Proceedings of the Standing Senate Committee on
Social Affairs, Science and Technology
Issue 23 - Evidence - October 25, 2012
OTTAWA, Thursday, October 25, 2012
The Standing Senate Committee on Social Affairs, Science and Technology met this day at 10:29 a.m. to study prescription pharmaceuticals in Canada (topic: Post Approval Monitoring).
Senator Kelvin Kenneth Ogilvie (Chair) in the chair.
[Translation]
The Chair: Welcome to the Standing Senate Committee on Social Affairs, Science and Technology.
[English]
My name is Kelvin Ogilvie. I am a senator from Nova Scotia and chair of the committee. I will ask my colleagues to introduce themselves, beginning on the right.
Senator Seidman: Judith Seidman, from Montreal.
Senator Seth: Asha Seth, from Toronto.
Senator Moore: Wilfred Moore, from Nova Scotia.
Senator Munson: Jim Munson, from Ontario, but my heart is in New Brunswick.
Senator Mercer: I am Terry Mercer, from Nova Scotia.
The Chair: Thank you, colleagues, and welcome to our witnesses, collectively. I will introduce you when I call on you to present. We have an agreement that I will call you in the order that you appear on the agenda. I understand that there is a third member with Rx&D who is present in the audience and, if necessary, who can be called forward to help with questions, and we have agreed to that.
In that context, I want to remind us all that we are studying prescription pharmaceuticals in Canada. In this phase of our study, we are focusing on post-approval monitoring. Our first set of witnesses, on behalf of Rx&D, are Ken Hughes, Vice-President, Scientific and Regulatory Affairs; and Stan Glezer, Vice-President, Evidence, Value and Access, Sanofi.
Please go ahead, gentlemen.
Ken Hughes, Vice-President, Scientific and Regulatory Affairs, Rx&D: Mr. Chair and honourable senators, thank you for inviting Rx&D back to the committee. I am a biomedical scientist by training and am Vice-President of Scientific and Regulatory Affairs at Rx&D, Canada's research-based pharmaceutical companies.
Joining me today is Dr. Stan Glezer, Vice-President of Evidence, Value and Access with Sanofi Canada, a global and diversified health care leader in Canada. He is also a physician by training.
New medicines and vaccines investigated and developed by our more than 50 member companies represent some of the most advanced, safe and effective treatments available to help Canadians live longer, better and more productive lives. Our medicines also ease the burden on the health care system by avoiding more costly hospitalizations and invasive procedures.
The innovative pharmaceutical sector is a key player in Canada's knowledge-based economy. We account for some 46,000 well-paying direct and indirect jobs in Canada. Last year alone, we invested over $1 billion in research and development, and contributed some $3 billion to the Canadian economy.
This past April, Rx&D President Russell Williams appeared before you to discuss our industry's position on the fundamental importance of clinical trials to our country, to Canadian patients and to our economy. He spoke of Rx&D's commitment to doing our part to improve the environment for clinical trials excellence and the highly ethical manner by which we interact with all stakeholders, as articulated in our Code of Ethical Practices.
Our members work alongside health care professionals, consumers and federal and provincial regulators to promote the appropriate use of our medicines. Our members also work with the same partners to avoid and reduce the number of adverse events and medication errors.
As the committee has already heard, pharmaceutical manufacturers are required to monitor the use of their products and report serious adverse reactions from Canadian and global sources on a timely basis, as regulated by Health Canada. Our members are more than willing partners in an effort to ensure their products are safe and effective. Canadian regulations require the filing of periodic and annual reports, providing comprehensive global summaries of known safety information for a given product. Risk management plans are yet another tool that has been adopted in Canada and internationally.
We support the changes that Health Canada has been making in response to the Auditor General's report, and we are encouraged by Health Canada's recent steps to increase the quality and quantity of the reports they receive. We welcome the ongoing shift to a fully electronic system and agree with Health Canada's efforts to enhance its work with other global regulators to improve information sharing and coordination.
Health Canada's broader modernization efforts will also bring Canadian regulations to a point where they will reflect international best practices, with a focus on managing the benefit/risk profiles of each product. That effort will be a shared responsibility of manufacturers and regulators. These changes will apply throughout the product life cycle, including post approval.
No system of this type is perfect and no drug is completely without risk, but a primary reason for the progress that we have made is that all key players in pharmacovigilance are part of the discussion. Our members without exception want to know the rules and expectations so we cannot only meet them but exceed them wherever possible.
In testimony earlier this month, Health Canada acknowledged the importance of working with industry as a key part of ensuring medications are used safely and that adverse events are reported and analyzed appropriately. In order to be effective, the system needs to ensure all parties can work together — Health Canada, international regulators, industry, health practitioners and patients. While we believe the systems in place work well and all parties are working toward the same objective, there is one area where collaboration could be improved, and that is related to the level of transparency and openness associated with the Drug Safety Effectiveness Network, DSEN.
As you heard in testimony the other day, the DSEN "process is entirely independent of the pharmaceutical industry.'' Among other things, that means that a manufacturer is not advised if and/or when one of our medications is undergoing a post-market review for safety or comparative effectiveness. It also means the manufacturer will not know how the review will be conducted, what the eventual conclusions will be and how those conclusions will be used within our health care system.
Speaking as a scientist, the issues of safety, effectiveness and the appropriate use of medicines depend on a full and open scientific exchange based on solid evidence. Those who work in my profession are very much interested in establishing high standards for post-market research.
There are international examples that have adopted open, collaborative approaches. The Observational Medical Outcomes Partnership in the United States, OMOP, has as its main goal the assessment, feasibility and utility of using observational data to identify and evaluate the links between drugs and health-related conditions. What is important about this initiative is that it is an active collaboration that involves academia, industry and the Food and Drug Administration, all under the umbrella of the National Institutes of Health, or NIH.
Similarly, there is a multi-sector initiative in Europe called PROTECT, where again industry is included in any post- approval discussion to ensure the process is both rigorous and remains focused on patient care. We understand that Health Canada is on the PROTECT External Advisory Board.
Following our appearance today, I will ensure that members of this committee receive more information on both of these initiatives.
For scientists working in the field, the best decision making requires the best available information and access to the best science. Moving forward, better collaboration will be a key condition of success. We all want to ensure that Canada is aligned with efforts in support of patient safety around the globe.
Thank you. We look forward to questions and discussion.
The Chair: I will now turn to the Canadian Generic Pharmaceutical Association. We have with us Dr. Colin D'Cunha, Director of Global Medical Affairs for Apotex Inc.
Dr. Colin D'Cunha, Director, Global Medical Affairs, Apotex Inc., Canadian Generic Pharmaceutical Association: On behalf of the Canadian Generic Pharmaceutical Association and its member companies, I would like to thank the committee for this opportunity to participate in the committee's study on post-market surveillance.
The CGPA represents manufacturers and distributors of finished generic pharmaceutical products and active pharmaceutical ingredients in Canada. Generic drugs fill more than 60 per cent of prescriptions in Canada, even though they account for less than 25 per cent of the more than $22 billion that Canadians spend on prescriptions each year.
