Safety Observer N°97 – January 2014 page 1/17

Safety Observer Clinical Safety & Pharmacovigilance Intelligence Review

Issue N°97 – January 2014 Highlights The EMA has now published the revised version of GVP Module VII on PSUR, which brings revisions resulting from the finalisation of the ICH E2C(R2). The EMA has also released the final version of Vaccines-specific considerations guidelines, which complements the GVP Modules for this type of products. The EMA has announced that it will shortly start publishing summaries of the Risk Management Plan (RMP) for new medicines, as a new aspect of the new Pharmacovigilance Legislation comes into place. The FDA has extended the comment period on its proposed rule to align the process for safety label changes for originator and generic drug products, which would end the protection of generic drugmakers from injury lawsuits in the USA. The FDA has updated once again its MedWatch Alert on the leukaemia medicine Iclusig to announce that the product should return to market once new safety requirements have been satisfied by the manufacturer.

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In this issue

1. Regulatory Update .................................................................................................................... 3

1.1. Applicable Regulations, Guidelines and other Standards ............................................................ 3 1.1.1. EMA issues updated advice on Transfer of Marketing Authorisations ............................................. 3 1.1.2. EMA issues Final GVP Module VII on PSURs ................................................................................ 3 1.1.3. EMA issues final Vaccine-specific GVP guidance .......................................................................... 3 1.1.4. ANSM issues order on financial and criminal penalties ................................................................ 3

1.2. Developments to watch ............................................................................................................ 4 1.2.1. EMA to prepare guidance on Post-Authorisation Efficacy Studies ................................................... 4 1.2.2. FDA extends comment period for Proposed Rule on label changes ................................................ 4

1.3. Beyond the borders of Safety Observer ...................................................................................... 4 1.3.1. Canada to implement new Pharmacovigilance Legislation ............................................................. 4 1.3.2. Australia provides additional guidance on E2B submissions ......................................................... 5 1.3.3. Switzerland issues revised instructions on Clinical Trial Safety Reporting ...................................... 5 1.3.4. Mexico issues revised Drug Safety Guidelines ............................................................................. 5

1.4. The Safety Observer Tracker ..................................................................................................... 5

2. Safety Update .......................................................................................................................... 6

2.1. Colchicine (Colchicine Opocalcium® and Colchimax®) .............................................................. 6

2.2. Methylphenidate ADHD Medications (Ritalin®, Concerta®, etc.) ................................................ 6

2.3. Capecitabine (Xeloda® and generics) ........................................................................................ 6

2.4. Naftidrofuryl (Praxilène® and generics) ..................................................................................... 6

2.5. Estradiol-containing creams (Linoladiol®N and HN) .................................................................... 6

2.6. Acipimox-containing medicines ................................................................................................. 7

2.7. Recombinant factor VIII (Kogenate® or Helixate NexGen®) ....................................................... 7

2.8. Ponatinib ( Iclusig®).................................................................................................................. 7

3. Quality Assurance, Inspections and Audits ................................................................................ 8

3.1. RQA issues revised booklet on Pharmacovigilance Auditing ....................................................... 8

3.2. France launches pilot phase for new format of inspection report ................................................. 8

3.3. DKMA updates information about Pharmacovigilance Inspections .............................................. 8

3.4. Austria issues revised Pharmacovigilance Inspection Questionnaire ........................................... 8

4. Drug Safety and Business Risk.................................................................................................. 8

4.1. Merck and Fosamax ................................................................................................................. 8

4.2. Sanofi-Pasteur and Gardasil ...................................................................................................... 8

5. Other relevant Information and Resources ................................................................................. 9

5.1. US Food and Drug Administration (FDA) .................................................................................... 9

5.2. European Medicines Agency (EMA) ......................................................................................... 10

5.3. UK Agency (MHRA) ................................................................................................................ 12

5.4. French Agency (ANSM)........................................................................................................... 12

5.5. Other Sources ........................................................................................................................ 14

6. Time to Register ..................................................................................................................... 15

7. About the Authors .................................................................................................................. 17

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1. Regulatory Update

1.1. Applicable Regulations, Guidelines and other Standards

1.1.1. EMA issues updated advice on Transfer of Marketing Authorisations (09-Dec-2013) The EMA has issued updated post--authorisation procedural advice for users of the centralised procedure. The changes relate to the Transfer of Marketing Authorisations in relation to the new EU Pharmacovigilance Legislation. Amongst other changes, it is specified that a switch from a DDPS to a Summary of the Pharmacovigilance System or the first introduction of a Summary of the Pharmacovigilance System cannot be included as part of the transfer application (see Question 15.2).

