EU Pharmacovigilance Legislation (EU NL)

1. EU Pharmacovigilance Legislation (EU NL) • Regulatory Implementation status • Overview and industry challenges Anne-Marie De-Ferran Associate VP QPPV Office Manager QPPV Office&PV Policy Global Pharmacovigilance& Epidemiology April-2014 QPPV Office Global Pharmacovigilance & Epidemiology Sanofi

2. LPC Newcomers – October 14th to 15th – Chilly-Mazarin EU Legal Framework for Pharmacovigilance Applicable to the 28 Member States and Adopted by Norway, Iceland & Liechtenstein [European Economic Area (EEA) countries]

3. Regulatory Network Key European Authorities in PV Heatlh Authorities of each Member State National Competent Authorities (NCA) The Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human, examine any question relating to marketing authorisation of a medicinal product in two or more Member States in accordance with the mutual recognition procedure or the decentralised procedure Helps protect and promote health in Europe by evaluating medicines for both human and veterinary use EMA Executive body of the European Union responsible for proposing legislation, implementing decisions, upholding the Union's treaties and day-to-day running of the EU The Committee for Medicinal Products for Human Use is the committee at the EMA that is responsible for preparing opinions on questions concerning medicines for human use. CHMP The committee at the EMA that is responsible for assessing and monitoring safety issues for human medicines. PRAC

4. Agenda • Regulatory Implementation status • Overview of Major Regulatory Milestone of the EU Pharmacovigilance Legislation • Industry Challenges

5. EU PL – Regulatory Implementation status

6. EU Pharmacovigilance Legislation Regulation 1235/2010 1027/2012 Directive 2010/84/EU 2012/26/EU • Promote and protect public health by reducing burden of ADRs and optimising the use of medicines • Clear roles and responsibilities • Robust and rapid EU decision-making • Engage patients and healthcare professionals • Science based - integrate benefit and risk • Risk based/proportionate • Increased pro activity/planning • Reduced duplication/redundancy • Increase transparency and provide better information on medicines Applies on 2-Jul-2012 Applies on 5-Jun-2013 some articles apply on 4 Dec 2012 Applies on 21-Jul-2012 Applies on 28-Oct-2013 Applies on 10-Jul-2012 Art.29/ 38 apply on 10 Jan 2013 Implementing Regulation 520/2012 198/2013 () PV fees – Regulation (draft) PAES delegated act (draft) Applies on 31-Dec-2013. Good Pharmacovigilance Practices (GVP) Regulatory & procedural guidance EMA Information & Communication Learn more on EU-PL: EMA website European Commission website

7. 5No Draft Directive 2010/84/EU Transposition in Member States • Overviewof the transposition status from the Directive 2010/84/EU within each Member State • Directive effective date at National Level: 21-July-2012 (MRP/DCP products) • National Legislation release date: EU NPL Transposition Status in 31 Member States National Legislation: 26 Final Last update: 01-April-2014

8. EU PV legislationstatus • Implementation of the Pharmacovigilance legislation in July 2012 • March 2014 : In EEA, final transposition of Directive 2012/84/EU into 26 national legislations (5 missing) • Amendment on directive and regulation released in Q3 2012 following “Mediator stress test” • The majority of the 15 GVP Modules has been now published, pieces are still expected. • “Pharmacovigilance” legislation in name only • Global impact; leaves virtually no function untouched • Massive changes in multiple processes required, new skill sets required. • Lack of harmonisation with non-EEA countries • Increased bureaucratic burden with no contribution towards promoting patient safety.

9. Updates to the PV legislationsince July 2012 • Amendment of the PV legislation • Recent pharmacovigilance incidents in the EU have shown the need to strengthen three aspects of the pharmacovigilance legislation • Release of Dir. 2012/26/EU [25 Oct. 2012] / Reg. (EU) 1027/2012 [14 Nov. 2012] Main focus on: • In case of urgent safety issue Automatically assessed at European level [Art 107i (Dir.)] • Notification of MA status WW when safety concern [Art 23a (Dir) / Art 13a (Reg) – Art 14b (Reg.) / Art 123 (2) (Dir.) ] • Art 23 (Reg) (c)-(d) • GVP modules status • 5 New, 3 Revised, 3 Expected • Implementing Regulation 198/2013 on black symbol of 7 March 2013 • Adopt black symbol (▼) to identify medicinal products that are subject to additional monitoring • PAES • Delegated act on PAES - Public consultation conducted from Nov. 2012 till Feb. 2013 • Future PV fees

