HEAL Committee Meeting

STANDING COMMITTEE ON HEALTH

COMITÉ PERMANENT DE LA SANTÉ

EVIDENCE

[Recorded by Electronic Apparatus]

Thursday, November 27, 1997

• 1105

[English]

The Chair (Ms. Beth Phinney (Hamilton Mountain, Lib.)): I call to order the Standing Committee on Health. This is our seventh meeting.

Our witnesses are from Health Canada, and our principal witness is Dann Michols. He's the director general of the therapeutic products directorate of the health ministry.

Dann, would you introduce the people with you, then the floor is yours.

Mr. Dann Michols (Director General, Therapeutic Products Directorate, Health Canada): Thank you very much. As mentioned, I am director general of the therapeutic products directorate.

With me is Mary Carman, who is the director of the bureau of pharmaceutical assessment and will be explaining her role in a moment; and Jean Lambert, who is the director of the Quebec region, but he is also carrying responsibilities for our compliance and enforcement activities and will be getting into more detail on that side as well.

May I start?

The Chair: Yes.

Mr. Dann Michols: Thank you very much for the opportunity to meet with you and to present. As I mentioned, we are the regulators for drugs and medical devices in Canada, and the products you have in your terms of reference are drugs and are regulated at the moment as drugs in Canada.

We have prepared some material for you. You should have a binder that we have pulled together to speak to a wide range of issues or activities that we undertake, and in my presentation I will be going through the binder to give you a feeling for the material that is in there. The binder is bilingual. There is a briefing note on each one of those activities that may cause you to ask questions or want more information, and we'd be delighted to provide it.

You should have also a copy of slides we have prepared for my comments, followed by some from Mary and some from Jean. It was my intention to go through this slide deck and speak to a couple of highlights, referencing those highlights to the material that is in the binder. Hopefully at the end of the presentation you will have a good understanding of the current regulatory framework for herbal remedies, traditional medicines, homeopathic preparations, vitamin-mineral supplements, those substances that are in your mandate.

I must apologize most profusely. When we were in the process of copying the French version of the slide presentation, our copier broke down. It is being copied now. It should arrive momentarily. So there is a French-language deck that I should have before the end of the presentation, and again I apologize. It would appear that Murphy's Law holds within the Food and Drugs Act as well as other places.

We've chosen to present the slides to you in hard copy as opposed to asking you to view the screen. It will save everybody's neck muscles.

The first slide concerns therapeutic products regulation enabling legislation, and the tabs that relate to this particular slide are tabs 4, 5 and 6 in your binder, when you have an opportunity to get to the binder.

Basically in Canada there are two pieces of legislation that pertain to the regulation of the products you have in your mandate: One is the Food and Drugs Act and its regulations; and the second is the Controlled Drugs and Substances Act and its regulations.

There are a couple of other pieces of legislation that have a peripheral impact on our activities: obviously, the Department of Health Act, the Access to Information Act and Privacy Act, and the Financial Administration Act and regulations. But in Canada, it is principally the Food and Drugs Act and the Controlled Drugs and Substances Act that govern our regulatory activities vis-à-vis these substances.

• 1110

The second slide is on delegated authority. I have done a very simple chart here on delegated authority. In the binder, in section one, there is a range of organizational charts for the Department of Health. On the slide you have here, I have simplified it to represent the delegated authority.

In the Food and Drugs Act, the minister is responsible for a range of activities. Those responsibilities have been delegated to my position as director general of the therapeutic products program.

Within this program, there are a number of activities that have to do with product assessment. Those belong to the bureau of pharmaceutical assessment. Mary Carman is the director of that, and she'll be going into detail on the processes there.

There's also a range of activities that have to do with establishment licensing and compliance in enforcement activities. Those are in the bureau of compliance and enforcement. Jean Lambert is the director in that area, and he will be getting into more detail in that area.

But basically, the Minister of Health has the responsibility for regulating these products, and that authority has been delegated to my position.

Within the Food and Drugs Act are two definitions that pertain to your mandate. The first is the definition of a food. The second is the definition of a drug.

In the Food and Drugs Act, a food is:

any article manufactured, sold or represented for use as food or drink for human beings, chewing gum, and any ingredient that may be mixed with food for any purpose whatsoever.

So that's the definition of a food. There's material in your binder, tabs 35 through 39, that presents additional information for the sister organization within Health Canada, the foods directorate, that regulates foods.

On the next page is the definition of a drug. The definition of a drug in the Food and Drugs Act is the prime reference for what is considered to be a drug in Canada. Consequently, this is regulated by my organization. In the act, under the definition of a drug, it says:

any substance or mixture of substances manufactured, sold or represented for use in

(a) the diagnosis, treatment, mitigation or prevention of a disease, disorder or abnormal physical state, or its symptoms...

or any substance or mixture of substances designed to restore, correct, or modify organic functions.

So a drug doesn't have to be just sold. It can be set up and represented for use. It can be samples given away or whatever.

Also, the third definition has to do with disinfection in food preparation places, so that's not particularly germane to your mandate, but the first two bullets are. I think you can see from the breadth of substance that's included in the Food and Drugs Act under the definition of a drug that there is not much, if anything, in this country that makes a claim or is to be used for a therapeutic, preventative, or diagnostic purpose that is not defined as a drug in Canada. Therefore, it comes within the purview of my organization.

My organization is the therapeutic products directorate. It manages the therapeutic products program. On this slide, you have the mission statement for my organization, which is basically to ensure that the drugs, medical devices, and other therapeutic products available in Canada are safe, effective and of high quality. It's a fairly straightforward statement. It covers a lot of ground.

The second bullet lists all of the substances or products that fall within our responsibility.

The first is pharmaceuticals, those synthetic products that you tend to think of as drugs, prescription, and non-prescription products.