Link to EMA Guidance Document (EMEA-H-19984/03 Rev 37)

Link to EMA Guidance Document (EMEA-H-19984/03 Rev 37 – Changes Highlighted)

1.1.2. EMA issues Final GVP Module VII on PSURs (12-Dec-2013) Following the consultation conducted between April and June 2013, the EMA has now released the new version of the GVP Module on PSUR, which brings revisions resulting from the finalisation of the ICH E2C(R2) guideline on “Periodic Benefit-Risk Evaluation Report (PBRER)”, and additional guidance based on the experience gained since the implementation of the first version in July 2012. The comments received during the consultation and a version with tracked changes are also available. The Introductory Cover Note of the GVPs has been updated accordingly.

Link to EMA GVP Page

Link to EMA GVP Development Page (Comments & Tracked Changes Version)

Direct link to GVP Module VII Rev.1

1.1.3. EMA issues final Vaccine-specific GVP guidance (12-Dec-2013) Following the consultation conducted between April and June 2013, the EMA has now released the final version of the first Product or Population-specific considerations guidelines that are expected to provide additional guidance to the GVP Modules. This document covers Prophylactic Vaccines and provides guidance on specific aspects to be considered regarding the Risk Management System, PSUR, Signal Management, and Batch Recall and Quarantine. In addition, the EMA has published the comments it received during the consultation period and the final module is also available with tracked changes.

Link to EMA GVP Page

Link to EMA GVP Development Page (Comments & Tracked Changes Version)

Direct link to Vaccine-specific GVP Guideline

1.1.4. ANSM issues order on financial and criminal penalties (20-Dec-2013) The French Agency has updated the public health code with new provisions on financial and criminal penalties, which will apply from 01-Feb-2014. Criminal penalties (including fines) can be increased in case of serious violations or risk for public health. New penalties are planned for MAHs who fail to communicate new information influencing the evaluation of risks and benefits or fail to transmit data requested in the defined timelines.

Link to the order n°2013-1183 dated 19-Dec-2013 (in French)

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1.2. Developments to watch

1.2.1. EMA to prepare guidance on Post-Authorisation Efficacy Studies (10-Dec-2013) As announced earlier, the EMA held a two-day workshop on 24 and 25-Oct-2013 to discuss “methods for efficacy studies in everyday medical practice”, which is the first step in the development of guidance on post-authorisation efficacy studies (PAESs) as defined in the new pharmacovigilance legislation. The highlights from this workshop were initially published on 27-Nov-2013 but an update has been published on 10-Dec-2013, which provides a summary of the discussions on the main topics: pragmatic trials, observational studies, registries, the use of electronic health records and methods to control for confounding.

Link to EMA Event Page

1.2.2. FDA extends comment period for Proposed Rule on label changes (18-Dec-2013) As announced in our previous edition, the FDA has released a proposed rule to speed up the dissemination of new safety information by allowing generic drug makers to use the same process as originators to update safety information in the product labeling. Under the proposal, generic manufacturers would also be required to inform the brand name manufacturer about the change. The FDA would evaluate the proposed change and make a decision applicable to both generic and brand drugs. The FDA also plans to create a web page where safety-related changes proposed by all drug manufacturers would be posted while the FDA is reviewing the change. This new proposed rule would make generics manufacturer responsible for their product label, thus closing a regulatory loophole currently protecting these companies from injury lawsuits. Critics are arguing this could drive up the cost of generic drugs. The FDA has announced that it has FDA has decided to extend the comment period by 60 days and is now expecting comments on the proposed rule by 13-Mar-2014. A link to the accompanying Regulatory Impact Analysis has also been included.

Link to FDA News Release

Link to Federal Register Notice

Direct Link to Proposed Rule

1.3. Beyond the borders of Safety Observer

1.3.1. Canada to implement new Pharmacovigilance Legislation (06-Dec-2013) The Government of Canada has introduced new legislation with a view to improve patient safety. The changes include increased authority to impose regulatory action, stronger requirements for ADR reporting and stiffer penalties in the event of non-compliance. Some of the provisions, such as increased fines and penalties, will become law immediately whereas other changes require supporting regulations, which will be published for consultation in due course. The information published by Health Canada includes the News Releases, a Questions and Answers Document, and links to the text of the Bill.

