Final Update and Response to OAG Recommendations for the Regulation of Pharmaceutical Drugs

Health Canada's Action Plan

The Findings of the Auditor General: Canada has one of the safest and most rigorous systems in the world, but is always looking for ways to improve. In November of 2011, the Office of the Auditor General tabled their audit on the Regulation of Pharmaceuticals in the House of Commons. The audit covered a period of two calendar years (2009 to 2010). The Auditor General did not question the safety or effectiveness of drugs authorized by Health Canada, but made 10 recommendations to strengthen and improve processes that are already in place. The Auditor General's 10 recommendations fall under three themes: Safety, Timeliness and Transparency. This document outlines how Health Canada has addressed and completed all of the recommendations.

Safety

Canada has one of the safest and most rigorous drug safety systems in the world. To identify health and safety risks as quickly as possible, Health Canada encourages Canadian consumers and health professionals to report adverse reactions and requires industry to do so. In January 2013, Health Canada took steps to encourage adverse reaction reporting for hospitals as part of the accreditation process. The audit recommended that Health Canada take measures to strengthen this on-going work to ensure consistency and attention to issues that pose the highest risk.  To further support this work, on December 6, 2013, the Government of Canada introduced the Protecting Canadians from Unsafe Drugs Act (Vanessa's Law) to help better identify potentially dangerous drugs and ensure the quick recall of unsafe drugs.

The Department formalized and documented internal processes related to conducting safety assessments as well as launched a Safety Labelling Stakeholder Notification System on the Health Canada website in February 2013. These improvements will fine-tune Health Canada's already robust processes for managing and mitigating risks and communicating those risks to Canadians. Health Canada has developed a triage system to ensure that those issues with a higher risk are dealt with first. Health Canada continues to develop a two-pronged approach to electronic adverse reaction reporting involving both an electronic gateway for large industry use and a web-based portal for small and medium sized manufacturers. Industry partners are currently being registered for the electronic gateway and the interface for the web-based portal has been developed and technical progress is on-going. This approach will bring Health Canada in line with other regulators and will allow the Department to more efficiently identify safety signals related to clinical trials.

In October, 2011, Health Canada implemented performance standards for several Post-Market Surveillance Activities including Signal Assessments, Risk Management Plan Reviews, and Periodic Safety Update Report Reviews for Pharmaceuticals.  The new standards will help to identify and provide Canadians with new safety information in a more timely manner. Overall, In Fiscal Year 2013/2014, 90% (349/386) of the Pharmaceutical Post Market Surveillance Activities were completed within target. In 2014 HPFB also began publishing plain language summaries of post-market drug safety reviews to provide Canadians and healthcare professionals with greater access to drug safety information and to provide context on the Health Canada decision-making process. Health Canada is also finding improvements to the process of communicating risks.

Timeliness

In April 2011, Health Canada's Pharmaceutical Program user fees were increased for the first time in 15 years. These increased fees stabilized funding related to the delivery of regulatory services and were invested in hiring and training new scientific experts, and improving business processes and systems. As a result, Health Canada greatly improved its ability to meet its performance standards associated with reviewing drug submissions. While the audit made recommendations regarding Health Canada's need to improve in this area, the OAG examined the two years prior to the arrival of these new resources and thus these improvements were not apparent during the course of the audit.

Since 2011, Health Canada has consistently met its internationally benchmarked performance standards for new drug submissions which are in line with other regulators around the world. Further, the Department has eliminated the backlog of submissions associated with generic drugs in the Fall of 2013. This improvement in the ability to make decisions in a timely manner has been achieved by securing a robust team of scientific experts, updating and streamlining the review process via increased use of electronic tools, and increasing our partnerships with foreign regulators.

In addition, Health Canada has secured agreement from the United States Food and Drug Agency to make use of their electronic system for filing drug submissions. To move to a fully electronic environment in January 2014, has streamlined the administrative filing process for both industry and the Department and thus reduce overhead costs and improve processing times. This cost effective approach completely maintains Health Canada's ability to make independent decisions on drug submissions.

Transparency

Health Canada has taken significant action to improve transparency and openness in the regulatory process governing pharmaceutical drugs. Specifically, the Health Products and Food Branch 2012-2015 Strategic Plan includes transparency and openness as principles that cut across the three Branch priorities: The Regulatory Roadmap, Operational Excellence and The People Agenda. Health Canada recognizes that Canadians' expectations for clear, accurate, timely and relevant information are increasing and the objective is increased transparency and openness throughout a product's life cycle (pre and post-market). Recent work to increase openness and transparency includes the launch of a clinical trials database in the spring of 2013. While Health Canada has long encouraged its industry partners to register on international clinical trials databases, this is the first time a Canadian database has been made available. Making this information available publicly on Health Canada's website to provide some assurance to Canadians who are interested in participating in a clinical trial that the trial has been approved by Health Canada, and will also keep medical professionals informed as to the latest developments in pharmaceutical drugs. In April 2014, a Transparency and Openness Framework was launched and the Department began transparently publishing summaries of drug safety reviews.

