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Safety Observer Issue N°128 - November 2016

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Clinical Safety & Pharmacovigilance Regulatory Intelligence Review

Issue N°128 - November 2016

HIGHLIGHTS

The EMA announced it has now started giving open access to clinical reports for new medicines authorised in the EU. For every new medicine, the clinical reports submitted in the context of marketing authorisation applications will be directly accessible to the public.

The EMA Management Board has adopted a reflection paper on the development of a European medicines web portal. This multilingual website will provide open access to free, reliable and unbiased information on all medicines authorised in the EU.

The EMA has released new training modules to prepare for the implementation of the new EudraVigilance System. The new and revised modules published recently cover a range of topics including the new EudraVigilance functionalities, the implementation of ISO ICSR/ICH E2B(R3), and the Revised EudraVigilance access policy.

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IN THIS ISSUE

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

1.1 Newly Applicable Standards .............................................................................................................................. 3 1.1.1 EMA starts providing public access to clinical reports .................................................................................. 3 1.1.2 New ANSM guidance to support the submission of variations ..................................................................... 3

1.2 Developments to Watch ..................................................................................................................................... 3 1.2.1 EMA gives the go-ahead to European medicines web portal ....................................................................... 3 1.2.2 EMA issues Training Material related to new EudraVigilance System .......................................................... 4

1.3 Beyond the Scope of Safety Observer ............................................................................................................... 4 1.4 The Safety Observer Tracker ............................................................................................................................. 5

2. Product Safety Announcements ............................................................................................................................ 5

2.1 Rivaroxaban (Xarelto) ........................................................................................................................................ 5 2.2 Levetiracetam (Keppra) ..................................................................................................................................... 5 2.3 Testosterone and anabolic androgenic steroids .............................................................................................. 6 2.4 Cough and cold products in children ................................................................................................................ 6

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

4. Other Publications by Regulatory Agencies .......................................................................................................... 7

4.1 US Food and Drug Administration (FDA) ........................................................................................................... 7 4.2 European Medicines Agency (EMA) .................................................................................................................... 9 4.3 UK Agency (MHRA) ........................................................................................................................................... 12 4.4 French Agency (ANSM) ..................................................................................................................................... 12

5. Quality Assurance, Inspections and Audits ......................................................................................................... 13

6. Drug Safety and Liability Risk .............................................................................................................................. 13

7. Other News and Resources .................................................................................................................................. 13

8. Conferences and Training Events ........................................................................................................................ 14

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1. REGULATIONS, GUIDELINES AND OTHER STANDARDS

1.1 Newly Applicable Standards

1.1.1 EMA starts providing public access to clinical reports (20-Oct-2016) The EMA announced it has now started giving open access to clinical reports for new medicines authorised in the EU. For every new medicine, the clinical reports submitted by pharmaceutical companies to EMA in the context of marketing authorisation applications will be directly accessible.

It is expected that this will facilitate the independent re-analysis of data by academics and researchers after a medicine has been approved, which will contribute to increase scientific knowledge and potentially further inform regulatory decision making in the future. This increased transparency should also benefit innovation as the experience of others should support more efficient medicine development programmes.

The website will include the clinical reports contained in all initial marketing authorisation applications submitted to the EMA from 01-Jan-2015 and in extension applications submitted from 01-Jul-2015. The documents are published after the European Commission has made a decision on the application or when applications are withdrawn before an opinion has been given.

As a first step, the EMA has published data for two medicines, Kyprolis (carfilzomib), an orphan cancer medicine for the treatment of multiple myeloma, and Zurampic (lesinurad), a medicine for gout. Data will be progressively added online for all applications concerned.

→ Link to EMA Press Release

1.1.2 New ANSM guidance to support the submission of variations (20-Oct-2016) Following the publication of several documents on the submission of variations in June 2016, the French Agency has issued a new template for the certificate of translation and the list of documents to be submitted for type II variations.

→ Link to the dedicated page of the ANSM website (in French)

1.2 Developments to Watch

1.2.1 EMA gives the go-ahead to European medicines web portal (07-Oct-2016) The EMA Management Board has adopted a reflection paper on the development of a European medicines web portal. This multilingual website will provide access to free, reliable and unbiased information on all medicines authorised in the EU and for all stakeholders. The portal is required by the 2010 pharmacovigilance legislation and is planned to provide comprehensive information across the medicine lifecycle, from clinical trial information to adverse drug reaction reports.