Link to Health Canada Page

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1.3.2. Australia provides additional guidance on E2B submissions (12-Dec-2013) The TGA has published a set of Frequently Asked Questions regarding the use of the E2B format for ICSR submission to the Australian Agency. This follows the November 2013 announcement that the TGA will accept ADR reports in E2B format by email, which will be subsequently uploaded to the TGA database. A dedicated email address has been established for this purpose. The current submission methods will continue to be available and the E2B format cannot be used for Clinical Trial reports at this stage.

Link to TGA FAQs on E2B Reports

1.3.3. Switzerland issues revised instructions on Clinical Trial Safety Reporting (18-Dec-2013) The Swiss Agency has published updated instructions on Safety Reporting requirements applicable during Clinical Trials. Only SUSARs occurring at a Swiss trial centre are subject to expedited reporting and the sponsor has an obligation to submit an annual Safety Report. The instructions and associated template is provided in English, but it is also available in German, Italian and French.

Link to SwissMedic Page

1.3.4. Mexico issues revised Drug Safety Guidelines (Dec-2013) New guidance documents have been published on the Cofepris Website. Most importantly, this includes a revised guideline on Pharmacovigilance for Clinical Trials, which also covers requirements for Non-Interventional Trials. In addition, the list of procedures required for Pharmacovigilance Units has been revised and another guideline has been published to cover aggregate reporting requirements.

Link to Cofepris PV Page (in Spanish)

1.4. The Safety Observer Tracker This section includes a cumulative list of the future deadlines for implementation and end of consultation periods, which are associated to the most important announcements made in the current and previous issues of Safety Observer. For your convenience, a link to the main sources is provided and we also specify the issue where the corresponding article can be found.

By When ? What ? Issue 13-Mar-2014 FDA consultation on Proposed Rule for generics safety label

changes (Link + Link) 96 + 97

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2. Safety Update

2.1. Colchicine (Colchicine Opocalcium® and Colchimax®) ANSM warns about risks of overdose (16-Dec-2013) Following the reporting of deaths due to overdose, the French Agency has highlighted the risks associated with this drug used to treat gout. Cases are mainly related to non-compliance with the approved indications and posology, and the inappropriate management of overdose clinical signs.

Link to ANSM Press Release (in French)

2.2. Methylphenidate ADHD Medications (Ritalin®, Concerta®, etc.) FDA warns about priapism risk (17-Dec-2013) The FDA has warned that methylphenidate products, one type of stimulant drug used to treat attention deficit hyperactivity disorder (ADHD), may in rare instances cause prolonged and painful erections known as priapism. The drug labels and patient Medication Guides have been updated accordingly.

Link to FDA MedWatch alert

2.3. Capecitabine (Xeloda® and generics) ANSM warns about rare and severe skin reactions (19-Dec-2013) This oral treatment is used to treat breast, colon or stomach metastatic cancers and the French Agency has highlighted the risks of rare and severe skin reactions such as Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN).

Link to ANSM Press Release (in French)

2.4. Naftidrofuryl (Praxilène® and generics) ANSM communicates on the restrictions of use (20-Dec-2013) Following a re-evaluation, French Agency has concluded that the risk / benefit balance is only favourable in the treatment of intermittent claudication in patients suffering from peripheral arterial obstructive disease but it is unfavourable in other indications.

Link to ANSM Press Release (in French)

2.5. Estradiol-containing creams (Linoladiol®N and HN) EMA recommends new restrictions to improve Benefit Risk Profile (20-Dec-2013) The EMA CHMP has concluded that the two high-strength estradiol-containing creams may continue to be used for topical treatment of diseases of the genital area in menopaused women. Some restrictions are however recommended regarding the approved indications and the duration of treatment, as it is considered that long-term use could carry risks similar to systemic hormone replacement therapy (HRT), which include venous thromboembolism, stroke and endometrial cancer. The review of Linoladiol N and Linoladiol HN follows a national re-registration procedure for Linoladiol N in Germany, during which the German BfArM concluded that its benefit-risk balance was unfavourable. As the product is also authorised in other countries, the BfArM subsequently initiated an EU referral procedure. The CHMP recommendation will be sent to the European Commission for adoption of a legally binding decision.

