Health Canada s NHP Vigilance Activities

Transcription

1 Health Canada s NHP Vigilance Activities Canadian Health Food Association (CHFA) East October 3, 2013 Scott Sawler Director General Marketed Health Products Directorate

2 Overview NHP Program & MHPD Activities Updates on Current Initiatives for NHPs Adverse Reaction (AR) Reporting Provisions Periodic Benefit Risk Evaluation Reports (PBRERs) Canada Vigilance Projects (e-reporting) Poison Control Center Project Look-Alike Sound-Alike (LASA) Plain Language Labelling (PLL) Advertising Education & Outreach Update on Domestic AR Reporting Looking Forward 2

3 Health Canada Health Products and Food Branch Natural Health Products Program Natural Health Products Directorate (NHPD) Marketed Health Products Directorate (MHPD) HPFB Inspectorate (HPFBI) Natural Health Products Directorate Marketed Health Products Directorate HPFB Inspectorate Targeted oversight: authority for implementation of the NHPR. Surveillance: authority for post-market surveillance, risk communications and regulatory oversight of advertising. Rapid response: authority for compliance monitoring, including industry inspections and product investigations. 3

4 Current MHPD Vigilance Activities The Marketed Health Products Directorate monitors and collects AR and medication incident data; reviews and analyses marketed health product safety data; conducts risk/benefit assessments of marketed health products; communicates product related risks to health care professionals and the public; carries out regulatory advertising activities; develops policies to effectively regulate marketed health products; conducts active surveillance. 4

5 Updates on Current Initiatives 5

6 NHP Vigilance Activities: AR reporting Natural Health Products Regulations outlines requirements for AR reporting for NHPs by Industry (Section 24). Industry: Mandatory reporting of all serious domestic ARs and all serious foreign unexpected ARs to Health Canada (expedited). Healthcare practitioners and consumers: voluntary reporting. Canada Vigilance AR Database Monitored by Health Canada for safety signals Online searchable database accessible to the public Also monitored: World Health Organization AR Database 6

7 NHP Vigilance Activities: Safety Summary Reports Safety Summary Reports (SSRs) are mandatory for Industry to prepare and maintain for each licensed NHP (Section 24 of NHPR). SSRs must include all domestic ARs, and all serious, unexpected foreign ARs. Allows for continual assessment of relevant safety data through life-cycle of product(s). If a safety issue is detected, Health Canada may request SSRs (mandatory to submit). Health Canada follows standards set by the International Conference on Harmonization (ICH). 7

8 Periodic Benefit Risk Evaluation Reports Former international standard for safety reporting was the PSUR format (Periodic Safety Update Report) [ICH E2C(R1)]. In 2012 the European Union enacted new pharmacovigilance legislation, and transitioned from PSUR to PBRER format (Periodic Benefit Risk Evaluation Reports) [ICH E2C(R2)]. MHPD is developing guidance for the preparation of summary reports. Currently, all formats are accepted for an NHP SSR (i.e., PBRER, PSUR, Annual Summary Report formats). SSRs are an important tool in the ongoing monitoring of the safety of NHPs. 8

9 Update: Canada Vigilance Projects Implementation of a pharmacovigilance database to manage both Clinical Trial and Post-Market AR Reports to enhance the overall efficiency of processing and managing adverse reaction reports over the life cycle of a product. Implementation of Electronic Reporting of all ARs (domestic and foreign) coded with MedDRA for small, medium & large Industry to account for varying technological capability. Includes data analysis capabilities including a data mining and signal detection tool. Incorporates international standards as recommended by ICH. Brings Health Canada in-line with other Regulators (FDA, EMA, etc.) who have e-reporting. 9

10 Update: Poison Control Centre Project Collaborative pilot project between the MHPD and Canadian PCCs to determine the value of PCC data as a source of NHP ARs. Retrospective analysis: PCCs receive a large number of NHP ARs. Prospective data gathering: Hundreds of NHP ARs reported by the PCCs to Canada Vigilance. Volume comparable to all other sources combined together; ARs are still being submitted. The project showed that PCC data are useful for: Signal detection Providing information for existing assessments within MHPD Detecting patterns of product misuse and abuse Identifying the presence of potentially poor quality foreign products on the Canadian market Certain products may have labelling to report directly to PCCs (e.g., benzocaine), which bypasses reporting to Health Canada A national system for the sustained availability of PCC data as a source of domestic AR data would be beneficial - being investigated currently. 10

