PACP Committee Report

Theme

Audit Recommendations

Health Canada’s Overview of Audit Findings

Actions to address recommendations

Current Status

Safety

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.

•     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.

•     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.

•    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.

•    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.

Completed July 2011

Completed December 2011

Gateway Pilot to be completed Summer, 2012

Timeliness

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.

•    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.

•    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.

On target (June 2012)

On target (July  2012 and next fiscal year)

Transparency

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.

•    The Auditor General found that, despite commitments to increase the transparency of authorized clinical trials (such as in the 2007Blueprint 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 HC’s clinical trial inspection findings on the HC website annually to make this information more accessible to Canadians.

•    Health Canada is also taking action to publish more information regarding inspection reports.

•    Since 2007, Health Canada has been encouraging clinical trial registration and disclosure of information in publicly accessible registries recognised by the World Health Organisation (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 Organisation.

•    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.

•    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.

•    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.

•    In March 2012, the Department published a summary report of HC’s clinical trial inspections and has committed to update and publish updated reports on the HC website annually.  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.  The March report provides the results of clinical trial inspections conducted by HC’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 found at:http://www.bing.com/search?q=health+canada+summary+report+of+inspections&src=IE-SearchBox&Form=IE8SRC

Completed November 2011

Initiated May 2012 (scoping & feasibility to be completed by September 2012. Implementation timeline dependant on option chosen (i.e. need for consultation)

Targeted for December 2012

Completed 2010/2011

Completed March 2012

Timeliness

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.

The OAG findings have identified three areas where Health Canada should meet its service standards for all 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.

•    Since June 2011, Health Canada has been closely monitoring its ability to meet performance standards, through monthly dashboards, as well as quarterly and annual reports.

Cost Recovery Initiative

•    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.

Foreign Regulatory Information

•    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.

Improving Processes and Systems

•    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.

•    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.

On target

Completed

Pilot was initiated in October 2011

Generics Pilot to be assessed in Fall 2012

In progress

Evaluation will be completed by March 2014.

Completed May 2011

On target

Timeliness

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.

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.

•    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.

•    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.

Completed March 2012

On target (December 2012 and 2013)

Transparency

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.

•    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.

•    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.

Consultation completed (December 2011) Final report completed May 2012

Launch on target for June 2012

Transparency

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.

•    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.

•    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%.

•    A new HC 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.

•    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.

Completed November 2011

Completed April 2012

On target

(Report completed April 2012)

Fall 2012

Safety

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.

•    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 is assessing options for a notification system that would make new drug information accessible to Canadians in a timely manner.

•    In October, 2011, MHPD 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.

•    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. 

Completed October 2011

On target for September 2012

Safety

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.

•    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.

•   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).

•   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.

•   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.

Completed 2011-2012

Tracking tool  implemented July 2011

On track to be completed March 2013

Timeliness

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.

•    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.

•    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.

•    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.

Completed March 2012)

On target (December 2012)

On target     (March 2013)