23 February 2016 EMA/711053/2010-Rev.1 Veterinary Medicines Division Incident management plan for medicines for veterinary use 1. Introduction A crisis management plan regarding safety issues for centrally authorised products (CAPs) for veterinary use has been in place in the European Medicines Agency (EMA or the Agency ) since its adoption by the Committee for Medicinal Products for Veterinary use (CVMP) in April 1999. To account for changes both in the European veterinary medicines environment and organisation changes within the EMA, the document was revised in February 2004 at the CVMP plenary meeting. This incident management plan was developed in 2010 to take into account the experience gathered since 2004 and broadened the scope. The incident management plan defines a strategy for the rapid and efficient handling of incidents, mainly involving safety issues relating to veterinary medicinal products authorised in the European Union (EU), where action by the Agency was appropriate and/or mandatory. It also outlined the procedures and management structures put in place to evaluate a potential incident, manage the response, communicate with all involved parties within the regulatory network and concerned marketing authorisation holder(s) for veterinary medicinal products and effect closure of the incident. The incident management plan was initially implemented for a two year pilot phase. The incident management plan has been reviewed in 2015 and revised taking account the experience gained with the incidents handled to date. The scope of the incident management plan was originally limited to those products and procedures for which the Agency has a responsibility for coordination (e.g. CAPs and products subject to referral to the Agency) and was only applicable to other types of products where national competent authorities (NCAs) chose to implement the incident management plan or invoked it upon request. Following the experience gained since the incident management plan was developed, and in order to bring the veterinary plan more into line with the corresponding human plan in line with a recommendation from the Heads of Medicines Agencies (HMA), the scope has been broadened to include medicinal products authorised through mutual recognition and decentralised routes and through national procedures. In addition, the procedure for incident management has been further improved to enable the incident management plan to be triggered by the European Commission (EC) or the EMA in addition to NCAs with regard to non-caps, which is in line with the EU regulatory network incident management plan for medicines for human use (EMA/351583/2012). In addition it is considered appropriate to apply the procedure outlined in this incident management plan to any event (not only safety related) which is considered an incident with regard to veterinary 30 Churchill Place Canary Wharf London E14 5EU United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website www.ema.europa.eu/contact An agency of the European Union European Medicines Agency, 2016. Reproduction is authorised provided the source is acknowledged.
medicinal products to enable a more global approach at EU level in relation to their management to avoid them developing into crisis situations. Lessons learned have been considered and incorporated in the current document. 2. Principles of the incident management plan The general principle of the incident management plan is to establish an EU-centralised approach of early identification of potential incidents i.e. events which may potentially have a serious impact on animal and/or public health or the environment at EU level and which may necessitate taking urgent remedial action, as and when required to avoid them developing into a crisis. This is a two-fold process i.e.: a) the continuous monitoring of events and new information (proactive) to be routinely assessed on their potential to escalate into an incident; and b) the management of the response (reactive) through coordination of actions across the Member States (MSs) for a confirmed incident. Any implementation of this incident management plan emphasises the established right of the NCAs to take pre-emptive action at national level, in accordance with the provisions of Community legislation. The incident management plan shall not be invoked for purely national issues without a potential European interest e.g. not in the case of product defects for a purely nationally authorised product. The figure below identifies the main stages and actors necessary to coordinate the response for such incidents when coordinated action is urgently required at European level. Figure 1: The main stages of the incident management plan cycle EMA/711053/2010-Rev.1 Page 2/16
