New ASMF - Aim to support and improve the ASMF procedure across the European Regulatory Network

EMA has released the new ASMF guideline, which is effective from 1 October 2012. 

Updates: 

• ASMF holders shall not modify the contents of their ASMF (e.g. manufacturing process or specifications) without informing each Applicant/MA holder and each National Competent Authority/EMA. This obligation remains valid until the Letter of Access has been withdrawn by the ASMF holder. ASMF holders should provide the updated ASMF to all interested Authority/EMA. This obligation remains valid until the Letter of Access has been withdrawn by the ASMF holder. ASMF holders should provide the updated ASMF to all interested parties with reference to the revised version number.

• Any change to the ASMF should be reported by every MA holder to the relevant National Competent Authority/EMA by means of an appropriate variation procedure. A Submission Letter should be provided.

• In cases where the contents of the ASMF cannot be changed for a certain period of time because of other procedural provisions (i.e. mainly because of on-going MRP procedures), the ASMF holder should still provide the aforementioned data to the MA holder and National Competent Authorities/EMA making reference to this reason and requesting a later date of implementation. 

• At the occasion of the 5-year renewal of a medicinal product, MA holders are required to declare that the quality of the product, in respect of the methods of preparation and control, has been regularly updated by variation procedure to take account of technical and scientific progress, and that the product conforms with current CHMP/CVMP quality guidelines. They will also declare that no changes have been made to the product particulars other than those approved by the Competent Authority/EMA.

• MA holders should therefore verify with their ASMF holders whether the above declaration can be met in respect to the active substance particulars. In case changes have not been notified to the MA holder and National Competent Authority/EMA, the necessary variation procedure should be initiated without delay.

Reference: Guideline on Active Substance Master File Procedure

EMA publishes guidance on preparing and reviewing summaries of product characteristics

The European Medicines Agency has published guidance for pharmaceutical companies on how to prepare and review summaries of product characteristics(SmPCs) for human medicines.

The guidance consists of a set of presentations detailing the information that should be included in each of the sections of the SmPC, together with background information on SmPCs both as a presentation and a video. Two videos explaining how to complete the SmPC sections on the therapeutic indication and pharmacodynamic properties of a medicine and on undesirable effects are also available.

The guidance, prepared by the Agency's SmPC Advisory Group, outlines the principles in the European Commission's guideline on SmPC

It is intended to enable companies to make sure that the information in SmPCs is of high quality when they submit them to the Agency as part of applications for new marketing authorisations or updates to existing marketing authorisations.

The background presentation and video also aim to raise awareness of the information provided in SmPCs among healthcare professionals.

SmPCs are a key part of the marketing authorisation of all medicines authorised in the European Union and the basis of information for healthcare professionals on how to use a medicine safely and effectively. They are kept updated throughout the lifecycle of a medicine as new efficacy or safety data emerge.

Reference: How to prepare and review a summary of product characteristics

Blue-box requirements

Blue-box requirements: "Additional information on labeling/package leaflet that may be required nationally". It varies from country to country.

Blue-box requirements different for DCP/MRP and Centralized procedures. It covers following things:

• Price
• Reimbursement
• Legal status (Rx or OTC)
• Identification and Authenticity (Bar-codes)
• Symbols and Pictograms (for dizziness, recycling symbols or Radio-pharmaceuticals)

Recycling

Caution:

This medicine might compromise reactivity and ability to drive

Radiopharmaceuticals

Products containing inflammable material

Be careful

 - Don’t drive before reading the leaflet

Be very careful

- Don’t drive without an healthcare professional opinion

Warning, danger : do not drive

 - Don’t drive again without a doctor opinion

Further information:

1.Blue-box requirements apply to products authorised via a MRP or DCP

2.Blue-box requirements apply to products authorised via Centralized procedure

EU Paediatric Regulation - 1901/2006 & 1902/2006

In November 2001, the European Commission organised a “brainstorming” meeting with representatives of Member States and research-based industry. This was followed by the release of a public consultation paper in February 2002 on “Better Medicines for Children – proposed regulatory actions in paediatric medicinal products”. This paper represented one of the first steps of the Commission to address the problem. A reflection paper followed incorporating the comments received in June 2002. Over sixty sets of comments were received from interested parties and these were taken into account when drafting the proposal for the Paediatric Regulation.
In March 2004, the European Commission consulted on a draft Regulation on medicinal products for paediatric use. On 29 September 2004, the EU Commission released the first proposal for a Regulation on Medicinal Products for Paediatric Use together with an explanatory memorandum, the Extended Impact Assessment and a “questions and answers” document. Following the plenary vote of the European Parliament on the Commission’s proposal on 7 September 2005, the Commission has responded to the parliamentary amendments in the form of a modified proposal. Finally it was adopted by the European Parliament and the Council on 12 December 2006.
The Council of Health Ministers reached political agreement on 9 December 2006. The proposal for a Regulation on Medicinal Products for Paediatric Use went into a second reading in the European Parliament.
On 27 December 2006 the Paediatric Regulation – Regulation (EC) No 1901/2006 as well as the amending Regulation (Regulation (EC) No 1902/2006) – were published in the Official Journal of the European Union. Both entered into force on 26 January 2007.

Features of Paediatric Regulation:

• Establishment of Paediatric Committee (PDCO) with in the EMEA
• 5 paediatric sub-populations

• Paediatric Investigational Plan (PIP) requirement for; new MAAs, new indications,
• Approved products covered by IP
• Products not covered by patents
• Timing of PIPs
• Rewards and Incentives for the industry
• Provision for Waivers and Deferrals

PIP:

Paediatric Investigation Plan (PIP) = A research and development programme aimed at ensuring that the necessary data are generated determining the conditions in which a medicinal product may be authorised to treat the paediatric population.

Sponsors must possess a complaint PIP when applying for marketing approval of unauthorised drugs, or when applying for approval of new indications, pharmaceutical forms, or routes of administration for currently authorised drugs. The default situation is that a Marketing Authorisation Application should now include findings from the paediatric population.

EU PIP should include

• Measures to assess quality, safety and efficacy
• Timing of investigations 
• 5 subpopulations of children
• Formulation development
• For approved products; literature evidence and cross-referral

The requirement for new medicines:

• Marketing Authorisation Application (MAA) considered valid only if it includes one of the following:

• Results of all studies performed and details of all information collected in compliance with an agreed PIP

• A product‐specific waiver or a class waiver

• A deferral

• The PIP also to be included in the application
• The documents submitted to cover all subsets of the paediatric population

Medicinal Products subject to the requirement:

• Authorised medicinal products protected either by a Supplementary protection certificate (SPC) or a patent which qualifies for the granting of the SPC
• New medicinal products (not authorised)
• Medicinal products already authorised

• Applications for authorisation of new indications, new pharmaceutical forms, and new routes of administration

• Requirement covers both the existing and the new indications, pharmaceutical forms and routes of administration

Requirement excludes Marketing Authorisation Application (MAA) for:

• Generics or similar biological medicinal products
• Medicinal products authorised through the well‐established medicinal use procedure
• Homeopathic medicinal products and traditional herbal medicinal products authorised through the simplified registration procedures

EU PIP Waivers:

• If products or class is likely to be in-effective or unsafe in children
• Disease or condition only occurs in adults
• Product does not present a significant benefit over existing products
• Can be issued for one or more paediatric populations or for one or more indications

EU PIP Deferrals:

• When it is appropriate to conduct studies in adults before initiating studies in children because of safety concerns
• When studies in children may take longer than in adults
• May be requested at the same time as the PIP is submitted
• May be requested for specific paediatric populations on technical grounds – formulation development

Incentives/rewards for Industry:

• Paediatric scientific advice: free of charge
• PDCO assessments: free of charge
• Registered products with an SPC: 6 month extension of SPC (Supplementary Protection Certificate)
• Orphan products : Additional 2 years market exclusivity from 10 -12 years
• New type of marketing authorisation, the Paediatric Use Marketing Authorisation (PUMA), which allows ten‐years of data protection for innovation (new studies) on off‐patent products

Reference:

1. EMA: Paediatric Medicines

2. EMA: Report to the European Commission On companies and products that have benefited from any of the rewards and incentives in the Paediatric Regulation and on the companies that have failed to comply with any of the obligations in this Regulation, covering the year 2011

Goodbye to DDPS and Hello to PSMFs

New Pharmacovigilance legislation (Regulation (EU) No 1235/2010 and Directive 2010/84/EU) was adopted by the European Parliament and European Council in December 2010. The aim of the legislation is for better pharmacovigilance and better health protection and promotion.

The legislation is the biggest changes to the regulation of human medicines in EU since 1995. It has significant implications for applicants and holders of EU marketing authorizations. The EMA is responsible for implementing much of the new legislation, effective from July 2012.

