A guest blog co-written by Megan Riordon and Vero Briggs with a little input from me
Source of art (click here)
Whether you are a patient or a physician, you may have noticed that provision of prescription drugs has changed (several times) during the COVID-19 pandemic. Suddenly patients could only get one month supply of their medication from their community pharmacy, leading to extra dispensing fees and inconvenience for patients, as well as frustration for prescribing physicians. Why did this occur? To get an answer I went to our amazing team of pharmacists and consulted with them. Thanks to Dr. Vero Briggs and Megan Riordon for this insightful introduction into the complex world of Canada’s prescription drug supply chain, its vulnerability, and the consequences during the pandemic. More importantly, thank you for their always professional and helpful service to physicians and our patients.
Dr. Vero Briggs and Megan Riordon
This topic is near and dear to my heart in part because I have a talented pharmacist sister at Dalhousie University, Ms Dianne Cox, retired and currently in the role of Undergraduate Curriculum Administrator, who participates in training future pharmacists there.
Ms Dianne Cox
I have previously written on the topic before (click here), after a 2013 lecture on the topic by Dr. Jackie Duffin. Back then I noted “What drugs are missing? Common drugs, like diltiazem (an antianginal, antihypertensive drug), several common antibiotics (like tetracycline, cephalexin and amoxicillin+clavulanate). In Ontario, even Penicillin is missing on occasion. Hey Canada, the 1920’s are calling…they want their miracle drug back!”. So how is it in 2020? Sadly, drug shortages are more common and more often critical than they were 7 years ago.
Increasing numbers of drug shortages in Canada (click here).
Background on drugs in Canada1 Canada is a small market for drugs, as seen from a global perspective. We account for approximately 2% of the total global drug market whereas the USA is ten times larger: 20% of the market. Moreover, we don’t make our many of our own medications (by and large they come from India and China), making us vulnerable to supply chain interruptions, particularly during a global disturbance like the COVID-19 pandemic. Although we don’t make many drugs, we do have fairly strict regulations for drug import and use. Health Canada’s Food and Drugs Act and Regulations govern the importation and sale of drugs in Canada and only compliant products are permitted in Canada. If you think the government can dictate what drugs are produced or where they should be sold, you’re WRONG - Health Canada CANNOT require a pharmaceutical company to make a drug, make more of a drug, or change how much and to whom the drug is distributed! With these facts, the stage is set for potential drug shortages during the pandemic.
Let’s start by defining the term “drug shortage”2,3 Health Canada defines a drug shortage as a situation in which the manufacturer is unable to meet the demand for the drug. Such shortages may result from temporary or permanent disruptions in drug production or distribution. The fact is, we have been facing drug shortages on a regular basis for more than a decade, both for generic and name brand prescription drugs. It’s the continuous juggling act of pharmacists that often lessens the impact and makes the public and physicians somewhat unaware of this potential vulnerability.
What are the main causes of drug shortages4? Half the time drug shortages result from problems with production, with shipping delays and increased demand for a drug being #2 and #3 on causes of drug shortages. This graph shows the causes of drug shortages in the USA in 2019 (click here).
Here is a breakdown of why we have drug shortages in Canada:
- Production Issues / Manufacturing Disruption (55%)
Production problems may reflect issues with the quality of the product that requires reduced production to fix a problem or to address a recall, related to non-compliance with standard manufacturing processes. This latter problem occurs most often with foreign manufacturers. For example, a recent problem occurred with contaminated valsartan made in China that contained the cancer-causing chemical, NDMA.
These production shortages are most likely to occur when there is only one producer or when manufacturing techniques change. However, simple greed can be a factor. When profits dip, valuable but unprofitable drugs may be discontinued and no agency of government can prevent this. This can also happen when newer drugs absorb a company’s manufacturing capacity and so older, less profitable, agents are discontinued. In addition, drugs manufactured abroad may get caught up in international import regulatory issues. Other causes of drug shortages include shipping delay (19%) and increased demand (13%). Increased demand, due to increased use or hoarding, account for recent shortages in drugs such as propofol, which we use to sedate people for procedures, airway intubation and during mechanical ventilation. Supply Issues (3%) can also contribute to drug shortages. As global climate change worsens, weather extremes and natural disasters are more commonly responsible. For example, Hurricane Maria in Puerto Rico disrupted the supply of mini-bags, used to administer drugs intravenously for all of North America. The remainder of drug shortages (10%) result from miscellaneous causes.