Health Canada, specifically the Health Products and Food Branch, has highly skilled scientists and professionals who review drug submissions to help ensure that the drugs authorized in Canada are safe, effective and high-quality.  The Health Products and Food Branch has established a yearly process to ensure reviewers remain compliant and are aware of their conflict of interest obligations.   As part of the annual attestation cycle, as of the summer 2014, 100% of the Health Products and Food Branch employees, including reviewers, have declared that they understand and are in compliance with their Conflict of Interest obligations.  The department has completed its review of measures put in place to maintain the integrity of the drug regulatory process to ensure that they are effective and it will continue to monitor and update its processes as required. In addition to implementing the Auditor General's recommendations, Health Canada continues to build on its commitment to continuous improvement through the implementation of the Health Products and Food Branch Strategic Plan. This plan including its Regulatory Modernization and Operational excellence priorities will continue to increase drug safety, provide more timely decisions to industry and deliver more transparent and understandable information to Canadians.

Health Canada's Action Plan

1. The OAG recommended (4.35) that Health Canada strengthen its risk-based approach for monitoring and assessing clinical trial adverse drug reaction reports and for inspecting clinical trial sites, so potential safety issues are mitigated.
   • Theme: Safety
   • Health Canada's Overview of Audit Findings
     • The Auditor General found that Health Canada had a risk-based inspection strategy that included criteria to help inspectors consider a number of potential risk factors, such as the type of drug being tested, or the study's intended patient population. However, the report found that this process could be strengthened.
     • The Auditor General also found that the manual process used by Health Canada to receive Adverse Drug Reaction reports was labour intensive and could be made more efficient.
     • Health Canada has responded to this recommendation by strengthening its risk-based approaches for monitoring and assessing clinical trial adverse drug reaction reports and selecting clinical trial sites for inspection.
     • It is also pursuing electronic reporting initiatives to expedite the reporting of both foreign and Canadian adverse drug reactions. Enabling electronic submissions will speed the process and make it quicker and easier to identify potential drug safety concerns in clinical trials.
   • Actions to address recommendations
     • Clinical Trial Inspections
       • Status of actions as of June 2012:
         • Health Canada implemented a process detailing a risk-based approach to monitor and assess clinical trial adverse drug reaction reports, such that the safety information received for drugs in early development and/or being studied in high risk populations is being evaluated first. A strategy guide was developed as part of this process to help assessment officers constantly prioritize the highest risk safety signals. This will allow Health Canada to identify risks and notify appropriate parties in a timely manner.
           • Completed
         • Health Canada completed a review of the current risk-based approach to clinical trial site selection for inspection which will inform the development of a documented, enhanced site selection process.
           • Completed
       • Status of actions as of March 2013:
         • To strengthen the inspection strategy, Health Canada conducted a review of its existing process used to select clinical trial sites for inspection. The accompanying report was completed in July of 2012 and is being used along with feedback from program staff to inform the development of a documented, enhanced risk based site selection process.
           • Completed
         • New interim risk-based criteria were developed and piloted for use during FY 2012-2013 while the development of the new site selection process proceeds. A new work instruction which documents the revised risk based site selection process is being finalized. It is expected to be approved by April 2013 and implemented by December 2013.
         • As a final check, an internal audit conducted of the new site selection process has been scheduled for Spring 2014. The timing of the audit was planned so as to maximize the amount of data to be assessed. A report will be prepared by the end of June 2014 summarizing findings of the audit.
       • Status of actions as of June 2014:
         • The new site selection process is now in place. 51 recommendations of sites were received to date from the review directorates. The Directorates recently also implemented a new review recommendation process, which is expected to result in more referrals and a higher number of sites to be selected from the new lists. A hybrid process will continue to be used with recommendations coming from both the review bureaus and the inspectorate.
           • Completed
       • Status as of September 2014
         • An internal quality audit of the GCP inspection program conducted during fiscal year 13/14 verified whether quality activities and related results complied with planned arrangements and processes. However, due to the limited amount of data at the time of the audits, only a preliminary oversight of the enhanced risk-based process for selecting clinical trial inspection sites was captured. Therefore, the above-mentioned internal audit of the new site selection process was conducted to complement the first audit and included identified areas of strength as well as recommendations for improvement regarding the enhanced risk-based process for selecting clinical trial inspection sites. The final audit report has been finalized and approved by management.
           • Completed
     • Adverse Drug Reaction Reports for Clinical Trials
       • Status of actions as of June 2012:
         • Clinical trials have been included in the Canada Vigilance database since October 2011 and are also part of the scope of the electronic reporting initiative. This will make it quicker and easier to: identify potential drug safety concerns; synthesize this information; and make decisions. There are two electronic reporting initiatives underway, including a gateway for large manufacturers and a web-based system for small to medium sized manufacturers. Pilots for the gateway will take place in the summer of 2012, and a web-based system is currently under development.
