Blog

Jun 06, 2023

Tampered eye drugs were distributed in Newfoundland and Labrador, documents show

Thousands of patients in Newfoundland and Labrador could have received tampered

Thousands of patients in Newfoundland and Labrador could have received tampered eye medications without their knowledge for several years, documents obtained by CBC News reveal.

The drugs in question are injectable doses of Eylea and Lucentis, used to treat age-related macular degeneration. More than two million Canadians suffer from the condition, the leading cause of irreversible vision loss.

The drugs come in single-use pristine vials directly from the manufacturer, but a whistleblower has uncovered evidence that the vials were being tampered with to create multiple doses.

Ken Dicks, a pharmacist in central Newfoundland, sounded the alarm with provincial authorities in 2015 after he became suspicious that the drugs were being split into several doses at a pharmacy in Ontario and distributed into Newfoundland and Labrador.

"It's incredibly risky behaviour that is interfering with a commercial product, which is illegal," said Dicks.

The manufacturer of the drugs and Health Canada say that dose-splitting can increase the risk of contamination and subsequent infection.

Documents dated between June 2015 and August 2016 and obtained under the provincial Access to Information and Protection of Privacy Act (ATIPPA) — while heavily redacted — confirmed that dose-split products were entering and being distributed in Newfoundland and Labrador.

CBC News has identified the Ontario pharmacy in question as Advanced Care Specialty Pharmacy. The business operated out of a 65,000-square-foot facility in Oakville, just west of Toronto. According to the Ontario College of Pharmacists, the pharmacy closed in July 2021.

Under Section 8 of Canada's Food and Drugs Act, "no person shall sell any drug that (a) was manufactured, prepared, preserved, packaged or stored under unsanitary conditions; or (b) is adulterated."

Meanwhile Bayer, the manufacturer of Eylea, notes under its standard terms and conditions of sale that "under no circumstances may a customer multi-dose, compound or vial-split any Bayer product."

Attempts to reach former employees of Advanced Care Specialty Pharmacy were made, but CBC News did not receive any responses.

Eylea and Lucentis, manufactured by Bayer and Novartis respectively, are packaged in pristine vials meant for a single dose. The drug companies overfill the one-dose vials. Once the dose is withdrawn from the vial, the remaining medication is meant to be disposed of.

"The overfill is part of the packaging," said Dicks.

The manufacturers prohibit using the overfill because of a risk of contamination and infection, and direct it to be discarded.

"What's happening in dose-splitting is people are realizing that they can withdraw the overfill," said Dicks. "There's obvious commercial advantages.

"You're taking one product and creating four or five doses out of that one product," Dicks said, adding that there is no reason to interfere with the optimal product manufactured by the drug companies.

At $1,500 to $2,000 per injection, sales of Eylea and Lucentis are in the hundreds of millions of dollars a year in Canada.

Some patients are covered by insurance, while others are covered under provincial government health plans. Some people pay out of pocket.

In addition to the risk of infection, Dicks is concerned about whether dose-split eye injections effectively treat the patient's condition.

"We have no idea … because the product integrity has been breached."

Over the past eight years, Dicks has taken his concerns to Health Canada, the provincial government in Newfoundland and Labrador, including the premier and the minister of health, the National Association of Pharmacy Regulatory Authorities (NAPRA) and the Newfoundland and Labrador Pharmacy Board (NLPB), but has not been satisfied by their responses.

"Every effort to communicate was met with a rebuttal or a deflection … there's never been a satisfactory resolution," said Dicks.

A pharmacist in central Newfoundland for 32 years, Dicks was part of a task force in 2006 that wrote Health Canada's policy on manufacturing and compounding drug products in Canada.

Dicks was first alerted to the possibility that dose-split eye injections could be entering the province in 2015 when the provincial government issued a tender for dose-split Eylea and Lucentis to save money.

His concerns about dose-splitting were elevated when he examined dispensing records and discovered that the number of procedures done on patients didn't match the amount of product going through pharmacies.

"It was glaring," said Dicks. "It's in a one-to-one relationship with a procedure. It was easy enough to … research how many procedures are being done. And then the question became … where are the products to match those procedures?"

Documents obtained under the province's Access to Information and Protection of Privacy Act show that in early June 2015, the Newfoundland and Labrador government's Department of Health and Community Services issued a request for proposals (RFP). Citing an aging population being diagnosed with wet macular degeneration and a growing demand for these types of drugs, the provincial government was in search of a bulk deal.

