Email Website LinkedIn Twitter

Safety Observer Issue N°120 - February 2016

1

Clinical Safety & Pharmacovigilance Regulatory Intelligence Review

Issue N°120 - February 2016

HIGHLIGHTS

The EMA has now implemented the new process for notification of the EU QPPV contact details and the location of the PSMF through the Article 57 database. Since 01-Feb-2016, companies are no longer required to submit type IA variations to update this information.

The EMA has announced that it will soon hold a workshop to discuss the implementation of the international ICSR standard across Europe (ISO / ICH E2B(R3)), which implementation is foreseen in the third quarter of 2017.

The EU PSUR Repository will now enter the “switch-on” phase, which is a major milestone before this tool becomes mandatory from 13-Jun-2016. The switch-on phase creates a simulated mandatory use of the system for all authorities and MAHs are strongly encouraged to submit their information to the PSUR repository.

The U.S. Government Accountability Office (GAO) has released a new report showing that FDA expedites many applications but operates insufficient postapproval oversight due to the lack of reliable, readily accessible data on tracked safety issues and postmarket studies.

The Portuguese drugmaker Bial has suspended a phase 1 clinical trial following the death of one volunteer and the hospitalisation of five others in France. Regulatory Agencies are conferring to better understand the issue and the impact it may have on other trials with FAAH inhibitors around the world.

Safety Observer Issue N°120 - February 2016

2

IN THIS ISSUE

1. Regulations, Guidelines and Other Standards ...................................................................................................... 3

1.1 Newly Applicable Standards .............................................................................................................................. 3 1.1.1 EMA issues updated EURD list ....................................................................................................................... 3 1.1.2 EMA implements new process for notification of PSMF & EU QPPV details ................................................. 3 1.1.3 EMA provides updated guidance on submission of medicines information ................................................ 3 1.1.4 France updates procedure for the annual status of Pharmaceutical sites .................................................. 4 1.1.5 EMA launches new Service Desk portal ......................................................................................................... 4 1.1.6 EMA issues revised ICH E14 Questions & Answers document ....................................................................... 4

1.2 Developments to Watch ..................................................................................................................................... 4 1.2.1 EMA invites workshop on the implementation of E2B(R3) ........................................................................... 4 1.2.2 EMA issues comments to revised EudraVigilance Access Policy .................................................................. 5 1.2.3 EU PSUR Repository to enter “switch-on” phase .......................................................................................... 5 1.2.4 EMA initiates EU consultation on ICH E18 ..................................................................................................... 5

1.3 Beyond the Scope of Safety Observer ............................................................................................................... 5 1.4 The Safety Observer Tracker ............................................................................................................................. 6

2. Product Safety Announcements ............................................................................................................................ 6

3. Dear Doctor Letters and Safety Newsletters ......................................................................................................... 6

4. Other Publications by Regulatory Agencies .......................................................................................................... 8

4.1 US Food and Drug Administration (FDA) ........................................................................................................... 8 4.2 European Medicines Agency (EMA) .................................................................................................................... 8 4.3 UK Agency (MHRA) ........................................................................................................................................... 11 4.4 French Agency (ANSM) ..................................................................................................................................... 11

5. Quality Assurance, Inspections and Audits ......................................................................................................... 11

6. Drug Safety and Liability Risk .............................................................................................................................. 12

7. Other News and Resources .................................................................................................................................. 12

8. Conferences and Training Events ........................................................................................................................ 13

Safety Observer Issue N°120 - February 2016

3

1. REGULATIONS, GUIDELINES AND OTHER STANDARDS

1.1 Newly Applicable Standards

1.1.1 EMA issues updated EURD list (13-Jan-2016) The EMA has published an updated EURD list, which provides the EU Reference Dates, frequencies for submission of PSURs and related data lock points for a list of active substances and combinations.

As communicated earlier, the EMA has started the single assessment of active substances contained exclusively in nationally authorised medicines, which are also included in the EURD list.