       • Status of actions as of March 2013:
         • Due to the technical requirements in developing the gateway it was determined that Industry registration would be developed in a phased approach. The gateway project received its first sample scenarios in February 2013. Health Canada continues to register users to move them to electronic reporting which is on-going. The conceptual interface of the web-based portal has been developed and technical development is on-going. Going forward this will continue to improve the Department's ability to process and identify safety signals more effectively. This approach is also bringing Health Canada in line with other regulators (EMA, FDA, etc.) that work with electronic reporting.
       • Status of action as of June 2014:
         • Key trading partners are registered or in process of registering and they are now able to submit a digital file versus a paper copy thus eliminating the need for the printing, scanning and storage of paper documents. In April 2014, Health Canada received 28% of its adverse reaction reports electronically. It is expected this percentage will increase to 80% by the end of 2014.
           • Completed
2. The OAG recommended (4.36) that Health Canada should establish timelines for officially notifying clinical trial sites of non-compliant ratings and for reviewing proposed corrective measures to verify compliance with the Food and Drug Regulations
   • Theme: Timeliness
   • Health Canada's Overview of Audit Findings
     • In its review of six inspection reports with non-compliance ratings, the Auditor General noted that Health Canada took up to 142 days to notify entities of their rating. Furthermore, Health Canada took approximately 110 days to review corrective actions proposed by inspection entities.
     • Health Canada has risk-based processes in place for inspecting clinical trials and taking compliance action, including set timelines for companies to propose corrective actions. Health Canada is strengthening its Standard Operating Procedures (SOP) to include timelines for non-compliance rating notification and the review of proposed corrective actions. As a result, the Department has developed Standard Operating Procedures (SOP) that includes timelines for non-compliance rating notification and the review of proposed corrective actions.
   • Actions to address recommendations
     • Status of actions as of June 2012:
       • Health Canada is currently revising the Department's existing SOP for conducting clinical trial inspections. This revised SOP will establish timelines for key steps in the inspection process, including notification of non-compliant ratings and the review of proposed corrective measures. The revised SOP is targeted for completion by June 2012.
       • Training activities will be undertaken in July 2012 to support the consistent adherence to the SOP, in particular, to the newly established timelines for notification to clinical trial sites of non-compliant ratings and review of proposed corrective measures. Training and implementation will be completed by March 2013.
     • Status of actions as of March 2013:
       • The standard operating procedure was approved in June 2012.
         • Completed
       • Inspection staff were trained on the new SOP and it was fully implemented August 2012. All 17 Good Clinical Practices (GCP) program staff have reviewed the revised Standard Operating Procedure (SOP) through sub-committee meetings and additional training sessions and have confirmed their knowledge of the new procedures.
         • Completed
3. The OAG recommended (4.41) that Health Canada should fulfill longstanding commitments to enhance public access to information on authorized clinical trials, including the summary results of its clinical trial inspections.
   • Theme: Transparency
   • Health Canada's Overview of Audit Findings
     • The Auditor General found that, despite commitments to increase the transparency of authorized clinical trials (such as in the 2007 Blueprint for Renewal II), the amount of information that Health Canada has made available to Canadians has not changed.
     • Health Canada is taking action by implementing measures that encourage sponsors to register their clinical trials within a recommended time period. Health Canada will also, subject to feasibility publish an administrative list of clinical trials that have been authorised. It has also started publishing a summary report of Health Canada's clinical trial inspection findings on the Health Canada website annually to make this information more accessible to Canadians.
     • Health Canada is also taking action to publish more information regarding inspection reports.
   • Actions to address recommendations
     • Clinical Trial Registration
       • Status of actions as of June 2012:
         • Since 2007, Health Canada has been encouraging clinical trial registration and disclosure of information in publicly accessible registries recognised by the World Health Organization (WHO). Health Canada has recently added new text in the No Objection Letter, issued when a trial is authorized, to encourage sponsors to register their clinical trials within 21 days of the trial's onset. This will promote sponsors' voluntary registration in publicly accessible registries recognised by the World Health Organization.
           • Completed
         • Health Canada held Technical Discussions with stakeholders on regulatory modernization to explore options for including new information in product submissions to Health Canada, including a comprehensive list of all clinical trials and documentation that all clinical trials performed by the applicant or sponsor would be publicly registered in accordance with international accepted practice.
           • Completed
         • Health Canada is considering how it will publish an administrative list of clinical trials that have been authorised by Health Canada. The objective of this initiative is to publish in a timely manner high-level key information about each trial that has been authorised, providing sufficient information so that prospective clinical trial participants can make a more informed decision about participating in a clinical trial. With information about clinical trial authorisations, individuals can search other more comprehensive databases such as clinicaltrials.gov for additional details. It is expected that this project will be completed in 2 phases: 1) scoping & feasibility; 2) implementation. Phase 1 began May 2012 and is targeted to be completed by the end of September 2012. The timelines for Phase 2 will depend on the strategy chosen and the need for stakeholder consultation.
