Eurpean Medicines Agency Pst-authrisatin Evaluatin f Medicines fr Human Use Lndn, 6 th August 2008 Dc. Ref.: EMEA/361945/2007 Editin 00 Editin date: July 2008 EDITION 1 DATE PAGE/S REASON FOR CHANGE 00 JULY 2008 ADOPTION BY CHMP 01 02 1 This dcument will be updated n a yearly basis. 7 Westferry Circus, Canary Wharf, Lndn, E14 4HB, UK Tel. (44-20) 74 18 84 00 Fax (44-20) 74 18 84 16 E-mail: mail@emea.eurpa.eu http://www.emea.eurpa.eu Eurpean Medicines Agency, 2008. Reprductin is authrised prvided the surce is acknwledged
Page 2/27 INDEX 1. INTRODUCTION 2. AIM AND SCOPE 3. REFERENCES and RELATED DOCUMENTS 4. GENERAL REQUIREMENTS 5. PRE-PROCEDURAL PHASE 6. ASSESSMENT PHASE: PRE-AUTHORISATION 7. POST-AUTHORISATION ACTIVITIES FOR CENTRALLY AUTHORISED PRODUCTS 8. REFERRALS AND REVIEWS 9. INTERACTIONS WITH THE CHMP 10. COMMUNICATIONS ANNEX 1 - CHMP Infrmatin Pack - List f dcuments Nt attached ANNEX 2 CHMP Members Interactins with Applicants/MAHs during the Centralised Prcedure EMEA 2008 2/27
Page 3/27 1. INTRODUCTION This dcument utlines the rle, respnsibilities and tasks f CHMP members and describes interactins with EMEA staff r applicants in relatin t the different activities undertaken at CHMP level, irrespective f whether the members are acting as Rapprteur, C- Rapprteur, Peer Reviewer r CHMP member. 2. AIM AND SCOPE This dcument has been prepared fr use by bth CHMP members and EMEA staff t ensure that a cnsistent apprach is taken with respect t all evaluatins and mnitring f activities in the centralised prcedure, allwing a smth running f each prcedure and CHMP plenary sessins. The dcument als takes int cnsideratin the rle f the CHMP in Referrals and ther prcedures. 3. REFERENCES AND RELATED DOCUMENTS Regulatin (EC) N. 726/2004 Directive 2001/83 /EC as amended Vlume 2 - Ntice t applicants and regulatry guidelines fr medicinal prducts fr human use Rules f Prcedure fr the CHMP (EMEA/CHMP/111481/2004) Draft Explanatry Paper n the Functining f the EMEA Secretariat (EMEA/401604/2005 Ver. 1) Regulatry guidance webpage Full list f CHMP dcuments related t this Prcedural Advice can be fund in Annex 1 and in the CHMP Infrmatin Pack 4. GENERAL REQUIREMENTS The primary purpse f the CHMP (thrugh its members) is t prvide bjective scientific pinins t the Cmmunity and t Member States (MS) n applicatins/questins presented t the Cmmittee, with the supprt f the EMEA Secretariat which has a cmplementary rle t that f members and alternates f the CHMP. The EMEA Secretariat prvides technical, scientific, regulatry and administrative supprt t the Rapprteurs, C-Rapprteurs and their experts, ther members f the Cmmittee, Wrking Parties, Scientific Advisry Grups (SAGs) and ad-hc Expert Grups ensuring apprpriate crdinatin between all parties invlved. The EMEA Secretariat (thrugh its Scientific Cmmittees) cntributes t delivering science driven and cnsistent regulatry pinins. The EMEA Secretariat prvides high-quality supprt t its varius Scientific Cmmittees, their Wrking Parties and ther scientific fra (such as ad-hc Expert Grups) and crdinates the scientific resurces available within the EU Regulatry System. As a general rule, gd cmmunicatin and accurate timing are at the centre f any activity undertaken by the Cmmittee, therefre up t date cmmunicatin between all parties invlved (i.e. Rapprteur and C-Rapprteur assessment teams, Peer Reviewer(s), CHMP members, EMEA staff and applicants) are f great imprtance. The preparatin f assessment reprts, their circulatin and the prvisin f cmments are crucial t the evaluatin under the centralised prcedure and each f these actins shuld be made in accrdance EMEA 2008 3/27
Page 4/27 with agreed timetables. Any dcument requiring CHMP endrsement shuld be prepared using the relevant adpted template. CHMP members shuld nt verly cnsider current r previus natinal practices r experiences when perfrming their assessment but preferably develp a Eurpean viewpint when dealing with centralised prcedures. In additin, all CHMP members are expected t review and cmment n the Table f Decisins, Minutes and CHMP Mnthly Reprt t ensure accurate recrds f each meeting. The Minutes f a given meeting will be adpted at the start f the next CHMP plenary sessin. 5. PRE-PROCEDURAL PHASE 5.1. Eligibility t the Centralised Prcedure The CHMP review all eligibility requests made by applicants requiring that their medicinal prduct be evaluated under the centralised prcedure. Such eligibility requests are sent t the EMEA Secretariat, either as stand alne requests r as part f the Letter f Intent t submit if the request cmes in clse t the planned submissin date. The CHMP review all eligibility requests mentined n the agenda at any given CHMP plenary sessin and cnfirm whether r nt the applicant meets the relevant eligibility criteria t gain access t the centralised prcedure under the relevant pint f legislatin described in Regulatin (EC) N. 726/2004. In the event that CHMP cannt prnunce itself n the eligibility status during a given meeting, ne member (at the minimum) with relevant expertise will be appinted t act as spnsr and prepare a discussin paper clarifying the issue(s) at hand. This member will reprt back t the Cmmittee at the subsequent meeting. Based n this reprt, the CHMP will then be in a psitin t cnclude whether r nt the applicant meets the eligibility criteria t gain access t the centralised prcedure. The CHMP Secretariat will reprt the utcme t each applicant cncerned cpying the EMEA Prduct Team Leader (PTL) appinted fr any given prduct. 5.2. Appintment f Rapprteurs Any scientific evaluatin ging thrugh the Cmmittee will usually require the appintment f a Rapprteur, and if relevant a C-Rapprteur, chsen frm amngst its members including c-pted members and CHMP alternates. The appintment f the Rapprteur and C-Rapprteur fr centrally authrised prducts is made n the basis f bjective criteria, ensuring the prvisin f bjective scientific pinins and allwing the use f the best and available expertise in the Eurpean Ecnmic Area n the relevant scientific area. In the pre-authrisatin phase f the Marketing Authrisatin Applicatin (MAA), a Rapprteur and a C-Rapprteur will be appinted. Appintments will take place 6-7 mnths prir t the intended submissin date and are usually initiated fllwing the receipt f the applicant s Letter f Intent t submit and request t assign a Rapprteur and a C-Rapprteur fr the review f the MAA. On Friday f the CHMP week, the CHMP Secretariat will send ut t all CHMP members the list f prducts requiring appintment f Rapprteur/C-Rapprteur at the next meeting. CHMP members wishing t act as Rapprteur/C-Rapprteur fr a given prduct are required t fill ut a nminatin frm describing their prpsed assessment team and send this back t the CHMP Secretariat within specified timelines. All nminatin frms received will be reviewed and discussed in the presence f the CHMP Chairman prir t the subsequent CHMP meeting where the Cmmittee will adpt the frmal appintment f Rapprteurs/C-Rapprteurs as prpsed by the CHMP Chairman. The CHMP Secretariat will reprt the utcme t each applicant cncerned cpying bth Rapprteurs and the EMEA PTL appinted t the prduct. EMEA 2008 4/27