The changes to the EURD list are highlighted and concern only levofloxacin. Please note that as specified in the cover note, the “Publication Date” is not revised for all types of amendments and this column cannot be used to filter all amended substances in Excel.

→ Link to EMA Guidance Page (EURD list and PSUR Submission)

1.1.2 EMA implements new process for notification of PSMF & EU QPPV details (20-Jan-2015) As reported in our previous issue, the EMA announced on 18-Dec-2015 that the Article 57 database can be relied upon to provide the contact details of the EU QPPV and the location of the PSMF. Since 01-Feb-2016, companies are no longer required to submit type IA variations to update this information, which applies to both centrally and nationally authorised medicines, thus bringing significant simplification to the process for the notification of these changes for both companies and regulators.

Following the earlier announcement, both the EMA and the European Commission have issued new information to inform stakeholders about the implementation of this new process, including revisions to both the pre- and post-authorisation procedural advice for users of the centralised procedure.

→ Link to EMA News Release (18-Dec-2015) → Link to EMA Page on Data Reporting requirements for MAHs → Link to European Commission Statement → Link to EMA pre-submission guidance → Link to EMA post-authorisation guidance

1.1.3 EMA provides updated guidance on submission of medicines information (20-Jan-2015) The EMA has issued updated material related to the electronic submission of information on authorised medicines, as required under Article 57(2) of the 2010 pharmacovigilance legislation. Most of the revisions relate to the new process whereby the database should be used to notify changes to the contact details of the EU QPPV and the location of the PSMF.

The revised guidance includes the Legal notice on the implementation of Article 57(2), the Q&As on electronic submission of Article 57(2) data, the Detailed Guidance (Chapter 3.II: XEVPRM user guidance), and documents related to the data Quality Control methodology.

→ Link to EMA Data Submission Guidance Page → Direct Link to Legal notice on the implementation of Article 57(2) → Direct Link to EMA Q&As on electronic submission of Article 57(2) data

Safety Observer Issue N°120 - February 2016

4

1.1.4 France updates procedure for the annual status of Pharmaceutical sites (29-Jan-2016) The French regulations require all companies to submit an Annual Status Update (Site Master File) which collects a wide range of information including on Pharmacovigilance personnel and training. This status is used by inspectors to prepare inspection and since last year it should be submitted electronically using a web portal. The deadline for submission is 31-Mar-2016.

→ Link to the ANSM dedicated webpage (in French) → Direct Link to the ANSM guidance and procedure (in French) → Link to the annual status document (in French) → Link to the annual status document (French/English version)

1.1.5 EMA launches new Service Desk portal (01-Feb-2016) On 01-Feb-2016, the EMA launched an online EMA Service Desk portal, which is supported by the latest stable version of the main web browsers. The portal should be used to report an issue, request a service or ask a question about EMA systems in replacement of previously existing functional mailboxes.

In the transition period, any request submitted by email to the functional mailboxes will be transferred directly to the EMA Service Desk portal until 01-Mar-2016 when the mailboxes will be decommissioned.

The portal is intended to increase effectiveness and transparency throughout EMA’s IT Service Management processes and improve service quality. The portal offers a user-friendly environment with self-explanatory steps and allows to track the status of requests.

→ Link to EMA Service Desk Portal User Guide

1.1.6 EMA issues revised ICH E14 Questions & Answers document (01-Feb-2016) Following its publication by ICH in December 2015, the EMA has now released the revision of E14 Questions-and-Answers document on the Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs. In this document, the E14 Q&A on Concentration-Response Modelling (# 5.1) was revised to generate harmonised guidance on how concentration response modelling could be used for regulatory decision making.

→ Link to ICH E14 Q&As (R3)

1.2 Developments to Watch

1.2.1 EMA invites workshop on the implementation of E2B(R3) (13-Jan-2016) The EMA has announced that it will hold a workshop on 04-Mar-2016 to discuss with various stakeholders the implementation of the international ICSR standard across Europe (ISO / ICH E2B(R3)). The corresponding call for expressions of interest however closed on 01-Feb-2016.