• 1115

Second is biologicals, which includes vaccines, blood, blood products, tissues and organs, and the new range of biotechnology products being developed from recombinant DNA technologies.

Third is radiopharmaceuticals.

Fourth is complementary medicines, which is the broad term used to cover many of the products that are in your mandate, the term “complementary” meaning complementary to what one might consider the established medicine field, or the western tradition of medicine, if you like. These include herbal remedies, traditional medicines, homeopathic preparations, etc. It's not a perfect term—its use will be debated, I'm sure, by a number of your witnesses—but for the moment it's the best term to indicate these other types of medicines used in Canada that are not normally considered part of the established medical community.

Fifth is medical devices, as I've mentioned.

Sixth is nutraceuticals. On tab 28 of the binder, there is a reference to a policy activity we've undertaken. Nutraceuticals and functional foods are the products that fall within the grey area between the definition of a food and the definition of a drug. So if you have a product that is manufactured and tends to look like a food but wants to make health claims like a drug—and an example would be bran flakes for prevention of colon cancer or something along those lines—it falls in the cusp between foods and drugs. We are attempting to work in conjunction with our sister organization, the food directorate, to bring some appropriate regulatory framework to these products so that Canadians can benefit from these products that one thinks of as foods but are making drug claims. We have a policy initiative going in that area, and we can get into that in more detail.

Seventh is disinfectants.

Eighth is narcotic, controlled, and restricted substances, which fall under the regulation of the Controlled Drugs and Substances Act. Some of the products that fall within the categories you are examining are controlled substances under the definition of that act. In your binder, tabs 4, 5, and 6 speak in more detail about our enabling legislation, the Food and Drugs Act, and the Controlled Drugs and Substances Act.

Now I'd like to speak for a moment about risk management. Risk management and the principles of risk management are the underlying foundation for how we regulate many things in Canada, but particularly therapeutic products and food.

As for the steps that are taken, it's a fairly straightforward process within risk management, and Mary will be getting into a little more detail in reference to the evaluation of particular products. First we assess the benefits being claimed for a product and the risks being presented by a product. We determine whether the benefits are greater than the risks and we determine how we could mitigate the risks with additional information or particular controls on a product. We grant approval for the marketing of that particular product, based on whatever conditions we feel are relevant to the particular product, putting it into prescription status or non-prescription status or whatever. Then we monitor the product thereafter. But the basic concept is we regulate products according to the benefits and risks they present to the Canadian public.

The next slide is about risk factors. In the process of regulating therapeutic products, risks are presented by three different factors.

There are the risks presented by the substance in and of itself. Is it toxic? Is it toxic at a particular dosage level? Are there impurities in the product? And so on. So the actual substance in and of itself presents a set of risks.

• 1120

The second set of risks is presented pertaining to the claims that a particular product might be making. Obviously, the risks increase with the seriousness of the claim. A product that is claiming to address a rash potentially would not be as risky as a product addressing cancer, an HIV virus, or something along those lines. What the manufacturer is claiming for a particular product also presents a range of risks. The greater the risk, the greater the amount of evidence or information we require in order to agree with that particular claim.

The final set of risks has to do with the amount of information available that can be attached to the particular product once it's approved. Obviously, we attempt to provide a lot of information in a format that a consumer can understand as a patient package insert or as labelling on a package or whatever in order to reduce the risk. We make sure that this particular product is determined safe for its particular application. We determine that it addresses the claims that the manufacturer has for it. We also determine that it is being explained properly to the consumer so that the product is being used in the proper dosage form and in the proper situation.

The second bullet on there simply says that we attempt to graduate our regulatory activity, both in terms of the initial evaluation of the product and in any subsequent activity once the product is on the market, to the degree of risk represented by that particular product. So products of low risk receive a light touch from us as regulators. For products of high risk, we expend more resources in evaluating and monitoring.

The role of the regulator is simply an attempt to show you that what you have been asked in the objectives within your terms of reference is very similar to what we as regulators consider important. We do not exist to bar safe, high-quality, effective products from the market. We gain nothing from barring a product from the market that is useful to Canadians. It is our job to make those products accessible.

Our first objective is to ensure that the products that are accessible to Canadians are safe, effective and of high quality.

The second aspect of that is to facilitate the freedom of choice of Canadians. Those are the two objectives that you have been given. We believe that it must be the freedom of informed choice. In other words, there must be adequate information available to the consumer in a form that is easily digestible and connected to the products in order to reduce the risk of the use of these products.

Next, the Canadian regulatory framework is basically quite simple in conception. We regulate therapeutic products in Canada along two broad lines: the product and their claims; what we call product licensing, or the review and approval of the products in and of themselves.

We go through a process, which Mary will get into in more detail, that evaluates and monitors the products' safety and effectiveness. It links our activities in pre-market authorization to post-market monitoring, and basically tracks the products through their entire life cycle. We key on the products through the process of product licensing.

Through the process of establishment licensing we key on the facilities involved in the production and marketing of those products.

Jean will be presenting on our establishment licensing. Basically, that is the evaluation and the monitoring of the manufacturing facility in Canada and most of the developed countries against standards that are called good manufacturing practices, GMPs.

You will hear that acronym many times over the course of your responsibilities. Good manufacturing practices are international manufacturing standards against which we inspect and monitor the activities of manufacturers, distributors, importers, etc.

The next slide is on cost recovery. This slide is linked to tab 7 in your binders. The federal government has a policy that all government activities are to be reviewed for the opportunity to recover the costs from particular stakeholders, particular sectors of society, if they benefit from the government activities.

• 1125

About three years ago, in the program review exercise that was run by the government, the budget of my organization was cut 50%. My appropriations were reduced by 50%, and I was directed to enter into cost recovery consultations with stakeholders, primarily manufacturers, to put in place a series of fees to recover the costs of the activities we undertake in regulation.