Page 5/27 5.3. Pre-submissin meetings The EMEA Secretariat strngly recmmends having pre-submissin meetings with applicants fr MAA submissins, extensins f indicatin, legal status change (nn-prescriptin switch) and renewals. Such meetings usually take place a few mnths prir t the intended submissin date f the MAA (r the submissin f an applicatin fr a Type II variatin fr an extensin f indicatin r prir t a legal status change r prir t a renewal) and are a vital pprtunity fr applicants t btain prcedural, regulatry and legal advice frm the EMEA. In this pre-submissin phase, an applicant can als seek t meet directly with his appinted Rapprteur and C-Rapprteur t review preparatry aspects f the MAA frm bth a technical and scientific viewpint. The EMEA PTL fr the prduct shuld be made aware when such meetings take place and receive a cpy f the Minutes. 5.4 Requests fr Accelerated Assessment The applicant may request an accelerated review f his MAA. These requests shuld be supprted by an apprpriate justificatin and limited t cases where cmpelling public health reasns may require a quicker evaluatin and management f the applicatin. Upn receipt f such requests, the Rapprteur/C-Rapprteur will review the justificatin sent by the applicant and reprt back t the Cmmittee at the subsequent meeting using a pre-defined template. The EMEA PTL will infrm the applicant f the utcme. Currently such prcess ccurs prir t submissin but it is prpsed that in the near future such accelerated assessment will be perfrmed at Day 80 and a review f the applicant s arguments wuld be available at Day 90 f the prcedure. 5.5. Validatin f a Marketing Authrisatin Submissin, Line Extensin r Renewals The EMEA Secretariat will send t the applicant an acknwledgement f receipt f the MAA, line extensin r renewal dssiers and, within 10 wrking days fllwing such receipt, will cmplete its validatin. During the validatin, the EMEA PTL may cnsult the Rapprteur/C-rapprteur n the need fr actins relating t specific matters (scientific, regulatry, GCP/GMP inspectins etc ). Fr MAA, the EMEA PTL may als cnsult EMEA clleagues wrking within different scientific Cmmittees Secretariats such as the Secretariats fr the Cmmittee fr Orphan Medicinal Prducts and the Paediatric Cmmittee regarding queries arising n rphan drug designatin and paediatric investigatin plans and waivers. 6. ASSESSMENT PHASE: PRE-AUTHORISATION 6.1. Rles and Respnsibilities The rles and respnsibilities undertaken by a CHMP member will vary depending whether he/she is acting as a Rapprteur/C-Rapprteur, Peer Reviewer r CHMP member. 6.1.1. Day 0-120 Preparatin f the cnslidated List f Questins Rapprteur/C-Rapprteur The Rapprteur and C-Rapprteur will cnfirm the names f their assessrs (indicating if there are any changes frm thse appinted at the time f Rapprteurship nminatin). The Rapprteur and C-Rapprteur will ensure that all members f their assessment teams are EMEA 2008 5/27
Page 6/27 included in the EMEA Expert database with an updated declaratin f interest, cnfidentiality undertaking frm and curriculum vitae. The Rapprteur and C-Rapprteur with supprt f their assessment teams will prepare their preliminary assessment reprts using the adpted reprt templates. The assessment reprts shuld be prduced and circulated t the Cmmittee within agreed timetables and meet agreed guidance. The Rapprteur and C-Rapprteur r their assessment teams may cntact the applicant shuld the need arise. Such cntacts shuld be dcumented and any infrmatin prvided shuld be cpied t bth the Rapprteur and C-Rapprteur assessment teams and t the EMEA PTL in parallel. The Rapprteur and C-Rapprteur will participate in the telecnference with EMEA staff and Peer Reviewer(s) t refine the prpsed List f Questins (LQ) at Day 112. The Rapprteur and C-Rapprteur will update their assessment reprts taking int accunt the utcme f the EMEA/peer review telecnference and CHMP cmments received. The Rapprteur and C-Rapprteur will identify whether there is a need t recmmend a GxP/PMF inspectin r pharmacvigilance inspectin and/r prduct testing. If such need is freseen the request will be adpted by the Cmmittee and prcessed with the supprt f the Inspectin Sectr at the EMEA. Bth the Rapprteur and C-Rapprteur, with the supprt frm the EMEA PTL, shuld liaise in advance f the CHMP meeting where relevant LQ will be adpted in rder t find agreement (in discussin with CHMP members) n key issues and t identify any cntentius issues r areas f disagreement. Such issues shuld be brught ut t the attentin f the CHMP Chairman and CHMP members in advance f the plenary discussin, asking fr specific cmments. The Rapprteur and C-Rapprteur shuld identify whether there is a need fr an ad-hc Expert Grup meeting at this stage t discuss any aspect f the EU-Risk Management Plan (EU-RMP). If a meeting is needed the cmpsitin f the expert grup shuld be discussed between bth Rapprteurs and EMEA staff and presented by the Rapprteur during the CHMP discussin. Bth Rapprteurs and the EMEA PTL are respnsible t draft a List f Questins t be addressed by the experts identified. The Rapprteur with supprt frm the C-Rapprteur (r their nminated experts) will submit a brief Reader s Guidance summarising the stage f the prcedure and the issues identified when circulating their revised assessment reprts. During the relevant CHMP plenary sessin, the Rapprteur with supprt frm the C-Rapprteur (r their nminated experts) will present the prpsed List f Questins. Due t time cnstraint, it is essential that presentatins t the Cmmittee are fcused n the key issues identified in the MAA dssier and n the areas f disagreement/cntrversy. Redundancy and excessive backgrund infrmatin shuld be avided. Presentatins shuld nt exceed 10-12 slides at mst. Peer Reviewer(s) At the time f Rapprteur appintment, the Cmmittee will decide n the scpe f the peer review and the number f peer reviewers t be assigned in rder t ensure quality assurance t the draft List f Questins. CHMP members wishing t act as Peer Reviewer are nt required t fill ut the usual nminatin frm sent ut fr Rapprteurs appintment EMEA 2008 6/27
