17 February 2012 EMA/531641/2010 Compliance and Inspections

Transcription

1 17 February 2012 EMA/531641/2010 Cmpliance and Inspectins Pre-submissin instructin n the detailed descriptin f the pharmacvigilance system f a marketing authrisatin hlder; t be submitted with a marketing authrisatin applicatin fr a veterinary medicinal prduct 7 Westferry Circus Canary Wharf Lndn E14 4HB United Kingdm Telephne +44 (0) Facsimile +44 (0) inf@ema.eurpa.eu Website An agency f the Eurpean Unin

2 Cntents Cntents Intrductin Scpe f the DDPS Lcatin f the DDPS in the MAA and update f the DDPS Elements t be included in the DDPS Evidence Organisatin Lcatins, Relatinships and Rles Prcesses and Cntractual Arrangements Written prcedures Databases Training Dcument strage and archiving Quality Management Prduct specific addendum... 9 Appendix A Scpe f the DDPS Appendix B Statement signed by MAH and QPPV Appendix C - Curriculum vitae f the QPPV Appendix D - Prduct specific addendum EMA/531641/2010 Page 2/13

3 1. Intrductin Pharmacvigilance (PhV) invlves the detectin, understanding and preventin r minimisatin f the severity f adverse reactins caused by medicinal prducts. A PhV system enables the cllectin, mnitring, assessment and evaluatin f infrmatin related t adverse events. A Marketing Authrisatin Hlder (MAH), r prpsed MAH, is required t develp such a system and prvide a descriptin f that system as part f a Marketing Authrisatin Applicatin (MAA). This descriptin must include sufficient infrmatin t give assurance t the EU Regulatrs [the Natinal Cmpetent Authrities (NCAs) in Eurpean Member States and the Eurpean Medicines Agency (EMA)], that the MAH has an effective system. Fr the purpses f this dcument, MAH als refers t prpsed MAH where apprpriate. This dcument prvides clarificatin and further explanatin f the requirements fr a detailed descriptin f the PhV system (DDPS) given elsewhere 1, and describes hw the infrmatin shuld be presented in a MAA. It is applicable fr any veterinary medicinal prduct 2, whatever the authrisatin prcedure used, whether Eurpean r Natinal. The DDPS shuld cver the MAA in questin, but where the details differ frm the standard system, these particulars must be prvided in a Prduct Specific Addendum (See sectin 4.8 and appendix D). The DDPS prvides evidence that the MAH has the services f a qualified persn respnsible fr PhV (QPPV), and the necessary means fr the ntificatin f adverse events (AE). It is imprtant t remember that the MAH is ultimately respnsible fr ensuring that all PhV bligatins are fulfilled, even if PhV activities are sub-cntracted. If a MAH uses a 3 rd party (e.g. cntractr, licensing partner r ther cmpany) fr prcessing PhV infrmatin, this must be explained in the DDPS (See final paragraph f sectin 4.2.2). The DDPS is a dcument created fr the purpse f assuring the EU Regulatrs that an effective system is in place at the time f an MAA, and will be checked during a PhV inspectin. A Standard Operating Prcedure (SOP) fr PhV is nt equivalent t a DDPS and is nt cnsidered acceptable fr inclusin in a MAA. The dcument shuld describe all the essential elements f an effective PhV system, but shuld nt include unnecessary infrmatin. Step-by-step descriptins f prcedures must be laid ut in written prcedures, e.g. SOPs, and these may be requested at any time by the EU Regulatrs fr inspectin r assessment. Hwever, they shuld nt be included within the DDPS. (Inclusin f unnecessary infrmatin leads t the need fr variatins shuld that infrmatin be changed r remved at a later date.) EU Regulatrs may request infrmatin additinal t the cntents f the DDPS per se. This shuld be supplied separately, nrmally within 2 wrking days, and shuld nt frm part f the DDPS. Sme Member states, due t their natinal legislatin, may require the QPPVs t have specific qualificatins r experience. Please cntact the Member state in which yur QPPV resides t enquire f their requirements. 1 Eudralex - Vlume 9B, Guideline n mnitring f cmpliance with PhV regulatry bligatins and PhV inspectins fr veterinary medicinal prducts 2 Subject t any prduct specific amendments, if applicable (see sectin 4.8 and appendix D) EMA/531641/2010 Page 3/13