Link to EMA Press Release

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2.6. Acipimox-containing medicines CMDh endorses PRAC restrictions recommendation (20-Dec-2013) The Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) has endorsed the November PRAC recommendations and medicines containing acipimox should have their authorisations amended so that they are used only as an additional or alternative treatment in type IIb and type IV hyperlipoproteinaemia. The CMDh endorsed the PRAC recommendations by majority and its position will now be sent to the European Commission for the adoption of a legally binding decision.

Link to EMA Press Release

2.7. Recombinant factor VIII (Kogenate® or Helixate NexGen®) CHMP confirms PRAC recommendations (20-Dec-2013) The EMA CHMP has endorsed by consensus the December PRAC recommendations that the benefits of these factor VIII products continue to outweigh their risks in previously untreated haemophilia A patients, although the product information should be amended to reflect currently available information.

Link to EMA Press Release

2.8. Ponatinib (Iclusig®) FDA requires new safety measures for product to return to market (20-Dec-2013) The FDA has announced that it is requiring several new safety measures for the leukemia drug to address the risk of life-threatening blood clots and severe narrowing of blood vessels. The required measures involve label changes to reflect the risk, revised indications and dosage and administration recommendations. The Medication Guide will also be updated and the FDA has required a risk evaluation and mitigation strategy (REMS). In addition, the manufacturer must conduct postmarket investigations to further characterize the drug’s safety and dosing. Once these new safety measures are in place, ARIAD Pharmaceuticals is expected to resume marketing. This follows the October FDA announcement that Iclusig sales and marketing had been suspended in the USA, and an update shortly thereafter to allow treatment continuation in appropriate patients. In Europe, the EMA has taken steps to reduce the risk and has initiated a thorough safety review.

Link to FDA Drug Safety Communication

Link to The New York Times article

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3. Quality Assurance, Inspections and Audits

3.1. RQA issues revised booklet on Pharmacovigilance Auditing The RQA (Research Quality Association – formerly known as BARQA) has now published the first revision of its booklet on “Pharmacovigilance Auditing”, which is available for purchase at the price of 10 GBP (quantity discounts available).

Link to RQA Page

3.2. France launches pilot phase for new format of inspection report The objectives of the new format of inspection report are: to better integrate the risks for public health (in addition to the grading of findings) to help in the decision-making process (when administrative actions are required) to facilitate the follow-up on the identified risks by the inspected organisations A 1 year pilot phase has now been initiated to test the new format.

Link to ANSM Explanatory Note (in French)

3.3. DKMA updates information about Pharmacovigilance Inspections The Danish Agency has revised the information provided on its website regarding Pharmacovigilance Inspections. This information is presented as a Questions & Answers Document and covers various aspects, including legal basis, selection of companies for inspection and frequent/important inspection findings.

Link to DKMA Page

3.4. Austria issues revised Pharmacovigilance Inspection Questionnaire The Austrian Agency has published an updated version of the questionnaire that should be submitted to the Agency prior to the inspection.

Link to AGES Page (in German)

4. Drug Safety and Business Risk

4.1. Merck and Fosamax Merck offers $27.7 Million settlement over Osteoporosis Medication Merck & Co. has announced it was ready to pay $27.7 million to settle lawsuits related to charges that Fosamax (alendronate) caused osteonecrosis of the jaw. The deal would resolve around 1,200 of over 5,000 cases the company is facing.

Link to Reuters article

Link to PharmaTimes article

4.2. Sanofi-Pasteur and Gardasil 9 patients file lawsuit in France Victims of suspected adverse reactions have filed a complaint for aggravated deception. As there are many stakeholders, the procedure does not specifically mention Sanofi Pasteur MSD, who launched the vaccine in 2006.

Link to Yahoo article (In French)

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5. Other relevant Information and Resources

5.1. US Food and Drug Administration (FDA)

5.1.1. FDA issues new and updated Risk Evaluation and Mitigation Strategies (REMS) The FDA Amendments Act of 2007 gave FDA the authority to require a Risk Evaluation and Mitigation Strategy (REMS) from manufacturers to ensure that the benefits of a drug or biological product outweigh its risks. The list of REMS that have been approved by FDA was last updated on 20-Dec-2013. A new REMS has been issued for Iclusig (ponatinib), and additional REMS have been updated.

