Drug shortages ‘the new normal,’ and hard to fix
About a month ago, Health Canada announced that Canada has a shortage of injectable sodium bicarbonate. The drug is similar to baking soda, but used in emergency procedures, open-heart surgery, when people have buildup of acid in their blood, as an antidote for some poisons, and as part of some chemotherapy.
“There’s concern [over sodium bicarbonate products] because they’re used very widely; the shortage has the potential to impact a lot of different types of procedures or treatments,” says Supriya Sharma, chief medical advisor for Health Canada.
While similar to baking soda, it’s actually quite difficult to make correctly. Pfizer is the only company that sells injectable sodium bicarbonate to Canada, and it’s sold in vials or pre-filled syringes. The recent shortage happened for two reasons: earlier this year, manufacturing problems with the vials limited their availability. Then, in June, there was a recall on two lots of pre-filled vials due to fears of contamination. That tipped supplies into a shortage situation.
The drug is now being rationed in Canada. Hospitals and pharmacies are using alternatives where possible and the shortage is expected to ease with additional shipments from the manufacturer expected in early August and September, and be over by October.
Drug shortages quietly becoming the new normal in health care: In 2013-2014, there were shortages of more than 600 drugs in Canada, which lasted, on average, four and a half months. That’s lower than the high of more 1,000 drug shortages recorded in 2012, partially as a result of sanitation issues and a fire in a Canadian factory for Sandoz Canada.
It’s been a constant issue since, with everything from epilepsy drugs to widely used narcotics. Just this March, an Ontario-wide shortage of Fluorouracil, a chemotherapy drug, resulted in 35 patients having their treatments rescheduled.
In July, only about half of the usual amount of injectable sodium bicarbonate ordered is expected to be available. When that happens, companies, hospitals and pharmacies all have to scramble to find solutions.
The drug maker usually proposes an allocation of available stock based on past order histories, giving hospitals, for example, half of what they normally purchase. Allocation plans are then created locally, based on possible alternative therapies and acceptable delays in procedures.
Clarence Chant, director of pharmacy at St. Michael’s Hospital, says they have a pharmacist-led group that creates these plans. They meet multiple times a month because of the frequency of shortages. “We systematically go through it: We now know that drug X is short, is there availability from another company, other sources, how much do we normally use, what do we use it for, what alternatives can we seek?” he says. In more severe cases, “we take back floor stock, we engage our electronic systems, we use our pharmacists as our troops on the ground to encourage those switches and maintain what we have.”
Alberta, for example, reduced their use of injectable sodium bicarbonate from 2,000 vials a week to less than 400, “without impact on the quality of patient care,” according to Francois Belanger, the Chief Medical Officer for Alberta Health Services. They’ve also bought Continuous Renal Replacement Therapy bags, normally used for dialysis, which contain a less concentrated version of sodium bicarbonate that they can extract if necessary. Last on their list would be compounding, or concocting it themselves. “We looked at that, but making the compound is pretty labour intensive, and there is some risk in terms of sterility. That’s really the last resort,” says Belanger.
Finding workarounds and conserving drug stock is time consuming. The average pharmacist in the U.S. spends between 30 minutes and three hours per shift managing drug shortages. And “the resources dedicated to managing shortages seems to be increasing,” says Scott Gavura, Director, Provincial Drug Reimbursement Programs at Cancer Care Ontario. That’s an additional cost to hospitals – some Canadian hospitals have a full time staff person dedicated to these issues.
The impacts on patients
In many cases, conservation efforts around a drug – which might include alternatives – are successful and don’t impact patient care. That seems to be the case with sodium bicarbonate, as Francois Belanger noted above.
Yet alternatives may not always be available, might not be as effective, or might have side effects. People who are on long-term medications, or who have chronic or life-threatening conditions, might find a switch particularly difficult. Shortages can also disrupt clinical trials using a drug as part of their treatment.
A survey of nearly 100 U.S. hospital pharmacy staff reported that drug shortages were responsible for 47 incidents of patient harm from 2011 to 2012, including diseases that progressed where they otherwise wouldn’t have, debilitating side effects, and even death. Those results were echoed in a 2013 survey of oncologists published in the New England Journal of Medicine that found that in the six months before the survey, more than three quarters felt that a shortage had led to a major change in treatment.
Closer to home, physician Jacalyn Duffin, who created a website dedicated to the issue of drug shortages, first became aware of the impact of drug shortages when one of her patients refused to have her chemotherapy after an anti-nausea drug was unavailable. Her site includes dozens of stories from affected patients. “We’re just lurching from one little crisis to another,” she says.