2.1. Scope The scope of this incident management plan is defined by both the kind of events/new information and the type of veterinary medicinal products involved. Qualifying event/new information An event or new information may be related to the efficacy and/or safety, with or without a link to quality, of a veterinary medicinal product. An example would be an urgent safety hazard (i.e. a pharmacovigilance issue) or problems of viral contamination with biological products (quality and safety concerns). Likewise, events or information relating to products currently subject to referral or arbitration procedures (e.g. Article 78 of Directive (EC) 2001/82) by the Agency shall automatically fall within the scope of this incident management plan. It should be noted that situations arising purely from quality concerns without a safety component (e.g. product quality reports or defective product reports) should be dealt with in accordance to the Compilation of Union procedures on inspections and exchange of information 1,2 and the incident management plan will be triggered only in the cases when there is a major public health impact relating to the safety, efficacy and/or availability of medicinal products or where one or more Member States perceive that the measures currently foreseen in the compilations fail to result in adequate protection of animal health at Community level, thereby resulting in an incident requiring escalation within the Network. Qualifying veterinary medicinal product(s) This incident management plan applies to individual products or to several products in the same therapeutic class. It applies to CAP(s) and to products that may have been authorised through mutual recognition, decentralised or purely national authorisation procedures. 2.2. Definitions 2.2.1. Definition of an incident In the context of this incident management plan, an incident is defined as: An event or finding or new information that arises, irrespective of whether this is in the public domain or not, in relation to one or more veterinary medicinal products authorised in the EU, irrespective of the authorisation route, that could have a serious impact on animal and/or public health or the environment. The definition above does not exclude events that at first do not seem to have a serious impact on animal and/or public health or on the environment if they are in the public domain (irrespective of whether they attract media attention or not) and may lead to serious public concerns about one or more products. Likewise, cases where there may be a negative impact on the appropriate use of a product(s) or on their availability (e.g. resulting in discontinued use of the product(s)), also fall within the definition of an incident. 1 The SOP Dealing with Reports of Defective Medicinal Products (SOP/INSP/2018) applies in this situation. 2 N.B. The procedure for dealing with serious Good Manufacturing Practice (GMP) non-compliance includes reference to the CMDv Best practice guidance on collaboration between Member States in relation to serious GMP non-compliance issues which is currently under development EMA/711053/2010-Rev.1 Page 3/16
2.2.2. Definition of a crisis In the context of this incident management plan, a crisis is defined as a situation where, after assessment of the incident s associated risks, urgent and coordinated action within the EU regulatory network is required to manage and control the situation where routine measures or procedures are not deemed sufficient. An example of factors that might trigger a crisis include newly published data in scientific journals, coverage in the lay press and/or action taken by a non-eu regulatory authority, in terms of their actual or perceived impact on animal and/or public health or the environment. 2.3. Triggering an incident Incidents may be triggered by any stakeholder from the European Commission, the EMA or NCAs. Established systems used within the network will be continuously monitored as part of the routine screening process to identify events that may escalate into a potential incident and therefore trigger the incident management plan. Such established systems include the pharmacovigilance rapid alert (RA) and non-urgent information (NUI) system and the quality defect RA system, for example. Taking into account the scope and definition of an incident (or crisis) described above, all pharmacovigilance RAs would automatically trigger the incident management plan (please also refer to Section 4.11). However, where it is considered that issuing a RA will in itself be an adequate response to the situation then no further action will be required. Potential incidents may also be identified via other sources, for example, such as a NUI requesting advice from the incident review group, communication received from non-eu regulatory authorities or press or scientific publications, for example. EMA/711053/2010-Rev.1 Page 4/16
3. Incident and crisis management structures It is envisaged that during the three main stages of this incident management plan, different groups will be established (Figure 2). Each of these groups, although active throughout, has different management roles and responsibilities depending on the stage of the incident response and these are outlined in more detail below. Figure 2: Incident management plan groups and their roles EMA VCT Support role IRG PRA & formation of EMA VCT EU VCG Strategy definition & communications to involved parties EU Commission & NCAs Adoption of strategy & implementation EU VCG Monitoring implementation An overview of the incident management process is illustrated in figure 3. EMA/711053/2010-Rev.1 Page 5/16
Figure 3: Incident management procedure EMA/711053/2010-Rev.1 Page 6/16