       • Status of actions as of March 2013:
         • Phase 1
           • A 2012 survey of available Clinical Trial (CT) registries showed only 50% of trials authorised by Health Canada between May 2011 and May 2012, for the study of drugs in patients, were registered in public registries. It is expected that the CT database will significantly improve the amount and timeliness of information available on CT authorised by Health Canada.
           • In December 2012, Health Canada published a notice seeking comments from stakeholders on the clinical trial information that it intends to make available through the CT database. The consultation period ended February 2013.
             • Completed
         • Phase 2
           • Currently, a searchable database is being developed that will allow patients to verify if a trial is approved in Canada and permit them to search for trials that may be relevant to their medical condition. To-date, samples of the web interface have been circulated for comment and information pieces to add the CT database website are being drafted. Expected public access to the database is on target for April 2013.
       • Status of actions as of June 2014:
         • At the end of May 2013, Health Canada launched its Clinical Trials Database. The Clinical Trials Database is providing to the public a listing of specific information relating to phase I, II and III clinical trials in patients. The database is managed by Health Canada and provides a source of information about Canadian clinical trials involving human pharmaceutical and biological drugs. Patients can access the database to determine if a clinical trial has met the regulatory requirements. The database may also assist Canadians in finding clinical trials that might be relevant to their medical condition. The Clinical Trials Database is not a registry, and therefore, it does not contain comprehensive information about each clinical trial.
           • Completed
     • Clinical Trial Inspection Reports
       • Status of actions as of June 2012:
         • Health Canada is also exploring how it will publish inspection reports of individual inspections for compliance with Good Clinical Practices and Good Manufacturing Practices. It is expected that the project will be completed in two phases: 1) scoping and feasibility; 2) implementation. The timelines will depend on the outcome of the scoping exercise.
         • In March 2012, the Department published a summary report of Health Canada's clinical trial inspections and has committed to update and publish updated reports on the Health Canada website annually. This report will: improve transparency by making public a summary of Health Canada's clinical trial inspection findings; promote greater regulatory compliance; and provide a better understanding of regulatory oversight to stakeholders and the public. The March report provides the results of clinical trial inspections conducted by Health Canada's Inspectorate Program between April 1, 2004 and March 31, 2011. The report found that 92% of the 329 inspections conducted during that time period were assigned an overall compliant rating. Further details are available in the online report.
           • Completed
       • Status of actions as of March 2013:
         • Health Canada has completed Phase 1 of exploring how to publish inspection reports of individual inspections for compliance with GCP and GMP. These will be single-page summaries of individual inspection reports. In this scoping phase, we identified challenges to be addressed in information sharing and technology. A phased in approach to implementation will therefore be used, beginning with GMP reports, and then progressing to other inspection reports.
           • Completed
         • The next annual summary report is scheduled to be published in April 2013. An annual inspection summary report for all programs including GCP is expected to be completed in April 2013. This report will: improve transparency by making public a summary of HC's clinical trial inspection findings; promote greater regulatory compliance; and provide a better understanding of regulatory oversight to stakeholders and the public.
       • Status of actions as of June 2014:
         • Annual Inspection Summary Report was published in March 2014 and is posted on the "Compliance & Enforcement" section of the Health Canada's Web site.
           • Completed
4. The OAG recommended (4.53) that Health Canada should ensure that it meets service standards for the review of all drug submission types by giving due consideration to the appropriate allocation of additional resources from increased user fees charged to industry, to the use of foreign regulatory information, and to streamlining its review processes.
   • Theme: Timeliness
   • Health Canada's Overview of Audit Findings
     • The OAG findings have identified three areas where Health Canada should meet its service standards for the review of all drug submission types. These include:
       • Cost Recovery Initiative
         • The Cost Recovery Initiative was implemented on April 1, 2011, after the period of the audit (Jan 2009-Dec 2010). As a result, benefits of increased resources were not captured in the OAG report.
         • In the first year with updated user fees, Health Canada has been meeting most performance standards and has been decreasing drug approval backlogs through the implementation of HR, IT and financial plans.
         • New resources have assisted in reducing and eliminating the backlog on new drug submissions and will continue to assist in decreasing the generic drug submissions backlog.
       • Foreign Regulatory Information
         • Health Canada has increased its focus on international collaboration, including improved sharing of best practices and greater alignment with partners.
         • This increased use of outside expertise and information from other regulators is resulting in more efficient drug reviews and authorizations.
       • Improving Processes and Systems