We have introduced three broad categories of fees. The first is under a set of regulations called the “authority to sell” fees. Basically, those are annual licences for products. If a product is on the market, it is required to pay an annual licence. Those were introduced in January 1995.

The second set of fees, broadly, are what we call “drug evaluation” fees. Those are fees that we charge to manufacturers or sponsors for the evaluation of the dossier they are presenting to us seeking marketing authorization.

The “establishment licensing” fees are annual fees that will come into force in January 1998, which we charge annually to a range of facilities, manufacturers, distributors, importers and testing laboratories that we regulate.

It is that latter set of fees, establishment licensing fees, that the Minister of Health has exempted the products that are within your mandate from paying.

So they have been exempted from being required to apply an establishment licence and, consequently, having to pay for an establishment licence. They have not been exempted from the GMP requirements that are necessary to justify that licence, so we will continue to be inspecting the manufacturers and distributors of the products that are within your mandate, but they will not be required to hold an establishment licence and they will not be required to pay for that licence while your deliberations on this subject are under way.

On the next slide, on activities covered, I'd like to make it clear, if I may, that the revenue from the fees we collect do not go into the general revenue coffers of the federal government. They come back to us and they pay for the activities we undertake as regulators. So on this slide, I have indicated to you the sort of activities that are covered by the fees we collect.

The annual product fee covers our activities in collecting information and monitoring information on adverse drug reactions, all the health hazard investigation we undertake if a consumer or another manufacturer complains about a particular product and we send out our investigators to take a look at that product. If we take that product to our labs for analysis, those annual fees are covering the costs of that activity or covering a portion of the costs of that activity.

The second set of fees, the evaluation fees, are covering a portion of the cost of our product evaluation activity, the pre-marketing activity to evaluate the product to determine whether or not it should have a marketing authorization and be sold in Canada.

The third set of fees, the establishment licensing fees, cover our manufacturing and distribution inspection activities.

The fees we raise do not cover 100% of the costs of those activities, so all of those activities are being subvented or augmented to one degree or another by taxpayers' dollars.

• 1130

I'd like to speak for a moment about a couple of regulatory initiatives under way that pertain to your mandate.

The first is the Advisory Panel on Natural Health Products, which has been in existence for the last six months or so and is referred to in tab 14 of your binder.

Six months ago, at the request of the previous Minister of Health, Mr. Dingwall, we created an Advisory Panel on Natural Health Products. Its mandate was to provide us with advice on the application of the current regulations and policies for the regulation of natural health products and on the processes that we should undertake to review the current regulatory framework and to develop whatever new regulations and or new policies might be useful to more appropriately regulate natural health products in Canada.

This is a group composed of 19 people and it has very broad representation. It represents the industry, both on the complementary medicine side and the established medicine side. It represents academics working in both areas, health practitioners, medical doctors, pharmacists, herbalists and complementary medicine practitioners, and it has consumer representation as well. The full mandate of that organization and the full composition, with the requisite titles, are included in your binder at tab 14.

This group has met three times and has done some excellent work, I think, in reviewing and in making recommendations to us. The minister has asked that they be prepared to present their findings to you at your convenience. They feel they would be ready after the middle of January. They would have a report for you that they would be delighted to present in order to give you the benefit of their activity in this particular area, should you so wish. As I said, the panel has a very broad representation of views and interests.

The Chair: Mr. Michols, could you just let us know who that group is responsible to, who they are reporting to?

Mr. Dann Michols: Yes. That group has been set up to advise the regulator, myself and my staff, in the process of our activities. It is a group that is of particular interest to Mr. Rock, the Minister of Health. He has talked on several occasions with the chair and is looking forward to their presentation to you, if you so choose.

On the next page, you will see that EAC is shorthand for “expert advisory committee”. We have established six expert advisory committees within the therapeutic products program. One is an expert advisory committee on complementary medicines. All of these expert advisory committees are made up of scientists, health practitioners, academics and, in some cases, consumers, who have an interest in a particular area.

Tab 12 of your binder has some background information on all of our expert advisory committees. Tab 13 has more specific information on this expert advisory committee on complementary medicines, and you will see that from the composition of it, the titles, it represents practitioners, academics and scientists who have worked in the area of complementary medicines.

The mandate of this group is different from that of the advisory panel to the extent that this group is not involved in regulatory policy or activity. It is involved in advising us on the science and medicine connected to therapeutic products. They do not get involved in the “small p” politics. They do not represent stakeholders. They are on this expert advisory committee in their own right, for their expertise and experience. They advise our scientists and our staff medical officers and bring my staff closer to the actual activities within the community.

• 1135

You will see that there is provision for both core members and ad hoc members. There are particular members appointed—standing members, if you like—of this expert advisory committee. They have the opportunity to call any other experts they may wish, if they're dealing with a particular substance or a particular situation.

We have a number of other regulatory initiatives under way that you may be interested in. Prior to...this set of terms of reference to you, we had been undertaking a fair amount of work in the regulation of complementary medicines, herbal remedies, etc.

Some of these activities are referred to in the binder. We have been producing policy papers, regulatory option papers, particularly—as I mentioned earlier on the subject of functional foods and nutraceuticals—how they should be regulated. That policy paper, which is being sent out to a wide range of stakeholders, is in the binder at tab 28, for your reference, as are some of the other policy initiatives we have undertaken.

For many reasons that will become evident as you undertake your hearings, we have a particular challenge dealing with products that relate to particular medicinal cultures in Canada—traditional Chinese medicines, traditional ayurvedic medicines, traditional native North American aboriginal medicines.