As a reminder, the EMA published the final EU ICSR Implementation Guide on 21-Jan-2015 and the EudraVigilance Stakeholder Change Management Plan foresees the implementation of the new standard in the third quarter of 2017.

→ Link to EudraVigilance Page → Link to EMA Workshop Page

Safety Observer Issue N°120 - February 2016

5

1.2.2 EMA issues comments to revised EudraVigilance Access Policy (13-Jan-2016) As announced in our previous issue, the EMA issued a revised version of the EudraVigilance Access policy on 18-Dec-2015, which will provide increased access to ADR reports. The revised policy brings a series of changes, including access to more information for the public and academic researchers. MAHs will also be granted enhanced access in support of their signal detection and other pharmacovigilance legal obligations.

These changes will come into effect in the third quarter of 2017 in parallel with EMA implementing a series of technical improvements to the EudraVigilance system. The EMA has now published the overview of the comments received on the draft policy during the consultation closed on 15-Sep-2014.

→ Link to EMA Press Release (18-Dec-2015) → Link to EudraVigilance Page → Direct link to Overview of Comments

1.2.3 EU PSUR Repository to enter “switch-on” phase (18-Jan-2016) The European PSUR Repository was deployed in January 2015 to provide a secure electronic submission point and common storage place for PSURs, PSUR Assessment Reports, comments and final outcomes for both the PSUR Single Assessment Procedure and the pure National procedures. The use of the PSUR Repository is recommended and it will become mandatory from 13-Jun-2016.

Version 01.05 of the Repository is now available, which delivers all post-audit functionalities in line with the plan approved by the EMA Management Board in June 2015.

Most importantly, all ongoing procedures will “switch-on” on 11-Feb-2016 including procedures that were not previously in the pilot. As a result, the circulation of assessment reports and comments via email will stop and the PSUR Repository enhanced notification system will take over to alert NCAs.

All MAHs are strongly encouraged to submit PSURs and supplementary information for nationally authorised medicines to the PSUR repository in addition to the submissions to the relevant NCAs, knowing that submission to the PSUR Repository is already mandatory for centrally authorised medicines.

→ Link to PSUR Repository Page

1.2.4 EMA initiates EU consultation on ICH E18 (01-Feb-2016) Following its publication by ICH in December 2015, the EMA has now launched the EU Consultation on the ICH E18 Guideline on Genomic Sampling and Management of Genomic Data. This new guideline provides guidance on genomic sample collection to evaluate efficacy and safety of a drug for regulatory approval.

Comments are expected by 31-May-2016.

→ Link to EMA Page

1.3 Beyond the Scope of Safety Observer This section includes announcements collected through our secondary sources, which originate from authorities that we do not monitor systematically. For more information, please check our Q&As.

1.3.1 Japan issues English version of Q&A on Early Post-marketing Vigilance (08-Jan-2016) The Japanese PMDA Agency has published an English version of its Q&A on Early Post-marketing Phase Vigilance for Prescription Drugs, which was originally published in 2006.

→ Link to PMDA Regulatory Information Page

Safety Observer Issue N°120 - February 2016

6

1.4 The Safety Observer Tracker This section includes a cumulative list of the future implementation and consultation deadlines. For your convenience, a link is provided and we also specify the issue where the corresponding article can be found.

By When? What? Issue

16-Feb-2016 FDA Consultation on draft guidance on Safety Assessment for IND Safety Reporting (Link)

119

29-Feb-2016 EMA Consultation on draft revisions of GVP Module XV on Safety Communication (Link)

119

29-Feb-2016 EMA Consultation on new Biologicals-specific GVP guidance (Link) 119

01-Mar-2016 Implementation of 27th SOC in MedDRA (Link) 112

01-Apr-2016 EMA guideline on use of Pharmacogenomics in Pharmacovigilance comes into effect (Link)

118

31-May-2016 EMA Consultation on ICH E18 on genomic sampling and management of genomic data (Link)