3.1. Incident review group The incident review group is a dedicated structure for incident management and its composition is as follows: the EMA Head of Veterinary Medicines Department, who would act as chair; the Head of the NCA(s) triggering the incident or that are immediately identified as affected by the incident, or their nominated delegates; the EMA Head of Animal and Public Health or Veterinary Regulatory and Organisational support; the relevant rapporteur of the CAP or ongoing referral procedure/reference MS (RMS) expert(s)/lead MS(s) expert(s) for non-caps; the chairs of the Pharmacovigilance Working Party (PhVWP-V), CVMP and/or Coordination Group for Mutual Recognition and Decentralised Procedures - Veterinary (CMD(v)) and Inspectors working groups will be invited as appropriate to ensure a link with the relevant scientific committees or working party/group; and the relevant EMA project manager(s). Its main role is to: actively review, from a managerial point of view, incidents reported within one working day of receipt in terms of their animal and/or public health or environmental impact and ascertain whether the identified concerns are likely to be addressed through routine measures. The outcome of the incident review groups consideration would be communicated by the Agency on behalf of the incident review group to all involved parties. This also includes confirmation of issues which after review are not considered to comprise potential incidents; address requests for advice from individuals (via NUI) concerning a potential incident or intended referral procedure, in terms of the animal and/or public health or environmental impact and whether remedial action can be undertaken through routine measures; review other incidents (not reported via established systems, such as a RA or NUI) brought to the attention of the incident review group through existing EMA stakeholder networks and investigate the possibility of applying routine measures to address these concerns. Such concerns would normally be brought to the attention of the incident review group by means of a request from the triggering party e.g. where one or more Head of Agency requests the EMA to consider assisting the network with coordination of crisis measures; all [concerned] Members States would be informed of the outcome; following the review of an incident, taking into consideration the potential impact of the incident, decide on the need for a preliminary risk analysis for provision to the EU veterinary crisis group to determine if the incident is a potential crisis ; and invoke the formation of the EU veterinary crisis group (by the Head of Veterinary Medicines Division, informing at the same time the Executive Director of the Agency) and distribute the findings of the preliminary risk analysis, as appropriate. Additional issues that fall within the groups remit are: the need to prepare for any (media) queries or lines to take ; the identification of the most appropriate legal/regulatory framework to be used to address the situation (see section 4.1.2.); and EMA/711053/2010-Rev.1 Page 7/16
informing third country regulatory authorities where appropriate. 3.2. European Union (EU) veterinary crisis group In order to deal successfully with a crisis relating to veterinary medicinal products, an EU veterinary crisis group is created. The EU veterinary crisis group is convened when the incident review group is of the view that the incident is not likely to be addressed through routine measures i.e. confirmation of a crisis. For logistical reasons and rapid and efficient management, the core members of the EU veterinary crisis group must be kept to a minimum. For the same reasons, the group may need to operate even if under-represented and, where feasible, tele- or video-conferencing facilities may be used. Of course, additional members and expertise may be co-opted into the EU veterinary crisis group as the need arises. The core composition includes: the chair of the CVMP and/or the CMD(v); the chair of the PhVWP-V or vice chair (in case of a pharmacovigilance issue) or Inspectors working group (in case of a purely quality related issue); the rapporteur of the CAP or referral/article 78 procedure and/or a representative of the RMS/lead MS (for non-caps), supported by their scientific assessment team; the Head of Veterinary Medicines Division, who would act as chair; the Head of Veterinary Medicines Department, as well as the other members of the EMA veterinary crisis team (for further details, see section 3.3.); a nominated representative from the Medicinal Products Unit of the European Commission; and the Head of the relevant NCA(s) or their nominated representative particularly in cases where they initiate a request to EMA to assist with coordination. Its role is strategic and its responsibilities are to: 1) confirm (or not) the crisis; 2) initiate the crisis management steps of the incident management plan (or the relevant steps, where appropriate), including the communication strategy; and 3) agree on the closure of the crisis and ensure the production of the evaluation report by the EMA veterinary crisis team (lessons learned). 3.3. European Medicines Agency veterinary crisis team The EMA veterinary crisis team is the internal EMA crisis management structure which should become operational within the shortest possible timeframe and in parallel to the EU veterinary crisis group. It should be set up in such a way that it is also able to deal with crises arising during weekends or public holidays. The EMA veterinary crisis team has a core membership with optional/additional participants. The core members are: the Head of Veterinary Medicines Department, who would act as chair; the Head of Animal and Public Health or Veterinary Regulatory and Organisational Support; the relevant EMA project manager(s); and EMA/711053/2010-Rev.1 Page 8/16