These are products that have been used for centuries, if not longer, by these particular medicinal cultures in their particular practices. We appreciate that we have to develop regulatory mechanisms to deal with these products within the context of their own medical communities. As you know, they are now being used more broadly and being introduced into other communities, so we have to assure that the regulatory framework is capable of dealing with them within their own practice, as well as within practices outside of that.

Of particular importance are the traditional Chinese medicines. We were organizing a consultation process with the traditional Chinese medicine community. It is on hold, pending the activities of your committee.

We also realize, and I hope that you do, that there is a law of the land now that relates to the regulation of therapeutic products. Obviously there is an act and there are regulations on the books while you undertake your deliberations on whether or not the requirements of that act and regulations are appropriate to the times.

We have developed a number of interim compliance directives and activities to sensitively monitor and regulate these products while you undertake your deliberations. Those are available to you, should you be interested, and Jean will speak to a couple of them in a minute.

We are in the process, as far as resources allow, of strengthening and dedicating resources to the regulation of these products in a different manner than the regulation of the more established pharmaceuticals and biologicals, etc.

Let me speak for a moment at the last about comparative regimes for the regulation of these similar products—complementary medicines, natural health products—in other countries. Your mandate speaks to taking a look at some international regimes that might be used in comparison. There are several. In the binder we have prepared a note on the general international regulation of these products, and we have done a note on three particular regimes that we think will be of interest to you.

We can prepare any additional information if you wish, but basically we outline the regulatory framework that exists in the European Community, that which exists within the United States of America, and that which exists in Australia.

For obvious reasons, Europe has perhaps had a longer association with some of these products than North America has. The United States is, unfortunately, from time to time a stone's throw away, and Canadian regulatory practices are often compared to those of the Americans. We outline the framework in Australia because it is a country very similar to Canada in many ways in terms of its medicinal practices, its regulatory activities, the size of it, and its particular challenges.

• 1140

In terms of the first slide, which is generally on international regulation, I think you will see in your deliberations that most developed countries and certainly those in Europe, North America and Australia regulate natural health products that make therapeutic claims as drugs within their particular regimes. All of them require in one way or another evidence of safety and quality. Most of them have the same or similar good manufacturing practices as we do. There is a range of flexibility on the regulation of the effectiveness of these products, and I think you will be getting into that in some detail.

In terms of their effectiveness, the evaluation of traditional medicines in Canada and in most of these countries is traditionally handled in a different fashion from new established medicine products. The determination of whether or not these products are effective is in large measure done by reference to traditional literature, traditional references, and Mary will be getting into some of that.

As well, the World Health Organization came out—and there's a reference to it in your binder at tab 31—in 1992 and adopted a set of guidelines for the review of the safety of herbal medicines. Basically it was based on the principle that traditional products that have not demonstrated harm should not be treated in a very restrictive regulatory action. That is the basis of the regime we have tried to put into place in Canada.

On the next slide, the European Community more specifically, you will see that all member states are regulated by a European Community directive in this area. These products are regulated as medicines if they make therapeutic claims, but they do have flexibility for the effectiveness standards that pertain. They nonetheless have standards, GMPs, for the safety and quality of these products.

The Americans to the south have basically two pieces of legislation that pertain to these products. The first is the Federal Food, Drug and Cosmetic Act, which basically says herbal products that make therapeutic claims are drugs and require evidence of safety, quality and efficacy, exactly as it does in Canada.

There is a second piece of legislation, which was passed in 1994, called the Dietary Supplement Health and Evaluation Act, DSHEA for short, which states that herbal products that make functional claims—and to some extent that might be viewed as the second bullet within the definition of a drug in Canada—are defined as dietary supplements. They are not subject to safety, quality and efficacy standards, but the labels of those products must bear a disclaimer that says the FDA, the Food and Drug Administration, our counterparts, have not evaluated these products and do not necessarily support the claims that are being made.

Ms. Aileen Carroll (Barrie—Simcoe—Bradford, Lib.): Can you tell me a bit more about this acronym, DSHEA.

Mr. Dann Michols: In tab 32 of the binder there is a broader statement, but it is the Dietary Supplement Health and Evaluation Act.

Ms. Aileen Carroll: Thank you.

Mr. Dann Michols: Through the course of your deliberations you will undoubtedly hear reference to it.

The Food and Drug Administration, our counterparts, the regulators in the United States, served advance notice in February of this year that they would be proposing the establishment of good manufacturing practices for dietary supplements. We already have in place good manufacturing practices for dietary supplements because in Canada they are basically defined as drugs.

In November 1997, which is fairly recent, the FDA struck a review panel that is going to look, in much similar fashion to yourselves, at the regulatory regime to be applied to these products.

• 1145

Finally, in Australia, the regulatory regime is such that medicinal products are either registered or listed. The process of registration is very similar to our process of licensing. Low-risk products are listed. Most herbal remedies in Australia are considered to be of low risk, and consequently are listed.

Regulatory requirements still pertain that these products must adhere to standards of safety, quality, uniform labelling, and good manufacturing practice. They must not make false claims. And the manufacturer, although it does not have to submit for any sort of pre-market approval, must have data on record for the efficacy of the products it's manufacturing, and that material must be presented to the regulator on demand.

That's the conclusion of my broad comments on the regulation of therapeutic products in Canada.

The Chair: I wonder whether the committee would like to ask its questions now, because we've already taken almost half an hour.

Mr. Dann Michols: I'm sorry, Madam Chair, I was under the impression that we were to be available next Tuesday.

The Chair: Yes.

Mr. Dann Michols: We would be available for questions at that time, as well, so I was looking on it as two sessions.

The Chair: Right. Okay, that's fine. We're looking at it that way too. Do members want to ask you questions on your part now, or do they want to hear from all three, and then we won't have any questions today. We'll probably have to hold all the questions until next week.

Could I have a consensus?