Scope of Changes:

1. Authorization requirements: Say goodbye to DDPS (Detail Description of Pharmacovigilance Systems) and hello to PSMFs (Pharmacovigilance System Master File). All MAHs will need to create PSMFs and continuously update them.

2. Risk Management Plans:  All applicants submitting an initial MAA after 2 / 21 July 2012 irrespective of the legal basis of their MA application are required to submit an RMP. This includes generic MA applications.

• For pending initial marketing authorisation applications on 2 / 21 July 2012 which do not contain an RMP, there is no obligation to submit an RMP during the course of the evaluation procedure.
• For those MAs granted before 2 / 21 July 2012 with an existing RMP, the MAH should continue to operate and update the risk management plan.
• As set out in the Commission Implementing Regulation, the new format and content for RMPs shall apply from 10 January 2013 to new or updated RMP submitted as of that date. The template for the RMP will be updated and this is expected to be available around September 2012.
• Marketing authorisation holders (MAHs) are reminded that a summary of the RMP will be published on the European medicines web-portal for the centrally authorised medicinal products and on the national medicines web-portals for the nationally authorised medicinal products. This requirement also applies to existing medicinal products with an RMP.
• Its not required for  a traditional–use registration and homeopathic medicinal products registered via the simplified registration procedure.

3. Post-Authorisation safety studies (PASS) : The new procedures for submission and assessment of non-interventional PASS protocol, substantial amendments and final study results as provided for in Articles 107n to 107q of Directive 2001/83/EC only apply to PASS studies which have been imposed after 2 / 21 July 2012 as a condition to the marketing authorisation. Such studies shall be identified in the RMP. For the CAPs, they will also be incorporated in the Annex II of the marketing authorisation. For the CAPs it means non-interventional PASS imposed through a Commission decision issued after 2 July 2012 including those with an opinion which may have been adopted in the months just before July 2012. For NAPs, it is anticipated that it will be reflected in the national decision to the marketing authorisation.

Article 58 Applications

 

Medicinal products for human use are eligible for evaluation under Article 58 of Regulation (EC) No. 726/2004 if the are intended exclusively for markets outside the community. Eligible products include medicines that are intended for the prevention or treatment of disease of major public interest.

Following products are eligible for Article 58 of the Regulation (EC) No 726/2004:

• Vaccines that used in the WHO Expanded Program of Immunization (EPI)
• Vaccines for protection against a WHO 'public health priority disease
• Vaccines that are part of a WHO managed stockpile for emergency response
• Medicinal products for WHO target disease such as HIV/AIDS, malaria, tuberculosis, lymphatic filarisis, trachoma, leishmaniasis, schistomiasis, African trypansomiasis (sleeping sickness), onchocerciasis (river blindness), dengue fever, Chagas disease, leprosy and intestinal helminths.

Eligible products can include new pharmaceutical forms or routes of administration of medicinal products already authorized in the European Union, fixed combination products and generic products. 

Applicants need to request eligibility for evaluation under Article 58 for a medicinal products before submitting an application. The EMEA's Committee for Medicinal Products for Human Use (CHMP), evaluates data on the quality, safety and efficacy of the products contained in the application in collaboration with the WHO, before issuing a scientific opinion concluding on the benefit-risk ration of the product.

Eligibility request includes the following information:

• Evidence that the applicant is based in the European Economic Area (EEA).
• A draft summary of product characteristics (SmPC).
• A justification for product's eligibility for a evaluation under Article 58. It is recommended that any available epidemiological data on the disease, data on disease burden and a summary of any efficacy or safety data also be submitted.
• A statement that the applicant does not intend to market the medicinal product in the European Economic Area (EEA).
• The proposed classification for the supply of the medicinal product, i.e. not subject to medical prescription or subject to medical prescription. 
• A list of the countries in which the applicant intends to market the product.
• A declaration from the applicant agreeing on communication between the EMA and the WHO using the template "Agreement between EMA and the Applicant".

The eligibility of a product for evaluation under Article 58 is assessed on a case-by-case basis by the EMA in consultation with the WHO.

Once the EMA have received the eligibility request by the applicant it is sent to WHO. Within two months of the submission of the eligibility request, the WHO forwards its position to the EMA. THe EMA's CHMP then examines the eligibility for evaluation under Article 58, confirming or not confirming the WHO' position as appropriate. The applicant receives the WHO "eligibility feedback" letter and the EMA/CHMP eligibility letter. 