120

13-Jun-2016 European PSUR Repository will become mandatory to use (Link) 114

01-Jul-2016 Start of the transition phase for the implementation of international standards for the identification of medicinal products (IDMP) in Europe (Link)

118

Jul-2017 Implementation of the new EudraVigilance system in Europe (includes centralised reporting, E2B(R3), MAH obligation to monitor EudraVigilance for safety signals) (Link)

117

Oct-2018 Planned date for implementation of Clinical Trials Regulation (EU) No 536/2014 (Link)

119

2. PRODUCT SAFETY ANNOUNCEMENTS

No relevant announcement was identified in the period covered by this issue.

3. DEAR DOCTOR LETTERS AND SAFETY NEWSLETTERS

3.1 ANSM Dear Doctor Letters Dear Doctor Letters sent in January 2016 are now available on the French Agency's website (all in French). Letters associated to safety concerns include the following:

• Risperidone (Risperdal): reminder on the approved indications and the conditions of use in children • Fingolimod (Gilenya): risks associated with effects on the immune system • Erlotinib (Tarceva): new restrictions of indications

→ Link to ANSM Page

Safety Observer Issue N°120 - February 2016

7

3.2 MHRA Dear Doctor Letters The letters sent to Healthcare Professionals are routinely posted on the Agency’s website. The letters sent by the MHRA are presented in the subsequent issue of the MHRA “Drug Safety Update” bulletin. Only one letter was issued in December 2015:

• Galantamine hydrobromide (Reminyl): risk of serious skin reactions

→ Link to MHRA Page

3.3 New issue of MHRA “Drug Safety Update” The January issue of Drug Safety Update was published on 21-Jan-2016. It includes the following topics:

• Nicorandil (Ikorel): now second line treatment for angina – risk of ulcer complications • Levonorgestrel-releasing intrauterine systems: to be prescribed by brand name

→ Link to Drug Safety Update (January)

3.4 New issue of Australian “Medicine Safety Update” The Australian Therapeutic Goods Administration (TGA) has issued the new edition of Medicines Safety Update (Volume 7, Number 1, February 2016). The contents include:

• Mycophenolate mofetil – new contraindications relating to pregnancy and breastfeeding • Varenicline – risks of psychiatric symptoms and potential interaction with alcohol • Baclofen active pharmaceutical ingredient potential contamination

→ Link to Medicines Safety Update

3.5 New issues of Canadian “Health Product InfoWatch” The new issue of “Health Product InfoWatch” has been published, which provides an overview of health product advisories and safety reviews published in the previous month by Health Canada. The January issue was published on 28-Jan-2016. The monthly recap covers several medicinal products including Codeine-containing prescription products indicated for cough, Finasteride and Gardasil.

→ Link to Newsletter

3.6 New Issue of the French Bulletin "Vigilances" The new French "Vigilances" Bulletin, number 68, has now been issued. It includes a summary of recent pharmacovigilance news. As usual it also includes statistics on ADR notifications received during the third quarter of 2015, which show similar figures to the previous period.

→ Link to the Bulletin (in French)

3.7 New FDA Drug Safety Podcasts The FDA Drug Safety Podcasts provide emerging safety information about drugs in conjunction with the release of Public Health Advisories and other drug safety issues. Both Podcasts and Transcripts are posted on the FDA website and the following communications have been recently added:

• FDA cautions about dosing errors when switching between different oral formulations of antifungal Noxafil (posaconazole); label changes approved

→ Link to FDA Page

Safety Observer Issue N°120 - February 2016

8

4. OTHER PUBLICATIONS BY REGULATORY AGENCIES

4.1 US Food and Drug Administration (FDA)

4.1.1 New GAO report highlights shortcomings in FDA’s oversight of postmarket drug safety The U.S. Government Accountability Office (GAO) has released a new report showing that FDA expedites many applications, mostly through the fast track designation scheme, but available data provides insufficient postapproval oversight. This relates to the lack of reliable, readily accessible data on tracked safety issues and postmarket studies and a review of CDER database revealed problems with the completeness, timeliness, and accuracy of this data. These problems have prevented FDA from publishing statutorily required reports in time and have restricted the agency's ability to perform systematic oversight of postmarket drug safety.