What is the history of drug shortages in Canada?
- 2008 – Baxter’s heparin sodium linked to 350 adverse drug reactions (ADRs) of which 40% were serious and 84 resulted in patient death (heparin contamination; manufacturing plant in Changzhou, China, never inspected by China nor the FDA). This led to development and changes in the inspection and regulatory practices of drug manufacturing plants.
- 2011 – FDA drug shortage warning for 140 sole source injectable drugs (e.g. pantoprazole IV, all morphine injectables); Health Canada warned of worsening drug shortages.5
- 2012 – Significant drug shortages across Canada, mostly injectable medications for hospitals, due to Sandoz Canada scaling back production of certain drugs (mainly painkillers, antibiotics, and anesthetics) to upgrade operations after quality control assessments by the FDA who determined the factory fell short of its standards. In addition, a fire in the ceiling above the boiler room in Sandoz’s Quebec plant required halting production.
- 2015 – Health Canada announces Mandatory Reporting of Drug Shortages by drug companies.
- 2017 – Health Canada hosted website; put into effect a mandatory reporting policy “manufacturers will post all drug shortages, anticipated or actual as well as discontinuations, on drugshortages.ca, no less than 6 months in advance …. from when they become aware of it, to allow maximum opportunity for the healthcare system to react to the shortage.”
- 2019 – Formation of Tier 3 Assignment Committee (TAC) – management of Tier 3 Shortages (defined as a shortage with the greatest potential impact on Canadians where there are no available therapeutic alternatives marketed in Canada).
What about the US7?
On July 31, 2019, President Trump tweeted that “lowering drug prices for many Americans – including our great seniors! At my direction, [HHS Secretary Azar] just released a Safe Importation Action Plan”. Many state governments in the US passed or are considering legislation to allow importation of cheaper Canadian medications. The US population, and demand for medicines, is 10 times that of Canada and if only 10% of all US prescriptions were filled from Canada, our supply of medication would run out in only 224 days (click here).
What impacts do drug shortages have on patient safety7,8?
Shortages of prescription medications hurt patients and may even divert them to use medicines obtained via illegal online sources that distribute counterfeit, unapproved or substandard meds. As a physician I find I am sometimes unfamiliar with the alternative drugs that the patient must be switched to during a shortage. Often when a generic is in short supply the patient must be switched to more expensive brand-name drugs. It’s hard enough for patients to adhere to complex medication regimens and the confusion related to changes in medications caused by drug shortages, and the associated delays in therapy almost certainly hurt patients. When drugs like propofol, which are essential for interventional and surgical care, are in short supply things get even worse and procedures get cancelled or delayed.
Drug shortages are getting worse4?
Not only have the number of new backorders been steadily increasing, backorders are also persisting, as seen in this graphic (below).
How did COVID-19 impact drug shortages?
Prior to COVID-19, Canada was already facing at least 2,000 drug shortages in key therapeutic areas, including cancer, diabetes, and epilepsy. When COVID-19 was declared a global pandemic, community pharmacies saw patients begin to stockpile medications (similar to how people reacted with toilet paper). Hospital pharmacies also began increasing their weekly orders for medications anticipating increased demand (based on data that ICU patients with COVID-19 require more medication than non-COVID-19 patients in terms of sedation and analgesia).
On March 20, 2020, the Ministry recommended that community pharmacists dispense no more than a 30 day supply of medication in an effort to protect the Canadian drug supply chain and prevent even more shortages. The idea was that by dispensing smaller amounts of medications to everyone, the goal is for more people to get the medications they need at the right time while drug supply can be sustained overall. Interestingly, I don’t recall being notified of this, either as a practicing physician or in my role as Head of Medicine at one of Ontario’s major academic health sciences centers. I believe the government did pharmacists a disservice by not better communicating their policy change to patients and physicians, This left most patients frustrated with the only group they saw in the course of their care-the pharmacists!
Who manages drug shortages in hospitals?