Mr. Grant Hill (Macleod, Ref.): I would prefer to listen to the regulators and then have—

The Chair: Okay, it might make more sense. Okay, go ahead.

Mr. Dann Michols: It would be our preference, if I may say, because that will also give you a chance to look at some of the material in the binder. You might then be perhaps better informed for your questions.

Ms. Aileen Carroll: Then the same presenters will be returning on Tuesday so that opportunity won't be missed?

Mr. Dann Michols: Yes.

I'd like to ask Mary Carman to take you through the product licensing process. This is how we handle the pre-market authorization of things that are drugs in Canada.

Ms. Mary Carman (Director, Bureau of Pharmaceutical Assessment, Department of Health): I'd like to take you briefly through an overview of the product approval process. I'm not intending to get into detail, and I would be pleased to answer your questions at our next opportunity.

The Chair: Can you just hold it for a second? Does everybody know where we are?

Mr. Dann Michols: This is a presentation package that has Mary's name on it, so it's appropriate that she should speak to it.

Ms. Mary Carman: As mentioned by Mr. Michols, our primary thrust and focus in a product approval is risk management and risk assessment. Risk management encompasses, for therapeutic products, both the premise of risks and the premise of benefits, and they are balanced against one another. If I had a picture, it would be of a balance. We are always looking for the benefits of an intervention to outweigh the risks that may be attendant with that intervention.

I'd like to expand upon the risks and where they may present themselves from. Those of you who practise medicine in this group, or have received the practice of medicine, will recognize that your disease presents a risk to you, otherwise, we would not be looking for any intervention. So that's a principle within the risk side. The disease presents a risk. A headache, on the short term, may not be of high risk. A cancer may be of indeterminable risk.

• 1150

There is also the risk of the ingredient that you are assuming or taking into your body. There are known, in some instances, and in some instances unknown until they appear, risks to that ingredient ingestion. There can be and have been known to occur impurities or contaminants within the ingredient or the product, either through the manufacturing process, through an error, or naturally occurring. Those are limited through good manufacturing practice and investigation, but primarily through knowledge.

Then there is the risk of incorrect use by the patient. Taking the wrong drug at the wrong time or in the wrong dosage presents its own risk.

The benefits, or does the product do what it says it's going to do—that's why we use a short form—is a basic premise for medical practice: a benefit versus the risk that's already known. If you don't know of a benefit, if you can't understand that benefit, then the assumption is that the risk is too great.

The benefit comes from evidence of what it is going to do. Do you know that it actually will cure your headache or at least relieve it?

A benefit comes from knowing that the ingredient you're expecting to have in the product is there, in the amount it says is there, and that it has been shown to be effective.

The third benefit or manner to increase the benefit is that the labelling is clear to the patient as to when to use it, when you shouldn't use it, and how you should be using it.

If that balance is skewed, not to the benefit side, then an approval is not given. If the benefit is skewed to increase the benefit, an approval is given. They are not synonymous. The risks associated with an anti-neoplastic or a cancer treatment are generally far greater from the ingredient and the disease than they are in relation to something that may be approved for a non-prescription symptomatic ailment.

On the second slide, I'm going to go through a very brief overview of the regulation or the pre-market intervention that is currently in place in Canada, to give you an idea of the range. There are a number of tabs within your booklet—actually, tabs 15 through 21—that speak to a variety of these in more detail.

Regarding our lowest assessment and where we establish well-known ingredients for low-risk or specific non-prescription indication, you have two tabs, tab 19 and tab 21, where we're talking about a standard that we have put in place that the manufacturer tests to.

An example of that is fluoride for cavity prevention. Your fluoride toothpastes are drugs under the Food and Drugs Act and regulations, and there are standards for them. But it's a major public health measure, and if the fluoride was not there or was not available to you, then dental caries and all of the ensuing problems that could occur would not be remedied.

The pre-market assessment for those products is limited to an attestation by the sponsor, and I would draw to your attention—and I'm sure it's in the briefings—that the Food and Drugs Act is criminal legislation. With an attestation by the sponsor, the person who is going to market that product, that indeed they do meet all of the aspects of the standard—and there are quality, labelling and compositional aspects in that standard—then they can go to market. There is a performance target for that of 45 days, where we screen. Then it moves to market.

The next major level down is known ingredients for monograph standards, known ingredients with a little more risk. We're talking about something such as ASA or acetaminophen for your headache. It is well established that the risks of those products are reasonably well established; the benefits of those products for non-prescription indications are reasonably well established in dosage ranges. Again, the sponsor can attest to a label standard, we will screen against it, and they can go to market.

• 1155

There are ingredients that have traditional uses or published data that can be relied upon, and the traditional herbal medicines for OTC generally come within this category. Where it is published data, it has not been necessary to go out and conduct clinical trials on that data in order to demonstrate to the regulator that an adequate measure of safety and protection or efficacy and safety is known about that ingredient.

The next level up is where the ingredients are known. They're for prescribed uses, generally diseases that you can't self-diagnose or self-treat or self-monitor to know if the problem is being relieved. In addition to the general standard that the ingredient must work, we will want to know that the drug is indeed available from the particular formulation that sponsor is putting on the market. You would like to know that your anti-hypertension medicine, when you swallow it, actually releases the ingredient to your body and does what it is intended to do, because the cost or the risk of that not happening is greater.

If a known ingredient, one that is out there on the market today for a prescribed use, wants to come forward with a new indication, something novel, or a new group or population—it may be used in the elderly short term and we now want to use it in the pediatric long term—a new clinical data set and possibly more safety evidence would be required on that ingredient in order to gain market approval.