"The purpose of the RFP is to obtain the services of a contractor or contractors with the relevant experience and qualifications to prepare, dispense and distribute sterile compounded products," it said under a section of the documents titled Introduction and Scope.

Three weeks later, Ontario-based Advanced Care Specialty Pharmacy presented a 67-page proposal in response to the RFP. It outlined pre-existing experience with splitting vials, a list of qualified personnel on staff and its logistical storage and delivery capabilities.

"Advanced Care Specialty Pharmacy has been preparing compounded sterile products since 2009 and has prepared Remicade, Lucentis, Avastin, Eylea and other pharmaceuticals. We have prepared over 87,000 prefilled syringes," the executive summary in the documents read.

"The expertise of our pharmacy, our economies of scale and the ability to leverage our national distribution capabilities allows us to provide patients in Newfoundland and Labrador with significant cost savings."

In an email to CBC News, the Ontario College of Pharmacists said Advanced Care Specialty Pharmacy was closed in July 2021 but did not provide any reasons.

In 2017, Dicks hired Keith Morgan, a lawyer with 20 years of experience in pharmaceutical law, to help him investigate how the eye medications were being distributed in Newfoundland and Labrador.

"We know that it's been distributed throughout the province without patient contact…. We know these things have occurred," said Morgan.

The documents also revealed that the Ontario pharmacy had been distributing those products in the province since 2010.

An official in the N.L. government wrote in 2016 that "a number of ophthalmologists already use the services of the selected bidder for this type of product."

The documents revealed that in 2016, 13,000 eye procedures using Eylea and Lucentis had been performed in the province, and that the bulk of the billings under Newfoundland and Labrador Prescription Drug Program originated at one pharmacy in St. John's.

"What actually happened in the distribution is out of sight. But what we do know is that the billings occurred were heavily concentrated at one pharmacy," Dicks said.

Correspondences, also obtained under ATIPPA, show officials with the Newfoundland and Labrador government were close to accepting and entering into a deal with Advanced Care Speciality Pharmacy in 2016. However, at the last minute the contract was called off because of "procurement law issues."

In 2016, Dicks and Morgan filed a complaint to Health Canada that resulted in an inspection at the premises of the Ontario pharmacy splitting Elyea and Lucentis.

On Aug. 29, 2016, Health Canada inspectors visited Advanced Care Specialty Pharmacy's headquarters in Oakville, Ont.

As part of the documents obtained via ATIPPA, the inspectors' handwritten notes were also provided.

They found non-approved syringes and labelling, and multiple pre-filled syringes identified as Eylea without patient identification.

Then in 2019, Dicks and Morgan filed a second complaint after a package from Advanced Care Specialty Pharmacy was intercepted and handed over to Morgan's legal office.

Morgan said it looked nothing like what would have come from the drug manufacturer.

"There were no other markings, no ingredients, nothing else on the syringe whatsoever."

He contacted Health Canada to come to seize the package and to test it.

"They reviewed it and found that it was sterile and destroyed the sample, destroyed the product that we provided to them…. I was flabbergasted," said Morgan.

"This was evidence of what was a regulatory offence and they took it and they destroyed it."

Dicks was shocked that Health Canada didn't check if the medication was contaminated.

"What about the active ingredient, what about the efficacy?" said Dicks.

"If I or any pharmacist in Canada received insulin in a polybag, marked insulin … without any product parameters on it on a label, would they dispense that? No. No chance…. They'd have no idea what they were getting."

In 2022, Health Canada responded to both of Dicks and Morgan's complaints, saying it did not find evidence of non-complicance with the Food and Drug Act or its regulations, a response that both deem unsatisfactory.

Dr. Alan Cruess, an ophthalmologist in Halifax, regularly performs procedures injecting Eylea and Lucentis into a patient's eyeball every four to six weeks.

"I remember when these drugs were first proposed as therapy and I thought that this was really not going to fly," said Cruess. "But they've been a real game changer in the treatment of age-related macular degeneration, diabetic retinopathy and vascular obstruction in the eye."

But Cruess is not in favour of dose-splitting Lucentis and Eylea.

"Microbiological risks could be hazardous, you know, obviously, and … if the dosing isn't correct, then we might not see … an ideal outcome as we would expect."