→ Link to GAO Report Page → Link to The New York Times article

4.1.2 FDA 8th Annual Sentinel Initiative Public Workshop – Webcast available The Eighth Annual Sentinel Initiative Public Workshop took place on 03-Feb-2016 in Washington, DC and the webcast is now available. Presentations included an update on the state of FDA’s Sentinel Initiative, overview of the transition from the Mini-Sentinel pilot to the full Sentinel System, and description of key activities and uses of the Sentinel System in 2015. In addition, panelists discussed the future of the Sentinel System and opportunities to expand its capabilities.

→ Link to Sentinel Workshop Page

4.1.3 FDA to hold new conference on Liver Injury The FDA has announced that a public conference entitled “How Should Liver Injury and Dysfunction Caused by Drugs Be Measured, Evaluated, and Acted Upon in Clinical Trials?” will be held in East Hyattsville, MD on 23 and 24-Mar-2016.

This conference will be cosponsored with the Critical Path Institute (C-Path) to explore how best to measure, evaluate, and act upon liver injury and dysfunction caused by drugs used during clinical trials.

→ Link to Federal Register Notice

4.2 European Medicines Agency (EMA)

4.2.1 EMA issues material from workshop on the use of PK and PD measurements for DOACs As announced previously, the EMA held a workshop to discuss the utility of pharmacokinetic (PK) and pharmacodynamic (PD) measurements in the clinical use of the new direct oral anticoagulants (DOACs) and whether those could enhance the benefit-risk profile of these medicines by further reducing the risk of major bleedings while maintaining or improving the protection against thromboembolic events.

This workshop took place on 23-Nov-2015 and the objectives were to improve the understanding of the clinical use of DOACs, issues in relation to PK and PD measurements as well as priorities in future research.

In addition to the background document published earlier, the proceedings and the presentations from this workshop have now been made available.

→ Link to EMA Event Page

Safety Observer Issue N°120 - February 2016

9

4.2.2 EMA issues new Pharmacovigilance Risk Assessment Committee (PRAC) material The EMA routinely makes available the agendas, minutes and highlights of the Pharmacovigilance Risk Assessment Committee (PRAC).

→ Link to EMA PRAC Page

The minutes of the November PRAC meeting have now been published. The PRAC completed a review of HPV vaccines and concluded that available evidence does not support an association with CRPS or POTS syndromes. The following new Safety Signals were discussed:

• Axitinib – nephrotic syndrome • Bevacizumab – generalised tonic-clonic seizures • Human normal immunoglobulin – posterior reversible encephalopathy syndrome (PRES) • Mercaptopurine – lymphoproliferative disorders • Somatropin – hypersensitivity reactions • Tigecycline – hypofibrinogenaemia • Methotrexate – congenital cardiovascular anomaly • Selective serotonin reuptake inhibitors (SSRIs) – malformative risks in newborn and of risk of autism

→ Direct link to PRAC Meeting Minutes (03 to 06-Nov-2015)

The minutes of the December PRAC meeting have also just been published. The PRAC discussed two ongoing referrals but it did not initiate or conclude any safety referral at this meeting. The following new Safety Signals were discussed:

• Adalimumab – glomerulonephritis (GN) • Dabigatran – pulmonary alveolar haemorrhage • Flucloxacillin / paracetamol – metabolic acidosis • Infliximab – thyroid gland disorders • Olanzapine – drug reaction with eosinophilia and systemic symptoms (DRESS) • Vismodegib – angioedema

→ Direct link to PRAC Meeting Minutes (30-Nov to 03-Dec-2015)