Most of the generic drugs sold in Canada are made right here in this country. Canada's generic pharmaceutical industry operates most of Canada's pharmaceutical manufacturing capacity and employs more than 12,000 Canadians in well-paid, highly skilled R&D and manufacturing jobs.
Coming, then, to the perspective of pharmacovigilance, or drug safety, in Canada's generic pharmaceutical industry, monitoring the use and effect of medicines is an essential focus for any pharmaceutical company. Generic drugs are approved for sale by Health Canada and are identical or bio-equivalent to the innovator version. By the time a generic is licensed for sale in Canada, the active substances have been used for a substantial period of time and their safety profiles are better established compared to the early days of introduction.
Even so, Canada's generic pharmaceutical companies take our post-market surveillance efforts and responsibilities very seriously. All pharmaceutical companies in Canada are required to monitor the use and effect of a given medication and to detect, assess, understand and prevent any adverse reactions or any other medicine-related problems that arise. These activities and the science behind them are known as pharmacovigilance.
I am a member of the CGPA's Pharmacovigilance Working Group. This is a group of scientific experts from Canada's generic pharmaceutical companies that shares information about global best practices in pharmacovigilance, changes in international reporting priorities and various scientific developments.
Our goals in pharmacovigilance are to protect public health by monitoring the safety and efficacy of our products; to limit risk by employing iterative risk management throughout the product's lifecycle and by conducting signal detection and safety reviews of the data; to undertake effective risk management activities including risk communication, core safety information, registries and post-approval studies where necessary; and to focus on any product with an identified safety concern.
Canada's generic pharmaceutical industry operates in a global environment. More than 40 per cent of the generic drugs manufactured here are exported to the United States and more than 115 other countries worldwide. As you can imagine, other countries have a wide range of post-market surveillance requirements. Consequently, Canada's generic pharmaceutical industry is obligated to ensure that our procedures are as robust as possible and comply with the most stringent international pharmacovigilance regulations.
Generic pharmaceutical companies in Canada have standard operating procedures for the collection, assessment and reporting of adverse drug reactions in clinical and post-marketing experience. These procedures are compliant with national and international regulation and guidelines.
To meet regulatory obligations, our companies prepare safety reports, both the 7- and 15-day expedited reports for serious adverse drug reaction and lack of efficacy and the annual and three-year periodic safety reports required by Health Canada. We conduct ongoing monitoring and literature reviews on a global basis to identify any adverse drug reaction associated with the active substance.
Our companies also develop customized, ongoing safety evaluations for any products requiring post-approval risk management. Drugs in this category include isotretinoin, used for acne, and clozapine, used for treatment-resistant schizophrenia. Our risk management process is based on established practices in Europe and in the United States, where the program is known as Risk Evaluation Mitigation Strategy, or REMS.
From a recommendation standpoint, the generic pharmaceutical industry commends Health Canada for their advancements in the areas of technological efficiencies and increased transparency as outlined to this committee earlier by ADM Paul Glover.
We have identified some further improvements that could be made. I would like to briefly share these recommendations with the committee.
We should harmonize the birth dates of medicinal products to allow for operating efficiencies, allowing companies to prepare one report for all markets at the same time.
Health Canada should work with other agencies, such as the EMEA in the EU and the FDA in the U.S., to undertake a single-source or one-source literature review because right now, in these three broad markets, there are different strategies at play. This will allow for one concise, informative report, as opposed to many reports cluttering the system.
Health Canada should provide safety information freely and without charge. Charging is a barrier, compromising public health and limiting the ability of manufacturers to perform proper risk-benefit analysis and public communication.
Health Canada should take a leadership role in safety, working with all marketing authorization holders in conducting their own safety assessments. This is the current practice of the FDA.
Health Canada should take a leadership role in coordinating the risk management activities of all relevant manufacturers and marketing authorizations for the active substance, as opposed to dealing with each one individually.
Finally, post-marketing risk management activities should be identical for both brand name and generic products. This is the current practice, and it should continue. Generic products have the same risk management profiles as their brand name equivalents and should not be subject to additional requirements.
In conclusion, it is essential that all stakeholders play an active role in the drug monitoring program, ensuring that patients only receive safe and effective medicines.
Canada's generic pharmaceutical industry remains committed to maintaining good pharmacovigilance practices and to working collaboratively with both domestic and international health authorities and other stakeholders to minimize public risk and to ensure the safe use of generic drugs.
I look forward to your questions.
The Chair: Thank you very much.
I will now turn to BIOTECanada. We are pleased to have Andrew Casey, President and Chief Executive Officer; and Loretta Del Bosco, Director of Regulatory Affairs, Quality Assurance and Operations, Abbott Canada.
Welcome to you both.
Andrew Casey, President and Chief Executive Officer, BIOTECanada: Thank you to the committee for providing us with this important and timely opportunity to contribute to your work. This is, obviously, a very important area for our industry, and we greatly welcome the opportunity to be here today and provide our input. As you indicated, I am joined by Ms. Del Bosco from Abbot Laboratories. I will divide my time, with the committee's indulgence. She has far greater expertise in this area, so I will defer to her on a number of issues.
By way of introduction, BIOTECanada is Canada's national biotech trade association. We represent the biotech industry of Canada. We have 250 members that represent a very diverse industry. We span a number of different sectors, including agricultural and industrial. I was here earlier this morning, with Senator Mercer and his colleagues on the Standing Senate Committee on Agriculture and Forestry, speaking on other issues affecting another part of our industry. Here we are on a double bill, and I get to go on the pharmaceutical side, which is a very important part of our industry composition as well. We welcome the opportunity to comment.
Let me begin by expressing the industry's strong support for the review being conducted today. The industry shares the view that it is paramount that the Canadian regulatory system continues to be as good as or better than those in other jurisdictions. Our industry depends on a strong, transparent and effective regulatory system as it provides the industry with policy certainty and strengthens the industry's position globally.
Canadian biomedical innovation has a long and storied history in this country, from the development and introduction of insulin to treat diabetic patients the world over to the creation of a vaccine that has seen the virtual end of polio in most countries in the world. Throughout, Canada's regulatory system has been pivotal in supporting and guiding biological therapy research, which has led to these life-changing medical innovations.
Biologic innovation continues to bring great hope and advantages to patients in Canada and beyond. The Canadian industry is generating new research and products, from vaccines to treatments for cancer and even cures for rare diseases and long debilitating diseases such as hepatitis C.
The pace of this discovery is predicted to increase at unprecedented levels in the years to come, particularly as health care moves away from one size fits all to a more tailored personal approach. This shift brings with it the need to ensure that the Canadian regulatory system is fully enabled to plan for, regulate and monitor the safety and efficacy of emerging medicines and therapies.
BIOTECanada members and the industry more broadly have a long-standing commitment to ensuring that the regulatory system in Canada maintains its long-held reputation for science-driven decision making in regulating biologic medicines. This fundamental expertise in scientifically and clinically trialed regulation is at the core of the industry's ability to successfully develop products and medicines that are safe and efficacious for Canadian patients.