4 2. Scpe f the DDPS The descriptin shuld explain hw the PhV system described applies t the prpsed MAH, particularly if the PhV system spans a number f differently named subsidiaries and their parent cmpany, and any ne f thse cmpanies may be the MAH fr a particular MAA. MAHs shuld prvide a brief descriptin f the rganisatin f the cmpanies/subsidiaries/affiliates that may fulfil the rle f MAH and are directed by the PhV system described. It shuld be clear that the MAH named in the MAA is gverned by the PhV system. The descriptin shuld be written s that it can be applied t any MAA, whatever the authrisatin prcedure r whichever f multiple MAHs is the MAH fr a particular MAA. See Appendix A fr examples f different cmpany arrangements. 3. Lcatin f the DDPS in the MAA and update f the DDPS The DDPS f the MAH is submitted in Annex 5.20 f Part IA f a MAA 3. It shuld be versin-cntrlled and dated t enable the tracking f updates and crrectins. The Ntice t Applicants (as abve) requires that the CV f the QPPV shuld als be included in Annex 5.5. Any changes t the DDPS, nce the prduct t which the DDPS applies has been authrised, require a variatin 4 r gruped variatins. 4. Elements t be included in the DDPS The DDPS cmprises a number f required elements t assure the EU Regulatrs that the MAH can fulfil respnsibility fr the PhV f their prducts and can take apprpriate actin when necessary. If any f the required elements are nt included in the DDPS, the absence shuld be explained and justified Evidence Evidence shuld be presented t shw that the MAH has the services f a QPPV and the necessary means fr the cllectin and ntificatin f any AE ccurring either in the Cmmunity r a third cuntry. The evidence needs t include the fllwing elements: A statement, signed by bth a representative f the MAH (shwn at sectin f MAA) and the QPPV (shwn at sectin f MAA), declaring the availability f the QPPV and the means fr reprting AEs (see Appendix B). The representative/persn signing the DDPS statement n behalf f the MAH shuld have the authrity t d s. The persn signing n behalf f the MAH shuld nt be the same persn as the QPPV, unless there is n ther suitable persn in the MAH. The name and business cntact details f the QPPV within the EEA shuld be prvided in sectin f the MAA, and nt in the DDPS. A list f the cntact details f the lcal PhV cntacts r affiliates shuld be retained by the MAH and may be requested by the EU Regulatrs. Hwever, this des nt frm part f the DDPS. 3 Eudralex - Vlume 6B Ntice t applicants, Veterinary medicinal prducts. 6/b/vl6b_04_2004_final_en.pdf 4 Cmmissin Regulatin 1234/2008 (OJ L ) 1/reg_2008_1234/reg_2008_1234_en.pdf. and Guideline n the details f the varius categries f variatins t the terms f marketing authrisatins fr medicinal prducts fr human use and veterinary medicinal prducts (OJ C ) EMA/531641/2010 Page 4/13

5 A summary f the Curriculum Vitae f the QPPV with qualificatins, training and experience relevant t PhV (see Appendix C). The persnal and/r business cntact details shuld nt be included in the CV. If the QPPV des nt hld a veterinary r pharmaceutical qualificatin, the QPPV shuld have access t a veterinary surgen t assist with veterinary assessment f AE reprts. Nte that lists f scientific publicatins unrelated t PhV issues shuld nt be included. A summary f the jb descriptin f the QPPV, detailing the rles and respnsibilities fr PhV. Any PhV rles that are delegated t ther persns shuld be listed. Individuals shuld nt be identified by name but by their psitin in the rganisatin. Nte that rles and respnsibilities nt related t PhV shuld nt be included. Rles t be included: Establishment and maintenance f PhV system Ensure the accurate recrding f AEs Causality assessment f AEs Preparatin f AE and Peridic Safety Update Reprts (PSUR) Cnducting cntinuus/nging/peridic PhV evaluatin Timely transmissin f reprts and prvisin f ther infrmatin t EU Regulatrs, as required Training (i.e. general PhV; VeDDRA terminlgy; preparatin f PSURs). Cnfirmatin that alternative r back-up arrangements have been made t manage PhV activities during the absence f the QPPV, and a brief descriptin f thse arrangements. If a specific deputy is identified, this shuld nt be by name, but by their psitin in the rganisatin. Nte that EU Regulatrs may request the name and cntact details f a deputy separately. This infrmatin wuld nt be part f the DDPS. A cpy f the registratin 5 f the QPPV with the EudraVigilance Veterinary system r a letter frm the EMA cnfirming registratin, if apprpriate 6. Ensure any passwrd is masked. A cpy f a EudraVigilance training attendance certificate is nt acceptable as prf f registratin. MAHs shuld check with individual EU Regulatrs, and the Eudravigilance website 7, t ensure that the natinal requirements fr electrnic reprting are satisfied, as they can vary between EU Regulatrs Organisatin The functinal rganisatin and respnsibilities f all units invlved in PhV, frm the MAH t the pint at which the prduct is received by the custmer, shuld be described. The system descriptin needs t utline the rle f the MAH and whether the MAH is the parent cmpany r a subsidiary/affiliate. If the PhV prcedures vary with the identity/lcatin f the MAH, the differences shuld be described. A high level rganisatin chart shuld be prvided if it helps t clarify the descriptin. 5 Lg in t EudraVigilance Veterinary website at using persnal lg-in credentials. Select Manager Prfile, Printable versin and print page. 6 Where a MAH receives nly a small number f serius SAR reprts, then registratin fr Eudravigilance may nt be necessary. Hwever, this shuld be clarified with the NCA cncerned. Nte that this is nly likely t apply t Natinal MAs EMA/531641/2010 Page 5/13