Link to FDA REMS Page

5.1.2. New FDA Presentation Material The FDA has made available the material used to support several recent presentations. This includes: Priorities for CDER 2013-2014, which include some topics related to safety

Benefit-risk balance assessment during life cycle of medicinal products

Impact of PDUFA V from the risk management perspective

5.1.3. Drug Safety and Risk Management Advisory Committee: New material available The Drug Safety and Risk Management Advisory Committee met on 09-Dec-2013 in a Joint Meeting with the Gastrointestinal Drugs Advisory Committee to discuss biologics license applications (BLAs) for vedolizumab injection (proposed tradename ENTYVIO), submitted by Takeda Pharmaceuticals for the treatment of inflammatory bowel diseases (IBDs), ulcerative colitis (UC) and Crohn’s disease (CD). The slides presented at the meeting have been published, and recordings of the webcast are also available.

Link to FDA Page

5.1.4. Risk Communication Advisory Committee: New material available The Committee met on 17-Dec-2013 to discuss new methods for communicating risk information as part of Risk Evaluation and Mitigation Strategies (REMS) to Healthcare Providers and how to evaluate their effectiveness. Material from this meeting has been posted, including webcasts and presentations.

Link to FDA Page

5.1.5. FDA updates Drug Code Lists The FDA is now updating the National Drug Code Directory on a weekly basis, and it can be downloaded from their website.

Link to National Drug Code Directory Page

The “Drugs@FDA” Downloadable Data Files were last updated on 01-Jan-2014.

Link to Drugs@FDA Page

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5.1.6. 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 warns of serious skin reactions with the anti-seizure drug Onfi (clobazam) and

has approved label changes warns of rare risk of long-lasting erections in males taking methylphenidate ADHD

medications and has approved label changes FDA requires multiple new safety measures for leukemia drug Iclusig; company

expected to resume marketing

Link to FDA Page

5.2. European Medicines Agency (EMA)

5.2.1. EMA to start publishing RMP Summaries The highlights for the December CHMP Meeting includes a Procedural Announcement stating that the EMA will now start publishing summaries of the Risk Management Plan (RMP) for every new medicine, in line with the new Pharmacovigilance Legislation. The RMP summary will only be available in English as part of the EPAR, along with the other related documents. The EMA will announce shortly the publication of the first RMP summary on the EMA website.

Link to CHMP Meeting Statement

5.2.2. PRAC recommendations on Safety Signals The EMA now routinely issues the PRAC recommendations resulting from the assessment of safety signals. MAHs are legally obliged to monitor this information to keep informed about the PRAC recommendations concerning their products, which may require the submission of a Safety Variation. The recommendations on signals adopted at the December PRAC meeting were published on 17-Dec-2013 and includes recommendations to update the product information for the following combination of Product / Signal: Thiopental - Hypokalaemia and rebound hyperkalaemia The cumulative list of all safety signals discussed at the PRAC since September 2012 has been updated accordingly. It includes links to the corresponding PRAC minutes and specifies whether a variation was recommended.

Link to EMA Page

5.2.3. EMA updates information related to the list of Black Triangle Products As described in GVP Module X, the EMA is publishing the list of medicines under additional monitoring, which will be identified by a Black Triangle (▼) throughout Europe. 6 products have been added to the list, which specifies the reason for a product to be subject to additional monitoring.

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

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5.2.4. 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. As communicated separately, the PRAC reviewed information on the cancer medicine Iclusig (ponatinib) suggesting that vascular occlusive events occur at a higher rate than initially expected. The PRAC also recommended the suspension of diacerein-containing medicines, and restrictions of use for acipimox. The products concerned by new Safety Signals included Adalimumab, Bupropion, Glycopyrronium bromide, Goserelin, Leflunomide, Teriparatide, Paracetamol, and Calcium channel blockers.

Direct link to PRAC Meeting Minutes (04 to 07-Nov-2013)

5.2.5. EMA issues new CHMP Meeting Material The EMA has now started publishing the agenda of the Committee for Medicinal Products for Human Use (CHMP) and the minutes will be published once they have been adopted at the next meeting.

Link to EMA Press Release

The highlights for the December meeting of CHMP have been published. As communicated separately, the CHMP issued recommendations following the safety reviews for Estradiol (topical use) and Kogenate / Helixate NexGen. 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 as well as community reviews initiated.