No implementation date is communicated at this time, which will depend on agreement across the EU medicines regulatory network and the availability of financial and IT resources.

→ Link to EMA Press Release

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1.2.2 EMA issues Training Material related to new EudraVigilance System (12-Oct-2016) As reported when it was released in April 2016, the EMA has produced a document entitled: “EudraVigilance training plan”, which details the training curriculum to prepare all EudraVigilance Stakeholders on the changes to be introduced with the new EudraVigilance System expected to go live in November 2017.

In line with the plan, the Agency has released the first batch of the planned training modules. Some new and revised modules have been published recently, which cover the “Pharmacovigilance” section of the training program including the new EudraVigilance functionalities, the implementation of ISO ICSR/ICH E2B(R3), and the Revised EudraVigilance access policy. Slide decks and video recordings of these modules are available.

In addition, a new training video is now available on ISO ICSR standard implementation. Although this is not yet available on the EudraVigilance Training Page at the time of issue, the training video IT-M1 is now available on the EMA YouTube channel.

→ Link to EudraVigilance Training Page → Direct link to IT-M1 Training Video on ISO ICSR implementation

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 South Africa issues revised guideline for Post-Marketing Safety Reporting (26-Sep-2016) The South African MCC (Medicines Control Council) has issued a revised version of the guideline covering Post-Marketing Safety Reporting. The revised version does not include significant changes to the existing requirements. It however clarifies that the requirements do not apply to unregistered medicines. It also clarifies that the applicant needs to specify and communicate to the authorities the 12-month period used for the Summary Evaluation Statement, which must be submitted within 90 days of the Data Lock Point.

→ Link to MCC Post-Marketing ADR Reporting Guideline → Link to MCC Post-Marketing ADR Reporting Guideline (Track Changes version)

1.3.2 Australia issues new Pharmacovigilance guidance for consultation (31-Oct-2016) The Australian TGA has launched several consultations related to Pharmacovigilance and comments are expected by 16-Dec-2016.

This includes a consultation on the draft revision of the existing Australian guidance on Risk Management Plans for medicines and biologicals. In addition, a consultation has also been initiated on the draft of a new guidance on biovigilance responsibilities of sponsors of biologicals. As a reminder, “Sponsor” refers to the holder of the registration of a medicine for marketing.

→ Link to TGA Page on Biovigilance Consultation → Link to TGA Page on RMP Consultation

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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

21-Nov-2016 FDA Consultation on draft guidance on factors for REMS decision making (Link) 127

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

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Q3/Q4-2018 Implementation of the ISO IDMP standards in Europe (Link) 126

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

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2. PRODUCT SAFETY ANNOUNCEMENTS

2.1 Rivaroxaban (Xarelto) FDA concludes defective INR test device does not impact Xarelto’s safety (11-Oct-2016) The FDA has issued a statement regarding the results of its reanalysis, which concluded that Xarelto is a safe and effective alternative to warfarin in patients with atrial fibrillation. A similar conclusion had been reached by the European Agency, as communicated through a Press Release in February 2016.

This follows concerns and the subsequent recall of the Alere INRatio device, which was used to monitor warfarin therapy in the control group of the ROCKET-AF clinical trial supporting the 2011 approval of the blood thinner product. The FDA has completed a variety of analyses to assess the impact of the faulty device on the study results and found that effects were minimal. The FDA has made available detailed information on these analyses, including the Clinical, Statistical and Clinical Pharmacology reviews.

→ Link to FDA Statement → Link to EMA Press Release (05-Feb-2016)

2.2 Levetiracetam (Keppra) EMA recommends new measures to ensure safe use of Keppra oral solution (14-Oct-2016) The EMA has announced that several new measures have been put in place to ensure that the correct dosing syringe is used to measure Keppra oral solution, which is used in the treatment of epilepsy.

Cases of accidental overdose have been reported in the past, which occurred mostly in children when a wrong dosing syringe was used or because of a misunderstanding about how to measure the dose. Levetiracetam overdose often has no symptoms, but it may cause sleepiness, agitation, difficulty breathing and coma.