And of course then there are the new active substances, those that are isolated either out of the natural environment or synthetically through a variety of wonderful and miraculous processes. The data package on those I'll explain more elaborately in the next slide. It is full information on the safety, in animals, in humans, and in laboratories, of those products—clinical evidence of safety in humans, specific to that ingredient. And there is a full data package about the ingredient: how do you make it and how do you control the impurities that may intervene as you make that particular substance?

When that risk-to-benefit balance favours benefit, a notice of compliance or a DIN is issued. A DIN is a standard regulatory authorization. If you pick up your toothpaste tomorrow morning, look for something that says “GP” or “DIN” and has eight numbers behind it. It's a standard. All products, other than radiopharmaceuticals and whole-blood products, require a DIN prior to market, and they will display that DIN on their labelling.

A product that has a higher level, a new product coming into the Canadian market, will also have issued to the sponsor a notice of compliance saying they have met the requirements of a more detailed set of requirements under the regulations. The vast majority of products on the Canadian market have only a DIN. They do not go through the more elaborate process. Those that are prescribed and used within the medical community generally are new drugs and have a notice of compliance.

As for the traditional medicines, homeopathic medicines, and vitamins and minerals that are the subject of your discussion, those that have gone through the regulatory system go through with a DIN. They have not been subject to the notice of compliance.

On the next slide I'd like to focus on the new drugs, just to give you an example of the range. I want to try to focus on the range that separates the data evidence required for the products that are the subject of your review from the current regulatory requirements of a new drug coming to the Canadian market.

The risk assessments are based on evidence; they are not based on medical opinion or practice. There is a wide range of highly skilled and trained assessors within the program, with medical backgrounds, toxicology backgrounds—a wide variety—but our decision is based on the evidence that is presented by the sponsor and our assessment of that.

When a product comes in to us as a new drug, evidence, as is outlined in these broad categories, is presented to us. Those of you who have heard horror stories of truckloads of data—unfortunately it's true, although it's getting smaller in that they can put it on smaller discs. There are large volumes of data surrounding new chemicals coming to market that have experienced full animal safety study and full human clinical study. These studies are done according to standards that are recognized internationally.

• 1200

To indicate to you that not all natural health products enter the market as traditional medicines, one of the most successful cancer treatments in recent years is paclitaxel. It was originally derived from the Pacific yew tree. Fortunately, they have determined that there are semi-synthetic ways to make it and to not strip the bark from the tree. The ingredient, which occurs naturally, is separated from how it occurs in nature and has been studied. It is effective. There's high risk but it is very effective. It has full data packages, but it did not enter the market as a traditional herbal remedy.

The efficacy and safety surrounding products are based on the data packages that are presented, and on the results of the evaluations and assessments coming out of that data. If the data do not support a proposed indication, use or dosage regimen suggested by the sponsor, it is not approved. If the adverse profile or the risk profile of that product is not appropriately characterized from the data, we augment that as well. So the labelling that goes out and the product monograph that is published and approved with this product lists, in a very fulsome manner, the studies and outcomes of safety and effectiveness.

The products that you are speaking to generally do not have those data packages available, and we are not requiring them prior to pre-market assessment. I'd like to go through three of the categories that you are looking at on the final slide to highlight to you what is required for a select number of those products.

Homeopathic medicines have been around since the 1700s—homeopathic in high dilutions, which means very low concentrations of the labelled ingredient. They are currently approved and receive DINs. A large number are compliant within the Canadian regulatory system on the basis of product quality as demonstrated through our inspection process for good manufacturing practice, so they do not submit their chemistry and manufacturing information to us. We look at that to make sure their facility is on-line, and they are approved on the basis of internationally recognized pharmacopoeia references. One of them is the Homoeopathic Pharmacopoeia of the United States, which lists OTC—over-the-counter or non-prescription—levels of all of the chemicals within, and they're used and have been documented through the homeopathic practice of medicine.

You will read in many places that proving the effectiveness of a homeopathic remedy is not the same as a clinical trial conducted to today's scientific standards. That is correct but it is a practice that has derived benefit to a population, and it is low-risk when it is for self-medication and used by the consuming public, or used under the care of a homeopathic practitioner.

Claims are permitted for homeopathic remedies, and that is a relatively recent policy change for us. It was consulted on with the homeopathic community and the rest of our stakeholders. Again, those claims are permitted on the basis of published references that document the practice of homeopathic medicine.

• 1205

The reason and the substantiation for approving these products without doing a documentary evidence file for each of these ingredients are that there is a long history of recorded use of the stated dosage. That's the benefit side. There is a lack of reported harmful effect for that same long period of time. That's the safety effect. And they have been recorded as being effective within that medical practice over that period of time.

An example of this is arsenic. Arsenic in a high quantity is not something any of us wants to consume. Arsenic in a high-dilution homeopathic product is a basic tool for homeopathic practitioners to use within their practice. Arsenic in the same very low quantities does appear in some of the foods you eat. It's a natural contaminant in the soil. So when you're looking at an ingredient, you look at the concentrations and how it is presented as to what risk it presents.

There currently is a policy initiative to remove a number of prohibited substances. They are currently prohibited by regulation from a restriction of that regulation. I don't believe it's in your package and we will add it at our earliest opportunity. It does cover substances such as arsenic that are currently in regulation as being prohibited from being the active ingredient in a medicine.

Vitamin and mineral supplements are another level of ingredient or type of product that you're going to be looking at. Vitamins and minerals are not based on traditional usage unless you possibly consider scurvy as a traditional use.

Product quality for these products is again through GNP. The quantities and claims are referenced in regulation today. In your package there is a tab 29, which talks to a new initiative to remove the regulatory restriction and to permit expanded claims for vitamins and minerals on the basis of standards such as our label standards. That has been out for comment with our stakeholder groups.

The benefits and safety at stated dosage within the regulations of those vitamins and minerals have been demonstrated through scientific study. There is a continuing study on these according to today's standards.