         • Health Canada is looking at its business processes to find further efficiencies.
   • Actions to address recommendations
     • Monthly dashboards have been integrated into Health Canada standard business processes. These reports are all being used to monitor performance against the applicable standards.
       • Completed
     • Cost Recovery Initiative
       • Status of actions as of June 2012:
         • In 2011, revenue collected for drug submission reviews allowed Health Canada to augment our human resources: scientific experts, drug inspectors and from other Branches, or government departments.
         • Cost Recovery revenues have contributed to eliminating the backlog for innovative new drug submissions, as of December 2011, and meeting 100% of annual inspection targets and post-market drug surveillance standards.
         • In addition, the pharmaceutical program continues to address the large volume of applications for generic drugs. The Department has nearly doubled its chemistry review capacity for generic drugs review in the past year in order to address this backlog.
         • Fees will be reviewed by 2014 in accordance with the commitment made to Parliament
         • Completed
       • Status of actions as of March 2013:
         • The additional resources along with process improvements enabled Health Canada to reduce the generic backlog in the following manner:
           • Brand Name drug submission reviews have been surpassing the performance target requiring 90% of review decisions to be made on time. The focus for the next two years is to maintain this high level of performance, even while the number of submissions received is forecasted to increase. To this end, the overall improvements to the review process should help sustain this high level of performance.
           • In generic drug reviews, the number of generic drug decisions made monthly has increased significantly, which has reduced the backlog by half during the last 12 months. The elimination of the generics backlog is forecasted for the Fall of 2013, assuming similar numbers of decisions and volumes received as at present.
           • With the generics backlog expected to be eliminated, this will then advance the Department's efforts to reduce the average time to review submissions. The Department's strength in the near term lies in its ability to make more decisions and more of them on time.
       • Status of actions as of June 2014:
         • The generics backlog was eliminated in Fall 2013.
           • Completed
     • Foreign Regulatory Information
       • Status of actions as of June 2012:
         • A pilot for the use of foreign reviews was initiated in October 2011.Work has been initiated for the use of foreign reviews in the generic drugs area where industry has been encouraged to submit information about the generic approvals from other jurisdictions. Often, the generic drugs sold in the different jurisdictions are slightly different, so companies are asked to provide a comparison of the differences as part of the review process.
         • The results of the pilot have been encouraging and are being reviewed to explore the expansion of the pilot to include submission reviews of other products.
         • Full evaluation of the pilot will be completed by March 2014.
       • Status of actions as of March 2013:
         • The Use of Foreign Reviews pilot on generics was expanded to include other areas and the timeframes were adjusted in order to allow for more drugs to be included in the pilot. One of the major challenges of the pilot and main impetus for changing the pilot timeframe is the lack of availability of full unredacted foreign reviews. Given the security and system capability issues that relate to any transfer of confidential information these types of issues are not uncommon.
         • To optimize the use of foreign reviews, a Standard Operating Procedure for reviewers has been developed, Guidance to Industry has been published and enhancements were made to the current tracking systems. In addition, training to reviewers and other staff was conducted.
           • Completed
         • Health Canada has also worked to develop a monthly identification process with the Australian Therapeutic Goods Administration whereby a more timely way of identifying and exchanging information about products that are in queue can be undertaken.
         • In May 2012 a study for International Collaboration in the review of Generic Drug applications was completed. The study was based on a survey of six of the world's largest multinational drug companies (Teva, Watson, Mylan, Sandoz, Apotex and Dr. Reddy's) and drug regulatory authorities from the US, EU, Switzerland, Brazil, Australia, Singapore and the World Health Organization (WHO).
         • The study concluded that a collaborative review system properly organised and administered would be welcomed by the generic industry and added that the most important prerequisite to such a program would be harmonisation of as many technical requirements as individual laws would allow. The 3-yr pilot, interim operating procedures, common statement and initial areas of collaboration, are positioned to advance a longer term vision and impact, including potential to change the international generic drug business and regulatory model.
         • The project continues to be underway and will provide the real time context for evaluating the approach and tools for the use of foreign reviews. This project shows better tracking and more consistent use of foreign reviews in the area of pharmaceuticals, biologics and veterinary drugs. In addition, foreign safety reviews have been used for Risk Management Plans (RMP) and Periodic Safety Update Reports (PSUR). Completion of the project is anticipated to be August 2013.
       • Status of action as of June 2014:
         • Standard operating procedure for reviewers has been developed. Guidance to industry has been published and enhancements were made to the current tracking systems. In addition, training to reviewers and other staff was conducted. The UFR pilot officially ended on March 31, 2013 and the evaluation report was prepared.
           • Completed
     • Improving Processes and Systems
       • Status of actions as of June 2012:
         • The pharmaceutical program continues to strive to address the large number of applications for generic drugs through continuous process improvements and pilot projects to determine potential operational efficiencies. Addressing the generic backlog is an operational priority in 2012-2013.