10. EU NPL – Overview and industry challenges

11. Major Regulatory Milestones PSMF Fees Transparency xEVMPD WW MA status notification EU PV Legislation Oversight by QPPV PRAC Additional Monitoring Referral RMP ICSR Management and Reporting PASS/ PAES Signal Detection and Screening Renewals New PSUR/ PBRER

12. Transparency and Communication • Creation of medicines web-portals (EMA and each Member State) • PRAC Agenda, Minutes, including signal detection activities • List of products subject to additional safety monitoring • Summary of RMP for lay public • PASS protocols and public abstract of results • Community Reference Dates and frequency of PSUR submission • Final assessment conclusions of PSUR and Urgent Union Procedure • Information on Urgent Union Procedures • EU coordinated communication about safety issues • For products authorised in more than one Member States, EMA responsible for coordination (timetables) of safety announcements between national Competent Authorities • Eudravigilance publicly accessible • Online publication of suspected side effect reports since May 2012 (Centrally Authorised Products) • Information on Medicinal Products (xEVMPD)

13. EMA 7th scientific Committee (Replacing the PhVWP) Members: EU National Agencies, HCP and Patients representatives Key role in PV assessments: mandatory or consultative role Referrals (Art 20, 31, 107i) PSUR PASS protocols and results Signal detection Safety communication EURD lists Safety concerns : A major change in EU decision making process for safety issues Rapid risks evaluation in the context of the identified benefits Final responsibility for opinion on the risk-benefit remains with CHMP (centralised products) or CMDh(other products) PRAC (PV Risk Assessment Committee) • Additional monitoring • RMP • Renewals & annual assessment • Type II safety variations • PV audits, inspections requests & results

14. “The Pharmacovigilance Risk Assessment Committee (PRAC) is responsible for assessing all aspects of the risk management of the use of medicinal products [human use] approved in EEA. • This includes the detection, assessment, minimisation and communication relating to the risk of adverse reactions, having due regard to the therapeutic effect of the medicinal product. • It is responsible for the design and evaluation of post-authorisation safety studies and pharmacovigilance audit.” PRAC - Responsibilities Source: EMA webpagePharmacovigilance Risk Assessment Committee (PRAC)

15. The PRAC is composed of: • a chair and a vice chair, elected by serving PRAC members; • one member/alternate nominated by each of the 28 Member States; • one member/alternate nominated by Iceland and by Norway; • six independent scientific experts nominated by the EC; • one member/alternate to represent healthcare professionals nominated by the EC; • one member and one alternate to represent patients organisationsnominated by the EC. PRAC - Composition chair vice chair June RaineAlmaath Spooner Source: EMA webpagePharmacovigilance Risk Assessment Committee (PRAC)

16. CHMP Legally binding DECISION to MSs PRAC Recommendations – Process Flow • Referrals • PSUR Assessment • PASS Results Nationally Authorised Products Centrally Authorised Products (CAP) (including MRP & DCP) PRAC RECOMMENDATION If at least 1 CAP Member States Consensus* Majority Vote* OPINION* * If CHMP/ CMDh recommendations differ from those of the PRAC, the CHMP/ CMDh shall provide a detailed explanation of the scientific grounds for the differences with their recommendations.” Source: www.ema.europa.eu

17. PRAC - Volume of main activities[July 2012 July 2013] Source: PRAC minutes/ 7th EMA stakeholdersmeeting(June Raine)

18. New referral procedure ‘Urgent Union Procedure’ (107i) • Automatically assessed at European level • Triggered by a Member State or the European Commission • To provide a rapid evaluation of a safety issue linked with a medicine, regardless of its initial authorisationroute of the medicine • Scientific assessment lead by PRAC in collaboration with CHMP and Reference Member State • Public hearing may be organised depending of the seriousness of the issue • Re-examination not possible • National temporary measures are possible prior PRAC assessment • Outcome • No action, MAH further evaluation, PASS, RMP, Suspension of MA, Revocation of MA, No renewal of MA Referral proceduresA new pan-European assessment of safety issues