Link to CHMP Meeting Highlights (16 to 19-Dec-2013)

Link to CHMP Meeting Page (Agenda)

5.2.6. EMA to switch to electronic only notifications of referral The EMA has announced that it is changing its practices in informing marketing authorisation holders (MAHs)/applicants involved in a referral procedure. As of 20-Jan-2014, all correspondence related to a referral procedure will be sent electronically only (via e-mail and/or Eudralink) and MAHs /applicants need to ensure that the national competent authorities have the most up to date contact details.

Link to EMA Announcement

5.2.7. EMA interactions with Patients’ and Healthcare Professionals’ Organisations The EMA has published the minutes and presentations of the joint meeting of the Working Party with Patients’ and Consumers’ Organisations (PCWP) and the Healthcare Professionals’ Working Party (HCPWP), which took place on 25-Sep-2013. In the area of Pharmacovigilance, the topics discussed included the communication on additional monitoring, the draft rules of procedure for Public hearings, and the ADVANCE project, which concerns the study of safety and effectiveness for vaccines.

Link to EMA Meeting Page

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5.3. UK Agency (MHRA)

5.3.1. MHRA contributes to e-learning unit on ADR Reporting for nurses The MHRA has announced that it has teamed up with Nursing Times Learning to launch new and free interactive learning ADR reporting and the Yellow Card Scheme. The learning unit is designed to help nurses understand the importance of reporting suspected ADRs and know which type of situation should trigger a report. This new resource may be useful for companies in the implementation of e-learning tools.

Link to MHRA News Release

5.3.2. New issues of MHRA “Drug Safety Update” Bulletin The latest issue of Drug Safety Update (Volume 7, Issue 5, December 2013) was published on 16-Dec-2013. It includes the following topics: Rituximab: screen for hepatitis B virus before treatment Clopidogrel: risk of acquired haemophilia Ponatinib (Iclusig▼): risk of vascular occlusive events Dorzolomide hydrochloride/timolol maleate (Cosopt) eye drops: reports of eye injury Recombinant interferon-beta: cluster of reports of thrombotic microangiopathy

Drug Safety Update is available as a fully searchable online resource.

Link to MHRA Newsletter Page

5.4. French Agency (ANSM)

5.4.1. ANSM Dear Doctor Letters Dear Doctor Letters sent in December 2013 are now available on the French Agency' s website (all in French). Letters associated to safety concerns include the following: Ofatumumab (Arzerra®): Hepatitis B test before treatment Dihydroergotoxine: MA suspension Short-acting beta-agonists: restriction of indications in obstetrical indications Naftidrofuryl (Praxilene® and generics): indication restrictions Capecitabine (Xeloda®): risks of severe skin reactions Prasugrel (Efient®): increased risk of bleeding in patients with angina pectoris or MI Temozolomide (Temodal®): severe hepatotoxicity Ponatimib (Iclusig®): new recommendations on risks of vascular occlusion Pomalidomide (Imnovid®): risk minimisation measures and pregnancy preventive

program

Link to ANSM Page

5.4.2. Commissions / Committees in relation with Pharmacovigilance The Pharmacovigilance Committee issued minutes of the meetings of 10-Sep-2013. The discussion concerned the following products: Deferasinox, ivabradine, acitretine, Angiotensine II receptor antagonists.

Link to the minutes of the Committee – 10-Sep-2013 (in French)

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5.4.3. ANSM provides update on PRAC and CHMP activities Following the publication of PRAC minutes, ANSM issued a document in French which provides a summary of the discussions and decisions taken by the PRAC, together with ANSM positions and recommendations for Healthcare Professionals.

Link to ANSM synthesis for the PRAC meeting of December 2013 (in French)

In the same way, ANSM issued a summary of the discussions and decisions taken by the CHMP.

Link to ANSM synthesis of the CHMP meeting of December 2013 (in French)

5.4.4. ANSM issues a statement on lists of " useful or unnecessary, even hazardous drugs" The Agency highlights that these lists are issued by Healthcare Professionals on a personal basis and do not bind any health authority. ANSM reminds the process of marketing authorization at a local or European level and the follow up of the risks and the benefits during the drug lifecycle, including the Benefit-Risk review for older drugs. ANSM reminds that information on drugs is publically available in the drug database, which patients are invited to consult.