         • Health Canada has developed a mechanism to better obtain information from drug companies about anticipated submission volumes to allow for better forward planning.
           • Completed
         • In the past year, CRI revenues were invested in projects to improve information management and information technology capacity. Strategic investments include improvements to the Canada Vigilance system to continue strengthening Health Canada's ability to address drug safety concerns across the drug product life cycle; leveraging the US FDA Gateway to exchange drug submission information with industry in a secure electronic environment; and improving internal performance measurement systems.
       • Status of actions as of March 2013:
         • Health Canada has completed its evaluation of both internal and external methodologies to improve its performance. The Department has also made investments in its electronic processing architecture to ensure its reliability. With the finalization of the Cooperative Research and Development Agreement (CRADA) with the Food and Drug Administration, Health Canada will be implementing a single window application system for Drug submissions to both Canada and the United States.
         • To allow for better forward planning, in May 2011, Health Canada developed a mechanism to better obtain information from drug companies about anticipated submission volumes. To date, HC has been using this information to better plan its internal resources and determine when external expertise or advice is required. The information is also being used in the projection of submission volumes and related revenue.
           • Completed
         • Pharmaceutical revenue projections that were supported in part by pipeline information are currently within 5% of the forecasted amount year to date.
       • Status of actions as of June 2014:
         • For the past 2 fiscal years, (2012-13 and 2013-14) revenue received was within 5% of the revenue forecast. Continuous improvement in data collection and forecasting techniques are being applied to maintain the level of forecasting accuracy.
           • Completed
5. The OAG recommended (4.57) that Health Canada should regularly assess whether the procedures and guidelines, which were established to ensure timely, consistent and high quality review decisions, are interpreted and applied consistently by all four review bureaus.
   • Theme: Timeliness
   • Health Canada's Overview of Audit Findings
     • The audit highlighted that although the Department had in place a quality assurance system, it had not assessed whether its review bureaus interpret and apply review procedures and guidelines consistently. The audit found no evidence indicating that inconsistencies arose in the drug review process from the lack of regular assessment of employee adherence to quality documents.
       • Health Canada has good review practices, reviewer training, and regular evaluations of operating procedures in order to adapt to the changing regulatory environment and support reviewers' current knowledge on procedures.
   • Actions to address recommendations
     • Status of actions as of June 2012:
       • Health Canada has examined internal audit systems and has met with the European Medicines Agency to discuss both their review training program as well as their audit functions as it relates to standard operating procedure and guidance compliance to further align international best practices.
         • Completed
       • Health Canada is assessing whether the procedures and guidelines, that ensure timely, consistent and high quality review decisions, are being interpreted and applied consistently. Health Canada is taking two specific actions:
         • Developing a system, by December 2012, to assess and measure compliance with procedures and consistency of interpretation.
         • Implementing the system, including assessment of compliance with and consistent interpretation of procedures; and corrective actions, by December 2013.
     • Status of actions as of March 2013:
       • To date, an internal audit plan has been developed to: (a) assess compliance with the use and consistency of interpretation of the review procedures entitled: "Using the Pharmaceutical Safety and Efficacy Assessment Templates (PSEATs) to Prepare Reports on Submission for Marketing Authorizations" and (b) identify opportunities for improvements.
         • Completed
       • The goals of the audit are to increase awareness, use and consistency of use of the SOP, as well as continuous improvements to the procedure, review tools, and/or review training.
       • The audit began in April 2013 and the audit report is complete. The Management Response and Action Plan (MRAP) to be completed and improvements to be initiated by Dec 31 2013. This audit will contribute to improving the drug review approval process.
       • This audit system will contribute to improving the drug review approval process and in finding efficiencies.
         • Completed
6. The OAG recommended (4.63) that Health Canada disclose information related to new drug approvals in a timely manner and improve the transparency of "approvals with conditions", rejections, and withdrawals of new drugs so that Canadians and health care professionals can access information about these drugs.
   • Theme: Transparency
   • Health Canada's Overview of Audit Findings
     • To determine whether the Department had fulfilled its commitments for increasing the transparency of review decisions, the Auditor General examined the availability and the timeliness of the public disclosure of key documents to its website. The timelines were met for posting product monographs, but timelines were not met consistently for posting information about the reasons products had been approved.
     • Since 2005, Health Canada has disclosed information about new drug approvals (for novel therapies) which included safety, efficacy and quality (chemistry and manufacturing) considerations. However, the Auditor General found that information is not being disclosed on drugs that are rejected by the Department or on drugs that the manufacturer withdraws from the review process.