the relevant legal administrator. The Head of Development and Evaluation of Veterinary Medicines may also be included in the team depending on the nature of the crisis. Further optional/additional participants may be co-opted as necessary e.g. personnel from the Compliance and Inspections Department or the Agency press office and/or technical, secretarial and linguistic support. Its role is operational, acting as a support to the EU veterinary crisis group by providing the required administrative and scientific input and its responsibilities are to: 1) implement the decisions taken by the EU veterinary crisis group in a timely manner; 2) operate the crisis management steps of the incident management plan (or the relevant steps, where appropriate), including communication aspects, ensuring that all interested parties are rapidly and fully informed; 3) follow-up on the implementation, including communication aspects, and evaluation of the response; 4) propose to the EU veterinary crisis group any necessary remedial action for subsequent changes to the implementation; and 5) propose to the EU veterinary crisis group to close the crisis and produce an evaluation of the incident management plan implementation on a lessons learned basis. Below are given the specific tasks for the following members of the EMA veterinary crisis team: The Head of Veterinary Medicines Department is responsible for: organising and co-ordinating the actions of the EMA veterinary crisis team members; centralising all updated information related to the crisis; reviewing and approving all documents for external communication; and informing and coordinating with the Head of Veterinary Medicines Division of all developments. The Head of Service (e.g. Animal and Public Health or Veterinary Regulatory and Organisational support) is responsible for: coordinating cross-service activities or cross-agency (if appropriate) to ensure delivery of remedial actions. The EMA project manager is responsible for: managing the delivery of the activities for which the Agency is responsible in the incident management plan; liaising with the rapporteur/representative of the RMS/lead MS on all scientific aspects of the crisis and coordinating their input; liaising with the qualified person for pharmacovigilance (QPPV) of the MAH(s) and collecting all necessary information urgently, as necessary; collecting internal and external information on an ongoing basis in order to ensure that the safety profiles of the products are updated routinely; providing, on an ongoing basis, all updated internal and external information to the Head of Veterinary Medicines Department; and EMA/711053/2010-Rev.1 Page 9/16
ensuring that appropriate records of the crisis and its management are maintained, particularly the major events and key action points, in order to feed into the evaluation report. 4. Incident management procedure The incident management plan procedure consists of the following key steps: continuous monitoring of incidents; evaluation of the incidents to identify a potential crisis situation (including the need to prepare for any (media) queries and the identification of the most appropriate legal/regulatory framework to be used to address the situation); confirmation (or not) of a crisis and initiation of the crisis management steps of the incident management plan (or the relevant steps, where appropriate) including the communication strategy; monitoring of the initiatives taken and identification of the need for remedial action, where necessary; closure of the crisis; and conduct of a lessons learned exercise. 4.1. Outline of the steps of the incident management plan 4.1.1. Continuous monitoring of incidents and triggering the incident management plan Continuous monitoring of incidents will build on existing systems at central and national level to identify potential incidents. These include the pharmacovigilance RA/NUIS and quality defect RA system. Taking into account the scope and definition of an incident, a pharmacovigilance RA would automatically trigger the incident management plan. Efficacy and/or safety issues with or without a link to quality aspects may also fall within the scope of an incident. Purely quality related issues such as Good Manufacturing Practice (GMP) compliance problems which may lead to supply shortages may also trigger the incident management plan. The identification of incidents will rely on notification e.g. via RA/NUIS and/or on the existing communication structures that exist between the Agency and its collaborator, specialist and stakeholder networks. In the case of referrals prior discussion with the EMA, as detailed in the Notice to Applicants or relevant standard operating procedure (SOP), is recommended and will create an opportunity for discussion with the potential referring MS if the situation is considered a crisis and if the relevant Head of Agency wishes to request the EMA to play a coordinatory role, even before a formal referral procedure is initiated. In addition the incident management plan could be triggered upon receipt of, for example, communication from a non-eu regulatory authority or identification of an issue in the press or scientific publications e.g. concerning the presence of residues of phenylbutazone in horse meat. Where an individual seeks advice from the incident review group as to whether an issue represents a potential incident the request should preferably be circulated via the NUIS. EMA/711053/2010-Rev.1 Page 10/16