19. Processes for the management of adverse reaction reports need to be re-engineered and procedures will need to be amended in order to address the new requirements • New definitions, in particular for • Adverse Reaction: A response to a medicinal product which is noxious and unintended. • Includes medication errors and use outside the MA • Direct patient reporting • New Reporting arrangements • All EU and non-EU Serious ADRs to Eudravigilance (EV) only within 15 days , including consumer reports • All EU non-serious reports to EV only within 90 days • EV database is the single point of receipt for expedited reports • Until EMA can “ensure the functionalities of EV“ (not before 2015) - Transitional arrangements: • All national non-serious ADRs to Austria (for products under additional monitoring), Croatia, Denmark, Germany (for Vaccines only), Italy (except literature cases), Poland, and Romania (within 90 days) • Revised obligations for collecting reports in non-interventional/observational studies • All AE (serious or not [for EU at least] in a PV database , to allow reporting of all ADRs. • Literature monitoring (starting 2015) • EMA’s monitoring for a list of product in selected scientific literature • MAH’s monitoring for all other medical literature and other products ICSR Reporting and Management

20. Non serious case collection from all PAS: number one concern • Dir. Article 107(1) : • “MAHs shall record all suspected adverse reactions in the Union or in third countries which are brought to their attention, whether reported spontaneously by patients or healthcare professionals, or occurring in the context of a post-authorisation study”. GVP Module VI implies only if actively sought i.e. protocol driven • Q&A (July 2012) citing GVP Module VI: • all adverse events should be collected by the MAH and assessed as to whether or not they are suspected adverse reactions • Applies to all NIS, even if conducted outside Europe • Significant impact on all non-interventional field studies (NIS) which become more burdensome regarding AE collection than clinical trials. • New orientation: proposal of new requirements on management and reporting of suspected ADR originating in post-authorization studies • Based on feedback received from practical implementation of requirements set out in module VI • Public consultation on revised text S1 2013 - Still level of draft – final requirements may vary Post Authorisation Studies (PAS)Non-Interventional Studies (NIS)

21. Reports from PSPs / MRs • All to be classified as solicited in final GVP Module (July 2012), contrary to what was proposed in the April 2012 draft • Poorly documented reports; impossible to make informed causality assessment and attempts to follow up nearly always unsuccessful • Significant bureaucratic burden with no contribution to patient safety • Said to be based on FDA position but not consistent with 1997 guidance • Industry propose to revert to the April 2012 draft guidance • Clarify the definition and allow classifying into those that actively seek information and those that do not. • Actively sought = solicited • Others = implied causality • Longer term - collect data to assess impact on signal detection • Workshop conducted in June 2013 (@) Patient Support Programs (PSP) / MarketResearch (MR)

22. Signal detection in Eudravigilance by the EMA and NCAs (Published and managed by the PRAC) • Information on “validated” signals, Emerging Safety Issues and the outcome of signal assessments should be exchanged between competent authorities and MAHs. • Requirements for the MAH • To track and document all steps of signal detection and management, • To report to competent authorities validated signal detected from Eudravigilance (2015) and emerging safety issues such as safety issues arising from the signal activity which impact B/R balance and/or have an implication for public health • To monitor Eudravigilance outputs (2015) Signal Detection and Management

23. PRAC - Signal management process List of confirmed signals publishedn=144Feb 2014 MSs EMA [MAH] MSs EMA PRAC Decision Opinion Position CHMP/ CMDh EC Source: www.ema.europa.eu

24. EMA publications • PRAC recommendations on safety signals • MAHs to keep informed about the PRAC recommendations concerning their products. • A cumulative list of all signals per product discussed at the PRAC since September 2012 PRAC - Signal / Recommendations PRAC Signal Recommendations Supply Additional Information Regulatory Action nationally authorised medicines centrally authorised medicines actionable directly by the MAHs concerned CHMP Endorsement CMDh Endorsement MAHs are expected to take action according to the recommendations Source: EMA webpage – Signal Management

25. Scope amended • Analysis of the Benefit –Risk (B/R) balance of a medicinal product with cumulative review of safety issues, rather than a detailed listing of individual case reports in a period. • New concept of ICH E2C(R2) implemented in EEA • Requirements for PSUR proportional to the risks : Not necessary for low risk products • Generics/Well-established use products/ Traditional herbal products • EU Reference Dates and frequency (EURD) list • List of substances and combinations of active substances, identify PSURs to be submitted in accordance with the EURD as determined by the CHMP and CMDh following consultation with PRAC. • Frequency of PSUR/ PBRER specified in the Marketing Authorization or in EURD list • Variation Required • in case the PSUR cycle is stated in the MA and to align the MA in line with EURD list • for generics remove a previous standard PSUR statement or to align with EURD list New PSUR / PBRER – Periodic Benefit Risk Evaluation Report