Changes to the packaging material have been approved and clearer instructions have been included in the package leaflet in order to prevent medication errors and the risk of overdose.

→ Link to EMA Press Release

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2.3 Testosterone and anabolic androgenic steroids FDA approves new labeling on risks of abuse and dependence with anabolics (25-Oct-2016) The FDA has approved class-wide labeling changes to include a new Warning and an updated Abuse and Dependence section for all prescription testosterone products and other anabolic androgenic steroids (AAS).

Testosterone and other AAS are abused by adults and adolescents, including athletes and body builders, which is associated with serious cardiac and mental health risks. The Warning and Precautions section has also been revised to advise prescribers on the importance of measuring serum testosterone concentration if abuse is suspected.

→ Link to FDA MedWatch alert

2.4 Cough and cold products in children FDA issues reminder of current cough and cold treatment advice in children (04-Nov-2016) The FDA has issued a reminder that children under 2 years of age should not be given any kind of cough and cold product that contains a decongestant or antihistamine due to the risk of serious and possibly life-threatening side effects. These products should also be used with caution in children over 2 years of age.

A 2007 review found that cough and cold drug products caused many adverse reactions and manufacturers voluntarily removed OTC infant products due to these safety concerns.

→ Link to FDA Statement

3. DEAR DOCTOR LETTERS AND SAFETY NEWSLETTERS

3.1 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. The following letters were issued in September 2016:

• Fosphyenytoin sodium (Pro-Epanutin): medication errors and off-label use in children • Levonorgestrel-containing emergency hormonal contraception: interaction with hepatic enzyme inducers • Etoricoxib: revised dose recommendation

→ Link to MHRA Page (September)

The following letters were issued in October 2016:

• Flolan (epoprostenol): new formulation available with differences in storage and administration • Blincyto▼ (blinatumomab): cases of pancreatitis

→ Link to MHRA Page (October)

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

• Blincyto (blinatumomab): risks of pancreatitis • Topiramate: warning on the use for mood disorders (off-label use)

→ Link to ANSM Page (in French)

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3.3 New issues of MHRA “Drug Safety Update” The October issue of Drug Safety Update was published on 17-Oct-2016. It includes the following topic:

• Etoricoxib (Arcoxia): revised dose recommendation for rheumatoid arthritis and ankylosing spondylitis

→ Link to Drug Safety Update (October)

The November issue was published on 08-Nov-2016 and includes the following topics:

• Brimonidine gel (Mirvaso▼): risk of exacerbation of rosacea • Social media campaign to promote the reporting of suspected ADRs to the Yellow Card Scheme

→ Link to Drug Safety Update (November)

3.4 New issue of the French Bulletin "Vigilances" The new French "Vigilances" Bulletin, number 71, has now been issued. It includes articles on quantitative signal detection methods and on the new EudraVigilance System. A summary of recent pharmacovigilance news is also presented. As usual it also includes statistics on ADR notifications received during the second quarter of 2016, which show similar figures to the previous period.

→ Link to ANSM Bulletin "Vigilances" (in French)

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 October issue was published on 27-Oct-2016 and includes new labelling requirements for OTC acetaminophen (i.e. paracetamol) products labels. As usual it includes a monthly recap of Safety Reviews, which covers several medicinal products including gabapentin, imipenem, isotretinoin and Soliris (eculizumab) amongst others.

→ Link to Newsletter

3.6 New issue of WHO Pharmaceuticals Newsletter The latest edition of the WHO Pharmaceuticals Newsletter (N°5, 2016) is now available. Prepared in collaboration with the Uppsala Monitoring Center, it includes a section on Regulatory Matters and Safety of Medicines. This issue includes a report from the Asia-Pacific Economic Cooperation (APEC) Harmonization Center Pharmacovigilance Workshop in Seoul. As usual, the newsletter includes signals identified in the WHO VigiBase and the corresponding responses from MAHs, where available:

• Dimenhydrinate and erythema multiforme/Stevens Johnson Syndrome

→ Link to WHO Pharmaceuticals Newsletter (N°5, 2016)

4. OTHER PUBLICATIONS BY REGULATORY AGENCIES

4.1 US Food and Drug Administration (FDA)

4.1.1 New Public Summary of Drug Safety Oversight Board meeting A new public summary for the meeting of the FDA Drug Safety Oversight Board (DSOB) has been posted. The Board met on 19-May-2016 and was updated on Drug Safety Communications issued since the previous meeting in January 2016. In addition, the board was updated on the FDA Opioid Action Plan. Presentations were also given on “Safety Signals associated with iodinated contrast materials”, and on “implementing a Benefit Risk Counseling Framework for medications with REMS”.