Page 7/27 but just infrm the CHMP Secretariat f their interest fr a particular prduct (see sectin 5.2). The members appinted Peer Reviewer(s) are respnsible t judge the quality f the assessment reprts prduced by bth the Rapprteur and C-Rapprteur especially in relatin t ptential divergences in the scientific assessment fllwing SOPs in place and using pre-defined templates. The aim f the telecnference set up between the Rapprteur, C-Rapprteur, Peer Reviewer(s) and EMEA staff at Day 112 is t discuss and analyse critically the different bjectins and cncerns raised in the Rapprteur and C-Rapprteur assessment reprts and prpsed draft List f Questins. CHMP members CHMP members are t cntribute actively t the review system by prviding cmments n assessment reprts and identifying additinal majr bjectins/questins t be addressed by the applicant using pre-defined templates. Cmments n the MAA dssier and assessment reprts shuld be prvided in strict adherence t the adpted timetables. CHMP members are expected t wrk clsely with bth Rapprteurs in cmpiling such cmments and achieving a cnsensus psitin whenever pssible. Members shall prepare fr each CHMP meeting, in discussin with clleagues and experts in their natinal agencies, in rder t have a gd understanding and viewpints n the issues under discussin. T nte, that CHMP members can act as Peer Reviewer and can separately prvide cmments nt mutually exclusive. CHMP members will als cmment n the prpsed wrding f the Prduct Infrmatin. 6.1.2. Day 120-121 Applicant respnses t the List f Questins Rapprteurs and/r their assessment teams may discuss with the applicant the brad utlines f their respnse strategy including any withdrawal/limitatin f indicatins applied fr as well as mdified warnings regarding the precautins fr use f a prduct etc 6.1.3. Day 121-180 Preparatin f jint assessment reprt and List f Outstanding Issues as apprpriate Rapprteur/C-Rapprteur The Rapprteur and C-Rapprteur will evaluate the infrmatin submitted by the applicant in respnse t the issues raised by the CHMP. This evaluatin will then be shared with the Cmmittee as a Day 150 jint assessment reprt using the apprpriate template. The Rapprteur and C-Rapprteur will update the Day 150 jint assessment reprt t take int accunt CHMP cmments received. Bth Rapprteurs in liaisn with EMEA staff will identify a draft List f Outstanding Issues (if necessary) t be addressed by the applicant in writing and/r in an ral explanatin. The Rapprteur with supprt frm the C-Rapprteur (r their nminated experts) will submit a brief Reader s Guidance summarising the stage f the prcedure and the issues identified when circulating the Day 150 jint assessment reprt and present the prpsed List f Outstanding Issues during the relevant CHMP plenary sessin and cnsider whether there is a need fr a future ral explanatin. Again presentatins shuld be cncise and limited t a small number f slides. The Rapprteur, C-Rapprteur r any CHMP member may suggest t the Cmmittee the need fr a SAG/ad-hc Expert Grup meeting t be scheduled in rder t clarify the issues raised. In the event that a SAG (r ad-hc Expert Grup) cnsultatin is freseen, bth EMEA 2008 7/27
Page 8/27 Rapprteurs and the EMEA PTL (and RMTM if apprpriate) are respnsible t draft a List f Questins t be addressed by the experts identified. The draft List f Questins will be reviewed and adpted by the Cmmittee. If necessary, additinal expertise may be sught fr such grups. The EMEA will assist the Cmmittee by making prpsals fr the relevant expertise and the Cmmittee will als review, cmment and adpt the cmpsitin f the SAG/ad-hc Expert Grup and whether r nt additinal expertise is needed and will prpse participants n request. The EU-RMP must be finalised befre the Opinin, therefre any utstanding issues shuld be identified and included in the draft List f Outstanding Issues. In the event that n majr bjectins remain at this stage f the prcedure, bth Rapprteurs shuld strive t finalise their assessment reprt and update the prduct infrmatin in liaisn with the applicant in rder t be in a psitin t adpt an pinin at Day 180. CHMP members CHMP members will send their cmments n the Day 150 jint assessment reprt within agreed timelines. If it is likely that there will be a need fr additinal risk minimisatin activities which will invlve sme frm f cntrlled distributin r ther cntrl within each Member State, the Applicant may seek t meet with the cmpetent authrities f each Member State (between day 121 and Day 180) t discuss hw best this may be implemented. CHMP members shuld facilitate these meetings within his/her Member State. Feedback frm Member States shuld be transmitted back t the Rapprteurs and the EMEA PTL. 6.1.4. Day 180-181 Preparatin f the respnses t the List f Outstanding Issues and Oral Explanatin Rapprteurs and/r their assessment teams may discuss with the applicant the brad utlines f their respnse strategy t the List f Outstanding Issues including any regulatry advice at this stage f the prcedure. 6.1.5. Day 181-210 Opinin Rapprteur/C-Rapprteur The Rapprteur and C-Rapprteur will evaluate the infrmatin submitted by the applicant in respnse t the List f Outstanding Issues. This evaluatin will then be shared with the Cmmittee as a revised Day 150 jint assessment reprt. The Rapprteur and C-Rapprteur will update the revised Day 150 jint assessment reprt t take int accunt CHMP cmments received. Bth Rapprteurs in liaisn with EMEA staff will identify whether there is a need fr an ral explanatin and amendments t the List f Outstanding Issues. In the event that a SAG/ad-hc Expert Grup cnsultatin has ccurred, the Chair (r a cre member in his absence) will be invited t reprt back t the Cmmittee n the utcme f the discussin. If n ral explanatin is necessary, the Cmmittee will adpt an pinin at the relevant CHMP meeting (in line with the adpted timetable). EMEA 2008 8/27