11 Update on Look-Alike Sound-Alike (LASA) Feedback gathered via the Spring 2013 consultation on the revised guidance for LASA brand name review identified the desire for a separate guidance for LASA for OTC products (NHPs and nonprescription drugs). In respecting the feedback gathered and Health Canada s directions for balanced regulation of health products, work will be done to identify an approach that upholds safety standards while at the same time recognising the nature of the products and the marketplace. As the next step in the process of developing a name assessment framework for OTC products, more discussion will be held on risk mitigation strategies appropriate for the prevention and management of confusion that can result from similar brand names. 11

12 Update on Plain Language Labelling Proposed amendments pre-published in CG1 in June 2013 with comment period closing in early September The new regulations would introduce for human drugs (nonprescription and prescription drugs and biologics) the following 5 targeted requirements: Plain language labelling to assess elements such as colour contrast, font size and layout of text Contact information to report problems Drug facts tables to present key information in a standard format for non-prescription drugs Mock-ups of labels and packages for review Look-alike-sound-alike (LASA) evidence that drug names will not be confused with other authorized products Stakeholder feedback is currently being compiled and analysed. 12

13 Update: NHP Regulatory Advertising Activities All Advertising Activities FY All Product Lines NHPs % NHP Complaints Requests for Clarification Advisory Opinions * 3 Media, Ministerial Requests, QP *Exempted NHPs only 13

14 Update: Education & Outreach for NHP AR Reporting Education / outreach to stakeholders important for increasing awareness of AR reporting, both voluntary (consumers, HCPs) and mandatory (industry). Carried out by MHPD and RAPB in collaboration NHP Education / Outreach : Focusing on healthcare practitioners Educational Institutions (Canadian Naturopathic Schools; Universities) Conferences Emergency Room Physicians Member Associations New Frontiers: Incorporation of AR Reporting into college / university curriculums (already part of Naturopathic Schools of Medicine) CAND Needs Survey 1) few NDs are aware of reporting process and tools available through the MedEffect Web portal, 2) many NDs (~50%) have not reported ARs to HC NDAssist pilot project Create linkage to the MedEffect Web portal in order to increase awareness of, and encourage, AR reporting to HC Preliminary discussion with CMA for collaborative projects 14

15 Update on Domestic Adverse Reaction Reporting 15

16 Update on Domestic AR reports (All Products) Canada Vigilance Database: January 1, 2012-March 31, 2013 Radiopharmaceuticals (0.68%) Vaccines and Diagnostics (1.05%) Biotechnology Products (38.61%) Pharmaceuticals (56.63%) Blood Products & Biologics (1.45%) Cells, Tissues, and Organs (0.12%) Natural Health Products (1.46%) 16

17 Update on Domestic NHP AR Reports Non-Serious Serious (to March 31) 17

18 Update on NHP Domestic AR reports Sources of NHP AR Reports (January 1, March 31, 2013) Community Hospital Market Authorization Holder 600 NHP AR Reporter Types Physician Pharmacist Other HCP Lawyer Consumer or other non HCP 18

19 Looking Forward 19

20 Health Product Vigilance Key element of the life-cycle approach of health products. Compliance Enforcement 20

21 Vigilance Activities NHP vigilance oversight is dynamic/flexible, and is applied using a risk-based approach. Highest level of compliance and enforcement and safety surveillance reserved for the most serious risk. Increased oversight may also be needed for products with low certainty or low information on risk profile. Can we profile our vigilance activities in a better way? Compliance and Enforcement Labelling revisions Risk Communication Increased Oversight: Targeted monitoring of CV database / Request for additional safety data from Industry Standard Monitoring: Enviroscanning (literature, foreign regulatory agencies) Routine monitoring of Canada Vigilance AR database Advertising complaints 21

22 Drivers for Change Following the Pathway for Licensing, it is time to re-balance the pre- and post-market oversight. The life-cycle approach to health product regulations needs to be supported by enhanced post-market oversight. The need for proactive and systematic approach to obtaining and evaluating evidence in support of both the benefits and risks of a health product. 22

23 Safety Surveillance Continuum Spontaneous Pre-organized, Continuous Clinical Trials DSEN (study design) DSEN (Active Surveillance) DSEN (database analysis) Pharmacoepidemiological studies Patient, product registries Sentinel systems Proactive Risk Management Plans / PV Plans Issue-specific reports Prescription Event Monitoring ITS analysis of sales data Mining of electronic health records Drug utilization studies Solicited Reporting External canvassing Stimulated Reporting Targeted analysis of spontaneous reports Data mining of spontaneous reports Periodic reports (PSUR, Annual, DSUR) Reactive Spontaneous AR, AE and Med Incident Reporting 23