I will pass the microphone to my colleague.
Loretta Del Bosco, Director, Regulatory Affairs, Quality Assurance and Operations, Abbott Canada, BIOTECanada: My name is Loretta Del Bosco, and I am the Director of Regulatory Affairs, Quality Assurance and Operations at Abbot Laboratories Limited. Abbot is a broad-based, global health care company with over 2,000 employees in Canada working in specialty pharmaceuticals, nutrition, diagnostics and medical devices.
Abbott actually manufactures one of the world's leading biological therapies, Humira, which provides relief to patients suffering from inflammatory conditions such as rheumatoid arthritis, psoriasis and Crohn's disease. I am pleased be here today to represent the members of BIOTECanada's Health Advisory Board. I also serve as Co-Chair of the Rx&D Regulatory Affairs Committee.
My remarks today will highlight the unique regulatory features of biological medicines. I would like to compliment the highly competent regulatory professionals at the Biologics and Genetic Therapies Directorate, BGTD, and the Marketed Health Products Directorate, MHPD, at Health Canada. Over the past few years, I have had the pleasure of working with them on an industry basis to eliminate the regulatory backlog for product approvals, advance the concepts of regulatory modernization, develop guidance for subsequent entry biologics and, most recently, establish the principles associated with a rare disease product regulatory structure.
Biologic medicines, as a class, comprise products such as vaccines, hormones such as human growth hormone, enzyme replacement therapies for rare diseases, and monoclonal antibodies used in the treatment of many diseases including rheumatoid arthritis and cancer.
The main distinction between biologic products and pharmaceuticals is that biologic drugs are complex protein products grown in living cells rather than molecules synthesized by chemical processes. Since biologics are generally large, complex molecules, they normally cannot be formulated into tablets and are infused or injected into patients.
The regulatory principles for biologic therapies and vaccines are similar to other pharmaceuticals and are duly regulated by Health Canada. Biologics must be demonstrated to be safe, efficacious and of good quality via rigorous validation of the development and manufacturing processes, three phases of clinical trials and significant post- marketing requirements. Examples could include lot-by-lot testing as well as risk management plans. However, given the complexity of biological medicines, there may be additional Health Canada requirements that these products are required to meet to address the complexity of the manufacturing process, clinical trials and ultimately at the post- market level.
In terms of chemistry and manufacturing, the discovery of DNA and the development of genetic engineering techniques have given rise to the ability for medical sciences to create these new medicines by inserting the gene for the desired protein product into a bacterial, mammalian or even plant cell and turn that cell into a factory for the desired therapy or vaccine. Because it can take thousands of tries to develop the one cell line that will safely, reliably and consistently produce a product like Abbot's Humira, once that line is established it becomes the source for all future production of the product and rarely, if ever, is changed.
The complex manufacturing process associated with creating a new cell line and growing it to produce a biologic product requires specialized regulatory processes, which is why we frequently say "the process is the product.'' Even minor changes in the manufacturing process can impact the final product, and therefore the safety and efficacy of the therapy. As such, Health Canada requires separate regulatory validation, review and approval for every manufacturing change associated with a biologic product. Manufacturers must demonstrate that there is no significant change in the product associated with the manufacturing. In the rare case that a change is detected, a clinical trial will be required to ensure that there is no impact on the safety and efficacy of the drug.
In terms of clinical trials, biologic drugs must adhere to stringent clinical trial requirements. In addition to the usual safety and efficacy trials, biologics must also demonstrate that they do not provoke any unwanted immune reaction in a patient. Because biologics are proteins and are injected into the body and in some cases directly into the bloodstream, they can interact with the body's immune system. In some cases this is desirable and in some cases it could limit the effectiveness of the drug or cause an adverse event. Immunogenicity can be unpredictable and difficult to detect, especially in a new therapeutic area. The immunogenicity trials are carefully designed to include enough patients to detect any possible effects.
Any new drug requires careful post-marketing safety and efficacy monitoring to identify any unpredicted adverse reactions or efficacy concerns, and BIOTECanada and its members are committed to this monitoring. In many cases, manufacturers invest heavily in their own patient registries or observational studies to track patient outcomes and any adverse reactions. Manufacturers of biologics may also conduct risk minimization activities such as developing educational material for health care professionals and patients, and establishing controlled distribution systems for their products. In addition, patient support programs are often implemented for biologics, and they also provide real life safety data to manufacturers.
Any safety and efficacy concerns that arise from these activities are reported promptly to Health Canada as required by law. In some cases, a safety signal may be detected by the manufacturer or by Health Canada. When this occurs, both the manufacturer and Health Canada work together to develop a health care professional communication and a public communication. This should not be seen as a failure of the regulatory system but rather as a demonstration that the post-market safety system is working. As the understanding of a product safety profile becomes more robust, the labelling is updated to ensure the most optimum use of the product.
Exciting new challenges and opportunities lie ahead in biological therapies. The most recent is the arrival of new drugs that are linked to a genetic marker to identify the patients that will benefit from a new therapy. Many BIOTECanada members are working closely with several companies to develop these personalized medicines, and we believe that the precise use of powerful medicines will bring new hope to patients and more value to the health care system overall. These therapies, however, come with new regulatory challenges as both the genetic diagnostic and the drug must be evaluated as a package.
In conclusion, it is clear that this review by the committee is timely. Our knowledge about the biology of disease and its genetic roots grows daily. Biotechnology will continue to be a potent force in health care, from the identification of potential disease, development of specialized drug therapies, and even cell- or tissue-based therapies at some time in the future. Companies are already racing to develop these technologies. Both they and the patients waiting for these therapies count on our regulatory authorities to validate their safety, efficacy and quality, and all the members of BIOTECanada stand ready to work with this committee and Health Canada to ensure that Canada continues to have a world-leading regulatory system for biologic therapies.
The Chair: I will now open the floor to senators for questions.
Senator Munson: Thank you for being here this morning.We heard a statement that Health Canada must show leadership. Is leadership lacking at Health Canada when it comes to post-approval monitoring of prescription pharmaceuticals? What kind of leadership are you looking for?
Dr. D'Cunha: We are looking for more leadership driving collaboration with all the stakeholders. We would like Health Canada to convening more meetings of the pharmaceutical industry, health care practitioners and patient groups so that all stakeholders are at the table. We need more of that.
Mr. Casey: In our experience with Health Canada, they have demonstrated a great deal of leadership. I think they understand what their role is and where they need to go. I think they are driving it. We have seen the response to the Auditor General's report. They have acted fairly proactively on that. We are encouraged by the steps they have taken, and I think they understand that Canada is a small piece of the global puzzle. They recognize the role they can play in leaning on other jurisdictions and learning from best practices. We are very encouraged by that as an industry.
Senator Munson: How do we compare with the health department of the United States? Do you have any comparative studies in terms of pharmaceutical companies working with the U.S. Department of Health, for example?