→ Link to DSOB Public Summary

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4.1.2 FDA invites workshop on the Sentinel PRISM Program As reported in our previous issues, the FDA has announced that a public workshop entitled “The Sentinel Post-Licensure Rapid Immunization Safety Monitoring (PRISM) Program” will be held in Bethesda, MD on 07-Dec-2016. The purpose of this workshop is to describe the Sentinel Initiative and PRISM program, which is used in the evaluation of vaccine adverse events. The workshop will present how PRISM is used by the FDA with case examples. Discussions should also cover the future direction of PRISM in terms of expansion and further integration into the regulatory review process. Registration is open until 23-Nov-2016.

→ Link to Federal Register Notice + Correction Notice → Link to FDA Event Page

4.1.3 FDA announces 9th Annual Sentinel Initiative Public Workshop The Ninth Annual Sentinel Initiative Public Workshop will take place on 02-Feb-2017 in Washington, DC and a live webcast is also available for those unable to attend in person. Topics will include an overview of the current state of Sentinel System safety surveillance activities and uses of the Sentinel System in 2016. Panelists will also discuss the future of the Sentinel System and opportunities to expand its surveillance capabilities.

→ Link to Sentinel Workshop Registration Page → Link to Federal Register Notice

4.1.4 FDA Workshop on Cardiovascular Toxicity Assessment in Oncology Trials Cardiotoxicity is a well-established complication of oncology therapies and the FDA invited a public workshop to discuss the cardiovascular toxicity assessment within oncology clinical trials. The objectives of the workshop were to discuss a number of topics including the cardiovascular Adverse Events reporting within oncology clinical trials, the implementation of cardiovascular prevention strategies and the design and implementation of cardiovascular safety registries. The workshop took place on 22-Sep-2016 and the slides and webcasts are now available on the FDA website.

→ Link to FDA Event Page

4.1.5 Drug Safety and Risk Management Advisory Committee: New material available The Drug Safety and Risk Management Advisory Committee met again on 15 and 16-Sep-2016 in a Joint Meeting with the Psychopharmacologic Drugs Advisory Committee and the Pediatric Advisory Committee to discuss the appropriate development plans for establishing the safety and efficacy of prescription opioid analgesics for pediatric patients, including obtaining pharmacokinetic data and the use of extrapolation.

The Drug Safety and Risk Management Advisory Committee met again on 05-Oct-2016 in a Joint Meeting with the Anesthetic and Analgesic Drug Products Advisory Committee to discuss issues related to the use of naloxone products in the community setting.

The minutes of these meetings are now available on the FDA website in addition to other meeting material, including slides and webcasts.

→ Link to FDA Page

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4.2 European Medicines Agency (EMA)

4.2.1 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 agenda and highlights of the latest PRAC meeting were published on 28-Oct-2016. The PRAC did not initiate or conclude a safety referral at this meeting. According to the agenda, the following new Safety Signals have been identified and considered:

• Enzalutamide – hepatotoxicity • Nivolumab, pembrolizumab – transplant rejection • Flucloxacillin – acute generalised exanthematous pustulosis (AGEP)

→ Direct link to PRAC Meeting Highlights (24 to 27-Oct-2016)

4.2.2 PRAC recommendations on Safety Signals The EMA 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 list of signals discussed at the PRAC meeting of 26 to 29-Sep was published on 25-Oct-2016 and includes recommendations to update the product information for the following signals:

• Levetiracetam (oral solution) – Medication errors associated with accidental overdose • Metronidazole – Severe hepatic and neurologic toxicity in patients with Cockayne syndrome

In complement, the EMA has published the corresponding document entitled: “New product information wording – Extracts from PRAC recommendations on signals”, which is available in all EU languages.