6 Lcatins, Relatinships and Rles The fllwing elements are required: The identificatin and lcatin f the cmpany units r ther rganisatins invlved in the principal EEA and glbal PhV activities. Specific affiliates/distributrs shuld nt be listed in the DDPS, but the infrmatin must be prvided separately at the request f the EU Regulatrs. The pint(s) in the Cmmunity at which PhV data e.g. AEs, PSURs and glbal PhV data may be accessed must be identified. This may be described r indicated in the rganisatin chart (See 4.2 abve) and/r diagram(s). The lcatin f the main databases invlved in PhV. A database n a server utside the EEA is acceptable prvided it can be accessed frm within the EEA. The relatinships between the different units invlved in pharmacvigilance activities e.g. distributrs/cntractrs, lcal ffices/affiliates, head ffices/parent cmpanies where apprpriate. T include: The lcatin and rles f each unit e.g. head ffice, lcal ffice etc. shuld be described, identifying which is respnsible fr data gathering, recrding, assessment, reprting and archiving. Reprting interactins and the psitin f the EEA/natinal QPPV r lcal PhV cntacts within the rganisatin must be described. The MAH shuld clarify whether the QPPV is directly emplyed by the MAH r subcntracted. A summary f the PhV activities cnducted at each unit, e.g. receipt f AEs, cllectin and fllw-up f AE infrmatin, assessment f seriusness and causality, strage f AEs, preparatin f PSURs etc Prcesses and Cntractual Arrangements The fllwing elements shuld als be described: The flw f AE reprt infrmatin e.g. spntaneus AEs and PSURs frm the surce t the pint f receipt by the EU Regulatrs shuld be described and/r depicted in ne r mre diagrams shwing the timelines invlved. The capture f the EU Regulatr s case reference shuld be shwn r described. The fllwing shuld be included, where apprpriate: Different types f AE reprts Animal AEs including safety, lack f efficacy and unauthrised use Human AE reprts Ptential envirnmental prblems Investigatin f the validity f withdrawal perids Transmissin f any infectius agent via a veterinary medicinal prduct Different surces EMA/531641/2010 Page 6/13

7 Persn administering veterinary medicinal prducts (wner/farmer) Human/animal healthcare prfessinals EU Regulatrs Literature searches Different types f reprting (describe legislative reprting prcedures including timelines) Expedited reprts (Serius animal AEs and all human AEs) Nn-expedited reprts (PSURs) Agreements with ther rganisatins, such as c-marketing partners and PhV sub-cntractrs shuld be identified and respnsibilities fr PhV activities briefly described. It shuld be clear which rganisatin is respnsible fr which PhV activities including translatin f primary recrds, veterinary evaluatin and VeDDRA cding as apprpriate. Hwever, the actual agreements shuld nt be included in the DDPS Written prcedures It is essential that a PhV system is cntrlled by clear written prcedures, including SOPs if apprpriate. Quality management is an essential feature f any system reliant n data. Checking and crsschecking are imprtant steps in the management f data and shuld be included in written prcedures. Assurance shuld be prvided that all relevant tpics are cvered, r will be by the time the prduct is marketed. If any tpic is nt cvered, an explanatin shuld be prvided. Cpies f written prcedures r SOPs shuld nt be included in a MAA, nr shuld the specific titles, numbers r versin dates f the SOPs. The Cmmissin guideline prvides a full list f the tpics that wuld be expected t be cvered by written prcedures. Hwever, frm the experience f EU Regulatrs, sme tpics require further clarificatin and these are listed belw. The cllectin frm all surces, fllw-up, prcessing, quality cntrl (including duplicate detectin), assessment, classificatin, veterinary/scientific review, and reprting (including expedited and electrnic reprting) f AEs. Cmmunicatin with EU Regulatrs and animal health prfessinals regarding changes t benefit-risk balance f prducts and requests fr infrmatin. Interactin between safety issues (PhV) and prduct defects (quality) i.e. prduct defects that culd lead t PhV issues Staff training. Nte that ne r mre tpics may be cvered by a single written prcedure, r a single tpic may be included in mre than ne written prcedure Databases The means by which PhV data is recrded shuld be described, whether paper recrds, spreadsheets, a database develped in-huse r a prprietary database. EU Regulatrs are flexible as t whether a MAH has an electrnic database, depending n the number f reprts the MAH receives. Hwever, EU Regulatrs wuld prefer all MAHs t have sme frm f electrnic strage fr PhV data e.g. spreadsheets. Nte that the descriptin shuld be brief and technical specificatins f the database shuld nt be included. The Cmmissin guideline utlines the tpics that wuld be expected t be EMA/531641/2010 Page 7/13