The Chair: I am not seeing a response, so perhaps you could ask another question.
Senator Munson: I ask these questions about the United States because when watching newscasts from the United States of America, I find that the ads between the news stories are more frightening than the news stories because they tell of all the side effects of the drugs they are advertising. "If you take this drug, you may die or at least be sick to your stomach.'' It goes on and on. We do not see that kind of thing here. Based on some of their advertising, I would not take any drugs. There are warnings there, and I am trying to find a comparison to what we do in this country.
Is there any difference between the post-approval responsibilities of the patented drug industry and the generic drug industry? If yes, could you please describe it?
Stan Glezer, Vice-President, Evidence, Value and Access, Sanofi, Rx&D: I would not comment on the differences. I can comment on our responsibilities as the patented pharmaceutical industry. We are obliged to report the adverse events to Health Canada, and that process continues throughout the product life cycle. When we start the clinical development, all the known information about the benefits and the risks associated with the products are summarized in a document called an investigational brochure.
Any new serious unexpected related events are reported on a continuous basis to the regulator and to the investigators in the study.
The data is accumulated throughout the clinical development that forms the clinical package being submitted to Health Canada within the framework over the regulatory approval of the product and based on the decisions of the regulator, which is summarized in the product monograph.
When you are referring to those ads coming from the U.S., we do not have the same framework for advertising, obviously. However, whenever we do provide the communications, they have to be within the context of the product labelling, and they should ensure appropriate balance between the benefits and the risks being adequately described.
Following the introduction of the product into the market, we are in a situation again where if we do get new safety information, it is being provided on an individual basis if it meets the criteria that I mentioned. We provide a periodic summary to be provided to the regulator in the form of the periodic safety update reports. In addition, should any significant information emerge such as, for example, data from the clinical trial that has come after the product approval, which might have a potential of changing the risk-benefit profile, we are engaging in the discussion with the regulator, which might trigger multiple consequences. It might trigger the change in the product monograph, which will then change the sequence of communication; it might trigger advisories to health care professionals and, potentially, to the public.
In addition to what was happening in the past, and I think this is a significant investment that we have seen in the past years, there was mention in the opening remarks of the risk management plans that are now being introduced to the Canadian framework, where we are not only looking at events that are occurring on a continuous basis but also discussing with the regulator potential risks that might occur and agreeing on the steps to be undertaken throughout the communication, promotional, educational and other activities, in collaboration with the health care professionals, to mitigate those risks before they materialize.
The Chair: Dr. D'Cunha, anything that is different. Please do not repeat that, but the question is: What are the differences? Would you focus on that aspect?
Dr. D'Cunha: Ditto, except for the fact that the information from clinical trials that an innovator discusses with Health Canada, if it is not in the public domain, the generics do not get to see it.
Senator Seidman: Gentlemen, during the first phase of our study on clinical trials, we learned that certain considerations prevent the inclusion of some subgroups in these drug studies, such as seniors, children and pregnant women. Given this, would you support the development of a mandatory or enforced automatic reporting mechanism for these vulnerable population subgroups that are excluded from the original trials of a particular drug?
Mr. Hughes: Our pharmaceutical industry is mandated to make adverse reports to Health Canada. ADM Glover described the difficulties in mandating throughout all the stakeholders in this particular space, like health care professionals, but our industry is mandated to make these reports.
On the individual subsets, the "often'' drugs, the pregnant women and the pediatric situations, the risk management plans are independent of the individual trial. The approach is to balance risk and benefit associated with the individual trials. The scientific rigour associated with that would be applied to any situation based on its individual merits.
The Chair: I think the question is that once it is approved, then the drug can be prescribed for any member of society. There are groups who are not normally included in the clinical trial itself. Those were mentioned.
I think the question — and Senator Seidman will correct me if I have misinterpreted this — is more along the line how does one ensure that the experience of those subgroups, once they have been prescribed the drug, is collected in a manner that provides additional advice to physicians as to the safety of these drugs and those subgroups. Have I captured it?
Senator Seidman: Yes, you have captured it.
Mr. Hughes, you said "mandated,'' but you notice I said "enforced,'' which is a little different. I think the chair has accurately elaborated on the question.
Dr. D'Cunha: Sure.
Mr. Glezer: To clarify, there is no discrimination in safety reporting of the different populations that are exposed to the product, whether those are in label, off label, subgroups. No matter what that is, we are currently reporting all of the information.
Should there be enforcement, I am not sure that this is needed for that specific population; I think we are more open to discuss the safety reporting overall because there is no reason as to why you would make it stronger for one population as opposed to the other.
The other comment is that, again, the risk management plans are there to mitigate the potential risks in the population that might not have been studied, as well as in the populations that were studied. This is part of the discussion with Health Canada upfront throughout the process.
Last, but not definitely least, if you look at the discussion around the regulatory organization of this company and potential introduction of the progressive licensing that would allow for the labelling changes throughout product life cycle based on their emerging evidence, that adds an additional step to formalizing the incorporation of the evidence about this kind of utilization into what we know about the product and how we communicate about it.
The Chair: To further clarify your answer, in the response, the report on an adverse reaction, is the age and gender of the patient identified in the report?
Mr. Glezer: Yes, if this information is available. Obviously, patient confidentiality is something that we have to respect. However, when we do receive the report of an adverse event we typically do the follow-up, if it is at all possible, to see what are the circumstances around the report. Gender and age-related information is typically the standard part of that investigation.
Senator Seidman: Yesterday, when our witnesses were here from the three professional groups — that is, physicians, nurses and pharmacists — we did discuss this and I did ask the same question. They suggested that post-market studies on subgroups should be attached to preapproval.
It is a fairly serious issue in the sense that not 100 per cent of adverse reactions are reported. In fact, we heard something like 20 per cent. The issue is this: Is there some way to immediately flag — and this is what I am trying to get at here — subgroups who have not been included in the clinical trial so that that alone gives access immediately to more vulnerable people? Is it indeed the case that there should be some kind of post-market study attached to preapproval? I know the FDA, for example in the last couple of years, has acquired new regulatory powers as far as this is concerned for post-marketing studies or clinical trials. The FDA can actually require post-marketing studies or clinical trials at the time of approval or after approval, if they become aware of new safety information.
This kind of automatic, immediate flagging might go a long way to saving particularly vulnerable segments of the population who were never included in the clinical trial.
Mr. Glezer: From the research methodology, when we are designing a trial, it is for a well-defined population. From the practicality standpoint, flagging everything that is not included would be a bit challenging.
That being said, when we are in discussions with Health Canada around risk management plans, this is where the specific discussion about the highest potential risks and the most vulnerable populations come into play. This is where the discussion happens as to what needs to happen in order to mitigate those potential risks. Those might represent the populations that you have mentioned, which might or might not have been studied, such as the elderly and patients with significant organ failures, paediatric and other populations, but it will also include populations where there are known risks.
For example, if you know your product might be harmful for patients with heart failure, within the risk management plan you will identify it as a high-risk population. With Health Canada, we agree with the key safety messages that should be part of any safety communication when we are discussing a product on the market.