The 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.

It should also be noted that a correction to the list of signals discussed at the PRAC meeting of 30-Aug-2016 to 02-Sep-2016 was published on 28-Oct-2016.

→ Link to EMA Page

4.2.3 EMA issues “Meeting Highlights” of last CHMP Meeting The highlights of the October meeting of the CHMP have been published. As communicated separately (see Section 2), the Committee recommended measures to ensure that the correct dosing syringe is used to measure Keppra (levetiracetam) oral solution, and thus avoid medication errors.

The CHMP has also concluded that metformin-containing medicines can now be used in patients with moderately reduced kidney function for the treatment of type 2 diabetes, after a review found that current scientific evidence does not justify a contraindication in patients with moderate reduction of kidney function.

The Agency has announced some changes in the way the results of the CHMP meetings will be communicated from now on. The Highlights will no longer include the opinions on safety variations/PSURs, which will be included in the minutes of the CHMP meeting published approximately one month after the Committee meets.

→ Link to CHMP Meeting Highlights (10 to 13-Oct-2016)

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4.2.4 Industry stakeholder platform on the operation of EU PV legislation As already mentioned previously, the EMA hosted the tenth industry stakeholder forum on the operation of European Union pharmacovigilance legislation on 21-Sep-2016.

Presentations included recent Regulatory Science initiatives such as the PROTECT and WEB-RADR projects. In addition to the presentations published earlier, the video recording from this meeting is now available.

→ Link to EMA Meeting Page

4.2.5 EMA to host workshop on “big data” The EMA has announced it is organising a workshop on 14 and 15-Nov-2016 to identify opportunities for big data in medicines development and regulation, and to address the challenges of their exploitation. It is recognised that big data has the capability to contribute to the benefit-risk assessment of medicines.

The workshop will review the advances made in the field of big data and the opportunities for its application in medicine regulation. It is intended this will help regulators determine the best approaches to using big data for the development, authorisation and post-marketing surveillance of medicines.

The Agenda for the workshop is available on the Event Page and a live broadcast will be offered.

→ Link to EMA News Release → Link to EMA Event Page

4.2.6 EMA issues updated EURD list The EMA has published an updated EURD list, which was last revised on 19-Oct-2016. It provides the EU Reference Dates, frequencies for submission of PSURs and related data lock points for a list of active substances and combinations including those contained exclusively in nationally authorised medicines.

The changes to the EURD list are highlighted. 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.

The Introductory Cover Note to the EURD list was also revised but no significant change was identified.

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

4.2.7 EMA issues revised Pharmacovigilance System Manual The EMA has published a revision of its Pharmacovigilance System Manual, which supersedes the 2014 version. This document provides an overview of the Agency’s organisational structure, responsibilities, procedures, processes and resources. It also describes arrangements for compliance management, including audits.

→ Link to EMA PV System Manual

4.2.8 EMA issues new booklet on European Regulatory System for Medicines This booklet describes how the European regulatory system for medicines operates. It explains how medicines are authorised and monitored in the EU and how the European medicines regulatory network works to ensure that patients have access to high-quality, effective and safe medicines.

→ Link to EMA booklet on European Regulatory System

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4.2.9 EMA issues new information on outcome of PSUR assessment for NAPs Following the implementation of the single assessment 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 or updated since our previous issue and variations are required for the following substances:

• Doxazosin • Botulinum toxin a (various forms) • Cefoperazone • Paclitaxel • Hydromorphone • Bendamustine hydrochloride • Testosterone and Testosterone undecanoate

The EMA has also announced the availability of a new search page to help users find the outcomes of PSUSA procedures, which can now be searched and filtered.

→ Link to PSUR Single Assessments search page → Link to EMA News Release on new search page

4.2.10 CMDh issues new PSUR Assessment Reports for NAPs In line with the Best Practice Guide to facilitate European Work Sharing of PSURs for Nationally Authorised Products (NAPs) during the transition period, the conclusions of the Assessment Report are published on the CMDh website. Following the implementation of the Single Assessment Procedure for NAPs, this will be gradually replaced by the publication on the EMA website started in July 2015.