26. EU Renewals Addendum to Clinical Overview • Renewal submission at least 9 months before expiry • Package consolidated quality, safety and efficacy, including all variations • Request an Addendum to Clinical Overview (ACO) including an Expert Statement without PSRs* submission • Final guidelines on renewal process published in Q2/Q4 2012 • Actually content corresponds to a “mini PBRER" • 2/21 Jul 2012 • Renewalincl. CES+ Renewalincl. ACO with expert statement • PSRs* when needed + No more PSRs • Literature ref Literature ref + • Summary of PSMF • RMP when needed • History of PV inspection and summary of non compliance * PSR: considered abbreviation PSR for PSUR, PSUR addendum, Summary Bridging Report and line listing

27. Scope Any study relating to an authorized medicinal product conducted with the aim of identifying, characterizing or quantifying a safety hazard, confirming the safety profile of the medicinal product, or of measuring the effectiveness of risk management measures. • When imposed by a competent authority : • As an obligation as part of a marketing authorization or under specific circumstances (well established products) • PRAC or to the competent authority of the concerned member state provide • Endorsement/ Objection: Draft protocol /amendment • Recommendation: final study reports and abstracts. • When voluntarily initiated by a marketing authorization holder including studies proposed and committed in the Risk management plan (RMP) Post-Authorisation Safety Study (PASS)

28. Post-AuthorisationEfficacyStudies (PAESs) Objectives Studies aimed at determining clinical outcome following initial assessment based on surrogate endpoints Studies on combination with other medicinal products Studies in sub-populations Studies in the context of the European standard of care Studies linked to a change in the understanding of the standard of care for the disease and/or the pharmacology of the medicinal product Studies aimed at determining the long term efficacy of a medicinal product Studies in everyday medical practice Draft Delegated act on PAES

29. New RMP Template, new requirements • Obligation to demonstrate the effectiveness of risk minimization measures contained in the risk management plans • Key measures of RMP will be included in the Marketing Authorizations (MA) as conditions with deadlines for the fulfilment • Publish a summary of RMP in lay language • Explicit legal basis to request a RMP in an application for Marketing Authorization • For all new Marketing Authorizations (including generics) • For authorized products if there are safety concerns Risk Management Plan (RMP)

30. List of medicines under additional monitoring – Monthly update since April 2013 • Mandatory • All new active substances (MA from 1-Jan-2011) • All biological products, including biosimilars (MA after 1-Jan-2011) • Following PRAC recommendation • Authorised products subject to Post Authorisation Study • Authorised products with conditions or restrictions for the safe and effective use • Medicines will be removed from the list • 5 years after Union Reference Date • or until all conditions are fulfilled • SmPC and PIL statement • Medicines under additional monitoring • “This medicinal product is subject to additional monitoring” preceded by a black symbol()+ standardised explanatory sentence • For all other medicinal products • Healthcare professional and patients asked to report any suspected adverse reaction  Product Information change: Additional Monitoring scheme

31. Agency / NCA Publications EMA website : EMA Annual list National Agencies websites • Action/ Information related to Registered medicinal products in the EU • MA refused, revoked or suspended, withdrawn / • Supply prohibited / Commercialisation stopped / • Non Renewal/ B/R re-assessment (new risk & change in the existing risk) MAH notification + reasons MAH Notification of MA events status Transparency increasedArt 23a (Dir) / Art 13a (Reg) – Art 123 (2) (Dir.) / Art 14b (Reg.) • MA refused, revoked or suspended • Supply prohibited • Commercialisation stopped • Grounds Art 116/117(i) efficacy, negative B/R, quali-quantitative composition ) NCA and EMA EU WW • + reasons (e.g. safety, efficacy, quality, commercial ) • Other (i.e Commercial) • Same information, in national languages, for the products registered or marketed in the country NCA or EMA EU