Clearly, practicality must be kept in mind. Information overload is as damaging as lack of information. That is why we are trying to have this dialogue with the regulator as to the most relevant parts to be proactively communicated into every single segment.
Another thing, in terms of the transparency, is what is included and not included in the clinical trials. As you are probably aware, almost every clinical trial we conduct, depending on the phase, is reported on the clinical trial registries where the inclusion and exclusion criteria are clearly identified. After the clinical trial is completed, we publish the results. If for some reason they were not published in a specified time frame, the results are posted on the public registry as well. In addition to proactive communications within the risk management plan, there is the open and transparent communication on all the research findings from the clinical trials that the industry is conducting.
[Translation]
Senator Verner: On October 3, when Paul Glover appeared before us, he said that, despite the lack of a statutory obligation, the industry may submit a risk management plan when there is a request of approval for a new drug.
Would you agree to amend the legislation so as to make risk management plans mandatory, the way they are in the United States and in the European Union?
[English]
Mr. Glezer: The risk-benefit discussion is part of the standard framework within the process of the introduction of the product to the regulator. We commend Health Canada as there has been increasing collaboration to have this dialogue way before the product comes to submission. We have those discussions as early as the Phase II studies when we are planning further research to be conducted.
Every product is different in terms of its benefit-risk profile and the risks that need to be mitigated. Therefore, the consideration for the potential risk management plan absolutely happens in every single case. However, whether this discussion will result in the decision to proceed with the plan is subject to the individual cases. Would we be open to having this discussion upfront? Yes, in every single case. Do we need to have a formalized plan in every single case? I think that is something that should be the outcome of this discussion as opposed to being mandated.
Mr. Hughes: A question was asked earlier about Health Canada taking a leadership role. The development of the risk management and mitigation plan is intrinsic to the development of the process going forward. It is being led by Health Canada very strongly and is inclusive of all stakeholders to ensure these risks are managed appropriately so the risk-benefit analysis as we move forward is appropriate for the patient.
Dr. D'Cunha: To clarify, in the U.S. the Risk Evaluation and Mitigation Strategies, or REMS, does not cover all molecules. It is scoped up based on the safety profile of the molecule. It is a three-step process, including a med guide, a communication plan and, the most severe form, elements to assure safe use. In the new legislation tabled in 2012, Europe requires a risk management plan for every molecule. However, the ones where the risk is minimal have routine pharmacovigilance.
If it is the wisdom of the committee to say every molecule must have an RMP, you will have a template. What is more important, as touched on by my colleagues, is that the depth of the activities should be graded to the safety profile of the molecule. There are some where you need to do more and others where you clearly need to do less.
Ms. Del Bosco: Working with Health Canada, we have absolutely seen an increasing rigour with respect to risk management plans. BIOTECanada continues to work, similarly to Rx&D, with respect to ensuring that there is an evolution of risk management plans. However, there are different severities of what must happen with risk management plans.
[Translation]
Senator Verner: That does not really answer my question. I understand that there are differences between Canada and the European Union, as well as the United States. But as you know, the intent of Bill C-51 was to make risk management plans mandatory.
If that obligation was back on the table, would you agree to support it?
[English]
Ms. Del Bosco: I think the response would be that we would absolutely want to sit at the table and discuss the moving forward of what these risk management plans would be.
I think it is important because the comment has already been made that creating risk management plans to tick off and just say, "Do normal pharmacovigilance activities, that is it; that is all you need for this product'' could be an administrative burden for everyone without necessarily bringing additional benefit to the whole process. It is a case-by- case basis. We do ongoing safety reporting already. Do we need to have something that is called a risk management plan for some molecules that just says, "Risk management plan: Do your monitoring activities?'' I think that is the only thing.
It is really to sit down and see the complexity of what would be required both from Health Canada and BIOTECanada, I think.
[Translation]
Senator Verner: My question perhaps is for the actual industry, so for Mr. Glezer, for example. Has Sanofi-Aventis already prepared a risk management plan? If memory serves, there was a small controversy with the European Union in 2009 concerning one of your products — I believe it was Lantus.
At that stage, did you have to prepare a risk management plan to make sure that the controversial statements about the drug were refuted?
[English]
Mr. Glezer: To clarify, I am here to represent the industry, not necessarily Sanofi. However, I would be comfortable answering that question because I was involved in the Lantus case and in many other discussions around risk management plans for our products.
In general, yes, we have been engaged with Health Canada in a number of discussions around the risk management plans for the products we are planning to introduce to the market. I have experience with the risk management plan that went on after the product introduction with the knowledge and understanding surveys to measure the effectiveness of measures to mitigate the risks. It was a successful experience.
In the specific case that you mentioned around Lantus, this is a situation where this product has been on the market already; there has been well-established product monograph and use. A concern was raised regarding a potential safety signal coming from the observational studies. The company has engaged in proactive dialogue with regulators around the world, including here in Canada, in terms of what the required activities would be in order to properly assess and communicate this risk. What occurred in that specific situation was a communication around the potential risk. There was a commitment for further studies to be conducted in this area. Those studies have now been completed, including one of the largest global initiatives, driven here from Canada, which has generated the strongest data set in this area, in fact certifying that this signal did not prove to be true.
Yes, absolutely there was engagement and a plan of action that was developed, mutually agreed upon with the regulators, deployed and coming to a conclusion.
Senator Mercer: Thank you, everyone, for being here this morning. We appreciate your time and your testimony.
I have only one question. I was a bit shocked to see in the report from the Canadian Generic Pharmaceutical Association your recommendation number 3, which states, "Health Canada should provide safety information freely and without charge.'' You go on to say, "Currently, Health Canada requires payment for this information.''
I am a little shocked by that. Safety information — and particularly the safety of drugs — should be readily available to the public immediately upon finding that there is an issue, because it is a safety issue and a health issue.
How long has this been going on? How long have they been charging for this information?
The Chair: Would you explain the background of the statement?
Dr. D'Cunha: Certainly. The background of the statement is as follows: Health Canada does a good job in the Canada Vigilance Program of publicizing high-level information on individual adverse case reaction reports. In terms of the depth and the quality of the information, if you want more information, you have to file a request under the Access to Information Act, and that is when you fork out the money.
For instance, if I wanted to go and see the safety profile of molecule AAA, this is what I will see today in the public domain: I will see a report involving a female, age 57, with concomitant medications and adverse reactions identified in the report. If I wanted to drill down into the narrative or the quality of the information and other such information, I would have to file an access to information request. I would be charged and I would get that data. It is the depth of the data to allow us, as a pharmaceutical manufacturer, to comply with our obligations to properly assess our molecules.
Senator Mercer: I find it very puzzling, chair, that we would be in that position.
The Chair: I wonder if any of you could expand on this a little bit. Your answer suggests that you are looking at an individual reaction posting by Health Canada with regard to a particular drug.