A Canadian survey of 1,187 anaesthesiologists published in 2013 found that 10 percent of those surveyed believed that the shortages resulted in more postoperative complications, like nausea or vomiting. Four respondents said a shortage resulted in death.
But on the whole, hospitals manage to accommodate most without seriously impacting patients, says Chant. “I think we’re limping along fine,” he jokes.
Jennifer Gibson, director of the Joint Centre for Bioethics at the University of Toronto, agrees. She was part of a team that developed ethical guidelines around how to ration drugs if necessary, in response to the 2012 shortages. “That  crisis was averted, but a few weeks ago I got a call from the emergency operations about the sodium bicarbonate shortage, asking if we thought the ethical guidelines would still be relevant,” she says. They are – but judging from the success of conservation efforts, it looks like they won’t be needed this time, either.
“All signs are pointing in the direction that we aren’t in a crisis, but this is the time when it’s worthwhile to think, okay, if push came to shove, how would we manage a more scarce supply,” she says.
Pfizer became the only supplier of injectable sodium bicarbonate in Canada when it purchased Hospira in 2015, which was then the largest producer of generic injectable drugs in the world.
This kind of consolidation has been common over the past decade, with the industry now dominated by large, multinational companies. A full third of all pharmaceuticals are produced by just 10 drug companies. That means there are often only one or two companies that make a product – or one company might contract out production to another, so even if there are two to buy from, there’s really only one producer.
Meanwhile, those companies have increased their outsourcing of all stages of drug production, from sourcing the raw materials to manufacturing and packaging. More and more drugs are manufactured solely in countries like China and India. And companies that manufacture drugs in Western countries now source both raw materials and active pharmaceutical ingredients (APIs) from overseas companies as well – 80 percent of APIs, for example, are sourced from overseas. Those ingredients are more likely to be contaminated or counterfeit.
Similar to other industries, many pharmacies, manufacturers and distributors also now use a just-in-time model, which minimizes the amount of stock they have on hand, and can make them more vulnerable to shortages.
All of this makes the supply chain vulnerable. Single source suppliers are the link that’s most vulnerable in the chain, according to a 2012 report to the House of Commons on the issue. “All witnesses agreed that the most avoidable cause of drug supply disruptions was the tendency to award single source contracts for bulk purchases or for manufacturers to rely on single suppliers for their raw materials and APIs,” it reads.
That’s especially true for generic medications, which have low profit margins, so companies might choose not to make them, says Joel Lexchin, an emergency physician and professor emeritus at York University. “Sometimes something else comes along that has a better profit margin, so you drop the ones with the lowest profit margin and you pick up the others,” he explains. “My view on this is that aside from accidents, where there’s a fire or something like that, most drug shortages come down to money issues.” That’s one reason why even though anyone can make sodium bicarbonate, Pfizer is the only large supplier.
Sometimes drug shortages are caused by a lack of raw materials to make the drugs, or unexpected spikes in demand following an outbreak or changes to clinical guidelines. But the most common cause by far is manufacturing issues, which are responsible for more than 60 percent of shortages. Some examples are bacterial contamination, particulates like glass in vials, impurities in the drug, or the drug crystallizing.
A manufacturing issue usually leads to a temporary shut down in production to fix the issue – whether through upgrading equipment or decontaminating it. If the facility makes more than one drug, that can have ramifications for other products as well.
With only a few companies making a drug, a tenuous supply chain, thin financial margins and manufacturing challenges, it doesn’t take much to spark a shortage.
Some wonder if we need to raise prices on generic drugs to fuel the market and give companies enough profit margin to act differently. Others, like Lexchin, believe Canada needs a crown corporation to make crucial drugs. That’s what they do in Sweden, where a crown corporation is required to have the capacity to make all approved drugs.
According to a report on potential solutions by the Multi-Stakeholder Steering Committee on Drug Shortages, one answer is to address the supply chain issues. That means industry needs to do better due diligence on the companies they outsource supply and manufacturing to, and having clear internal protocols for reporting and addressing issues as they happen. Avoiding sole sourcing practices and having alternative sub-contractors set up is also key.
Group purchasing organizations – which buy drugs in bulk – should follow the same principles. Many have now moved towards having more split contracts, where multiple companies are engaged to supply a single drug, so that if one has an issue, the other can supply the entire market.
Another recent improvement is that Health Canada now requires drug manufacturers to report both actual and anticipated shortages on drugshortagescanada.ca. That advance notice is key to give pharmacists a chance to react early and conserve more stock, and seems to be helping.
Despite these moves, nobody’s happy with the current number of shortages, says Gavura. “I think all players in the system are challenged by this, and in our dialogue with manufacturers, they said they find it equally challenging,” he says. “Everyone is looking for ways to make the system work effectively, but it’s a struggle.”