32. The objective is to better identify the drugs within the ICSRs -Individual Case Safety Reports • Create a list of all medicines authorised and registered in EU • Identify medicines accurately, especially medicines included in reports of suspected adverse reactions • To improve signal detection accuracy and capabilities • A number of Data elements/set for medicinal products were required by July 2012. • Product Information • A description of the strength of the active substance(s) • A description of the medical device(s) • The pharmaceutical dose form • The route(s) of administration • An electronic (not a scan) copy, including date of last revision, reference numbers and document language of SmPC, MAH responsible for batch release • Maintenance of data to be set up. Mandatory as of June 2014 • Clarification of the language requirements depending on the authorisation procedure : • National official languages for National Procedures • English text for CP; English Core European text for MRP/DCP “Article 57” – xEVMPDExtended EudraVigilance Medicinal Product Dictionary

33. Pharmacovigilance System Master file (PSMF) Document describing the company’s PV system Replaces the Detailed Description of the Pharmacovigilance System (DDPS) Presents the management organisation of the Company PV system from a corporate perspective including its affiliated entities in respect of the applicable regulatory requirements. Includes additional descriptions process (RMP, Safety commitments…) and figures pertaining to the company portfolio, and results from system audits and Key Performance Indicators. Tool for QPPV to maintain oversight with the Pharmacovigilance System in the company. Provision of a soft or a hard copy of the PSMF within a 7 day time-frame if requested by an authority or at an inspection. Supervisory authority for PV is the Competent Authority in which the PSMF is located PSMF Summary - Key elements of the Pharmacovigilance System To be included in application for any Marketing Authorization (MA), whatever the registration procedure in module 1.8.1 of the dossier at the time of the renewal, or through Type IAIN variation not later than July 2015.

34. The MAH shall have permanently and continuously at its disposal an appropriately Qualified Person responsible for PharmacoVigilance” (QPPV) in the EU. • The QPPV must be appropriately qualified i.e. adequate knowledge and skills to manage the PV system as well as expertise/access to expertise in the following areas: • Medicine, Pharmaceutical Sciences, Epidemiology, Biostatistics • If the QPPV does not have basic medical training, access to a medically trained person must be available and documented in the PSMF. • The QPPV must reside in the EU [extended to Norway, Iceland or Liechtenstein (EEA)]. • NCA’s have the option to request the nomination of the PV contact person at national level reporting to the QPPV. • A contact person at national level may also act as the QPPV. The QPPVrole: RegulatorybackgroundEuropean Legislation [DIR Art 104(3)(a)]

35. QPPV oversight =The QPPV should know everything (1) • Establish and maintain the MAH’s PV system • Have sufficient authority to influence the performance of the quality system and the PV activities • Promote, maintain and improve compliance with the legal requirements • To be compliant with legislative requirements • Tools and processes: • ICSR reporting and submission data • IT systems (database changes, validation status, failures during validation etc.) • aggregate report processes • SDEAs • SOP • Trainings • Compliance evaluation/reporting (ICSR, document submission, safety variation –labelling update etc. – both global + local ) • Quality of data (PBRER, B/R evaluation –ensuring correctness and completeness of data)

36. QPPV oversight =The QPPV should know everything (2) QPPV must have an overview of the safety profiles and any emerging safety concerns in relation to the medicinal products for which the MAH holds authorisations • Products and Processes: • Safety profile of new INNs coming to portfolio (projects, in-licensing, due diligence) • Be aware of any conditions or obligations as part of the MAs and other commitments relating to safety or the safe use of the products; • Signal detection and management • Benefit-risk information • Risk management and risk minimisation measuree.g. be aware of the content of RMP • Be aware of PASS requested by a competent authority including the results of such studies • Be involved in the review and sign-off of protocols of PASS conducted in the EU or pursuant to a RMP • Risk communication (referrals, Product Alerts, product withdrawal ….)

37. QPPV oversight =The QPPV should know everything (3) • Ensuringresponse to any request from the CA and the Agency for the provision of additional information necessary for B/R evaluation • Providing any other information relevant to the benefit-risk evaluation to CA and Agency; • Providing input into the preparation of Regulatory action in response to emerging safety concerns (e.g. variations, urgent safety restrictions, and communication to patients and healthcare professionals); • To be contact point for PV inspections Acting as a single contact point for the Competent Authorities on a 24-hour basis Must be located in the EEA