8 included. Hwever, they are individually listed belw, with additinal infrmatin where apprpriate, fr clarificatin purpses: The means f PhV data strage shuld be identified and briefly described. A statement that the electrnic database(s) has been validated. If the database is capable f assisting the cmpilatin f safety reprts and perfrming expedited and electrnic reprting this shuld be described. The methd(s) f electrnic reprting, f cases ccurring in bth the EEA and 3 rd cuntries, via the EudraVigilance Gateway, EVWeb, MAH Simplified Electrnic Reprting Frm (SERF) r ther methd, must be indicated. Further infrmatin can be btained frm the Eudravigilance veterinary website 7. A statement regarding the cmpliance f the systems with internatinally agreed standards, i.e. data elements e.g. VeDDRA, species, breed etc., fr electrnic submissin f AE reprts 8. This shuld be prvided, if apprpriate. The MAH shuld describe the tls r appraches used fr detecting signals. The persn r grup respnsible fr the peratin and management f the database shuld be indicated. It is als preferable that MAHs have databases fr the cntrl f submissin f PSURs, fr prduct infrmatin and fr recrding f sales infrmatin etc Training Describe the PhV training given t all persnnel, including cntractrs, wh may be invlved in PhV. Persnnel, shuld nly be identified by their psitin in the rganisatin, nt by name. Briefly describe the training system. Describe the type and frequency f training given, and the pst hlder wh prvides it. Specify wh e.g. technical staff, sales, custmer services etc. is trained by whm. State where the training recrds f trainees and the CV and jb descriptin f the trainer(s) are filed. Nte that cpies f persnal training recrds shuld nt be included in the DDPS Dcument strage and archiving PhV dcumentatin shuld be stred securely. The lcatin f dcumentatin including riginal AE reprts frm the primary surce, PSURs, QC recrds relating t AE prcessing, SOPs and training recrds etc. shuld be identified. Als, the site where prduct sales figures can be accessed fr PhV shuld be identified. The length f time fr which paper cpies f riginal reprts are archived in the EEA shuld be indicated. The EU Regulatrs wuld expect this t be at least fr the life f the prduct plus sme time (t allw fr expiry f the prduct). EU Regulatrs may request the identificatin f Guideline n data elements fr the electrnic submissin f adverse reactin reprts related t VMPs authrised in the EEA EMA/531641/2010 Page 8/13

9 the pst hlder(s) respnsible fr archiving, and a descriptin f the validatin and quality standards applied t archiving, but this shuld nt frm part f the DDPS Quality Management The verall system shuld be briefly described, utlining the elements that are cvered as per the Cmmissin guideline. These shuld include the use f written prcedures. Nte that, althugh it may be helpful, there is n requirement fr certificatin t a particular standard. During the assessment f the DDPS additinal infrmatin r assurance abut the Quality Management system may be requested by the EU Regulatrs, but it shuld nt frm part f the DDPS Prduct specific addendum Whilst nt part f the main system descriptin, this shuld be prvided, if apprpriate, in sectin 5.20 f the MAA in an Annex t the MAH DDPS. Risk management systems r pst-authrisatin requirements shuld be included here if apprpriate. Where apprpriate, a brief descriptin shuld be given f the nature f any agreements fr sub-cntracting and c-marketing/c-licensing, specifying regulatry respnsibilities and PhV activities. In particular, the c-marketing arrangements within the EEA shuld be identified and the distributin f the majr respnsibilities between the parties shuld be clarified. If there are n subcntracting, clicensing r c-marketing arrangements within the EEA fr the prduct that is the subject f the prduct-specific MAA, the MAH shuld include a clear statement t this effect. The MAH shuld identify precisely hw the nrmal system is amended t accmmdate the specific prduct. See Appendix D fr an example. EMA/531641/2010 Page 9/13