Just to give you an example of the range of ingredients, vitamin A is an essential element. You take it. There is a limit that is non-prescription. At a higher limit it is available only on prescription.

As one of its active metabolites within its metabolic pathway in the body, vitamin A as it presents in your retina is called retinoic acid. It doesn't stay there for long. It's part of its natural process.

Retinoic acid is a drug that's used for a very scarring form of acne. It's used in an oral dosage form and it is known to cause malformations in fetuses.

Vitamin A is a teratogen in various forms and at very high levels. Vitamin A in the levels that are consumed in your daily diet and in non-prescription remedies is not a teratogen. Again, the risks are known and they are quantified and continue to be elaborated.

The third area I'd like to highlight is traditional herbal remedies. In this I will restrict my comments to those that are of plant material only. Those are the current policies we have published today. They're approved on the basis of established GNP compliance and on non-prescription or self-medication claims based on published references. A variety of references can be documented. Again, it is a long history of use at those stated dosages for those benefits, it is a reported lack of harmful effect that provides this risk to benefit...that we are not looking for new data.

I would remind you that as an ingredient is used outside of its traditional use or at higher levels, we do hear and take action then on ingredients that present problems. There is a very finite list of ingredients that have been documented in the traditional literature that are now being shown to have a hazard. They are serious complications; they are not simple rashes. So we will restrict their sale from the consuming public. That risk assessment is made on those products.

• 1210

One of the examples I would like to give you is echinacea. You grow it in your garden. It's a beautiful purple coneflower. I grow it in my garden and I think it's wonderful. It's approved and will receive a drug identification number and is used to treat your cold. That is documented in the traditional literature at levels and is not a problem.

We will not issue a DIN for that product for the claim to prevent autoimmune disorders. It has not been established, and if it were established we would then look at whether or not it was a diagnosis for a treatment that the consuming public would want to use that ingredient for, without speaking to another health care practitioner. But that's a “what if”. That data has not been presented, but it is widely touted on the Internet and the lay press and is used by many people, I'm sure, for that indication.

I've tried to present to you a range of initiatives and opportunities that you can think about. If you have further questions on Tuesday I'd be pleased to answer them. My colleague will give you the other pillar. This is the assessment side and the other pillar is our enforcement, compliance and inspection. Thank you.

[Translation]

Mr. Jean Lambert (Director, Quebec Region, Department of Health): Good morning. My name is Jean Lambert and I am the regional director of health protection for the Quebec Region. At the national level, I am also the director for the compliance and enforcement pillar of the therapeutic products programme.

This morning, I'd mostly like to cover the establishment licensing framework as well as the good manufacturing practices which are closely related to it.

On the first page, I divided the presentation between four headings. Starting from the left and from the top, we find first the establishment licensing regulations that will come into effect on January 1st 1998. With these new regulations, we're trying to establish a uniform framework for the implementation of good manufacturing practices to ensure compliance for all products manufactured and sold in Canada. Obviously, the regulations encompass products imported into Canada as well.

The establishment licensing framework is in accordance with the risk management principles established within Health Canada.

We have given you a quick overview of our regional offices. Five regions have been established. Starting from the West, the first region is the Western Region which includes British Columbia and Alberta. The Central Region covers Saskatchewan and Manitoba and its head office is located in Winnipeg. We have the Ontario Region with its head office in Scarborough, then the Quebec Region where the office is in Longueuil, outside Montréal, and finally the four Atlantic Provinces, where the office is located in the Dartmouth area.

The establishment licensing framework is based at the regulatory level on Division 1A of the Food and Drugs Regulations, which should come into effect on January 1st 1998. We also refer automatically to the good manufacturing practices which are part of Division 2 of the same regulations.

Why was the establishment licensing framework established?

• 1215

By the way, the elements I'm going to describe in terms of the establishment licenses and the good manufacturing principles can be found under tabs 22 and 23 in your binder.

First, we wanted to set a uniform framework for all products under these regulations. Previously, radiopharmaceuticals as well as biologics did not come under Division 2 which governed good manufacturing practices; they had to be licensed.

From January 1st 1998, the entire framework will be made uniform by ensuring that all products defined as drugs are subject to good manufacturing practices as well as to the establishment licensing framework, of course, taking into account the exemption announced with regard to products such as natural medicines, homeopathic products and vitamins/mineral supplements.

The establishment licensing framework targets various activities. There are people doing product analysis, distributors, wholesalers, importers, packers and labellers as well as manufacturers. The level of accountability is therefore increasing throughout the regime, from analysis to manufacturing.

The establishment licensing framework also applies to foreign sites. Consequently, importers must ensure that products coming from foreign sites also comply with good manufacturing practices. Foreign sites come under the regulations since they are listed by the Canadian importer in his license application where he must demonstrate that good manufacturing practices have been complied with, or because a license has been granted to an exporter overseas.

As we mentioned earlier, the establishment licensing framework is very closely linked to good manufacturing practices. The official current edition of good manufacturing practices is the fourth edition and it deals in a general way with requirements relating to good manufacturing practices. We are now preparing the next edition which will not be identified by a number but by its publication year. The 1988 edition will hopefully be published in early 1988.

Besides the framework directives, we have annexes. They have already been developed or we are working on it. They deal specifically with some product categories and complement or complete the framework directive. Indeed, one of the annexes deals with herbals and another one deals with homeopathics.

Very succinctly, good manufacturing practices touch upon several elements. On the following page, you can see all elements governed by good manufacturing practices: premises, equipment, personnel looking after product manufacturing and handling, sanitation, raw material and finished product testing, quality control for finished product and raw material, records and other files that are maintained, sampling, data on stability to ensure product effectiveness for the foreseen period, as well as a sterile products element.