24 How Could Post-Market Oversight Look? Re-balance between active and passive surveillance. Post-market reporting requirements indexed against product risk. Targeted surveillance of conditionally licensed products informing product licensing. A focus on proactive analysis of market data through research to assess trends and a predictive model that can forecast safety signals. May involve partnerships with Industry and other stakeholders. Continuous assessment of feedback received from users of risk management approaches (e.g., Canada Vigilance, risk communications) to assess effectiveness. 24

25 Questions? 25

26 Annexed Slides : Case Studies Case Study 1 Anaphylactic Reaction to a Non-Medicinal Ingredient Domestic case reported to Health Canada: Life-threatening anaphylaxis in a peanut-allergic and asthmatic child, associated with the use of ear drops containing peanut oil. Package was labelled: Do not use if allergic to peanuts; peanut oil listed as a non-medicinal ingredient (NMI). Issue: Lack of awareness about peanut oil as NMI. HC actions: Priority food allergens, including peanuts and peanut oil, must be clearly labelled in plain language (peanut, not arachis) Premarket (NHPD) informed companies to use peanut and not arachis for new applications and licensed products Canadian Adverse Reaction Newsletter (CARN) case presentation January, 2013 to inform healthcare practitioners and consumers 26

27 Case Study 2 Suspected Quality Issue with a Foreign Product Domestic case reported to Health Canada: Life-threatening methemoglobinemia (MetHb) in elderly patient, associated with the ingestion of a foreign product. Suspicion that the product may have compromised quality (contamination, adulteration), as labelled ingredients were not associated with MetHb. HC actions: Laboratory testing results: inconclusive. No identified adulterants or contaminants that could explain the reaction Market verification: suspect product was not found at retail level in region where AR occurred Risk Communication: Foreign Product Alert to be issued. 27

28 Case Study 3 Multiple foreign cases of serious (life-threatening, fatal) ARs are reported by another regulator, suspected to be associated with an NHP (marketed worldwide). Safety signal not seen in Canada Vigilance database. HC Actions: Foreign regulator consulted for follow-up information Safety Summary Reports (SSRs) requested by Health Canada from company to further analyse the potential safety signal Review of SSRs by Health Canada: No significant safety signal detected Conclusion: No significant change in the risk: benefit profile of products 28

29 Health Canada s NHP Vigilance Activities The case studies highlight vigilance tools used by Health Canada: Case Study 1: Targeted Monitoring of the Canada Vigilance database Used to identify potential signals of new safety information from the Canada Vigilance database. Safety signals are evaluated by both scientific and clinical experts to determine if there is a causal association between the AR and the product / ingredient. Monitoring via: Health Products- Targeted Medical Events Designated Medical Events New Active Substances 29

30 Health Canada s NHP Vigilance Activities Case Study 2: Collaboration with Canadian Poison Control Centres The serious case of MetHb detected by PCC Ongoing, voluntary reporting by PCCs in Canada post-pilot project Highlights that ARs may get reported by healthcare practitioners/ consumers to PCCs or other centres, and not Health Canada. Particularly important in the case of foreign health products (e.g., via personal importation, purchased online) Any ARs associated with these products would not get submitted by a licensed Canadian company (i.e., mandatory NHP AR reporting) 30

31 Health Canada s NHP Vigilance Activities Case Study 3: (1) Collaboration with International Regulatory Agencies (2) Request for Additional Safety Data (SSRs) from company International collaboration: Health Canada is an active participant in a number of different international discussions. Permits exchange of important information between Health Canada and other regulators that may affect the health of Canadians. SSR requests: Health Canada may request these safety reports to monitor and/or further assess the safety of a health product(s). Allows overall assessment of cumulative safety data, both domestic and international ARs, to determine if the benefit:risk profile of the product has changed. Industry may submit these reports on a voluntary basis as well. 31

32 NHP Program Organization Chart Natural Health Products Directorate HPFB Inspectorate Marketed Health Products Directorate Core functions include developing policies and guidelines for the Natural Health Products Regulations, managing and processing submissions for product, site and clinical trial authorizations, implementing the Education and Outreach Program for the Natural Health Products Regulations, information dissemination to the public, and internal and external networking. Responsible for branch-wide compliance and enforcement activities, enabling consistency of approach across the spectrum of regulated products. Core functions are compliance monitoring, and compliance verification and investigation, supported by establishment licensing of drugs and medical devices, and laboratory analysis. Monitoring and collecting adverse reaction and medication incident data. Reviewing and analysing marketed health product safety data. Conducting risk/benefit assessments of marketed health products. Communicating product related risks to health care professionals and the public. Overview of regulatory advertising activities. Providing policies to effectively regulate marketed health products. Active surveillance and drug effectiveness project. 32