10 Appendix A Scpe f the DDPS Examples f different cmpany arrangements that culd be described in the DDPS f an MAH. Example 1. A small cmpany present in ne EEA cuntry with prducts nly authrised in that cuntry. Cmpany A, lcated at ne site in the UK, has a number f natinally authrised prducts, which are sld thrugh whlesalers r veterinary surgens. Example 2. A small cmpany present in ne EEA cuntry with prducts authrised in ther EEA cuntries. Cmpany C, based entirely in Belgium, markets its prducts in Belgium thrugh lcal whlesalers and in ther EEA cuntries thrugh distributrs, either under the MAH s name r the distributr s name. Example 3. A larger cmpany, based in ne EEA cuntry, but with lcal subsidiaries in sme ther EEA cuntries, which may be MAH f sme prducts. Cmpany D, based in an EEA cuntry with subsidiary cmpanies in ther EEA cuntries, markets its prducts thrugh distributrs in thse cuntries where it des nt have a lcal presence. Natinal subsidiary cmpanies are MAH fr sme prducts. Example 4. A glbal cmpany based in a nn-eea cuntry, with natinal subsidiary cmpanies in sme EEA cuntries. These subsidiaries will be MAHs. A glbal DDPS is submitted. Cmpany F, based in the USA with subsidiary cmpanies in sme EEA cuntries, markets its prducts thrugh distributrs in thers. Example 5. A cmpany that subcntracts its PhV activities t a third party. Cmpany G, based in France, with ther named sub-cmpanies (affiliates) in France, subsidiary cmpanies in ther EEA cuntries and uses a third party fr prcessing PhV infrmatin. Any f the affiliates r subsidiaries may be MAH, but their cmpany name des nt indicate that they may be related t Cmpany G. EMA/531641/2010 Page 10/13

11 Appendix B Statement signed by MAH and QPPV Statement regarding services f QPPV and availability f necessary means fr ntificatin f Adverse Events. a) Where the DDPS applies directly t the MAH and the declaratin is signed by a representative f the MAH (Cmpany A). The applicant and the QPPV declare that the applicant has the services f a Qualified Persn respnsible fr PhV (QPPV) and has the necessary means fr the cllectin and ntificatin f any adverse reactin suspected f ccurring either in the Cmmunity r in a third cuntry. Signed Signed Fr and behalf f Cmpany A (MAH) QPPV Date: dd/mmm/yy b) Where the DDPS belngs t a parent cmpany (A) and the declaratin is signed by a representative f the parent cmpany, but the MAH (B) is an affiliate, r similar, f that parent cmpany. [Parent cmpany name (cmpany A], including any affiliates, and the QPPV declare that the applicant has the services f a Qualified Persn respnsible fr PhV (QPPV) and has the necessary means fr the cllectin and ntificatin f any adverse reactin suspected f ccurring either in the Cmmunity r in a third cuntry. Signed Signed Cmpany A Signed QPPV Date: dd/mm/yy Cmpany B (MAH) Date: EMA/531641/2010 Page 11/13

12 Appendix C - Curriculum vitae f the QPPV Cntact details Curriculum vitae f the QPPV Name: Address: Dr J Brwn A Cmpany Regulatry Affairs Qualificatins 1986 Degree in Veterinary Medicine Bristl University Prfessinal experience present Regulatry affairs manager and QPPV at A Cmpany Regulatry affairs fficer at A Cmpany Senir partner in mixed practice Junir partner in mixed practice Lcum veterinary surgen in small animal practices Curses and cnferences etc PhV fr the Veterinary Industry Management Frum, Lndn EMA/531641/2010 Page 12/13

13 Appendix D - Prduct specific addendum Prduct name (Natinal) Type f Marketing Authrisatin (Natinal/MRP/DCP/EUCE) Marketing Authrisatin Hlder Prduct specific details: Scpe Identificatin f psitin f MAH in rganisatin described in 2.3 Evidence Organisatin QPPV (natinal and/r EEA) and psitin in rganisatin Prduct specific agreements fr sub-cntracting and/r c-marketing etc fr PhV Named Distributrs Differences, frm main descriptin, in respnsibilities fr PhV activities Databases Training Dcument Strage and Archiving Written prcedures EMA/531641/2010 Page 13/13