Health Committee on Feb. 5th, 2008

[Dr. Pier-Giorgio Fontana]

The progressive licensing framework is an attempt by Health Canada to address the issue of updating the regulations and to be in line with the way new pharmaceutical products now are being developed. There is an awareness, obviously, that there are some limitations, as I mentioned, as to what controlled, double-blind, randomized clinical trials can do. They have come to grips, really, with the realization that approval cannot be a point-in-time approach but needs to be based on the life cycle of the product. That's what progressive licensing means, that you monitor the safety of the product. You study very well during the clinical program, but then obviously when the drug reaches the population at large you may see some new events that may alter the safety benefit. Progressive licensing will provide the regulatory framework to address this life cycle concept.

This is not only in Canada but also in the U.S, which is the critical path. Through the critical path there are some consortia in terms of the science that will help make that risk assessment more predictable. Now we're working on biomarkers, on solid science, and again, through progressive licensing we will have a framework to accommodate these evolving thoughts as to the most effective way of managing the drug throughout the life cycle.

[Patrick Brown, Conservative, Barrie, ON]

Do you think the proposed life cycle approach would increase or decrease the number of warnings and advisories that Health Canada would make? Additionally, do you think Health Canada should have the power for a recall?

[Dr. Pier-Giorgio Fontana]

Yes. I believe that progressive licensing will also help the manufacturer to know exactly what the requirements or the standards are that TPD expects. We certainly encourage, as I mentioned, the harmonization of the standards, recognizing that the Canadian population is a small one so there is a need to have access to international databases, and this is where we need to have consistency of the nomenclature, consistency of standards in phase 4.

The structure of phase 4 studies can be very expensive because they involve large cohorts, so we need to make sure we address the right questions. A study that is done without proper scientific questions being addressed would not be a useful study and it would waste a lot of effort. So we have to ensure that we do the right study and that this study will comply with the evolving regulations we have been seeing.

[Patrick Brown, Conservative, Barrie, ON]

Could you touch briefly on what the costs are of these phase 4 trials so as to maybe get an understanding of it? What percentage of the drugs produced by your companies would go through phase 4 trials?

[Dr. Pier-Giorgio Fontana]

I don't know. Every study is different, depending on the number of patients. But they are expensive in terms of the resources. Also, at the sides you have to have expert people within the company. You have epidemiologists. You have groups of people looking at the signals that might be emerging.

This is an expensive effort. That's why we need to ensure that there is international cooperation, so that eventually the study could be manageable at the national level.

[David Skinner]

Regarding your earlier question about the impact of the progressive licensing framework, one of the core messages we'd like to deliver is that we don't want to lump all products together in one framework. The progressive licensing framework, if you look at the life cycle that they've described, starts with pre-clinical trial, clinical trial, new drug submission, new chemical entity, and all that.

When it comes to self-care products, none of that applies. They've been on the market for 20, 50, sometimes 100 years. They've been through all of that. If a product has been switched from prescription to non-prescription status, they've already had 20 years of experience with all of that.

So to have the same kinds of requirements that are anticipated for new chemical entities apply to everything under part C of the regulations would be a tremendous cost barrier to things like anti-dandruff shampoos, sunscreens, and other things that you can use every day for yourself. So that's a big thing.

With respect to the authority to recall, yes, I believe they should have the authority to recall. Health Canada has the ability to cancel your licence to market, so it's a very sharp tool with a big consequence. They can't say they want you to recall a product and keep it off the market while its under study. All they can do is say your product can no longer be marketed.

So they can take a product off, but it may be killing a mouse with a shotgun.

[The Chair, Conservative, Joy Smith]

Thank you, Mr. Skinner, Mr. Brown.

Monsieur Malo.

[Luc Malo, Bloc, Verchères—Les Patriotes, QC]

Thank you, Madam Chair.

Thank you, ladies and gentlemen.

Dr. Fontana, when my colleague asked about the accessibility of studies earlier, your answer was that the studies are available through the association's portal. Since these studies come from the industry, what do you do to make sure that even the greatest sceptics can feel comfortable that the studies are balanced and objective?

[Dr. Pier-Giorgio Fontana]

All studies, as I mentioned, will be registered through public databases. The quality of those studies is discussed with the regulatory agencies and is reviewed by ethics advisory boards. So there are at least two levels of scrutiny with respect to the scientific methodology and whether the right questions are answered. This is not done exclusively by the manufacturer, so there is peer review. The information will become available, but at the outset there is a level of scrutiny that we encourage.

[Luc Malo, Bloc, Verchères—Les Patriotes, QC]

You all more or less said that the rules should be brought into line with international standards. I was wondering if those included ICH standards. It has shortened evaluation periods in its criteria. I ask the question because I wonder whether shortening the evaluation period for a drug would not have major repercussions on public health.

[Dr. Pier-Giorgio Fontana]

The length of a study varies depending on the disease. I think there are obviously international standards with respect to the length of a study. To demonstrate the efficacy of a product you don't necessarily have to test the product for a year. However, certainly for safety, studies are required to be longer.