4.1.2. Evaluation of the incidents to identify a potential crisis situation Involvement of the incident review group Any party within the EU Regulatory Network (e.g. MSs, EMA or the European Commission) can report incidents when they consider that the situation with respect to a product may no longer be managed by routine measures, including those foreseen within the compilation of Community procedures, at national or EU-level either due to the nature of the incident or as a result of Community legislation. On the basis of the evaluation of the incident, the incident review group will determine whether or not the incident is likely to be managed by routine measures, consider the potential impact of the incident and then decide on the need for a preliminary risk analysis to determine whether the incident represents a potential crisis. As highlighted previously, the outcome of the incident review groups review will be communicated by the Agency on behalf of the incident review group to all involved parties, leading to the end of the incident review group involvement including whether any issues were not considered to represent potential incidents, in which case no further action would be required from an incident management perspective. Next to reviewing incidents in terms of their impact on animal and/or public health or on the environment and identifying the most appropriate legal/regulatory framework to be used, the incident review group will have to consider the need to prepare for any (media) queries. To allow for replies to such queries the chair of the incident review group will either ask the Agency (for CAPs) or the RMS or lead MS (for non-caps) to consider the preparation of lines to take. In situations where both CAPs and non-caps are involved, the EMA will take the lead in relation to the preparation of lines to take, in close collaboration with the involved MS(s). Only the agreed identification by the incident review group of a potential crisis, based on the information available at that time, will trigger the invocation of the EU veterinary crisis group (i.e. the incident review group being of the view that the animal and/or public health or environmental concerns are likely not to be addressed through routine measures). Regarding the involvement (or not) of the EU veterinary crisis group during this review period, the incident review group will also take into account the following: any new and major scientific findings of general animal or public health or environmental relevance which may affect the European Commission s policy in the medicinal product area and may require Community action (e.g. emerging diseases); and any outstanding scientific information related to veterinary medicinal products authorised at national level which may also have an impact at EU level (e.g. on similar products or products of the same class). Preparation of a preliminary risk analysis In order to decide if the crisis management steps of the incident management plan should be initiated, taking into consideration the potential impact of the issue, the situation should be carefully assessed on the basis of a preliminary risk analysis. This is to be drafted by the CVMP (co)-rapporteur(s) and the EMA for CAPs, the RMS(s) for products authorised via mutual recognition and decentralised procedures and/or the lead MS for nationally authorised products. Situations characterised by involvement of both CAPs and non-caps will require representation of the various structures within the EU regulatory network. The lead for such situations in relation to the preparation of the preliminary risk analysis will always be at the level of the CVMP (co)-rapporteurs. There should, however, in all situations be a close collaboration with any MS(s) identifying (a) potential issue(s). EMA/711053/2010-Rev.1 Page 11/16
The preliminary risk analysis will elaborate on a number of elements of the main options available to address the situation. In particular, the following needs to be undertaken: hazard identification: collection of the information; identification of the information sources; checking of the accuracy; elaboration of the characteristics of the risk(s) associated with the new findings in as quantitative a way as possible; risk analysis: preliminary analysis of the wider impact of the risks and of the main options available to address the situation; review of previous/already existing risk assessments on the same issue; and communication to the public: preparation of lines to take when it is decided that a crisis exists. It is important to emphasise that such analysis will be undertaken in a tight timeframe and therefore in no way can it form the basis for regulatory action. This timeframe is set by the incident review group in response to the level of urgency of the issue. In order to allow for efficient decision-making it is important for the preliminary risk analysis to clearly state the various options for managing the incident/crisis which will be discussed between the incident review group and the party responsible for drafting the preliminary risk analysis before finalisation of the preliminary risk analysis. Once the preliminary risk analysis has been drafted and finalised, it is the incident review group s responsibility to pass this on to the EU veterinary crisis group. 