Page 9/27 If an ral explanatin is freseen, the applicant will be invited t discuss their psitin and clarify any utstanding issues the Cmmittee may have. The Cmmittee will adpt an pinin at the subsequent meeting if timetable allws. When finalising the pinin bth Rapprteurs are respnsible t ensure that the Package Leaflet is in line with the prpsed SPC. CHMP members and EMEA staff (sectin als applicable fr pst-authrisatin variatins) The EMEA PTL is respnsible fr the finalisatin f the scientific CHMP assessment reprt ensuring that all necessary justificatins n the utcme f the scientific assessment are sufficiently substantiated and accurately reflected in the final assessment reprt and prduct infrmatin. The Rapprteurs assessment reprt r critique, any ther relevant cntributins, divergent views expressed by the Rapprteurs cmpared t the verall cnclusin reached at CHMP level shuld be carefully cnsidered. Rapprteurs are reminded f their respnsibilities t prvide clear justificatins t the EMEA PTL fr the finalisatin f scientific CHMP assessment reprt especially when the views f the Rapprteurs may differ frm the verall cnclusin endrsed at Cmmittee level. The EMEA Secretariat will prvide an imprtant input t the peer review system, in terms f quality assurance and guardian f the regulatry and scientific cnsistency. When finalising the pinin, the Rapprteurs, CHMP members and EMEA staff will ensure that apprpriate pst-marketing cmmitments are being set up. This will include any additinal risk minimisatin activities which shuld be included in Annex II (and IV) f the pinin as apprpriate. The Cmmittee will agree n the Letter f Undertaking prvided by the applicant (if necessary). In additin the CHMP will ensure that any extra cmmunicatins that have been identified as necessary are tabled and reviewed by the CHMP as apprpriate (questin-and-answer dcuments, cmmunicatin actin plans, lines t take etc ). 6.1.6. Re-examinatin prcedure under Article 9(2) f Regulatin EC N. 726/2004 (new applicatins) In the event that the applicant appeals an pinin taken by the Cmmittee and infrms the EMEA f such curse f actin, the CHMP will appint a different Rapprteur and C-Rapprteur fr the re-examinatin prcedure. Such appintment will take place at the subsequent meeting fllwing the receipt f the applicant written ntice. The newly appinted Rapprteurs will nly crdinate the evaluatin fr the duratin f the re-examinatin prcedure. During this stage, the Cmmittee may als wish t discuss whether a SAG/ad-hc Expert Grup cnsultatin is necessary and whether such grups need t be enriched with additinal experts. The applicant may als at its wn initiative request the cnsultatin f a particular SAG. The riginal appinted Rapprteurs shuld keep in mind that if the re-examinatin prcedure revises the previus pinin adpted by the Cmmittee, respnsibilities will g back t them and the prduct infrmatin may have t be finalised in a very shrt timeframe. 6.2. Other Prcedures Article 58 f Regulatin (EC) N. 726/2004 When the EMEA receives an applicatin within the cntext f Article 58 - CHMP Scientific Opinin in cperatin with WHO - the Cmmittee will appint a Rapprteur and C-Rapprteur wh will be respnsible fr the prcedure (see sectin 5.1). Bth Rapprteurs will recmmend t the Cmmittee whether pssible nminatin f WHO Experts is freseen fr the assessment review. If agreeable, the Cmmittee may ask WHO t prpse experts fr certain areas f expertise. Experts appinted will be allwed t participate in the discussin n prducts. In additin bservers frm WHO and Natinal Cmpetent Authrities (NCA) frm develping cuntries may als attend relevant Wrking Parties EMEA 2008 9/27
Page 10/27 and CHMP plenary discussins. Participatin at a plenary CHMP meeting r attending relevant Wrking Parties discussins will nly be pssible prviding that the nminated experts are included in the EMEA Expert database with an updated declaratin f interest, cnfidentiality undertaking frm and curriculum vitae. Article 83 f Regulatin (EC) N. 726/2004 When a Member State (MS) envisages the need t make a medicinal prduct available fr cmpassinate use, the NCA f that MS must ntify the EMEA. Further t the ntificatin and request by MS(s), the CHMP will appint a Rapprteur and a C-Rapprteur (if necessary) t prepare an pinin n the cnditins fr use, the cnditins fr distributin and the patients targeted by the cmpassinate use in a given therapeutic indicatin. Once adpted by the Cmmittee, pinins related t cmpassinate use are nt binding n MSs, hwever MSs shall take int accunt any available pinin. Scientific Advice CHMP members are encuraged t take an active rle as peer reviewer f the scientific advice letters prepared by the Scientific Advice Wrking Party (SAWP) and cmment apprpriately. The SAWP Secretariat is als strngly invlved in the peer review f applicatins as part f the quality assurance expertise. The SAWP shall transmit their cnclusins fr Scientific Advice and Prtcl Assistance t the CHMP fr frmal adptin. Innvatin Task Frce The Innvatin Task Frce Grup is in charge f assessing the scientific basis f the regulatry requests frm applicants t assess whether r nt prducts being develped are cnsidered medicinal prducts eligible t the centralised prcedure. In cases that are nt straight frward, the Cmmittee will appint ne f its members t act as a CHMP Crdinatr t review the draft reprt and reprt back t the Cmmittee n whether the prduct can be cnsidered a medicinal prduct r nt. The Cmmittee will adpt the relevant Regulatry Advice Reprt. 7. POST-AUTHORISATION ACTIVITIES FOR CENTRALLY AUTHORISED PRODUCTS In the pst-authrisatin phase f the Marketing Authrisatin, the Rapprteur will take the lead rle alng with the EMEA PTL wh will be the primary cntact pint fr the Marketing Authrisatin Hlder (MAH) 2. The Rapprteur, the C-Rapprteur if necessary, their assessment teams respectively and the EMEA PTL will be invlved in numerus activities. 7.1. Variatin Type II 90-Day - Extensin f Indicatin Pre-submissin meeting See sectin 5.3. Cnfirmatin f the invlvement f the C-Rapprteur by the CHMP If apprpriate, bth the Rapprteur and C-Rapprteur teams will be invlved in the assessment f the Type II variatin fr an extensin f indicatin. The MAH must send a letter f intent at least 2 mnths befre the planned submissin date. With the receipt f this letter (r at the latest at the time f 2 Rapprteurs shuld remind applicants that planned future variatins shuld always be discussed with the EMEA PTL prir t submissin. EMEA 2008 10/27