Let us suppose there have been a number of such individual reports to Health Canada. Does Health Canada at some point provide a more detailed, readily available, accessible commentary with regard to the drug and the general circumstance, free of charge?
Dr. D'Cunha: Our experience to date is that after the safety signal has been identified and validated to be acted upon, then they will sit down with the respective manufacturers and design the public communication that my colleague spoke about, and then it will come out free of charge. However, the process of identifying a safety signal requires a little more information as you go about taking your obligation seriously.
Senator Mercer: Let us be clear. I am looking at it from the public's point of view, but it is also important from the industry's point of view so that you can understand what happened. If there is a particular situation with a particular patient with a particular background, I would assume that it might give you an inkling as to what went wrong and whether there is something that needs to be corrected or if it was just a one-off issue. This is a serious thing.
The Access to Information Act is there to protect Canadians' privacy. This does not reveal the name of the patient. Even if you get access to the information, it would not give you the name of the patient; it would just describe the circumstances of the patient and the details of his or her health condition as they were taking this drug, I assume.
Dr. D'Cunha: Not all the detailed information that is needed. If I may clarify, what the manufacturer received directly from a member of the public or a health care professional, we will have all the information that is provided to us. In the course of your study, you were briefed that Canadians, whether you are a health care professional or a member of the public, can choose to directly report to the MedEffect program of Health Canada. That is the information the manufacturer does not see, except for what is posted in the public domain, and it may well be about your molecule.
The Chair: I would like to have input from either Mr. Hughes or Mr. Glezer. Mr. Glezer, you indicated you were willing to comment.
Mr. Glezer: The process we are currently following, as I described earlier, is that when we see something serious, unexpected and potentially related to the drug, whether this is an individual report or study findings, we report this to Health Canada. We also provide periodic safety update reports with a summary of the safety information that has been accumulated. As you can appreciate, there are lots of situations where a potential relationship might not be excluded, and there are different things that can occur with people taking the drug, whether or not it is related to the drug, as the population grows.
The decision about whether the information represents a signal is something that is subject to the appropriate statistical and epidemiological analysis, and it is subject to the comparison to what is happening in this population normally, without the drug. If you see that something is starting to happen more frequently, then that would constitute a signal.
There is a risk in overreacting to this. To the comment that was made earlier: If you see panic, you actually might prevent patients who could benefit from the drug from taking the drug. That can actually cause harm.
Therefore, what goes into the public domain is carefully weighed by the regulator, and usually in discussion with the manufacturer. The rest of this is subject to continuous evaluation. If it is deemed appropriate, it will be reflected in the product monograph, public advisories, communication to the health care professionals, and it might impact your activities within the risk management plans. Multiple steps are taken to take this information into account, and this is in the public domain.
Ms. Del Bosco: I would like to add that if there is a safety signal that does come up that is not just related to the product itself but, rather, to a therapeutic class, for instance, then Health Canada actually goes further and contacts all manufacturers. When there are updates to safety, especially safety updates to our labelling, then, if there is a generic compound in Canada, they are also told to update their product monograph with that information. Therefore, it is a consistency with respect to safety if there is a safety signal that appears that is not product specific but, rather, could be class specific, or if there was a generic of that particular product.
Senator Moore: Thank you, witnesses, for being here. I want to follow up a bit on that line of questioning.
It sounds like this issue arises when a safety signal is issued. Is that right? That is what I am hearing, "safety signal.'' What is that? Who issues that? Does Health Canada issue that, and why?
Mr. Hughes: As a consequence of the pharmacovigilance process, the safety signals are detected as a consequence of the monitoring, which is agreed up front in the risk management plan in the medication plans. The people who are going to accrue the data determine appropriately that there is a risk signal and act on it, get that data in real time. That would be the company that has the product, and the regulator. As a consequence of that risk mitigation, it is dealt with. In terms of the communication down the line, my colleague Mr. Glezer has reviewed it accordingly.
Senator Moore: The information that Dr. D'Cunha mentions he has to apply for is created by whom? By the company that creates it, the manufacturer?
Mr. Hughes: It is a reaction, a process of the risk mitigation plan, which people who determine and report adverse events pour into that plan.
Senator Moore: Patients report adverse reactions to whom? Whom do they report to? To the manufacturer?
Mr. Glezer: There are multiple sources of this information and multiple channels as to where the information could be reported. Clearly, the information could be reported to the manufacturer or to Health Canada. When the manufacturer receives the information that is deemed to be something that is unexpected, related, and serious, we do provide this information to Health Canada. As I mentioned, we do provide a periodic summary of all the information we receive as well.
Senator Moore: Health Canada is a depository of all these reports?
Mr. Glezer: That is accurate.
Senator Moore: Some of which you create or supply.
Mr. Glezer: Yes, and some come from independent sources.
Mr. Hughes: There are multiple mechanisms to report.
The Chair: We heard in previous testimony the many ways in which information comes to Health Canada. That is not the primary issue. The issue is the question that Dr. D'Cunha raised and attempted I think to explain that this is a secondary step to the appearance and identification of —
Senator Moore: I know, but it sounds to me like he is planning to get his own information back. That is all I am getting at. I do not understand that. Partially, he is.
The Chair: Dr. D'Cunha, I think you have gotten us outside our scope. Can you pull this back?
Dr. D'Cunha: You do not pay to get the information you submitted because you know your reports. It is the ones you do not, and the situation my colleague described in an ideal world works fine if there is only one manufacturer. When it is generic, you have multiple manufacturers with the same molecule.
Senator Moore: There are competing interests.
Dr. D'Cunha: I will close my remarks with a comment. The NMRA in the U.K. and the Dutch MEB provide those reports free to all manufacturers of all marketing authorizations.
The Chair: The point is you would like to see the in-depth information behind the alert available for free. Is that correct?
Dr. D'Cunha: That is correct.
The Chair: Thank you.
Senator Moore: I want to get to a question for Dr. Hughes. You say that a manufacturer is not advised if and/or when one of your medicines undergoes a post-market review for safety or comparative effectiveness. The manufacturer will not know how the review will be conducted and what the conclusion may be and how those conclusions will be used. It sounds to me from your report that in the U.S. and in Europe there are agencies set up whereby there is an open and collaborative approach between the manufacturer and the regulator.
I expect you would have asked Health Canada to set up a system that would permit a collaborative approach so these issues that you mentioned will be dealt with in an open and transparent way so that everyone knows what is going on. That is fundamental to me.
Mr. Hughes: That is indeed our ask. The reality is that we will get the best data and the best practices based on information sharing and working together. Therefore, a situation where a particular group, a major group, is excluded from the deliberations will not be helpful, and that is why I give the examples of RMOP and PROTECT, which I would be happy to provide additional information as you go through your program.
Senator Moore: Please give that report to the clerk of the committee.
Mr. Hughes: Absolutely. There is a big difference between independence and isolation. If you have all the information based on good discussion, you can make an independent decision based on the information you have. If you isolate yourself from a source of information, perhaps your decisions would be less well informed, so the group's ask is that we ensure we are interacting in the maximum effective way to ensure all the information is on the table so those independent decisions made are the most meaningful.