ANSM Press Release (in French)

5.4.5. ANSM Actu: the newsletter of ANSM ANSM has published the seventh issue of its newsletter, which reports on the DHCP letters and the press releases published in October/December 2013.

Link to ANSM Actu

5.4.6. ANSM and CNOM ANSM and the French National Council of Physicians have announced that they will work jointly on actions to promote patient safety. This partnership includes drug safety monitoring, Benefit-Risk evaluation and distribution of safety information.

Link to the ANSM webpage (in French)

5.4.7. ANSM issues new template for Annual Status Update The French regulations require all companies to submit an Annual Status Update (Site Master File – Annual Update of Pharmaceutical Sites) which collects a wide range of information, including on Pharmacovigilance. The template has been updated.

Link to the Annual Status (in French)

Link to the Annual Status (in bilingual version)

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5.5. Other Sources

5.5.1. New issue of Adis Pharmacovigilance eNewsletter The Adis in-touch Pharmacovigilance is a quarterly eNewsletter bringing news, views and events. This issue includes free access to highlighted articles from Adis and a couple of feature articles on Atomoxetine / Suicidal Ideation, and on Pradaxa / Oesophageal ulcer. Meeting Reports from the recent ISoP Annual Meeting in Pisa, and ICPE in Montreal are also presented. The newsletter also includes a selection of ADR case reports published in Reactions Weekly and Pharmacovigilance Insight in the third quarter of 2013.

Link to Adis in-touch

5.5.2. New issue of WHO Pharmaceuticals Newsletter The last edition of the WHO Pharmaceuticals Newsletter (N°6, 2013) is now available. Prepared in collaboration with the Uppsala Monitoring Center, it includes a section on Regulatory Matters and Safety of Medicines. The newsletter also includes signals based on the information available in the WHO Global database VigiBase and responses from MAHs: Abiraterone and Thrombocytopenia (& Response from Janssen) Baclofen and Renal failure Golimumab and Meningitis (& Response from Janssen Biologics B.V.) Pazopanib and Pericardial Effusion

Link to WHO Pharmaceuticals Newsletter (N°6, 2013)

5.5.3. New issue of IMB Drug Safety Newsletter The last edition of the Irish Medicine Board Drug Safety Newsletter (Issue N°58) was made available on 20-Dec-2013. The contents include: Intravenous iron-containing medicines: Risk of allergic reactions Cabazitaxel (Jevtana): Potential for medication error due to incorrect reconstitution Medicines subject to additional monitoring requirements

Link to Newsletter

5.5.4. New issue of CIOMS Newsletter The last edition of the CIOMS Newsletter (N°9, December 2013) is now available. It includes a report from the meeting of the Working Group for the revision of the 2002 Ethical Guidelines for Biomedical Research. It also provides an overview of upcoming meetings of the active CIOMS Working Groups.

Link to CIOMS Newsletter

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5.5.5. New issue of Japanese PMDSI Newsletter The Pharmaceuticals and Medical Devices Safety Information (PMDSI) Newsletter is issued based on safety information collected by the Japanese Ministry of Health, Labour and Welfare (MHLW) and is intended to promote safer use of pharmaceuticals and medical devices by healthcare providers. The English Summary of the latest edition of the Newsletter (Issue N°308) is now available and includes: Review of Driving Precautions in Package Inserts of Ethical Drugs Important Safety Information: Bosentan Hydrate Revision of Precautions: Donepezil Hydrochloride (and 5 others) List of Products Subject to Early Post-marketing Vigilance

Link to PMDA Page

5.5.6. Japanese PMDA provides updated list of drugs under review The Pharmaceuticals and Medical Devices Agency (PMDA) has updated its webpage where it provides information on drug risks under review by the PMDA/MHLW, which can be based on safety information submitted to the Japanese Agency or due to communication from foreign drug agencies. The information published has been updated to include a Summary Report on the Surveillance of HPV Vaccines.

Link to PMDA Page

5.5.7. New issue of PRM Newsletter The latest issue of the PharmacoEpi and Risk Management (PRM) Newsletter, which has been created by the MAPI Research Trust, has now been published. It includes an article that provides a summary of resources for the conduct of multi-national pharmacoepidemiology studies in Europe, including the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP), and the International Society of Pharmacoepidemiology (ISPE).

