, is work with current manufacturers to better understand and alleviate the quality-related disruptions in production that can lead to shortages, and expedite inspections of additional manufacturers that are interested in starting new production of products that have been in short supply.

The AHA had asked the FDA to "do even more to end this shortage by pushing current manufacturers to not only continue to produce these products at their maximum capacity but also to make investments to ensure an increasing supply for the future."

The 4 companies currently manufacturing IV saline — Baxter Healthcare, B. Braun, Hospira and Fresenius Medical Care — are working to restore the supply of IV saline and other saline solutions, says Ms. Hamburg.

http://www.outpatientsurgery.net/newsletter/eweekly/2014/04/29/fda-attempting-to-ease-drug-shortages

ISPE Announces Development of New Drug Shortages Prevention Plan for the Pharmaceutical Industry

ISPE, the International Society for Pharmaceutical Engineering, announced today that it will work with stakeholders world-wide to produce a Drug Shortages Prevention Plan to guide the pharmaceutical and biopharmaceutical industry in establishing reliable, robust and resilient supply chains that provide quality medicines to patients without interruption. The Plan, which will be based on ISPE research with the input of its membership, company leaders and regulators, will serve as a roadmap that when implemented, can significantly reduce drug shortages. The Plan will address optimal organizational strategies, such as aligned governance and communication practices, effective manufacturing and quality systems, and appropriate measures of supply chain robustness and quality. This effort addresses rising concerns around drug shortages within companies, among global health authorities, and for patients who depend on a reliable and available supply of quality medicines. 

The ISPE Drug Shortages Prevention Plan will be the Society's second major output on this topic since launching its Drug Shortages Initiative in 2012. This second phase of the Initiative is aimed at addressing the root causes of drug shortages to prevent delay of supply. The 2013 survey   provided clear evidence that mitigating shortages requires a holistic approach that encompasses both the organizational and technical issues affecting drug manufacturing and quality. "How much of the increasing number and severity of incidents of drug shortages within our industry are fundamentally tied to a lack of understanding, or even concern for, the risk profiles of our current supply chain structure?" commented Andy Skibo, Regional VP, Biologics Supply, AstraZeneca/MedImmune. "I therefore welcome ISPE's initiative to tackle the root causes of shortages for the benefit of all stakeholders—ISPE Members, industry companies, regulators and health authorities, third-party providers and patients."

The ISPE Drug Shortages Prevention Plan will provide a key component of the Society's input to a European multi-association task force, moderated by ISPE, which intends to provide EMA a proposal and plan that address the prevention of drug shortages due to manufacturing quality issues. "I'm delighted to be collaborating with colleagues from the Parenteral Drug Association to deliver our proposal to the EMA later this year, and appreciate the support we are receiving from EFPIA, EGA, AESGP and PPTA as well as regulators representing the EMA, the UK, Irish, Spanish and French national agencies," said Dr. John Berridge, ISPE's Advisor and inter-Association task force moderator.

In 2012, ISPE formed a Drug Shortage Task Force in order to help stakeholders better understand the root causes of global drug shortages and to define mitigation strategies that can help prevent drug shortages. In ISPE's initial approach to this challenge, the group led a comprehensive survey in 2013 that revealed multi-factorial causes of drug shortages, as well as success strategies for avoiding supply interruptions. Those companies that have adopted organizational drug shortage prevention strategies, including contemporary governance, progressive cultures and effective quality systems, were successful in the avoidance of drug shortages and supply interruptions. "Our research findings indicated that, while shortages are often the result of quality systems or related deficiencies, what was equally profound was that those companies with dedicated and sophisticated systems for avoiding drug shortages were clearly more successful in avoiding supply disruptions and shortages," said Nancy Berg, ISPE's President and CEO. "Recognizing the impact of these success strategies motivated ISPE to develop its Drug Shortages Prevention Plan and to develop guidance on organizational strategies for drug shortages prevention, which include the engagement of company leadership and execution of governance, culture, especially a culture of quality risk management throughout the supply chain, and insightful quality metrics."

ISPE's Drug Shortages Prevention Plan will feature an organization and product lifecycle approach to ensuring a more reliable supply of medicines through development of company-wide drug shortages strategic plans, aligned governance, good communication, ongoing capability building (which includes training), proactive regulatory interaction and integrated quality systems. The development of industry-wide quality metrics is being addressed by the Society through a parallel Quality Metrics Initiative, led by another ISPE expert team recommending to FDA and other health authorities a set of common metrics on which the health and reliability of a company's production and quality systems and products can be assessed.

http://www.marketwatch.com/story/ispe-announces-development-of-new-drug-shortages-prevention-plan-for-the-pharmaceutical-industry-2014-04-28