It is pharmacists, not physicians, who work at the coal face when it comes to managing drug shortages. The Department of Pharmacy Services (Pharmacy) is responsible for managing the hospital medication distribution system in collaboration with Program Managers and Directors and in compliance with federal and provincial laws, regulations, and standards of practice. Medications used in the hospital are procured and distributed by Pharmacy as per KHSC Administrative Policy 14-040 Medication Procurement, Preparation, Distribution, and Storage. Our pharmacy has a standardized process of sourcing alternative suppliers of a drug should the regular supply be unavailable, or available in reduced amounts, to ensure stock levels are maintained or to implement a plan to address the drug shortage in the Hospital when no alternatives are available.
How come I’m not aware of most of the drug shortages?
Typically doctors become aware of drug shortages only when they are forced to replace one drug with another. It’s usually an annoyance more than anything else. Patients became aware of drug shortages during the COVID-19 pandemic because suddenly they could only pick up one month’s supply at a time, and in many cases, this led to them paying more dispensing fees (the charge associated with the pharmacist dispensing the drug). The individual amount of the dispensing fee is set by each community pharmacy/pharmacy chain to help cover the business expenses that accompany dispensing a medication (including pharmacy technician and assistant salaries, rent, pharmacy software, packaging supplies, inventory tracking, and patient records). Dispensing fees vary from about $4 (e.g. Costco) to $12 per medication so during COVID-19, some patients would be paying this fee each month for their 1 month supply instead of paying the fee once every 3 months for a 3 month supply). When the government mandated to limit prescription size to one month, this was not accompanied by public education that this was about to happen, nor was there a buffering program to avoid increased dispensing fees. Some pharmacies chose to waive the dispensing fee for low-income seniors and pharmacists were authorized to use their clinical judgment to dispense a 3 month supply when deemed necessary. The Ministry has since announced that they would cover the extra co-payments for ODB patients.
As Megan and Vero have so clearly outlined, medication shortages are not new to Canada, much the same message Dr. Duffin and I transmitted in 2013 (click here). If you are wondering why you, as a health care worker or physician, were blissfully unaware of drug shortages before the pandemic, you can largely thank our hard-working pharmacists. They are problem solvers and often buffer both the prescribers and the patients from the worst effects of the shortage (i.e. they manage behind the scenes in Pharmacy and prescribers are only notified when a change in practice is required). Pharmacy maintains a weekly Backorder Report for Drug Shortages and determines potential alternatives when possible (e.g. different supplier of same drug, different concentration or format size, different route, therapeutic alternative). They use their knowledge of historical usage and current stock to predict when supplies will likely run out and they either get an alternative drug supply or communicate to staff and prescribers, as necessary. So, if pharmacists are guilty of anything, it’s not complaining enough - they are busy making our system, with its increasing holes and flaws, work!
What is being done to mitigate drug shortages?
There are efforts to prepare for and be proactive in the management of drug shortages. During the pandemic we ran out of many anesthetic agents required to maintain patients on ventilators or to perform surgery, such as propofol. Pharmacists have created critical medication lists (e.g. Medically Necessary Hospital Drug List) and assign therapeutic alternatives which could be substituted. When substitutes exist for scarce drugs, the pharmacist will often make auto-substitutions or offer “pharmacist suggests” alternatives. Unfortunately there is not always a good substitute. They are also engaged in robust multi-disciplinary drug shortage teams involving pharmacists, physicians, nurses, patient advocates, and legal/ethical experts.
As prescribers, we can’t really prevent drug shortages, but when they occur, they can minimize their impact by assessing whether their patients still require the scarce medicine and discontinuing the drug when possible. As in the pandemic, we can behave responsibly and not stockpile or overprescribe medications. This requires busy physicians to spend more time on renewing prescriptions that are dispensed in smaller amounts and to adhere to restrictions.
A final note: Canada does have a number of generic drug manufacturers and they are represented by the CGPA. This group has a good section on their perception of the genesis of drug shortages. As of March 14, 2017 all companies are required by law to post information on actual and anticipated drug shortages as well as drug discontinuations on a website operated by Bell Canada under contract with Health Canada. They believe they are addressing the problem by building manufacturing capacity (click here).
Clearly these efforts are insufficient and the pandemic suggests Canada needs more capacity for manufacture of name brand and generic medications.
In conclusion, a big thank you to our amazing pharmacists, who are making our rather imperfect drug supply system work. Canada needs more drug manufacturing capacity. Physicians need to join pharmacists in advocating for a single national drug supply management system.