Page 11/27 the variatin submissin by the MAH), the EMEA PTL will cnfirm with the Rapprteur and C- Rapprteur whether there is a need r nt t invlve the C-Rapprteur in the assessment f the variatin. The EMEA PTL will infrm the CHMP Secretariat f the utcme in writing. The Cmmittee will cnfirm the C-Rapprteur s invlvement at the relevant CHMP meeting. EMEA 2008 11/27
Page 12/27 Preparatin f the Request f Supplementary Infrmatin/Opinin Rapprteur/C-Rapprteur The Rapprteur and C-Rapprteur will ensure that all members f their assessment teams are included in the EMEA Expert database with an updated declaratin f interest, cnfidentiality undertaking frm and curriculum vitae. The Rapprteur and C-Rapprteur with their assessment teams will prepare their preliminary assessment reprts using the apprpriate templates. The assessment reprts shuld be prduced and circulated t the Cmmittee within the agreed timetables and meet agreed guidance. EU-RMP submitted as part f the variatin applicatin f the extensin f indicatin will be frwarded by the EMEA PTL t the EMEA RMTM fr cmments. The EMEA RMTM s cmments will be frwarded t the Rapprteur s and C-Rapprteur s teams during the assessment. The Rapprteur and C-Rapprteur are expected t assess and prvide cmments n the EU-RMP. The Rapprteur and C-Rapprteur will prepare jintly the Request fr Supplementary Infrmatin (RSI) (r pinin) taking int accunt the CHMP cmments received and circulate it t the Cmmittee prir t the CHMP meeting. If apprpriate, the CHMP Chairman shuld be made aware by the EMEA PTL in liaisn with the CHMP Secretariat f any cntrversial issues identified in the RSI in advance f the CHMP meeting The Rapprteur and C-Rapprteur (r their nminated experts) will present the prpsed RSI (r pinin) during the relevant CHMP meeting which will be adpted by the Cmmittee nce they, tgether with the EMEA PTL have finalised the CHMP RSI ((r pinin) t be sent t the MAH. As in the Pre-authrisatin phase, any cntrversial issues may lead t further discussins with ther Expert Grups and an Oral Explanatin by the MAH may be envisaged. The Rapprteur, C-Rapprteur, r any members f the Cmmittee may suggest t the Cmmittee whether a SAG r ther ad-hc Expert Grup meeting shuld be cnvened (see sectin 6.1.3 - Pre-Authrisatin part f the dcument). When finalising the pinin the Rapprteur (and the C-Rapprteur if invlved in the prcedure) is/are respnsible t ensure that the Patient Leaflet is in line with the prpsed SPC. The Rapprteur, C-Rapprteur and CHMP members will need t agree n the wrding f the pst-authrisatin cmmitments t be perfrmed by the MAH pst pinin. CHMP members As in the pre-authrisatin phase, CHMP members are t cntribute actively t the review system by prviding cmments n the Rapprteur and C-Rapprteur preliminary assessment reprts and prpsed RSI within agreed timelines (see sectin 6.1.1 - Pre-Authrisatin part f the dcument). CHMP members and EMEA staff See sectin 6.1.5 in the pre-authrisatin part f the dcument. EMEA 2008 12/27
Page 13/27 7.2. Variatin Type II 60-Day Rapprteur CHMP members The Rapprteur with supprt f their assessment teams will prepare their preliminary assessment reprts using the adpted reprt templates. The assessment reprts shuld be prduced and circulated t the Cmmittee within agreed timetables and meet agreed guidance. If cntrversial issues have arisen during the assessment, the EMEA PTL after cnsultatin with the Rapprteur will infrm the CHMP Secretariat s that the issues identified can be presented and discussed during the relevant CHMP meeting. In the event that the issues remained unreslved, the Rapprteur will prepare a RSI taking int accunt the CHMP cmments received and circulate it t the Cmmittee prir t the CHMP meeting. The prpsed RSI will be presented and adpted during the relevant CHMP meeting. The Rapprteur, tgether with the EMEA PTL, will finalise the CHMP RSI (r pinin) t be sent t the MAH. CHMP members will send their cmments n the preliminary assessment reprt f the Rapprteur within agreed timelines. CHMP members will als cmment n the prpsed wrding f the Prduct Infrmatin. 7.3. Variatin Type II 30-Day Exact implementatin f prpsed wrding fr the Prduct Infrmatin Fr the purpse f implementing the exact amendments t the Prduct Infrmatin (Summary f Prduct Characteristics (SPC) and/r Labelling and/r Package Leaflet) requested by the CHMP as a result f a previusly assessed prcedure (e.g FUM, PSUR, etc), an administrative 30-Day type II variatin is carried ut. The Rapprteur will assess the dcumentatin prvided by the MAH (mainly t ensure cmpliance with the CHMP request) and prepare a shrt assessment reprt fr the Cmmittee. Urgent Safety Restrictin Variatin (USR) Where a USR is being cnsidered, the Rapprteur shuld prepare a shrt assessment reprt fr circulatin t the CHMP (and PhVWP as apprpriate). This reprt will assess relevant data, review the prpsed changes t the Prduct Infrmatin and prpse timelines. CHMP members will cmment n the assessment reprt, the need fr a USR and n the prpsed wrding f the Prduct Infrmatin. Once the wrding is agreed at CHMP level, the MAH will initiate the USR. The EMEA PTL will infrm the CHMP n the start f the prcedure and prvide relevant timelines fr cmments n the Prduct Infrmatin wrding. In parallel, the EMEA PTL will circulate t the CHMP, a Press Release, questin-and-answer dcument, Dear Healthcare Prfessinal Letter (DHPL) and Actin Plan fr cmments. The Rapprteur and the EMEA PTL will review the CHMP cmments and prpse any revisin f the wrding t the MAH fr agreement. If n majr bjectins are received by the CHMP members within 24 hurs after the start f the prcedure, the changes in the Prduct Infrmatin can be implemented by the MAH. The Rapprteur will circulate the preliminary assessment reprt, CHMP members will cmment and the updated assessment reprt will be circulated by the Rapprteur within the EMEA 2008 13/27