Marguerite McCarthy, 59, from Coley's Point, Newfoundland, learned she had macular degeneration at the age of 52. Two of her elderly aunts have the disease but she was surprised to start losing her sight so young.

"Everything started going cloudy … felt like my eyes were closing, like getting smaller and smaller. Everything was going black and cloudy."

Since her diagnosis, McCarthy has been relying on injections to avoid losing her sight.

"To be able to see my kids and my grandkids, that's a lot to me. Just be able to have my own independence … I think I'd rather lose a leg than lose my sight because my sight's everything."

McCarthy used to get injections of Eylea but because it was so expensive she switched to an off-label alternative that is a fraction of the cost.

"There was no way could I afford $3,800 every six weeks," McCarthy said.

McCarthy is left with a lot of questions about where her injections of Eylea were sourced.

"It makes me very angry, very upset," said McCarthy.

"If it's from the hospital, from some pharmacy outside, I have no idea. We're not told any of those things. Well, I don't really ask, but I'm going to start asking a lot more questions now."

Dicks said it is every patient's right to know how they get their prescriptions.

"These products are no different than your insulin … patients are autonomous and should be able to go source their prescription from their preferred health-care provider."

The documents Dicks and Morgan obtained under ATIPPA also revealed that the provincial government asked the provincial pharmacy board to investigate a report of Lucentis billing discrepancies that would "contravene the Pharmacy Act and the dispensing standards set out by the Newfoundland and Labrador Pharmacy Board."

CBC News made multiple requests to Health Canada, the government of Newfoundand and Labrador and the Newfoundland and Labrador Pharmacy Board for an interview. All of them declined the request.

Health Canada responded selectively to a list of questions. It said: "In response to health-care system pressures, there is a growing, national trend towards reliance on a third party to make and supply these prepared products on a larger scale….

"Recognizing that these large-scale, outsourced drug preparation activities may carry risk of harm to patients if errors occur, Health Canada is exploring options for a regulatory framework to oversee the safety and quality of drugs prepared or sold in Canada through outsourcing arrangements."

Meanwhile, in an email, Noelle Patten, registrar of the Newfoundland and Labrador Pharmacy Board, said that the board has not received a complaint against an N.L. pharmacy or pharmacy professional related to dose-splitting.

Patten encourages "anyone who has concerns about a specific pharmacy or pharmacy professional to share that information with NLPB so that any potential patient safety issues can be assessed and addressed using our scope as outlined in the Pharmacy Act, 2012," she wrote.

The billing discrepancies that dose-splitting creates could be substantial, but exactly who along the distribution chain is directly pocketing the extra money is not clear.

"It's an iceberg, right? You don't see 90 per cent of what's happening," said Dicks.

"It is a national issue. It's one that we understand has tentacles all across Canada," said Morgan.

Bayer did act, said Dicks, when he and Morgan brought dose-splitting to the company's attention.

"Bayer came out very quickly and said, 'This is inappropriate, this is illegal, this shouldn't be happening….' So they were very firm."

In 2022, the company issued a directive expressly prohibiting dose-splitting Eylea.

CBC News has learned that Bayer is suing another pharmacy, operating in Gloucester, Ont., for $15 million for alleged vial-splitting of Eylea.

In July 2015, the Quebec Order of Pharmacists fined a Montreal pharmacist $50,000 and suspended his licence for 19 months for dose-splitting Lucentis.

Both Eylea and Lucentis Eylea are now available in pre-filled syringe form, directly from the manufacturer in an effort to combat dose-splitting.

There is only one sure way for patients receiving Eylea or Lucentis injections to find out if they are getting the product straight from the manufacturer, said Morgan.

"Simply go to the pharmacist and ask for their pharmacy record … and if it doesn't appear on their pharmacy record … I would say 75 per cent of the cases for Newfoundland, it's not, then at that point go to your doctor, go to your ophthalmologist and ask them where did this product come from?"

Dicks says for the past three decades, he has gone to work every day trying to do what's best in his patient's interest

"No one should have to wonder when they go to the pharmacist: 'What is the product integrity of the product that I'm getting?' But in this case, they're not even wondering because they don't know."

If you have any tips about this story, please call Chris O'Neill-Yates at 709-687-5702 or send an email to [email protected].