The MAHs of products for which there are no routine PSUR submission requirements have to take account of final assessment conclusions and submit a variation within 90 days, as necessary.

The summary of the PSUR Assessment Report for human coagulation factor VIII inhibitor bypassing fraction has been published on 21-Oct-2016.

→ Link to Summaries of Assessment Reports

4.2.11 EMA issues outcomes of imposed non-interventional PASS for NAPs The EMA has created a new page on its website where it will publish the regulatory outcomes following the assessment of final study results of imposed non-interventional post-authorisation safety studies (PASS).

Whereas the outcomes associated to PASS for Centrally Authorised Products (CAPs) are published as part of the European Public Assessment Report (EPAR), this new page only lists the outcomes for active substances contained in Nationally Authorised Products (NAPs).

Where required, MAHs for products containing the active substance concerned by the PASS final report should submit a variation to align their marketing authorisation with the adopted outcome. MAHs for products containing the same active substance but not concerned by the PASS should consider whether the proposed changes apply to their products.

The outcome of the assessment of new PASS final study results has been published and a variation is required for the following substance:

• Trimetazidine

→ Link to EMA outcomes of imposed PASS

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4.3 UK Agency (MHRA)

4.3.1 Drug Analysis Prints renamed to Interactive Drug Analysis Profiles The MHRA has issued an update indicating that the former “drug analysis prints” have been renamed to “interactive Drug Analysis Profiles” (iDAPs). Each iDAP contains complete data for all spontaneous suspected adverse drug reactions reported to the MHRA via the Yellow Card Scheme or from pharmaceutical companies. iDAPs enable to interact with the data through a number of filters directly on the website.

→ Link to MHRA Page → Link to iDAPs Page

4.3.2 MHRA updates toolkit to minimise the risks of valproate during pregnancy The MHRA has updated the information in the toolkit on the risks of valproate medicines in female patients. The Agency has worked with industry, healthcare professionals and patient groups on this toolkit to ensure female patients are better informed about the risks of the epilepsy medicine during pregnancy. The page now includes learning video for GPs.

→ Link to MHRA Page

4.4 French Agency (ANSM)

4.4.1 ANSM provides update on PRAC/CHMP/CMDh meetings Following the PRAC meeting of October 2016, the ANSM has issued a document to summarise the PRAC decisions. The document does not include any ANSM recommendation.

→ Link to ANSM release – October 2016 PRAC (in French)

Following the CHMP meeting of October 2016, the ANSM has issued a document to summarise the CHMP decisions. The document does not include any ANSM recommendation.

→ Link to ANSM release – October 2016 CHMP (in French)

Following the CMDh meeting of October 2016, the ANSM has issued a document to summarise the CMDh decisions. The document does not include any ANSM recommendation.

→ Link to ANSM release – October 2016 CMDh (in French)

4.4.2 ANSM issues English version of its 2015 annual report Following the publication of the initial Report in French last August, the ANSM has now issued the English translation of its 2015 Annual Report.

→ Link to the ANSM 2015 Annual Report (in English)

4.4.3 Commissions/Committees in relation with Pharmacovigilance The Pharmacovigilance Committee has issued the minutes of the meeting of 17-May-2016 where the following topics were discussed:

• Ginkor: Risk / Benefit ratio to be re-evaluated • Tolicizumab: national monitoring to be continued and alert to be sent to the European Rapporteur • NSAIDs: new effects identified in the literature to be evaluated at the European Level

→ Link to ANSM PV Committee minutes – 17-May-2016 (in French)

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5. QUALITY ASSURANCE, INSPECTIONS AND AUDITS

5.1 New ANSM injunction letter published Injunctions are administrative measures taken by ANSM after inspections in case of deficiencies that should be solved within a set timeframe. One new injunction letter has been issued for Laboratoires Besins International, which includes a deficiency related to Pharmacovigilance, amongst others. A deficiency was identified in the oversight of the Pharmacovigilance System by the Qualified Pharmacist.

→ Link to Laboratoires Besins International (in French)

5.2 MHRA provides summary of GCP Symposium 2016 The latest MHRA Inspectorate blog update provides a short summary of the annual GCP Symposium, which was held on 20 and 21-Sep-2016. Approximately 450 delegates attended the event to hear presentations on various topics including the Reference Safety Information (RSI), effective CAPA and Data Integrity. An update on the EU Clinical Trials Regulations was also presented.