Page 14/27 7.4. Renewal agreed timelines. A discussin during the relevant CHMP meeting will take place and the Rapprteur will present the subject t the Cmmittee. During a 30-Day type II variatin dealing with an USR issue, the 60-Day type II variatin assessment as described abve (sectin 7.2), is fllwed but with shrter timelines Renewals fllw the same timeline as the 90-Day type II variatin assessment described in sectin 7.1. Pre-submissin meeting As fr a majr Type II variatin planned submissin, a pre-submissin meeting might be scheduled (see sectin 5.3). Preparatin f the Opinin Rapprteur/C-Rapprteur CHMP members The Rapprteur with his/her assessment team will prepare the preliminary assessment reprt using the Renewal template. The C-Rapprteur will cmment n the Rapprteurs s assessment reprt befre circulating the Jint Rapprteur s and C- Rapprteur s assessment reprt t the Cmmittee within the agreed timetables and meet agreed guidance. In case a RSI is needed, the Rapprteur and C-Rapprteur will prepare jintly a RSI taking int accunt the CHMP cmments received and circulate it t the Cmmittee prir t the CHMP meeting. The prpsed RSI will be presented and adpted during the relevant CHMP meeting. The Rapprteur and C-Rapprteur tgether with the EMEA PTL will finalise the CHMP RSI t be sent t the MAH. Bth Rapprteur will then assess the respnses f the MAH and this assessment reprt will be circulated t the Cmmittee fr cmments. In the preliminary assessment reprt, the Rapprteur and the C-Rapprteur will make a recmmendatin, if applicable, n the validity f the renewed MA (unlimited validity r ne further 5-year perid renewal required) as well as n the future PSUR cycle. The Rapprteur will present the prpsed recmmendatin and the Pharmacvigilance grunds fr this prpsal during the relevant CHMP meeting. The Cmmittee will subsequently adpt the pinin fr the renewal. CHMP members will send their cmments n the preliminary assessment reprt f the Rapprteur and n the assessment f the RSI, if applicable, within agreed timelines. 7.5. Annual Re-assessment / Cnditinal Renewal Annual re-assessments and cnditinal renewals fllw the same timeline as the 60-Day type II variatin assessment described in sectin 7.2. EMEA 2008 14/27
Page 15/27 Rapprteur CHMP members The Rapprteur and his/her assessment team will prepare the preliminary assessment reprt within the adpted timelines and will circulate it t the Cmmittee. In exceptinal cases where a RSI is necessary, the Rapprteur will assess the respnses f the MAH and will circulate this assessment t the Cmmittee. The Rapprteur and his/her assessment team will update the preliminary assessment reprt with CHMP members cmments within the adpted timelines and circulate it t the Cmmittee. If during the assessment there are n grunds fr the MA t remain under cnditinal apprval r exceptinal circumstances, the Rapprteur will infrm the Cmmittee during the relevant CHMP meeting. CHMP members will send their cmments n the preliminary assessment reprt f the Rapprteur within agreed timelines. 7.6. Extensin Applicatins Such applicatins will be treated similarly t new MA applicatins in the pre-authrisatin phase invlving the Rapprteur and if apprpriate als the C-Rapprteur. The prcedure invlving the Cmmittee will be the same as described in sectin 6.1. 7.7. Pst-authrisatin Cmmitments (PSURs/FUMs/Specific Obligatins) The Rapprteur will circulate t the Cmmittee the preliminary assessment reprt f the PSURs, FUMs r Specific Obligatins within the adpted timelines. CHMP members will cmment within the agreed timelines and the Rapprteur will circulate the updated Assessment Reprt fr adptin by the Cmmittee. If further issues are identified fr discussin with the MAH a timeframe fr respnses t these issues shuld be prpsed by the Rapprteur in his/her assessment reprt. If any cntrversial issues arise during the assessment, the Rapprteur with the help f the EMEA PTL may decide t bring the subject t the attentin f the PhVWP and the CHMP. Where an updated Prduct Infrmatin is prpsed, the Rapprteur shuld prpse apprpriate wrding t be intrduced in the SPC and Patient Leaflet, as apprpriate. 7.8. Pharmacvigilance Handling f safety issues (prcess being currently updated, further infrmatin will be prvided in the near future). Signal Detectin (SD) (prcess being currently updated, further infrmatin will be prvided in the near future). 7.9. Re-examinatin prcedure Article 6(9) f Regulatin EC N 1085/2003 (type II variatins) In the event that the applicant appeals an pinin taken by the Cmmittee and infrms the EMEA f such curse f actin, the CHMP will appint a different Rapprteur and C-Rapprteur fr the re-examinatin prcedure. Such appintment will take place at the subsequent meeting fllwing the receipt f the applicant written ntice. The newly appinted Rapprteurs will nly crdinate the evaluatin fr the duratin f the re-examinatin prcedure. The Cmmittee may als wish t discuss whether a SAG/ ad-hc Expert Grup cnsultatin is necessary and whether the SAG/ ad-hc Expert EMEA 2008 15/27
Page 16/27 Grup need t be enriched with additinal experts. The applicant may als at its wn initiative request the cnsultatin f a particular SAG. Original appinted Rapprteurs shuld keep in mind that in case the re-examinatin prcedure revises the previus pinin adpted by the Cmmittee, the prduct infrmatin may have t be finalised in a very shrt timeframe. 8. REFERRALS AND REVIEWS 8.1. Referrals Whenever an arbitratin mechanism is being invked, a scientific evaluatin f the matter will be undertaken by the Cmmittee. Cmmunity arbitratin mechanism may be invked n the basis f the fllwing articles: 1. Article 29(4) f Directive 2001/83/EC as amended ( Mutual Recgnitin and Decentralised referral ) 2. Article 30 f Directive 2001/83/EC as amended ( Divergent decisin referral ) 3. Article 31 f Directive 2001/83/EC as amended ( Cmmunity interest referral ) 4. Articles 35 and 36 f Directive 2001/83/EC as amended ( Fllw-up referrals ) 5. Articles 5(1), 6(12) and 6(13) f Regulatin (EC) N. 1084/2003 (Variatins t MAA) Start f the referral prcedure (CHMP plenary meeting) - First CHMP meeting fllwing ntificatin f a referral Rapprteur and C-Rapprteur(s) (if applicable) will be appinted during the relevant CHMP meeting. A 60 days timetable will be adpted by the CHMP after agreement with Rapprteur/C- Rapprteur(s). Rapprteur/C-Rapprteur(s) in cnjunctin with the EMEA PTL will prpse a draft LQ t be addressed t the MAH(s). CHMP members will be invited t cmment n the prpsed LQ* at the latest during the CHMP plenary meeting. The prpsed timetable and List f Questins will be adpted during the CHMP meeting. *If the referral is triggered by a MAH, it shuld be nted that the prcedure will nt start with a LQ but with the dcumentatin submitted by the MAH as basis fr the assessment. Day 20 Day 25 Rapprteur/C-Rapprteur(s) will circulate their assessment reprts n the MAH(s) written respnses; if applicable the draft SPC/Labelling/PL will be annexed t the pinin. CHMP members will cmment n Rapprteur/C-Rapprteur(s) assessment reprts and draft SPC/Labelling/PL (if applicable). Day 30 CHMP plenary meeting The Rapprteur/C-Rapprteur(s) will draft a LOI t be answered in writing and/r in an ral explanatin (the CHMP shuld be infrmed n the likelihd f a future ral explanatin). If at this stage n prpsal f SPC/labelling/PL has been given, it shuld be requested in the LOI. EMEA 2008 16/27