Senator Moore: Have you formally or otherwise made this ask of Health Canada?
Mr. Hughes: Of DSEN, yes, and we would like to continue making them and have repeated it here today.
Senator Moore: What response are you getting? Is there any interest at all? Are you getting yes, no or we want to talk about it and pursue one of these other models?
Mr. Hughes: Testimony has already said that DSEN operates in the absence of industry. Our ask is that it would be better served by having industry at the table to make the best independent decision.
The Chair: We had them before us, Senator Moore, so this ties in.
Senator Moore: It sounds like the department is saying no.
The Chair: We have that evidence on record, and the comments today are relevant to that, but the testimonies have to be taken together.
Senator Moore: Thank you.
Mr. Hughes: To conclude, I offered RMOP and PROTECT as international best practices by way of comparison.
Senator Martin: Mr. Hughes, I heard you say you interchanged safety signal with the risk signal. We are just talking about adverse effects, correct? If these safety signals are just adverse situations that have been reported, they are signals, but you are using safety. However, you did interchange and use the word "risk'' as well. Do you understand it to be both?
Mr. Hughes: Yes.
Senator Martin: Having said that, I know that Health Canada is collecting this data, and it comes from various sources. We heard from the health professionals yesterday. Is your definition of adverse effects congruent or clear or similar to what the health professionals understand it to be and similar to what the public understands it to be in that yesterday with the health professionals some said it was clearly defined and another witness said not quite? I am curious whether you as an industry feel that this understanding is clear among yourselves and whether it is congruent with the health professionals, which would be very important.
Mr. Hughes: I can speak to that. There is no limitation on how an adverse event can be reported. In terms of understanding what an adverse effect is and how it impinges on a particular file in terms of regulating a medication through its life cycle, the interactions between Health Canada and the manufacturer and everyone involved defines that. The information comes in and is processed accordingly so the appropriate scientific rigour can generate whether there is a genuine risk or safety signal that needs to be acted upon.
The context of this is negotiated within the risk management plan between Health Canada and the company involved. The understanding of that risk management plan is superb, of course, and that is how it is built, and so it moves forward under that basis.
Dr. D'Cunha: We are bound by the regulatory definition of an adverse drug reaction. As part of the PV practice, we follow the Health Canada guidance document most recently published in March 2011, where if a health care professional phones it in, the front-line drug safety professional working for a company asks this direct question: "In your professional view, is it related or not to the drug in question?'' If the answer is yes, it is confirmed by a medical professional, whether it is a pharmacist, nurse or physician. If the answer is no, for purposes of the regulatory definition, it is not considered an adverse drug reaction; so the data is collected, but it is not reported out as a reaction. That is the regulatory definition we all operate under.
Mr. Glezer: To clarify, when we are talking safety, the adverse effects we observe and those related which we call reactions are considered in the ballpark of the safety information. However, this is not the only information comprising safety. For example, unusual lack of efficacy might also be part of the safety information, so there are other things in there.
What is of importance, however, is the detection of the new safety signal we did not know about that might impact the benefit-risk profile because those are the ones that will trigger further action.
Senator Martin: Thank you for that.
Mr. Glezer, I see your comment that information overload can be damaging and that it is important to organize information so that people looking at it do not have an overreaction to something. I can understand the depth of information.
Dr. D'Cunha: Our ask presented to the department in the fall of 2007 was to not publish it in the public domain. We are very comfortable with what we see there. However, please make more detail available to us if we have the authorization for that molecule. That is what the United Kingdom and the Dutch regulator are doing. We know that is a global company.
Senator Martin: However, did you not say the detail is there but it is a matter of going deeper and asking for those details? Do you have access to that if you ask within the process of how it is set up?
Dr. D'Cunha: No. If you pay the fee, you get the detail.
The Chair: This was the issue, Senator Martin. As they begin to drill down, then Health Canada charges for the individual detail.
Senator Martin: Thank you. That is the piece I was not sure about. It is available but there is a fee for certain information at a deeper level.
Dr. D'Cunha: I am comfortable with what I see in the public domain. I am not suggesting all the minutia should be there, but for the safety professionals who need to see it to analyze it, it should be available.
Senator Martin: I asked this yesterday of the health professionals. Would the industry support a legislative provision granting authority to the Minister of Health to issue mandatory drug recalls? If not, why, and if yes, under what conditions? We heard from the health professionals under which conditions they would support that. I am curious, as an industry, what is your view on mandatory recalls?
Dr. D'Cunha: From my perspective, working for industry and as a physician licensed in Ontario, if a drug is not safe or if the quality is not there, it really should not be on the market.
The Chair: Witnesses, could you make your observations on this, and we will try to pull this to an answer that is meaningful to us with regard to post-approval surveillance.
Mr. Hughes: Mr. Glover in his testimony stated that there are plenty of mechanisms by which people can be encouraged to withdraw, but I would like to agree with my colleague that it is not the intent of anybody to have an unsafe or non-efficacious medication on the marketplace, and it would be withdrawn as a matter of policy.
Mr. Glezer: As we discussed on the other matters, I think it will be beneficial to everyone to ensure this happens through a collaborative process where the full set of information is being exchanged, but I agree with the intent of ensuring that only the safe and quality products are on the market.
Ms. Del Bosco: There are nuances, too. It is not just safety; it is safety, efficacy and quality. Everything taken together is important when we are talking about recalls, so it is complex.
Senator Raine: I wanted to go back to the question of having to apply for freedom of information. It is not only the cost, of course, but there must be a time delay as well. Does it take longer to apply for freedom of information to get the information that would be helpful in terms of understanding what is happening with adverse drug reactions?
Dr. D'Cunha: In the past, yes, but with the technological advances, I see hope.
The Chair: This is our understanding from your comment in your report. We understood, up to this point, that after Health Canada makes a statement with regard to a given reaction in a given drug, that if you wanted the detailed information you could get it, but you needed to pay for it and that was the issue that you identified in your submission to us. Is that correct?
Dr. D'Cunha: That is correct for reports that did not come to us as manufacturers in the industry.
The Chair: How did freedom of information come into this particular line?
Dr. D'Cunha: That is the access route.
The Chair: This is the access route. You pay for the information, and if you pay you get it. Your request is not having to pay for it.
Dr. D'Cunha: That is correct.
Senator Raine: I know there is off-label use. How is that regulated or determined? Is that a good practice? When doctors and pharmacists are getting their information, how important is it that they listen to the follow-up from the sales people who call on them to inform them? Is there any control over what those people are saying with regard to off-label use?
The Chair: I will interject at this point. We have a whole study coming up on off-label use, so I will deny the question at this point because it does not relate directly to post-approval surveillance. If you have a question with regard to the surveillance, I will allow it but not getting into the off-label use. We will do a study on that.
Ms. Del Bosco, what is your answer with regard to surveillance?
Ms. Del Bosco: I wanted to specify, and I think it was mentioned before, that we also under post-marketing report any adverse event that comes in for unapproved indications as well.