Types of applications:

The following types of application can be submitted under Article 58:

• Full complete (or full/mixed) applications
• Well-established use applications
• New fixed combination applications
• Informed consent applications
• Generic applications
• Hybrid applications
• Similar biological applications

Time period

The evaluation procedure follows the same steps and time-frame as the centralsied procedure. As the evaluation is a partnership between the EMA and WHO, WHO experts provide input to the procedure. Total time for evaluation is takes 300 days.

Reference:

1. Guideline on Procedural aspects regarding a CHMP scientific opinion in the context of cooperation with the World Health Organisation (WHO) for the evaluation of medicinal products intended exclusively for markets outside the community.

Referral Procedures

A medicinal product can only be placed on the market in the European Union (EU) when a marketing authorisation (MA) has been issued. There are different types of procedures, national authorisation, centralised procedure (CP), mutual recognition (MRP) and decentralised procedure (DCP). If a MA has granted for particular product by CP, applicant can launch product in entire community at same time. If a MA has granted by particular member state, product can launch in own territory only.

If no MA has been granted in the Community, the applicant can also make use of a DCP and submit an application in all the MSs where he intends to obtain a MA at the same time, and choose one of them as reference MS. The decentralised procedure is to be used in order to obtain marketing authorisations in several Member States where the medicinal product in question has not yet received a marketing authorisation in any Member State at the time of application.

In cases where national authorisations are requested for the same medicinal product in more than one Member State (MS) and the applicant had already received a marketing authorisation in a MS, the applicant can submit an application in the MS concerned using the procedure of mutual recognition. The MSs concerned should then recognise the MA already granted by the reference MS and authorise the marketing of the product on their national territory.

In centralised procedure, product information (SmPC, Labelling and Package leaflet) of the community marketing authorization is same in all countries. But in case of other procedures (DCP & MRP), potential differences are there in product information due to divergent decisions taken by some member states (i.e. medicinal product is approved in different indications in several MSs), could have an impact on the final marketing authorization and free movement of goods in European union.

There are several procedures that involved parties (i.e. MSs, applicant/MAH, the European Commission) have through a referral to address such heterogeneity of MAs and resulting prescribing information following authorisation (via national procedure or MRP) or prior to authorisation (via MRP or DCP), in order to achieve harmonisation of such information.

A referral is an European procedure that allows to address any concerns related to a medicinal product via an arbitration mechanism leading to an EU-wide, binding decision. When a Member State (MS), Applicant, Marketing Authorisation Holder (MAH) or the European Commission (EC) decides to initiate a referral, a notification form is sent to the CHMP/European Medicines Agency Secretariat, clearly identifying its legal basis, the product(s) concerned and a detailed explanation of the issue(s) referred.

Types of Referrals - Legal basis

From Directive 2001/83/EC
Article 29(4) referral ("Mutual Recognition and Decentralized Referral"):  If the MS involved in a MRP/DCP fail to reach an agreement within the 60-day period in the coordination group procedure, a referral according to Article 29(4) shall be triggered. The referral is then triggered by the reference MS in the MRP, on the grounds of potential serious risk to public health, where no agreement was reached during the coordinating group procedure on the assessment report (AR), the SmPC, the labelling or the Package Leaflet (PL), prepared by the Reference Member State (RMS)

Article 30 referral ("Divergent Decision Referral"): An article 30 (1) referral may be initiated when divergent decisions have been adopted by MSs concerning the authorization, suspension or withdrawal of a particular product. For example, where such medicinal product has been nationally authorized in two or more MSs and the authorization diverge (e.g. different indications, contraindications or posology). It may be triggered by the EC, a MS, a MAH or an Applicant.

An article 30(2) referral may be initiated for the same reasons stated above when the medicinal product is on the list laid down yearly by the coordination group.

Article 31 referral ("Community interest referral"): It may be initiated in specific cases where the interest of the community is involved. The expression 'Community interest' has a broad meaning but it refers particularly to the interests of the public health in the Community, for example following concerns related to the the quality, efficacy and/or safety of a medicinal product or new Pharmacovigilance information.

Article 31(1) referral relates to a medicinal product while article 31(2) referral refers to a class/range to medicinal products. Both may be triggered by the EC, a MS, a MAH or an Applicant.