The agenda and highlights of the January PRAC meeting have been published. As communicated separately, the PRAC adopted a strategy on measuring the impact of pharmacovigilance activities. The PRAC discussed two ongoing referrals but it did not initiate or conclude any safety referral at this meeting. According to the agenda, the following new Safety Signals have been identified and discussed:

• Cisplatin – peripheral arterial thromboembolic events (ATEs) and arterial occlusion • Cytarabine – benign intracranial hypertension • Dapagliflozin – pancreatitis • Gefitinib – pneumatosis intestinalis • Levetiracetam – potential medication errors due to a new presentation of syringes • Loratadine – QT prolongation and Torsade de Pointe • Natalizumab – necrotising retinitis • Quinine – increased mortality risk in heart failure patients with/without concomitant use of beta-blockers • Warfarin – calciphylaxis

→ Direct link to PRAC Meeting Highlights (11 to 14-Jan-2016)

4.2.3 EMA updates the list of Black Triangle Products As described in GVP Module X, the EMA is publishing the list of medicines under additional monitoring, which must be identified by a Black Triangle (▼) throughout Europe. The list specifies the reason for a product to be subject to additional monitoring and 8 new products have been added to the list in January 2016.

→ Link to EMA Page: Pharmacovigilance / List of Black Triangle Products

Safety Observer Issue N°120 - February 2016

10

4.2.4 EMA issues new CHMP Meeting Material The highlights of the January meeting of the CHMP have been published.

The CHMP has started a review of all metformin-containing medicines, which is used for treating type 2 diabetes. This review was requested by the Dutch medicines agency due to concerns regarding the consistency of the advice for patients with reduced kidney function.

The “Meeting Highlights” are presented in a tabular format, which allows users to view the main opinions adopted at the meeting, including on safety variations/PSURs.

→ Link to CHMP Meeting Highlights (25 to 28-Jan-2016)

4.2.5 EMA 9th stakeholder forum on new Pharmacovigilance legislation – Video available As reported earlier, the EMA hosted the ninth stakeholder forum on the implementation of the new Pharmacovigilance legislation on 15-Sep-2015. The objectives of this meeting were to review the current status of implementation and discuss areas of improvements and priorities for the future with a panel of stakeholders, including the industry but also patients and healthcare professionals.

In addition to the agenda and presentations made available earlier, video recordings of the meeting sessions are now available on the EMA website (go to “Multimedia” Tab).

→ Link to EMA Meeting Page

4.2.6 EMA issues new information on outcome of PSUR assessment for NAPs Following the implementation of the single assessments of PSURs for active substances contained only in Nationally Authorised Products (NAPs), the EMA is routinely publishing the results of these procedures, which may lead to a variation of the marketing authorisations. In such case, the information published includes the scientific conclusions, a timetable for implementation, and the wording of the product information.

Pharmaceutical companies are advised to regularly monitor this information to check for outcomes relevant to their products in order to submit the corresponding variations.

The outcomes of new PSUR single assessments have been published since our previous issue and variations are required for the following substances:

• Spironolactone • Trandolapril/verapamil • Tenoxicam • Argatroban • Ofloxacin • Influenza vaccine (surface antigen, inactivated)

→ Link to PSUR Single Assessments Outcomes Page

4.2.7 EMA adopts strategy to measure the impact of pharmacovigilance activities The EMA has announced that the PRAC committee has adopted a strategy for measuring the impact of pharmacovigilance activities, which should allow to determine which activities are most successful, improve pharmacovigilance practices where necessary and promote best practice.

The strategy builds on existing activities in the Member States and EMA, and relies on a collaborative approach with stakeholders, focusing on four key areas:

• Measure the effectiveness of risk-minimisation measures on specific products • Measure the effect of specific pharmacovigilance processes • Investigate stakeholders’ engagement for successful implementation • Improve methodologies to assess how pharmacovigilance activities are translated into health outcomes

The document includes an Annex that provides an overview of associated activities and deliverables.