Mr. Hughes: Sales people do not promote off-label use, but physicians and patients make those decisions based on the need and based on risk management plans. All of that disclosure takes that into account.
The Chair: We are not going down the business practice route. We are trying to stick to the focus area.
Senator Munson: I have two questions on safety information for drugs. Health professionals often receive general information about drug products from manufacturers. This can include direct mailings, faxes and visits from company representatives. Do drug companies currently provide health professionals with safety information early in the post- market stage on new products? Does information from drug companies encourage caution in the use of new products?
Mr. Glezer: I will start, and please add to this.
When we are introducing the product to the market, obviously, the level of uncertainty about the product is high because there is less experience around it. Depending on the levels of risk with the product, within the scope of the risk management plan, we might actually plan for a staged introduction or a certain level of awareness or a certain level of specialization for the products that are high risk before the product is used.
Those are the exceptions. In the more general terms, when we are doing the promotional activities through the sales representatives or the educational activities around the therapeutic area within the context of continuous medical education, we are acting within the scope of what is approved by the product monograph based on the evidence available, and that includes the balanced provision of the efficacy and safety information.
The promotional material tools used by the sales representatives are subject to the approval by the appropriate bodies, and they all contain what is called "balanced copy,'' which summarizes the relevant parts of the product monograph with respect to the indications and the safety information in there. This is to reassure you that there is increased level of attention when we are in the new product introduction or in the new indication introduction, but we are in this scope of balanced information throughout the product life cycle.
Senator Moore: Ms. Del Bosco, I learned a new word — "immunogenicity.'' You say in your brief that immunogenicity trials are carefully designed to include enough patients to detect any possible effects. How many patients and over how long a period is that?
Ms. Del Bosco: Immunogenicity trials are rigorous trials, similar to most clinical trials. The complexity of the trial will determine the number of patients. This is pre-determined and pre-approved to Health Canada. We actually file clinical trial applications to Health Canada for approval.
Senator Moore: I am asking about the number.
Ms. Del Bosco: It has the criteria and number of patients; that is correct. Depending on the actual depth of the study, then it depends on the number of patients. It can range in the thousands of patients for immunogenicity but depends on the actual study taking place.
The Chair: I would like to come back to some things that have occurred during the course of the meeting.
Mr. Hughes at the outset and others of you have echoed the same thing, namely, that you have been pleased with Health Canada's response to the Auditor General's report. However, it does seem to me that thorough post-approval monitoring could very well develop information with regard to various subgroups in society that ultimately could not only lead to the directly obvious issue of how that drug affects that subset, but rather down the road with regard to personalized medicine in terms of the more information we collect, which gives us information on specific drugs interfacing in certain ways with certain subgroups of the population, the more knowledge we have down the road to being much more selective in the prescription of new medicines or which of the available choices are most effective for various subgroups.
That is not a specific question but relative to Senator Seidman's earlier question. Is there anything further any of you wish to add regarding this situation?
Mr. Glezer: I absolutely agree that if the utilization occurs in those populations, we need to be able to access the evaluation as to what it does in terms of the benefits or the risks to those patients. The challenge, however, is that even though those populations were not studied within the clinical development of a product, there is a high possibility that those populations will not be within the label and the indication. Moreover, they will probably find themselves into the warnings, precautions or even contraindications.
When we are going to evaluate this kind of utilization, we need to be careful so that it does not turn into actual encouragement of utilization in those populations and stimulation of the off-label use. If those populations are clearly identified as potential risk, we need to think of how to manage it within the risk management plan. If they are deemed to be important from the potential benefit perspective — for example, the pediatric population in a children's hospital for a new product — then we need to look at potential collaboration among industry, academia and the government in order to make sure that we can study those populations in the appropriate framework.
I think, again, the motion of Health Canada to move into the process of licensing opens up these kinds of possibilities.
Ms. Del Bosco: I simply agree.
Mr. Hughes: I would extend that and say that with the description of the value of the stuff we are talking about today, the pharmacovigilance program would generate those types of data. If we encourage more people to participate in that space so that the data becomes more substantial, then we can make those types of decisions to the benefit of patients down the line. If we are inclusive and the studies are broad, we will get that useful information in the future, absolutely.
The Chair: Senator Raine, did you have a question on this issue?
Senator Raine: Not specifically. It is on another topic.
The Chair: What is the question?
Senator Raine: I am very interested in bar codes, probably because with the XL Foods situation — and I was going to have steak for Thanksgiving dinner.
The Chair: Let us get to the question on pharmaceuticals.
Senator Raine: Are bar codes being used specifically for the medicines that are being produced? Is there a way to use bar coding to assist in the collecting of adverse responses so that, for instance, a medical practitioner would be able to scan the product and enter the data easily on that specific product because they have the medicine, it is marked, they scan it and it goes in?
Mr. Glezer: I do not think there is a uniform answer to this because it depends on how the product is being dispensed and used. Not all products are being delivered to patients in the original packaging. They might be repackaged by the pharmacy according to the prescription itself. In that circumstance, the bar coding might be a bit difficult to implement.
However, bar codes are broadly used with products that have individual doses that are being manufactured for patients, and they are increasingly used in situations, for example, of home care or hospital care.
Where the product was dispensed and is actually being registered through scanning the bar code, this is in place and growing. Obviously, if there is no additional clinical information about this patient, that will go into the patient's chart alongside the scanned bar code information, the fact that the prescription was delivered.
Mr. Hughes: There is also a big improvement with the vaccine space on bar coding as well. For that specific reason, we can see the advantages down the line.
Ms. Del Bosco: Bar coding is absolutely one of the tools used to ensure the quality of the product. For instance, we spoke about recalls before, lot-by-lot testing and lot-by-lot recall. That is one of the tools that can be used in terms of distributing the product and in terms of recalling it. It is an active tool, one of many.
Senator Raine: Thank you.
The Chair: It is not part of our study, but it has come up here today in a comment made by one of the senators, and it has come up elsewhere. It has to do with the information that comes with a prescription. More than one of you had made the point that if one scares patients in the type of information that is given and in the way it is given and they fail to take their prescription, their health may actually be at risk as a result of that. I have had cause to look at some of the documentation that comes along with even simple prescriptions, and it seems to me that it is correct there is virtually nothing that we deal with in this world that is not capable of killing someone, but one would be scared to death to use — we do not have them on the television screen, but we do have pages of documents with the prescription.
This is just an observation. If you folks can work collaboratively with Health Canada to get the risk-benefit ratio worked out more specifically and under the laws and liabilities of various countries, I think it will ultimately be to the benefit of our citizens.
I want to thank you for your testimony today, and I want you to think about the things we have discussed. If one of those "I wish I had thought of that then'' occurs to you, please communicate that subsequently with us. I believe there has been an indication of some information you will be providing to us, in any event. If any of you have further information that would be helpful, it would be most welcome.
I want to thank you on behalf of my colleagues for your testimony, and I want to thank my colleagues for the clarity of their questions to you.
(The committee adjourned.)