38. QPPV oversight =PV System compliance and quality • Approval/signatures required • PSMF • PSUR/PBRER approval • RMP approval • PASS approval (QPPV) • Internal audit • Ownsystem • Thirdparties • External partner audit • PV inspection • Competentauthority • EMA CA or EMA/PRAC negotiation(PBRER, RMP, PASS, DUS etc.) Joint studies Audit plan Periodic audit Compliance data Compliance CAPA -follow-up

39. Fees for PharmacoVigilance Legal proposal under discussion since June 2012 between European Commission, European Parliament, Member States (MS). On June 26, 2013 European Commission has adopted a legal proposal (@) In February 2014, EU MS have approved a compromise agreement between with the European Parliament on a draft regulation for establishing the long overdue EU pharmacovigilance fee regime (@) The final regulation needs to be approved by the Parliament and council once revised by the lawyer linguist. Agreement on 2 types of fees charged to marketing authorisation holders: Annual Flat Fee €67 per pharmaceutical form (eg tablets, drops and injectables) of medicinal products authorized at national level. This fee is intended to cover the costs of general pharmacovigilance activities of the EMA, such as safety data management, literature monitoring and information technology, notably maintenance of the EudraVigilance database. Pharmacovigilance Assessment Procedure Fees The EMA will charge fees for three pharmacovigilance assessment procedures performed at EU level to marketing authorization holders (MAHs) that have at least one product involved in such a Union-wide PV procedure: Assessment of PSUR – €19,500 per procedure, of which €13,100 is for national competent authorities (NCA); Assessment of PASS – €43,000, of which €18,200 is for NCA; and Assessments of referrals initiated as a result of PV data – standard fee of €17,9000, which can reach up to €295,000 in exceptional cases involving five and more active substances. Sharing of the referral fee revenue between the involved authorities: 1/3 for EMA - 2/3 for NCAs . The payment of the fee is divided between the MAHs, with each of them being charged a share of the fee that is proportionate to their share of products covered by the procedure. No double charging - Fees paid at EU level covered by the regulation not charged at national level. Small and medium-sized enterprises : fee reduction of 40% and micro-enterprises: exempted from any fees. Reductions from the annual flat-rate fee : specific types of medicinal products, (e.g generics.)

40. Conclusion (1) • The 2010 EU PV legislation is a massive undertaking for all parties; it offers opportunities, e.g.: • Focus has shift on benefit / risk balance with PBRER concept • Modular concept for RMP/PSUR • Less PSUR for mature and ‘safe’ products • Focus on signal rather than on ICSR evaluation • Integrated “signal-to-labeling” approach • Major step forward in transparency and stakeholder involvement • Big step toward harmonised pharmacovigilance processes and product evaluation throughout EU • PRAC is central to the EU PV legislation • …but seems also to generate bureaucracy, e.g.: • Complexity of the regulatory text corpus does not go toward simplification • AE reporting requirements in NIS go against the objective to develop real-life studies; AE reporting requirement in PSP is not reasonable • PRAC may be overwhelmed by the volume of activity 40

41. Conclusion (2) • The concept of risk proportionality is there, but… • Visible: new PSUR format with a more thoughtful and evaluative approach, no more PSURs for mature products, • Blurred: massive production of RMPs, logic of signal management at PRAC • The new framework for PV, based on collecting, reporting and analysing “non-ICSRs” safety events (signals, regulatory decisions…) is emerging painfully • Technology and budget constraints: Art 57 – xEVMPD, EMA website, PSUR repository, new Eudravigilance functionalities, centralisation of literature safety information… • No standard process/system for exchange of information regarding signals (e.g communication MAH PRAC) and regulatory decisions (art 23) • Anticipation of Budget increase with PV fees 41

42. Legislative texts

43. Replace volume 9A Good PharmacoVigilance Practices (GVP)

44. Final- planned 2014 • Module VI Rev. 1 – ADR • Public consultation (PC) - planned 2014 • Module XI - Public participation in pharmacovigilance - Q2 • Module XII - Continuous pharmacovigilance, ongoing benefit-risk evaluation, regulatory action and planning of public communication - Q2 • Module XIV - International cooperation- Q2 • PII – Biological medicinal products - Q2 Latest news since last meeting – GVP module update

45. Regulatory and procedural guidelines

46. EU PV REFERENCETEXTS QPPV Office Version as March 2014

47. Regulatory and procedural guidelines

48. Regulatory and procedural guidelines

49. Regulatory and procedural guidelines

50. EMA Information & Communication