There is a sense now that standards have been lower in recent years, but I do not agree, personally, with that view. As a matter of fact, if you look at the number of studies in the average new drug submission in the last 10 years, it has doubled. The number of studies that are required for a new drug submission has doubled. The number of patients has doubled.

I do not believe we are lowering the standards. I do not believe the time to review a drug is necessarily correlated with the outcome of that review. In other words, you could have an excellent review done in six months and a terrible review done in three years. So we have to be very careful about associating this concept of time with the quality of the data, the quality of the review.

The other thing I would add is that in Canada we see drugs actually available on the market significantly later than in some other jurisdictions, so there is time as well to observe the experience on the market.

I believe we have a system here in Canada, in some cases, where the international standard actually might not be followed. Health Canada was an observer of the International Conference on Harmonization. They endorse the standards that they feel are adequate, but the don't necessarily endorse others.

I hope this will address your question.

[The Chair, Conservative, Joy Smith]

You just have 50 seconds left, Monsieur.

[Luc Malo, Bloc, Verchères—Les Patriotes, QC]

I want to come back to the very first answer you gave me. I have quite a significant figure here. The figure is that 89% of studies show adverse or contentious effects which are not published in the scientific literature.

Can you comment on that figure?

[Dr. Pier-Giorgio Fontana]

The only thing I can say, again, is that virtually all studies are subject to regulatory scrutiny.

There's the editorial policy of a journal. You could submit a study to a journal and be refused publication. So I do not believe there is an intentional attempt not to disclose negative studies.

The other thing, too, is that the regulatory authorities do not discriminate in terms of saying, this study is positive, this study is negative. It's the bulk of the evidence, it's that risk-benefit balance that we look at. It doesn't necessarily come from one trial.

[Luc Malo, Bloc, Verchères—Les Patriotes, QC]

Are you saying that it is a question of methodology and that, in some studies, it is more...

[The Chair, Conservative, Joy Smith]

I'm sorry to have to interrupt you, Monsieur Malo.

Thank you, Dr. Fontana.

Mr. Fletcher.

[Steven Fletcher, Conservative, Charleswood—St. James—Assiniboia, MB]

Thank you, Madam Chair.

I want to go back to some comments that have been made already. One was made by my friend in the NDP, where she stated that it's your guys' job to make money and it's the government's job to ensure safety. There was no reaction from any of you. Do you accept that, or do manufacturers have some responsibility for safety?

[David Skinner]

Manufacturers ultimately bear the burden of safety and efficacy and quality. The regulations that are in play are there to protect the public from fraud and danger. Actually, it goes to the heart of a lot of issues we talked about, such as cost recovery.

Are the activity levels that go on within Health Canada to protect the public from fraud and danger a public benefit or is that a benefit to manufacturers? If it was a benefit to the manufacturers, certainly we wouldn't have criminal law outlining fraud and danger consequences.

So we do ultimately bear the responsibility. If there's an incident, regardless of what the regulations may say, the manufacturers are going to have to be accountable for that, in a commercial way, in a safety way, in every sense of the word.

[Steven Fletcher, Conservative, Charleswood—St. James—Assiniboia, MB]

Out of fairness, I wanted you to have an opportunity to clarify that.

[Dr. Colin D'Cunha]

From my perspective, if I may draw your attention to the bottom of page 2 from my presentation, it says, “To protect public health by monitoring for the safety and efficacy of our products.”

Enough said.

[Steven Fletcher, Conservative, Charleswood—St. James—Assiniboia, MB]

I love the different uses of words. In one of your comments you said that in an effort to get doctors to report, we need to “stimulate” them to do so. I wonder if--because I don't have enough time here to hear how you would stimulate doctors to do so--you could table to the committee a list of stimuli that would encourage that.

[Dr. Colin D'Cunha]

Being aware that the Canadian Medical Association is presenting to you on February 26, and as a member of the CMA, I'll defer to what the association tables before I decide to make further comment.

[Steven Fletcher, Conservative, Charleswood—St. James—Assiniboia, MB]

Okay.

We don't have time to hear it all now, but I would also encourage you to table to the committee any key gaps in current legislation or regulations in Canada for ensuring post-market safety of products. I think we would all be very interested in hearing what you have to say.

My last question is, does your industry support Health Canada's proposal to move to a life-cycle approach to regulating health products, which could include attaching conditions to the licences of products, which companies would need to fulfill to keep their products on the market?

[Dr. Pier-Giorgio Fontana]

Yes. We encourage the approach, as I mentioned earlier, through progressive licensing.

One area where again we should be cognizant, because the resources are limited and the data necessarily has to be large, is that we need to ensure that whatever we do will be Canadian regulation, structured in a different way but so that ultimately the standards that will be required for post-marketing are somehow homogeneous, so that the questions that are being raised through post-marketing trials are valid scientific questions with a very clear outcome.

There are epidemiological methodologies now that require scientific discussion. As I mentioned earlier, good science is not the prerogative for any group, and that's why we encourage the spirit of transparency and collaboration. ICH is a forum; CIOMS is a forum. There are all kinds of international fora to ensure that we are all aligned.

[The Chair, Conservative, Joy Smith]

Mr. Fletcher, you only have about 50 seconds.