Page 17/27 Or an Opinin will be adpted by the CHMP Between Day 30 and Day 60 (specific adpted timetable fr the prcedure t be fllwed) Rapprteur/C-Rapprteur(s) will circulate their assessment reprts n the MAH(s) written respnses t the LOI with the draft SPC/Labelling/PL.CHMP members will cmment n such dcuments. Day 60 CHMP plenary meeting A CHMP Opinin is adpted. It shuld be nted that fr referrals under Articles 30 and 31 the timetable may be extended allwing a ttal f 150 active days (60 days with a pssibility f extensin fr further 90 days). This extensin f timetable must be dne during a CHMP plenary meeting prir t reaching day 60 f the initial timetable. At all stages, the EMEA PTL will crdinate the prcedure and assist Rapprteur and C- Rapprteur(s) making sure that apprpriate regulatry guidance is prvided. 8.2. Reviews Article 20(1) f Regulatin (EC) N. 726/2004 The Cmmittee may be requested t issue an pinin when a Member State is f the pinin that the manufacturer r imprter established within the Cmmunity territry is n lnger fulfilling the bligatins laid dwn in Title IV f Directive 2001/83/EC. The CHMP will discuss and appint a Rapprteur and C-Rapprteur(s). A 60 days timetable will be adpted (please refer t the timetable stated abve in sectin 7.2). Rapprteur/C-Rapprteur(s) will prepare an assessment reprt n the scientific matter. CHMP members will cmment n the Rapprteur/C-Rapprteur(s) assessment reprt(s). Further t discussin, the CHMP will adpt an Opinin. Article 5(3) f Regulatin (EC) N. 726/2004 The Cmmittee may be requested t issue an pinin n any scientific matters cncerning the evaluatin f medicinal prducts fr human use fllwing a request frm the Executive Directr f the Agency, the Eurpean Cmmissin representative r a Member State. In the latter case, the request frm a Member State will need t be accepted by the Cmmittee. The CHMP will discuss and appint a Rapprteur and C-Rapprteur(s) (if necessary). A timetable will be prepared in accrdance with the urgency. Rapprteur/C-Rapprteur(s) will prepare an assessment reprt n the scientific matter. CHMP members will cmment n the Rapprteur/C-Rapprteur(s) assessment reprt(s). Further t discussin, the CHMP will adpt an Opinin, t be sent t the Eurpean Cmmissin (if the request riginated frm the EC) and t be published. At all stages, the EMEA PTL will crdinate the prcedure and assist Rapprteur and C- Rapprteur(s) making sure that apprpriate regulatry guidance is prvided. Article 107(2) f Directive 2001/83/EC, as amended When a Member State is cnsidering the suspensin r revcatin f the MA fr a medicinal prduct(s) authrised in its territry as a result f the evaluatin f pharmacvigilance data, a prcedure under Article 107(2) is initiated and the CHMP shall prepare an pinin within a timeframe EMEA 2008 17/27
Page 18/27 t be determined depending n the urgency f the matter. In relatin t variatins, as a result f the evaluatin f pharmacvigilance data, the prcedure can be initiated by the Member State(s) which is (are) cnsidering the variatin f the cncerned prduct(s). In principle the scpe f the prcedure is limited t the issues identified by the Member State(s). Given that pharmacvigilance evaluatins are frequently cnducted n drug substances rather than n individual medicinal prducts and in the interest f public health prtectin, a ntificatin under Article 107(2) and the subsequent CHMP pinin(s) may relate t an individual medicinal prduct r a range f medicinal prducts cntaining the same active substance. This shuld be made clear by the Member State(s) when ntifying the Agency f an Article 107(2). The cncerned MS(s) ntifies the EMEA f its intentin t suspend, revke r vary the MA and cnfirms the initiatin f an Article 107 using the Rapid Alert system. Upn receipt f the Rapid Alert ntifying f an Article 107(2) prcedure the EMEA will request Member State(s) t identify all cncerned prducts within a specified timeframe. A Rapid Alert frm (a) Member State(s) ntifying an Article 107(2) prcedure shuld always be accmpanied by an Assessment Reprt prepared by such Member State(s) and any ther relevant dcumentatin which shuld then be made immediately available by the EMEA t all CHMP members. The Member State(s) ntifying the prcedure shuld als make this infrmatin available t the cncerned MAH(s) in its (their) wn territry. Cnsidering the urgency f the matter it can be necessary t agree n a timetable by written prcedure. In exceptinal cases a CHMP Extrardinary meeting can be rganised.. Nrmally, in rder t cnsider the matter the CHMP shuld appint a Rapprteur and ne r mre C-Rapprteur(s) (CHMP Rapprteur/C-Rapprteur appintment EMEA/124066/2005). Hwever, when the timeframe des nt allw fr the (C-) Rapprteur(s) t be appinted in accrdance with the abve prcedure, the CHMP Chairman will appint a Rapprteur and C- Rapprteur(s) n an ad-hc basis. Rapprteur/C-Rapprteur(s) will present the issue and the assessment t the CHMP members during the relevant plenary meeting. Article 107(2) des nt prvide details n the prcedures leading t the adptin f an Opinin and n the pssibility fr MAHs t prvide written and/r ral explanatins. Althugh all reasnable effrts shuld be made t hear (in writing and/r rally) the MAH(s), there culd be circumstances where in rder t prtect public health the CHMP will decide t adpt an Opinin immediately r in a very shrt timeframe and therefre the CHMP may agree nt t hear the MAH(s) cncerned r t nly hear the brand leader. This decisin will be made by the CHMP n a case-by-case basis. In the case when the CHMP des nt cnsider that there is a need t immediately adpt an Opinin, the MAH(s) will in principle be given the pprtunity t cmment n the Assessment Reprts f the triggering MS(s) and/r prvide answers t a CHMP List f Questins. At all stages, the EMEA PTL will crdinate the prcedure and assist Rapprteur and C- Rapprteur(s) making sure that apprpriate regulatry guidance is prvided. Sampling and Testing (Art. 57 ( r ) f the EC Regulatin 726/2004) CHMP members will be asked t adpt/endrse a list f prducts t be tested during a Sampling and Testing Prgramme (this is usually dne in February/March f the year befre the prgramme is implemented). Fr thse prducts fr which the testing recmmendatins are nt available, the Rapprteur and C-Rapprteur fr each prduct will be asked t prvide relevant recmmendatins n the parameters t be tested when the prduct is included in a future sampling and testing prgramme. A template is annexed (Annex 1) in the Day 80 Assessment Reprt. Once the testing f a prduct has been cmpleted, the Rapprteur and C-Rapprteur fr each prduct will receive a testing reprt and, EMEA 2008 18/27