4.1.3. Confirmation of a crisis and initiation of crisis management steps Based on the preliminary risk analysis, the EU veterinary crisis group will then decide if the incident constitutes a potential crisis and, if so, whether the crisis management steps of the incident management plan (or parts of it, as appropriate/relevant) should be initiated. The veterinary crisis group may, however, consider that the incident does not have the potential for crisis. The EU veterinary crisis group is expected to elaborate on the communication aspects of the incident management plan resulting in the drafting of a communication strategy for use by the relevant regulatory authorities e.g. press releases or lines to take. The overall aim is to quickly convey a unified and targeted message to the public. The EMA veterinary crisis team will subsequently implement the decisions taken by the EU veterinary crisis group in accordance with the agreed timelines and will operate the crisis management steps of the incident management plan with respect to CAPs and activities within the remit of the EMA. Likewise for nationally authorised products the actions agreed will be taken by NCAs. Agreements reached at the EU veterinary crisis group have no impact on the rights of the NCAs to take pre-emptive action at national level in accordance with the provisions of Community legislation. If it is confirmed that the incident does not represent a crisis, the Head of Veterinary Medicines Division will inform the incident review group, who will communicate the conclusions of the EU veterinary crisis group to the triggering party and throughout the regulatory network, as appropriate. Key to this is ensuring continuous exchange of information throughout the process with all concerned parties. 4.1.4. Monitoring of the initiatives taken and identification of the need for remedial action The EMA veterinary crisis team will also, as part of the operation of the incident management plan, monitor the implementation of the actions taken including communication aspects. In cases where remedial action is needed, the EMA veterinary crisis team will propose the necessary changes (based on the evaluation data available at each implementation stage) to the EU veterinary crisis group. It is the EU veterinary crisis group's responsibility to approve such changes for subsequent implementation by the EMA veterinary crisis team. EMA/711053/2010-Rev.1 Page 12/16
4.1.5. Closure of the incident Where the incident review group consider that routine measures are sufficient to address the incident, communication will be sent by the Agency on behalf of the incident review group to all involved parties, leading to the end of the incident review groups involvement. This will be done once the agreed (regulatory) actions have been triggered (e.g. the notification letter from the triggering party for the launch of a referral or Article 78 procedure has been received by EMA and/or the adequate communication has been issued to inform stakeholders as applicable). Should the crisis management steps have been triggered, the crisis situation will be considered closed once the EU veterinary crisis group, based on advice provided by the EMA veterinary crisis team, has approved such closure. A letter will then be sent by the Agency to inform all involved parties. 4.1.6. Conduct of a lessons learned exercise and evaluation of incident management plan implementation It is of utmost importance to carefully monitor the adequacy of the various elements of the incident management plan. To this effect, lessons learned will be reviewed by the incidence review group after each initiation of the management steps of the incident management plan and each crisis initiated by the EU veterinary crisis group in order to identify any opportunities for improvement. This may include involvement of external parties (e.g. the pharmaceutical industry) as well as veterinarians and other animal healthcare professionals and their representatives. Any outcomes from this evaluation are to be incorporated into future revisions of the incident management plan. In addition, the operational aspects of incident management handling at EU level, including experience obtained with the preparatory steps leading to the decision to confirm (or not) the crisis, in order to further increase the efficiency of operation should be reviewed on a regular basis, as part of the lessons learned. The aim for the Agency is to make such evaluation available to NCAs and all other relevant bodies, normally through the Heads of Medicines Agencies and PhVWP-V, as appropriate, in order to ensure that best practice can be communicated and incorporated as appropriate into national incident management structures. EMA/711053/2010-Rev.1 Page 13/16
Figure 4: Overview of the incident management plan EMA/711053/2010-Rev.1 Page 14/16
Figure 5: Incident management plan procedure Sources of information/continuous monitoring Incident 1 Incident 2 Incident 3 Incident 4 Incidents etc. Sources of information RAs Referrals by Member States NUI (request for advice) Major GMP non-compliance Non-EU regulatory authorities; press, scientific publications etc. Internal evaluation (EMA, Member State, Head of Agency & other discussions) EMA/ NCAs/ European Commission Incident management initiation plan Initiation stage: preliminary risk analysis (PRA) for CAPs, non-caps or a combination EMA/711053/2010-Rev.1 Page 15/16
Figure 5: continued Incident management plan procedure Crisis validation and implementation stage 5. References European Commission (2011): Volume 9B of The Rules Governing Medicinal Products in the European Union Guidelines on Pharmacovigilance for Medicinal Products for Veterinary Use Part II: Guidelines for competent authorities and the Agency Section 4: Rapid Alert and Non-Urgent Information System in Pharmacovigilance European Medicines Agency in agreement with the European Commission (2014): Compilation of Community Procedures on Inspections and Exchange of Information (EMA/572454/2014 Rev 17) EMA/711053/2010-Rev.1 Page 16/16