Article 35 and 36 ("Follw-up referrals"): An article 36 referral my be initiated to resolve any post-harmonization divergences that may arise between MSs. It may be triggered by a MS when it is considered that a variation, suspension or withdrawn of a harmonized Marketing Authorization (MA) is necessary for the protection of public health.
These referrals may be triggered by MSs or MAH in the frame of follow-up procedure for medicinal products which have been granted a MA via MRP or which have been subject to complete harmonization in  the frame of a referral procedure.
Article 107 ("Unilateral action by MS in Urgent cases"):  This type of procedure is triggered when a Member state varies, suspends or revokes the marketing authorization for a medicine in its territory because of a safety issue. It informs the CHMP so that a EU-wide decision can be reached.
From Regulation (EC) 1084/2003
Article 5(11): This type of referral is triggered for a medicine that has been authorized by mutual recognition or via the dcentralised procedure when there is disagreement between member states on a variation (type IB)
Article 6(12) and 6(13): This type of referral is triggered for a medicine that has been authorized by mutual recognition or via the decentralised procedure when there is disagreement between Member states on a variation (Type II)
Article 6(12) ------------------------>May be triggered by a MS.
Article 6(13)------------------------>May be triggered by the MAH.
From Regulation (EC) 726/2004
Article 20: This type of procedure is triggered for the medicines that have been authorized via the centralsied procedure.The outcome of these procedures is published with the European public assessment report for the medicine.
From Regulation (EC) 1901/2006:
Article 29 (Paediatric): This type of procedure may be triggered by a marketing authorization holder when applying for a new indication, new pharmaceutical form or new route of administration for use in the paediatric population a product authorized under directive 2001/83/EC.
From Regulation (EC) 1234/2008:
Article 13: This type of referral is triggered for a medicine that has been authorized by mutual recognition or via the decentralized procedure when there is disagreement between MSs on a variation (Type II).

Reference:

1. Chapter 3 : Community referral Procedures, The Notice to Applicants Volume 2A Procedures for marketing authorization
2. Referrals procedures

EMA good pharmacovigilance practice modules for public consultation

EMA releases good pharmacovigilance practice modules for public consultation

The EMA has released the first batch of modules on Good Pharmacovigilance Practices (GVP) for public consultation until 18 april 2012.  

GVP is a set of measures drawn up to facilitate the performance of Pharmacovigilance in the European Union. They apply to marketing-authorization holders, the Agency and medicines regulatory authorities in EU member states and aim to improve safety for patients by strengthening  Pharmacovigilance  across the EU. They cover medicines authorized centrally via the agency as well as medicines authorized at the national level.  

GVP covers following aspects of safety monitoring of medicines. These are:

Module I: Pharmacovigilance systems and their quality systems

Module II: Pharmacovigilance systems master files

Module V: Risk management systems

Module VI: Management and reporting of adverse reactions to medicinal products

Module VII: Periodic safety update reports

Module VIII: Post-authorization safety studies

Module IX: Signal management

The release of these modules is a key deliverable of the 2010 Pharmacovigilance legislation, which will apply from july 2012. Each module was developed by a team consisting of experts from the agency and from EU member states.

The Agency is seeking comments on the practical implementation of the legislation as outlined int these modules. The underlying legal requirements cannot be altered through this consultation process.

Agency intends to finalize and publish these modules by July 2012, after comments from stakeholders have been taken into account.

Reference: EMA releases good pharmacovigilance practice modules for public consultation

PUMA

PUMA - Pediatric Use Marketing Authorization 

According to Article 30 of Regulation (EC) No 1901/2006 - The Paediatric Regulation, the paediatric use marketing authorisation (PUMA) is a dedicated marketing authorisation for medicinal products indicated exclusively for use in the paediatric population. It has been designed to promote paediatric development of already authorised products which are no longer covered by a supplementary protection certificate (SPC) or a patent qualifying for a SPC.

Incentives:

• 8+2 year period of data and market protection
• Partial exemption from the payment of fees
• ‘Automatic access’ to the centralised procedure
• A medicinal product for which a PUMA has been granted may retain the name of another medicinal product containing the same active substance for which the same holder has been granted an authorisation for use in adults

Required Documentation:

• Combination of new data and/or existing data
• Depending on the legal basis of the application, submission of literature and/or cross-reference to the dossier of another medicinal product may be used.
• A PUMA application has to contain the results of all studies performed and details of all information collected in compliance with an agreed Paediatric Investigation Plan (PIP). 
• PDCO opinion on compliance or the applicant’s compliance report must be provided in Module 1.10
• Risk management plan

Reference:

1. Regulation (EC) No 1901/2006 
2. Special Topics - Medicines for children - PUMA

European Medicines Agency publishes guideline on use of pharmacogenetics in evaluating pharmacokinetics of medicines

EMA guideline on use of pharmacogenetics in evaluating pharmacokinetics of medicines

The EMA has published has published a guideline advising pharmaceutical companies how to integrate studying the role of genetic variability between patients during development of medicines.