     • Transparency is a key strategic goal for the health products and food Branch. The Branch's Transparency and Openness Agenda focuses on making relevant, timely and useful information available to the public. Part of the commitments under this agenda includes increasing the amount of information publicly available on approved drugs for Canadians and health care professionals to make informed choices.
   • Actions to address recommendations
     • Status of actions as of June 2012:
       • The Department is improving transparency in the process of drug reviews. Public consultations were completed in December, 2011 on the Summary Basis of Decision (SBD) project, which aims to expand public access to information about marketed drugs. The final report of the SBD project was posted in May 2012. SBD made public positive decisions about new drugs.
       • Phase II of the SBD is being launched in June 2012 with the publication of a Notice to advise stakeholders that as of September 1, 2012, the SBD will be expanded to include a broader range of both positive and negative decisions.
     • Status of actions as of March 2013:
       • In June 2012, Health Canada launched Phase II of the SBD project. Phase II increases the transparency of the drug and medical device review process and provides Canadians with improved access to information about approved products. Phase II became effective with the publication of a Notice, Frequently Asked Questions document and Phase II Reader's Guides for Drugs and Medical Devices on Health Canada's website.
       • Since Sept 2012, four SBDs have been completed and posted under the Phase II of the SBD project and four more are under development.
       • A Post Authorization Activity Table (PAAT) is currently being developed as well as the PAT SOP. The PAAT is a Post Authorization Activity Table that is a component of Phase II of the SBD project. The table will accompany SBDs for New Active Substances (NAS) that received their Notice of Compliance (NOC) post Sept. 1, 2012. This table will provide summaries of submissions or applications for new uses of the product, and whether the decision was positive or negative. Completion is anticipated by April 2013.
     • Status of actions as of June 2014:
       • In FY 2013-14, a total of 43 SBDs were completed and posted under Phase II of the SBD initiative. Thirty-one of these SBDs were for pharmaceutical drugs, eleven were for biologics, and one SBD was for a Class IV medical device.
       • In addition, there were four medical device breast implant SBDs completed and posted in FY 2013-14, based on the manufacturers' annual updates that are ongoing part of Phase I.
       • As part of Phase II of the SBD initiative, Health Canada is now publishing Post-Authorization Activity Tables (PAAT, for drugs) or Post-Licensing Activity Tables (PLAT, for devices). The first such table was posted in April 2013, and in FY 2013/14, 45 PAAT updates were prepared and posted.
         • Completed
7. The OAG recommended (4.70) that Health Canada assess the risks posed by conflicts of interest to the drug review process, determine what measures are necessary to manage these risks and implement those measures.
   • Theme: Transparency
   • Health Canada's Overview of Audit Findings
     • The Auditor General found that while the Health Products and Food Branch's Conflict of Interest guidelines and Code of Conduct comply with government policy, the Department could benefit from developing risk-mitigation measures to address potential conflict of interest risks specific to the drug review process.
     • The Auditor General did not find any cases of Conflict of Interest (COI) at Health Canada during its review.
   • Actions to address recommendations
     • Status of actions as of June 2012:
       • In November of 2011, Health Products and Food Branch employees were asked to complete a new COI Declaration requirement to actively confirm that they have reviewed their conflict of interest obligations and have taken the necessary steps to address them, including by filing a Confidential Report to the department, if required. To date, 99% of active drug reviewers in the Branch have submitted their declarations, and the Branch is striving for 100%.
         • Completed
       • A new Health Canada Values and Ethics Code came into force on April 2, which includes Health Canada policy on COI and is in-line with the new TBS Code and COI policy.
         • Completed
       • In parallel, Health Canada commissioned an assessment of the risks of conflict of interest including the drug review process by a third-party advisor. Although no unreported or emerging COI was found, the report recommended areas for management action to mitigate COI risks.
       • Health Canada is in the process of building COI measures that respond to the recommendations and ensure continued COI compliance in HPFB to maintain the integrity of the drug regulatory process. Planned activities to reinforce the code include: distribution of hard copies of the Code to employees, communications to all staff, pop up to confirm compliance with values and ethics, and values and ethics training.
     • Status of actions as of March 2013:
       • As a result of the report and recommendations, HPFB:
         • Formalized a COI policy to require its employees, including drug reviewers, to annually declare they have met their COI obligations during the Performance Discussion Process (PDP). Guidance was issued to managers to discuss COI with their employees during their PDPs.
         • Launched a COI intranet site with links to relevant COI resources, including HPFB case specific examples, and COI training for employees and managers to improve COI awareness.
         • Completed
       • As a further assessment, HPFB will hire a consultant to perform a follow up assessment in FY 2013-14 to determine whether mitigation measures are achieving expected results. The third party consultant will conduct an evaluation of COI measures already implemented.
     • Status of actions as of June 2014
       • A third party consultant conducted the evaluation and presented a final report. The Branch has its assessed the measures it has put in place to maintain the integrity of the drug regulatory process and it will continue to monitor and update its processes as required.
         • Completed
8. The OAG recommended (4.96) that Health Canada should improve the timeliness of safety assessments and the implementation of related recommendations to update labels and to issue risk communications thereby ensuring that Canadians and health care professionals are informed of new drug information in a timely fashion.
