Chemo drug supplier says Ottawa, provinces declined to regulate

The head of the company linked todiluted chemotherapy treatments given to about 1,200 people in Ontario and New Brunswick said both Health Canada and the Ontario College of Pharmacists declined to regulate the company's work.

Marita Zaffiro, president of Marchese Hospital Solutions, which supplied the chemotherapy drugs cyclophosphamide and gemcitabine to five hospitals in Ontario and New Brunswick, wasquestioned by the standing committee on social policy at Queen's Park on Monday.

Zaffiro testified her company went to Health Canada and the Ontario College of Pharmacists to inquire about regulatory approvals. She said both declined.

She also said the company approached pharmaceutical regulators in New Brunswick, but they also declined.

Zaffiro said her company "still instituted the most stringent quality control measures we could devise. I have always ensured that our organization operated according to the highest level of quality it is a core value of which I would not deviate."

Her lawyer later clarified that Marchese notified Health Canada in December 2011, after the company won a contract to produce the intravenous drug mixtures.

It's the first time Zaffiro has spoken publicly since she released a statement onthe company's website on April 3 saying "variations were the result of the use of our preparation, which according to our current understanding was not consistent with the contract, the preparation or its labelling."

"Our first priority was to ensure that the right treatments reached patients. That has been done. Secondly, we need to understand how assumptions about product use which were not consistent with the contractually supplied preparation and labelling led to this issue."

Last Monday, the regional director of pharmacy services for Windsor Regional Hospital, anotheraffected hospital, told the committee abouthow pre-filled IV solution bags are known to contain overfill, an industry standard of adding 20 to 30 millilitres in each 250-millilitre bag. The amount of overfill depends on factors such ashow much air is in the bag and how long it's been out of the overwrap packaging, Christine Donaldson said.

The oncologist would prescribe a dose, to the milligram, based on the patient's weight and health status. The dose would be drawn up and the specific volume for each patient was injected into a small mini-bag that was delivered to the patient without any further dilution, Donaldson said.

When the Windsor hospital was notified by the pharmacy manager at London Health Sciences Centre, the hospital with the most affected patients, on March 27 at approximately 4 p.m., Donaldson said all product wasimmediately quarantined.

"After being notified, the fluid from one sample IV bag was extracted and it was verified that extra fluid was present in the bag beyond the labelled volume. With this result, I redirected the pharmacy staff to begin preparing allcyclophosphamide doses in-house and patient-specific. This practice continues to today," Donaldson said, according to a transcript of the proceedings on the legislature's web page.

The label on the bag from Marchese listed four grams of cyclophosphamide in 200 millilitres, Donaldson said.

Chemotherapy oversight questions

"The concentration was not specifically listed on the bag. However, the total drug quantity in milligrams, or in this case, grams, and the total number of millilitres was stated."

Donaldson was asked about Marchese's statement that the problem was in how the drugs were administered at the hospitals, not in how they were prepared.

"Do I believe that there were the stated milligrams, the right drug, in that product, in that package? I do. We haven't done a quantitative analysis ourselves. I believe that there was a product produced according to what they believed the final concentration should be for our facility. Unfortunately, I think there was not that oversight as far as the product produced and what the intended use was for our patients. "

David Mushyj, president and CEO of Windsor Regional Hospital, saidit isn't time to point fingers but to learn about how it happened and address system issues to avoid it happening in the future.

"[W]hen we got the IV bags, could we have weighed them? Sure. Could we have pulled every 10th or 20th bag, extracted saline out of it and measured every bag ourselves? Sure. We talked about that openly with our patients and families.

"Is that reasonable? This is one of, to my understanding, some 2,000 different types of drugs that we dispense out of the hospital on a daily basis. Is that reasonable? Should the oversight happen at the source? Should it happen at the hospital? Should it happen at both places? That's what we need to learn."

Regulatory oversight of admixing the bulk mixing of drugs for multiple patients in different locations without individual prescriptions needs to be tightened, federal and provincial health officials say.

Health Canada and the provinces and territories are working to improve oversight, including inspections, of companies that aren't federally licensed as manufacturers or provincially accredited as pharmacies.

At the time of the overdilution issue, Marchese Hospital Solutions, which supplied the drugs, was not accredited through Ontario's College of Pharmacists.

Ontario Health Minister Deb Matthews has posted regulations directing hospitals to purchase only from accredited suppliers.

Ontario's College of Pharmacists is also developing a regulation to give them access to inspect premises like Marchese Hospital Solutions, where pharmacists and pharmacy technicians practice, including where drugs are admixed.

The committee hasn't heard fromMedbuy, aLondon, Ont.-based group purchasing organization. Medbuyworks with hospitals to reduce the cost of their health-care supplies, including Marchese's sterile compounding services for chemotherapy.