How are good manufacturing practices implemented at the domestic level? With due regard to available resources and risk assessment, we established that manufacturers, importers and distributors of drugs in Canada had to be inspected on a biennial basis.

• 1220

Our system has recently been automated, since October, which makes it easier for us to draft reports or to search our databases, on distributors and importers among other things. We also collect data on each site to complete our data collection in order to issue establishment licenses.

The establishment licensing framework is of course complemented by inspection and compliance strategies. Our strategy is aimed at establishing what we call a single window approach for inspection. For instance, when a biological products manufacturing plant has to be inspected, an expert in that area will go along with the inspector in the region to ensure that a single visit takes place and that it deals with good manufacturing practices in the broad sense as well as with product specific requirements. It is therefore a team approach.

In terms of the compliance strategy, it goes without saying that there have already been good manufacturing practices for regular pharmaceuticals for several years. On the other hand, it is something new for some other product categories such as biologics. We want our approach to be based as much as possible upon a helping relationship with industry. To that end, we must do a site assessment and determine its compliance or non-compliance or whether no decision can be made yet for lack of information. If violations or problems are only minor in nature and if we are allowed to work together with the company to correct the situation or the shortcomings, we'll give the manufacturer or the importer an opportunity to submit an action plan. We'll cooperate with them to ensure compliance within a specified time frame.

We've had to visit all known companies in Canada with regard to the establishment licensing framework. We also do some checking of companies which export their products to Canada. We are working on it and we expect that everything should be in compliance and adequate by the end of 1998. Companies which are not in compliance by that date will not be authorized to carry on their pharmaceutical manufacturing, importing or distributing activities in Canada any longer. We are currently completing a directive aimed at ensuring uniform enforcement of good manufacturing practices by our personnel.

In terms of establishment licenses, we are also working together with companies to help them ensure compliance. Obviously, if any company is not in compliance and doesn't submit an action plan, we'll have to take steps to keep them from pursuing any drug related activity in Canada. However, they will have access to a two stage appeal process, with stage one being at the regional director level within the health protection branch and stage two at the level of the director general, therapeutic products programme, Mr. Michols.

To conclude, let's say that everything that has been done in terms of good manufacturing practices and establishment licenses has helped make our regulatory approach more uniform for domestic products as well as for foreign products. Through our work in that area, we have made a contribution to the harmonization of various enforcement standards. Establishment licensing systems already exist in several countries and our system will be very similar to theirs. We're also trying to harmonize our standard on herbal products with the WHO standard.

Another benefit that flows from all our efforts on the establishment licensing framework is the work we have undertaken on mutual recognition agreements. Our involvement at that level is relatively recent and I might summarize it in a few words.

• 1225

We're currently working together with several countries, EC members among others, to establish an equivalency among existing authorities. For instance, Canadian companies dealing with those countries will automatically be accepted on the basis of our establishment license. Similarly, European companies licensed by a national authority deemed equivalent to their Canadian counterpart will clearly be able to do business in this country at the conclusion of the confidence building process, which will take 18 months and should start at some point in early 1998, upon completion of the Canada-EC agreement. We'll then have 18 months to assess the GMP compliance of every system and to determine their equivalency. Once it is done, trade will become easier and we'll be able to ensure the health of people and the safety of products transiting from one country to another. We regard it, obviously, in a general sense as a compliance and risk management mechanism.

Thank you for your attention.

[English]

Mr. Dann Michols: That, then, is our presentation on the regulatory framework that exists in Canada for therapeutic products—this includes the products you have in your mandate—and the way we go about undertaking our activities to ensure that Canadians have access to products that are safe, effective, and of high quality.

I would make one final comment. The way we have gone about our business is highly consultative. When we move to consider regulatory change or want to investigate a new policy, we involve representatives from a wide range of stakeholders. Tab 11 within your binder lists the associations and organizations we consult on a regular basis for the review, revision, and upgrading of the regulatory framework within Canada.

In conclusion, thank you very much for giving us the opportunity and the time to present. We'd be delighted to answer any questions when you're ready.

The Chair: Thank you very much for coming. Thank you to Mr. Lambert and Ms. Carman for coming with you. We'll see you next Tuesday.

I think we'll be going into foods. Will there be another area also?

Mr. Dann Michols: There are a couple of issues within the food directorate that seem to be of interest to the committee. We would be prepared to present on those as well. There is a section within the binder that speaks to those food issues as well.

The Chair: We won't go into questions now.

Ms. Aileen Carroll: Just quickly, since you will be responding to our questions on Tuesday—I look forward to that—I just wondered if I should ask you for a little bit of information I will want on Tuesday. This is just in case you don't have it.

Ms. Carman, I would be most appreciative of knowing the cost to the manufacturer of the DIN process. I know that you may or may not have brought that. This would be much appreciated.

Mr. Michols, I would very much like to know how many committees have already looked at this, what the membership of those were, what their conclusions were, and when they submitted that. Also, the same applies to the group of 19. This is just so we can discuss it on Tuesday and so that I don't leave you without advance notice.

Thank you.

Mr. Dann Michols: Sorry, what was the reference to the group of 19?

Ms. Aileen Carroll: We have a new group meeting—

Mr. Dann Michols: So it's how often they met and that sort of thing?

Ms. Aileen Carroll: Just a little bit on them to put them into perspective.

Mr. Dann Michols: Yes. No problem.

Ms. Aileen Carroll: Thank you.

The Chair: Thank you again for coming. I would just let the committee know that we will be meeting on Tuesday at 11 a.m. We'll be continuing this. The steering committee met today.

We will be meeting, as far as we know—I don't see any reason not to—on Thursday, December 4. We will have both sides of the MAI argument. Hopefully, we'll have two on each side.

We have an ongoing discussion about travel. So the steering committee will be meeting again and reporting to you again.

The meeting is adjourned.