→ Link to EMA Page on Safety Monitoring → Link to PRAC Strategy Document

Safety Observer Issue N°120 - February 2016

11

4.3 UK Agency (MHRA) No relevant announcement was identified in the period covered by this issue.

4.4 French Agency (ANSM)

4.4.1 ANSM provides update on PRAC/CHMP/CMDh meetings Following the PRAC meeting of January 2016, ANSM has issued again a document on the ongoing evaluation of the risks of PML associated with natalizumab. ANSM recommends to strictly follow the SmPC and to monitor symptoms of PML.

→ Link to the ANSM release of January 2016 (in French)

Following the CMDh meeting of December 2015, ANSM has issued a document to summarise the decisions made. No specific French position or recommendation has been issued.

→ Link to the ANSM release of December 2015 (in French)

4.4.2 Commissions / Committees in relation with Pharmacovigilance The pharmacovigilance committee issued the minutes of the meeting of 20-Oct-2015, where the following topics were discussed:

• Varenicline: results of the national monitoring, national monitoring to be stopped • Pylera (bismuth, metronidazole, tetracycline): results of the national monitoring, national monitoring to

be continued and focused on serious side effects

→ Link to the Minutes of the Committee – 20-Oct-2015 (in French)

4.4.3 ANSM issues a new version of the thesaurus of Drug Interactions ANSM has issued the new version of the Thesaurus of Drug Interactions (previous version issued in July 2015). It includes the Thesaurus itself, the substance index and a document that describes the changes from the previous version.

→ Link to the ANSM webpage (in French)

4.4.4 ANSM issues its work program for 2016 In its work program on pharmacovigilance, ANSM plans to reinforce drug monitoring with new pharmaco-epidemiological studies, the inclusion of 12 substances in the Benefit Risk review process and the continuation of drug safe use monitoring.

→ Link to the ANSM work program for 2016 (in French)

5. QUALITY ASSURANCE, INSPECTIONS AND AUDITS

5.1 MHRA GPvP inspectorate issues blog update The latest MHRA blog update reports on the recent MHRA GPvP inspectorate activities to promote compliance and best practice. This relates to two events taking place in November 2015: The GPvP Symposium and the EU Pharmacovigilance Inspector Training session, which was also attended by Inspectors from outside the EU.

→ Link to MHRA Blog Release

Safety Observer Issue N°120 - February 2016

12

6. DRUG SAFETY AND LIABILITY RISK

6.1 Merck and Vioxx Drugmaker settles investors’ complaint over Vioxx heart risks More than 10 years after the drug was pulled from the market, Merck has announced it would pay $830 million to settle allegations that investors were not adequately informed about the heart risks associated with the Vioxx pain treatment, which covers investors who purchased stock from the company between 1999 and 2004.

→ Link to Reuters article

6.2 Mediator and Servier French Court orders Servier to indemnify 12 patients for anxiety damage The Court of Nanterre sentenced Servier to pay 1,500 Euros to 12 patients who had been exposed to Mediator, the anti-diabetic used as an appetite suppressant. It considered that Servier is liable for their anxiety associated to the risk of valvulopathy that led to the withdrawal of the product. 38 other patients have been dismissed because of the lack of proof.

→ Link to Les Echos article (in French)

7. OTHER NEWS AND RESOURCES

7.1 Man dies in Phase 1 Clinical Trial in France The Portuguese drugmaker Bial has suspended its phase 1 clinical trial on an endogenous neurotransmitter (Fatty Acid Amide Hydrolase) following the death of one volunteer and the hospitalisation of five others.

The clinical trial was performed by Biotrial in France and the ANSM immediately launched investigations and an inspection. The French Agency has issued various documents in relation to this issue, including the study protocol and a chronology of the events.

The FDA has announced it is conferring with the EMA and the French Agency to learn as much as possible to ensure that patients and investigators participating in clinical studies of FAAH inhibitors are fully informed regarding the risks and potential benefits of these drugs.