   • Theme: Safety
   • Health Canada's Overview of Audit Findings
     • The Auditor General Report did not question the quality of safety assessments conducted in Canada, but made recommendations towards strengthening the systems that Health Canada already has in place for monitoring drug safety.
     • The report included two case studies as examples of where the management of safety assessment recommendations could have been improved.
     • Health Canada has established new performance measurement standards for safety assessments and a notification system that would make new drug information accessible to Canadians in a timely manner.
   • Actions to address recommendations
     • Status of actions as of June 2012:
       • In October, 2011, Health Canada implemented performance standards for several Post-Market Surveillance Activities including Signal Assessments, Risk Management Plan Reviews, and Periodic Safety Update Report Reviews for Pharmaceuticals. The new standards will help to identify and provide Canadians with new safety information in a timelier manner. In 2011-2012, 91% of post market surveillance activities have been completed on time.
         • Completed
       • Health Canada is currently assessing options to implement a stakeholder notification system to inform generic drug manufacturers of new drug labelling information in a timely manner.
       • The implementation of the new notification system is expected to be completed by the end of the third quarter in 2012.
     • Status of actions as of March 2013:
       • The implementation of the Safety Labelling Stakeholder Notification System was delayed by 2 months in order to accommodate feedback that was received from Industry regarding the functionality of the system. The Department launched the Safety Labelling Stakeholder Notification System on the Departmental website on February 21, 2013. Information is posted monthly to reflect updated and/or new safety information regarding brand name pharmaceutical drug products.
         • Completed
     • Status of actions as of June 2014:
       • Overall, in Fiscal Year 2013/2014, 90% (349/389) of the Pharmaceutical Post Market Surveillance Activities were completed within target.
       • In 2014, the Department also began publishing plain language summaries of post-market drug safety reviews to provide Canadians and healthcare professionals with greater access to drug safety information and to provide context on the Health Canada decision-making process.
       • Health Canada is also finding improvements to the process of communicating risks.
         • Completed
9. The OAG recommended (4.97) that Health Canada establish a systematic process to implement safety assessment recommendations for marketed drugs, to ensure that the recommendations are handled appropriately and in a timely manner.
   • Theme: Safety
   • Health Canada's Overview of Audit Findings
     • The Auditor General Report did not assess the safety or effectiveness of drugs authorized by Health Canada. However, it did identify ways that Health Canada could strengthen and improve internal processes that were already in place.
     • Health Canada is establishing a systematic process to ensure that safety assessment recommendations for marketed drugs are handled in a more timely and appropriate manner.
   • Actions to address recommendations
     • Status of actions as of June 2012:
       • Since December 2010, new coordinator positions to track and follow up on MHPD safety assessment recommendations were created (staffing completed for 3 of 3 TPD review bureaus).
         • Completed
       • A tracking tool for innovator pharmaceuticals was developed and first used in July 2011 by one pre-market review bureau. The tool is now in use by MHPD and the 3 pre-market review Bureaus.
         • Tracking tool implemented
       • A tracking tool for safety recommendations for all pharmaceuticals is being finalised. The projected date to begin implementing this tool for all pharmaceuticals, including generic products is March 2013.
     • Status of actions as of March 2013:
       • Operating procedures have been implemented and are expected to help to ensure timely label updates to brand name pharmaceutical products so that Canadians and health care professionals are informed of new drug safety information in a timely manner. The new procedures were expanded and implemented covering all pharmaceuticals including generics by March 19, 2013.
         • Completed
10. It was recommended (4.109) by the OAG that Health Canada should consistently apply its risk-based standard operating procedures, so the priority of the drug complaints it receives is properly addressed and documented in a timely manner.
    • Theme: Timeliness
    • Health Canada's Overview of Audit Findings
      • The audit concluded that although Health Canada had risk-based standard operating procedures for prioritizing cases of non-compliance, it could not demonstrate that these procedures were consistently applied.
    • Actions to address recommendations
      • Status of actions as of June 2012:
        • Health Canada is improving on its risk-based standard operating procedures, so that high priority drug complaints received are addressed and documented in a timely manner. Specifically;
          • Procedures relating to handling drug incidents have been updated.
            • Completed
          • Staff will be trained on the revised procedures by December 2012.
        • The Department will review incident files by March 2013 to ensure that decisions and prioritization have been documented in accordance with the procedures. This will allow for consistency in the prioritization of drug complaints.
      • Status of actions as of March 2013:
        • Since operating procedures were updated in March 2012, each regional office involved in compliance verification work has documented that they have reviewed the updated SOPs as their training. Health Canada also held several webinar sessions for staff in September 2012 regarding certain elements of the SOPs as well as a three day training session in November 2012 to a number of inspectors where the relevant SOPs were reviewed.
          • Completed
        • The final deliverable of reviewing incident files has been completed by the end of March 2013.
          • Completed