Decision on pulled Novartis flu vaccine coming 'shortly'

TORONTO - Health Canada expects to make a decision "shortly" on what to do with a significant portion of the country's flu vaccine supply that has been in limbo since the end of last week.

TORONTO – Health Canada expects to make a decision “shortly” on what to do with a significant portion of the country’s flu vaccine supply that has been in limbo since the end of last week.

A senior official said Tuesday the department has finally been able to get information from the Italian regulatory body that initially suspended distribution of two types of flu vaccine made by pharmaceutical giant Novartis, a move that prompted a number of European countries and then Canada to place a hold on use of those vaccines.

Dr. Paul Gully, Health Canada’s senior medical adviser, said the department has been gathering information from the European regulatory agencies, Novartis and now the Italian body.

“We are at present collating all that information in a risk assessment and there will be a decision made very shortly on the situation,” Gully said in an interview.

He would not indicate how soon the decision might come. But it is clear that the department feels time is of the essence, given that this is typically when flu shot clinics and delivery efforts should be kicking into high gear across the country.

At least a couple of provinces — Saskatchewan and Prince Edward Island — have been badly hit by the stop-use order that Health Canada issued last Friday. Novartis was contracted to supply 20 per cent of Canada’s overall order this year, but is the main supplier for those two provinces.

If the Novartis vaccine isn’t cleared for use, other provinces and territories will be asked to share some of their vaccine with Saskatchewan and P.E.I. But that’s not ideal, Gully said.

“I mean it’s doable, and we have the processes to manage that. But it’s complex. And we don’t really want to get into that unless we have to,” he said.

“My understanding is that most of the countries (involved) do not use a large amount of this vaccine and they can take other actions because it wouldn’t necessarily affect their programs. That’s not the case for us,” Gully said.

The situation started when Novartis told the Italian regulatory agency that it had found a higher-than-normal level of protein aggregates in one batch of vaccine made at its plant in Siena, Italy. Aggregates are tiny clumps of proteins, the part of the vaccine that triggers an immune response in a recipient.

The Novartis vaccine Canada buys is made at the Siena plant. It is sold here under the names Agriflu and Fluad.

A Novartis senior executive said the company held back the affected lot and looked for but didn’t find the problem in other batches made at the Italian facility.

“We have not seen aggregates in other finished lots of the vaccine,” said Dr. Vas Narasimhan, the global head of vaccines development for Novartis Vaccines and Diagnostics.

From time to time the proteins in vaccines fall out of suspension and are visible to the naked eye. It is not uncommon, nor is it a sign that there is something wrong with the vaccine, said Narasimhan.

“There are no contaminants in the vaccine,” he insisted. “These aggregates are formed by proteins that are expected to be in the vaccine, predominantly hemagglutinin and neuraminidase, which are the two antigens that we’re using to stimulate the immune response.”

Hemagglutinin and neuraminidase are proteins that sit on the outer shell of a flu virus. Flu vaccines are designed to induce antibodies to these proteins so that if an immunized person comes in contact with influenza, those antibodies should kick into gear to prevent infection.

Narasimhan said all vaccines typically come with instructions that they should be shaken before use. Doctors know, he said, that if particles are seen after the vaccine is shaken, they should discard that dose or vial.

“We think that depending on temperature, depending on PH, depending on the strain we happen to use in a given year, you can see low levels of aggregates form on occasion. But generally speaking, these should go back into solution when shaken,” Narasimhan said in an interview from Cambridge, Mass.

In testing that Novartis has done, the aggregates in the affected vaccine go back into solution with shaking, he said.

Narasimhan said all batches of Fluad and Agriflu were tested for potency and safety, and all met the required specifications.

As a precaution, the Italian regulatory agency suspended delivery of vaccine from the plant to Italian customers. That set off a domino-like response across Europe, with Switzerland, France, Spain, Germany, Austria and Britain all taking some type of action.

The situation left Canada with virtually no choice but to follow suit, Gully said.

Canada and other countries use data gathered by the Italian regulator to license vaccines from the plant, though Health Canada conducts its own inspections of batches of vaccine once they arrive in the country.

“If another regulator makes a decision, we really are duty bound to find out whether they have information which we do not have and which would be relevant to our assessment of the vaccine,” he said.

The United States has not been affected by the issue. While it purchased Novartis vaccine this season, the product it bought, Fluvirin, is made at a plant in Liverpool, England.