→ Link to Pharmatimes article → Link to The New York Times article → Link to ANSM webpage with the protocol (French / English) → Link to ANSM webpage with the chronology (French / English) → Link to ANSM Press release (in French) → Link to FDA Statement

7.2 New issue of QuarterWatch The Institute for Safe Medication Practices (ISMP) has issued a new issue of QuarterWatch, the independent publication that monitors adverse drug events reported to the FDA. This issue includes a review of the following topics:

• Signals for new sleep medication suvorexant (Belsomra) • Opioids: Hydrocodone exposure declines while higher potency drugs increase • Update on new diabetes drugs blocking kidney glucose reabsorption

→ Link to QuarterWatch

Safety Observer Issue N°120 - February 2016

13

7.3 Health Canada provides updated Adverse Reaction Online Database The Canada Vigilance Adverse Reaction Online Database contains information about suspected ADRs submitted to Health Canada. The accessible database now includes data from 1965 to 30-Sep-2015.

→ Link to Health Canada Page

7.4 EUPATI launches new online educational toolbox As a part of the EU Innovative Medicines Initiative (IMI), the patient education project EUPATI has launched an online educational toolbox on medicines research and development (R&D). Primarily intended to patients, the freely-accessible toolbox includes materials covering various topics including clinical development and pharmacovigilance and available in seven languages. A presentation video about the new toolbox is available on the EUPATI website.

→ Link to EUPATI website

7.5 SCOPE project delivers new Work Packages The SCOPE project (Strengthening Collaboration for Operating Pharmacovigilance in Europe) is a three year EU-wide Pharmacovigilance project to help member states meet the requirements of the new legislation. The project is coordinated by the MHRA to enable National Authorities to operate the new requirements to the highest possible standards against agreed benchmarks and best practice.

A wave of Work Packages survey reports has been published recently that provides some insight into the practices of National Agencies with regards to Quality Management, Signal Management and Lifecycle Pharmacovigilance.

→ Link to SCOPE website

8. CONFERENCES AND TRAINING EVENTS

EMA/DIA Events → EudraVigilance and Electronic Reporting of ICSRs in the EEA

3 day-training course (see agenda for venues and dates) → Extended EudraVigilance Medicinal Product Dictionary (XEVMPD) Training Course

2 day-training course (see agenda for venues and dates)

DIA Events → Introduction to Signal Detection and Data Mining

March 07 in Washington DC, USA → Benefit/Risk Management

March 10 – 11 in Prague, Czech Republic → Premarketing Clinical Safety and Pharmacovigilance

March 21 – 22 in Washington DC, USA → 28th Annual EuroMeeting

April 06 – 08 in Hamburg, Germany → Signal Management in Pharmacovigilance

April 18 – 19 in Paris, France → How to Prepare for Pharmacovigilance Audits and Inspections

April 19 – 20 in Paris, France

Safety Observer Issue N°120 - February 2016

14

DSRU Events → Back to Basics in Pharmacovigilance

February 24 – 25 in Fareham, UK → EU Regulations and Guidelines for Pharmacovigilance

March 09 – 10 in London, UK → Introduction to Pharmacoepidemiology

April 14 – 15 in Fareham, UK

Other Events → Virtue Insight – 10th Pharmacovigilance 2016

February 23 – 24 in London, UK → RQA – Practical Pharmacovigilance Auditing

March 08 – 10 in Cambridge, UK → PSI – Structured Benefit-Risk Assessment: Methodology and Practice

March 08 – 09 in Heathrow, UK → IFIS – Pharmacovigilance Inspection (event in French)

March 10 in Paris, France → IFIS – Case Management (event in French)

March 11 in Paris, France → CBI – IDMP EU

March 16 – 17 in Barcelona, Spain → IFIS – Role, missions and responsibilities in Pharmacovigilance (event in French)

March 17-18 and April 08 in Paris, France → IFIS – Clinical Trials Safety (event in French)

March 21 in Paris, France → Faculté de Pharmacie – Paris V – Audit and Inspection in Pharmacovigilance (event in French)

March 21 in Paris, France → 2nd European QA Conference

April 27 – 29 in Nice, France