Link to PRM Newsletter N°17 (December 2013)

6. Time to Register

EMA/DIA Events

3 day-training course (see schedule for venues and dates) EudraVigilance and Electronic Reporting of ICSRs in the EEA

2 day-training course (see schedule for venues and dates) Extended EudraVigilance Medicinal Product Dictionary (XEVMPD) Training Course

February 17 – 21 in London, UK Excellence in Pharmacovigilance: Clinical Trials and Post-Marketing

February 25 in London, UK Introduction to Pharmacovigilance and Rules for Expedited Reporting of ICSRs in Europe

March 12 in London, UK 15th EudraVigilance Information Day

DIA Events

January 12 – 15 in Washington DC, USA Pharmacovigilance and Risk Management Strategies 2014

February 09 – 11 in Bethesda MD, USA Benefit-Risk Assessment from Inception to Maturation: Aligning Regulatory and Industry Goals

March 25 – 27 in Vienna, Austria 26th Annual EuroMeeting

Safety Observer N°97 – January 2014 page 16/17

DSRU Events

January 22 – 24 in Southampton, UK Medical Aspects of Adverse Drug Reactions

February 05 – 06 in London, UK Monitoring Safety in Clinical Trials & Drug Development

February 26 – 27 in Southampton, UK Back to Basics in Pharmacovigilance

March 12 – 13 in London, UK EU Regulations and Guidelines for Pharmacovigilance

Barnett Events

January 21, 12:OO PM to 01:30 PM Eastern Webinar – Quality Risk Management in Clinical Trials and Pharmacovigilance

January 15, 01:0O PM to 02:30 PM Eastern Webinar – Preparing for a Safety Inspection

January 24, 12:OO PM to 02:00 PM Eastern Webinar – Adverse Event Monitoring for CRAs

January 30 in San Diego CA, USA The Pharmacovigilance Audit: How to Prepare for an Inspection

March 04, 01:OO PM to 02:30 PM Eastern Webinar – Drug Safety and Pharmacovigilance

March 06 – 07 in Philadelphia PA, USA Adverse Events: Managing and Reporting for Pharmaceuticals

March 11 – 12 in San Francisco CA, USA Drug Safety and Pharmacovigilance

March 18, 09:OO AM to 10:30 AM Eastern Webinar – Quality Risk Management in Clinical Trials and Pharmacovigilance

Other Events

January 22 in London, UK EGA – 7th EGA Pharmacovigilance Discussion Forum

January 23 in Paris, France IFIS – Quality in Pharmacovigilance (event in French)

January 23 – 24 in Amsterdam, Netherlands Fleming – 6th Annual Pharmacovigilance & Risk Management Strategies Forum

January 23 in London, UK Management Forum – Pharmacovigilance and MedDRA

January 24 in London, UK Management Forum – MedDRA Coding and practical aspects

March 04 – 05 in London, UK Virtue Insight – 6th Pharmacovigilance 2014

February 11 in London, UK Management Forum – Essential Pharmacovigilance

March 03 – 05 in London, UK Management Forum – Advanced Pharmacovigilance

March 10 – 12 in Cambridge, UK RQA – Practical Pharmacovigilance Auditing

March 14 in London, UK MHRA Pharmacovigilance Inspections Symposium 2014

March 17 in Paris, France IFIS – Pharmacovigilance : Responsible Pharmacist missions / responsibilities (event in French)

March 20 – 21 in Paris, France IFIS – Pharmacovigilance : role, missions and responsibilities (event in French)

March 24 in Paris, France IFIS – Pharmacovigilance in clinical trials (event in French)

Safety Observer N°97 – January 2014 page 17/17

7. About the Authors

SUNNIKAN Consulting is offering a wide range of services related to Risk, Quality and Process Management Systems for Pharmaceutical Industry since 1996. SUNNIKAN Consulting’s areas of expertise cover Clinical Research, Regulatory Affairs, Pharmacovigilance, Computerized Systems, and more. For more information please visit SUNNIKAN Consulting’s website at: www.sunnikan.com

PV Focus is a small specialty company established since December 2004. Based in France, PV Focus has successfully centered its business on the provision of Pharmacovigilance Audits and related services to the Pharmaceutical Industry. Due to its experience of both Audits and Regulatory Inspections at a global level, PV Focus is a partner of choice to assist with the performance of Pharmacovigilance System Audits and can also support the preparation of Regulatory Inspections. For more information please visit www.pvfocus.com

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