Page 19/27 and if available, the cmments f the MAH n the testing results. The Rapprteur and C-Rapprteur will be asked t prvide advice fr fllw-up actins. EMEA 2008 19/27
Page 20/27 Dealing with Reprts f Defective Medicinal Prducts In the case f significant Quality Defects t centrally authrised prducts, the Rapprteur tgether with the Inspectin Sectr and Supervisry Authrity is expected t cntribute t an assessment f the nature, extent, urgency f pssible public health risk and evaluatin f the seriusness f the defect 9. INTERACTIONS WITH THE CHMP SAG/ad-hc Expert Grup meeting At any stage during the evaluatin prcedures (Day 120, Day 180, prir t an ral explanatin, during a re-examinatin prcedure r during a pst-authrisatin prcedure) the Rapprteur, C-Rapprteur r any CHMP member may suggest t the Cmmittee the need fr a SAG/ad-hc Expert Grup meeting t be scheduled in rder t clarify the issues raised. In the event that a SAG (r ad-hc Expert Grup) cnsultatin is freseen, bth Rapprteurs and the EMEA PTL (and RMTM if apprpriate) are respnsible t draft a List f Questins t be addressed by the experts identified. The draft List f Questins will be reviewed and adpted by the Cmmittee. If necessary, additinal expertise may be sught fr such grups. The EMEA will assist the Cmmittee by making prpsals fr the relevant expertise and the Cmmittee will als review, cmment and adpt the cmpsitin f the SAG/ad-hc Expert Grup and whether r nt additinal expertise is needed and will prpse participants n request. Fllwing the meeting f the SAG/ad-hc Expert Grup, its Chair (r a cre member in his absence) will reprt back t the Cmmittee n the utcme f the discussins. In case f an appeal prcedure, the applicant may request the invlvement f particular SAG. Cnsultatin with target grups In sme particular cases, the Cmmittee may suggest the need t cnsult a target grup f patients r healthcare prfessinals. If such cnsultatins are freseen the Cmmittee will agree t this external invlvement but als define the issues that these grups/rganisatins shuld lk int (i.e. patient leaflet, sme aspect f the risk management plan etc ). CHMP Wrking Parties CHMP members r experts can be appinted Chair r Vice Chair f a Wrking Party (WP) based n individual merit and ability. Fllwing nminatins f interest, the Cmmittee will frmally vte upn these nminatins and appint a Chairpersn and Vice Chairpersn. WP Chairpersns are respnsible fr updating the Cmmittee n the wrk f their WP, bth with respect t the develpment f guidance dcuments and n the input f sme WP in nging prcedures. WPs mandates and wrk prgramme are adpted by the Cmmittee and shuld be strictly adhered t by the WPs, any deviatins shuld be brught t the attentin f the Cmmittee. Fllwing experience gained in the centralised prcedure r feedback frm interested parties, the Cmmittee can prpse that a new guideline is needed r that existing nes are due fr an update. WP members can act as Rapprteur fr a particular guideline depending n his/her expertise and is then respnsible fr driving the prcess t create/update relevant guidelines. When presenting a new guideline r an update f an exiting ne, the Rapprteur and/r the Chairpersn f the WP shuld make a clear presentatin f the dcuments fr adptin / release fr public cnsultatin in rder t facilitate their frmal adptin by the Cmmittee. EMEA 2008 20/27
Page 21/27 During an evaluatin prcess, the Rapprteur, C-Rapprteur r CHMP members may suggest that a particular WP is cnsulted in rder t help reslving the issues identified in the applicatin. If agreeable t the Cmmittee, such cnsultatin will take place and the Cmmittee will adpt a List f Questins t be answered by the relevant WP. The Cmmittee will then adpt the reprt prduced by the WP in respnse t the CHMP cncerns. Cnsultatin f the BWP is always taken n bard fr any bilgic medicinal prduct. Invlvement f the CHMP Pharmacvigilance Wrking Party (PhVWP) This sectin will be updated fllwing the finalisatin f nging discussin with the PhVWP. Cnsultatin with the Paediatric Cmmittee (PDCO) Fllwing the Regulatin n medicinal prducts fr paediatric use cming int frce in July 2007, interactins between the PDCO and the CHMP are essential in rder t achieve apprpriate crdinatin between these scientific cmmittees. Further wrk n the practicality f such interactins is currently nging. Cnsultatin with the Cmmittee fr Orphan Medicinal Prducts fr Human Use (COMP) Interactins with the COMP take place n an ad-hc basis whenever issues are arising with regards t the rphan designatin f a medicinal prduct and als in the cntext f similarity assessment. Cnsultatin with the Cmmittee fr Advanced Therapies (CAT) The Regulatin n Advanced Therapies was adpted in Octber 2007 and fresees interactins between the CAT and the CHMP. Prcedures/guidance n such aspect will be develped ver the cming mnths. Cnsultatin with the Cmmittee fr Herbal Medicines (HMPC) Interactins with the HMPC and CHMP ccur n an ad-hc basis whenever there is a need fr such cnsultatins t take place. Cnsultatin with the Cmmittee the C-rdinatin Grup fr Mutual Recgnitin & Decentralised Prcedures (CMD(h)) Interactins with the CMD(h) and CHMP ccur n an ad-hc basis whenever there is a need fr such cnsultatins t take place, WP supprt, referrals, SPC harmnisatin etc Invlvement f the QRD PIQ-QRD reviews are necessary and Rapprteur might be invlved in such interactins. In additin checking f translatins by Members States are perfrmed with ptential liaisn with CHMP members r assessrs as apprpriate. Invlvement f the Name Review Grup (NRG) The NRG is invlved in checking the prpsed names fr medicinal prducts n behalf f CHMP. The Cmmittee then adpts the NRG prpsals. 10. COMMUNICATIONS Prduct-related annuncements EMEA 2008 21/27