→ Link to MHRA Blog Post

5.3 BfArM provides updated information on Pharmacovigilance Inspections The German Agency has updated the information on its website in relation to the Pharmacovigilance Inspections performed by BfArM. This includes a description of the steps in the process and links are provided to associated resources, including presentation material.

→ Link to BfArM Page (in German)

6. DRUG SAFETY AND LIABILITY RISK

6.1 UCB and Distilben A French court sentences UCB to indemnify a patient A woman suffering from infertility has won a lawsuit in appeal and obtained 126.000 € in compensation. This represents a new Court position as original prescriptions were not available to prove that the patient’s mother was exposed to Distilben during her pregnancy.

→ Link to Pourquoi Docteur (in French)

7. OTHER NEWS AND RESOURCES

7.1 Investigation of death during Phase 1 Clinical Trial in France Various articles have been published which point out shortcomings at both the ANSM and BIOTRIAL, the CRO in charge. Moreover, the media voiced accusations that ANSM wanted to hide some information, which the French Agency has refuted.

→ Link to Le Figaro article on Biotrial (in French) → Link to Le Monde article on ANSM (in French) → Link to the ANSM press release (in French)

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7.2 Social Media and Pharmacovigilance: French projects The French Academy of Pharmacy held conference on the use of social media in Pharmacovigilance. Different projects / tools used to scrutinize adverse reactions including projects financed by ANSM have been presented. The minutes and presentation slides are available on the website of the Academy.

→ Link to the webpage of the Academy of Pharmacy (in French)

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-Jun-2016.

→ Link to Health Canada Page

7.4 New TranScrip Commentary The consultancy company has published the slides it presented at the 3rd Annual Risk Management and Pharmacovigilance Summit on 27 to 29-Sep-2016 in Vienna. The presentation describes the results of a survey conducted to review the characteristics of outsourcing in Pharmacovigilance activities.

→ Link to TranScrip Commentary

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) → Introduction to Pharmacovigilance and Rules for Expedited Reporting of ICSRs in Europe

November 22 in Vienna, Austria

→ Signal Detection and Management Information Day: Key Principles, Processes and Responsibilities December 02 in London, UK

DIA Events → MHRA/DIA Excellence in Pharmacovigilance

November 14 – 18 in London, UK

→ Benefit/Risk Management November 21 – 22 in Basel, Switzerland

→ Signal Management in Pharmacovigilance November 23 – 24 in Basel, Switzerland

→ 13th DIA Japan Annual Meeting 2016 November 13 – 15 in Tokyo, Japan

→ Practical Guide for Pharmacovigilance: Clinical Trials and Post-Marketing December 12 – 13 in Dubai, UAE

→ Pharmacovigilance and Risk Management Strategies 2017 January 23 – 25 in Washington DC, USA

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DSRU Events → Pharmacovigilance in Products Subject to Licensing Agreements

November 16 – 17 in London, UK → 3rd European Conference on Monitoring the Effectiveness of Risk Minimisation

November 22 – 24 in Prague, Czech Republic → Monitoring Safety in Clinical Trials and Drug Development

February 08 – 09 in London, UK

Other Events → IFIS – Clinical trials vigilance (event in French)

November 15 in Paris, France → FDLI Webinar – Social Media: Innovative Uses and Practical Experiences

November 17, 02:00 to 03:30 PM ET → IFIS – Risk Management Plan (event in French)

November 29 in Paris, France → IFIS – PSUR writing in English

November 29 – 30 in Paris, France → IFIS – Missions and Responsibilities in PV for the Qualified Pharmacist (event in French)

December 08 in Paris, France → CBI – 2nd IDMP Update Forum

December 08 – 09 in Philadelphia PA, USA → IFIS – Quality in Pharmacovigilance (event in French)

December 09 in Paris, France → IFIS – Pharmacovigilance for assistants (event in French)

December 13 – 14 in Paris, France → Medicines for Europe (previously EGA) – 10th Pharmacovigilance Conference

January 25 in London, UK