The guidelines clarifies the requirements of the effect of genetic variability on the way of human body handles medicines. This includes how genetic variation can affect the absorption, distribution, metabolism and excretion of medicines by the body, which can in turn lead to differences in the benefits and risks of a medicines between individuals.

The guideline sets out the requirements and recommendations on:

• When pharmacogenetic studies should be performed;
• How these studies should be designed and carried out;
• How the clinical impact of genetic difference between patients should be evaluated;
• How dosing or treatment recommendations for genetic sub-populations should be studies;
• Consequences for treatment recommendations and labeling;
• The impact if interactions between medicines and of impaired or immature organ functions.

The guideline is adopted (19 Jan 2012) by the Committee for Medicinal Products for Human Use after incorporation of comments from the public consultation phase.

Companies applying for marketing authorization should follow the guideline from 1 Aug 2012.

Reference: Guideline on use of pharmacogenetics in evaluating pharmacokinetics of medicines

European Medicines Agency - Certificates of Medicinal products

European Medicines Agency - Post-authorisation - Certificates of medicinal products

The purpose of the EMA Certificates of Medicinal Products scheme is to support the work of Health Authorities outside the European Union. The EMA certificates are issued by the Agency, on behalf of the European Commission, to confirm the Marketing Authorization status of products either authorized by the  European Commission through the centralsied procedure or  products for which a centralsied application has been submitted to the agency. The certificates also confirm the Good Manufacturing Practice (GMP) compliance status of the manufacturing site's producing the medicinal product bulk pharmaceutical form.

The EMA can certify a product only if the valid application for marketing authorization or for the scientific opinion has been submitted to the agency via the centralsied procedure.

The agency can issue Certificates of Medicinal Products to support the work of Health Authorities in any country outside the European Union. Guidance on countries officially recognized by the European Union, their official names used can be found in the list of countries and territories.

Further information: 

1. Request Certificates of Medicinal Products

2. European Medicinal Agency Certificates of Medicinal Products Scheme

European Medicines Agency - GCP compliance - Q&A: Good clinical practice (GCP)

European Medicines Agency - GCP compliance - Q&A

European Medicines Agency has published Q&A document on GCP compliance inspections.It clarifies following issues:

• Investigational medicinal products (IMPs) in bioavailability and bioequivalence trials GCP matters
• Expectations of European Union (EU) competent authorities on the use of electronic trial master files
• Records of study subject data relating to clinical trials

Further information: Q&A: Good clinical practice (GCP)

European Medicines Agency - Document search - Public consultations

European Medicines Agency   - New Guideline on Active Substance Master File Procedure

The corrections introduced to this guideline aim to improve the ASMF procedure across the European Regulatory Network. The long term objective of these administrative amendments is to have a unique version of an ASMF for one active substance valid for the whole EU/EEA, and consequently one AR of  the ASMF recognized by all Competent Authorities. 

To this end, the annexes to the guideline have been revised, and one new annex introduced, so that assessment reports of an ASMF may be shared between the EEA National Competent Authorities, the EMA including all CHMP and CVMP Members and their experts, and the Certification of Substances Division of the European Directorate for the Quality of Medicines & Healthcare. 

Some minor textual changes in the main part of the guideline have been introduced as a consequence of the revised annexes.  

Further information:Guideline on Active Substance Master File Procedure 

European Medicines Agency - Audio and video on implementation of the new pharmacovigilance legislation

European Medicines Agency - Implementation of new Pharmacovigilance Legislation

European Medicines Agency has published audio and video content related "Implementation of new Pharmacovigilance Legislation

It includes information on following topics:

• Update from EMA on planning and prioritization.
• Feedback on the implementing measures for the performance of Pharmacovigilance activites
• Planning for guidance on transitional measures
• Pharmacovigilance system master file: An approach towards system simplification
• Good vigilance practice - structure, scope and planning
• Commission appointments to the Pharmacovigilance Risk Assessment Committee (PRAC)
• Periodic safety update reports: Update on union reference dates list
• Access to EudraVigilance data - demonstration
• Urgent union procedure, including the concept of public hearings
• Conclusions

Reference: Implementation of new Pharmacovigilance Legislation