Regulatry & Pharma News Update August 2015 REGULATORY NEWS Draft Addendum t ICH E6 Released ICH E6(R1) (Guideline fr Gd Clinical Practice) has been in place since 1996 but is underging revisin in the frm f an addendum (ICH E6(R2)) t encurage implementatin f imprved and mre efficient appraches t clinical trial design, cnduct, versight, recrding and reprting while cntinuing t ensure human subject prtectin and data integrity. This addendum has nw been released fr cmment and is available n the ICH website. The revised guideline includes mre detail n areas that have been ht tpics frm GCP inspectins in recent years. The changes include the fllwing: Sectin 1, Glssary - the fllwing definitins have been added t the glssary: Certified cpy Mnitring Plan Validatin f Cmputerised Systems Sectin 2, The Principles f ICH GCP an additinal sentence has been added t 2.10 s that it nw reads All clinical trial infrmatin shuld be recrded, handled, and stred in a way that allws its accurate reprting, interpretatin and verificatin. This principle applies t all recrds (paper r electrnic) referenced in this guideline. Sectin 4, Investigatr the fllwing additins have been made: 4.2.5 The investigatr is respnsible fr supervising any individual r party t whm the investigatr delegates study tasks cnducted at the trial site. 4.2.6 If the investigatr/institutin retains the services f any party t perfrm study tasks they shuld ensure this party is qualified t perfrm thse study tasks and shuld implement prcedures t ensure the integrity f the study tasks perfrmed and any data generated. 4.9.0 The investigatr shuld maintain adequate and accurate surce dcuments and trial recrds that include all pertinent bservatins n each f the site s trial subjects. Surce data shuld be attributable, legible, cntempraneus, riginal, accurate and cmplete. Changes t surce data shuld be traceable, shuld nt bscure the riginal entry and shuld be explained if necessary (e.g., via and audit trail). Sectin 5, Spnsr the fllwing additins/amendments have been made: TMQA 18E Libertn Brae, Edinburgh EH16 6AE, Sctland, UK t: +44 (0)131 450 7017 f: +44 (0)131 664 6794 e: inf@tmqa.c.uk www.tmqa.c.uk
5.0 Quality Management this is a new sub sectin which includes: 5.0.1 Critical Prcess and Data Identificatin, 5.0.2 Risk Identificatin, 5.0.3 Risk Evaluatin, 5.0.4 Risk Cntrl, 5.0.5 Risk Cmmunicatin, 5.0.6 Risk Review, 5.0.7 Risk Reprting. 5.2.1 an additinal sentence has been added which reads The spnsr shuld ensure versight f any trial-related duties and functins carried ut n its behalf. 5.2.2 an additinal sentence has been added which reads The spnsr shuld dcument apprval f any subcntracting f trial-related duties and functins by a CRO. 5.5.3(b) additinal wrding added which indicates what SOPs shuld cver. 5.5.3(h) new pint which reads Ensure the integrity f the data including any data that describe the cntext, cntent and structure f the data. This is particularly imprtant when making changes t the cmputerised systems, such as sftware upgrades r migratin f data. 5.18.3 additinal wrding has been added t prvide mre guidance in relatin t the extent and nature f mnitring. It defines n-site mnitring and centralized mnitring. 5.18.6(e) new pint which reads Mnitring results shuld be prvided t the spnsr (including apprpriate management and staff respnsible fr trial and site versight) in a timely manner fr review and fllw-up as indicated. Results f mnitring activities shuld be dcumented in sufficient detail t allw verificatin f cmpliance with the mnitring plan. 5.18.7 Mnitring Plan this additinal sub-sectin prvides guidance n what shuld be detailed in the mnitring plan. 5.20.1 additinal wrding added t describe what actin shuld be taken in the event f significant nn-cmpliance with the prtcl, SOPs, GCP and/r applicable regulatry requirements and als makes mentin f serius breaches f the trial prtcl r GCP. Sectin 8.1 Essential Dcuments fr the Cnduct f a Clinical Trial, Intrductin further guidance n essential dcument expectatins has been added. The deadline fr cmments n this draft addendum t ICH E6(R1) is 31 January 2016. http://www.ich.rg/fileadmin/public_web_site/ich_prducts/guidelines/efficacy/e6/e6_r2 A ddendum_step2.pdf MHRA GPvP Inspectins f Cntract Service Prviders The Medicines and Healthcare prducts Regulatry Authrity (MHRA) has embarked n a recent initiative t evaluate the feasibility f cnducting stand-alne inspectins f pharmacvigilance cntract service prviders. In July 2003 the MHRA intrduced a statutry pharmacvigilance inspectin prgramme f marketing authrisatin hlders (MAHs) in the UK. The revised 2010 EU pharmacvigilance legislatin and Gd Vigilance Practice (GVP) guidance has further strengthened the remit f the MHRA t inspect rganisatins that prvide cntract services fr pharmacvigilance. It s increasingly cmmn fr MAHs t utsurce pharmacvigilance activities t a cntract service prvider. Since the MHRA currently inspect the pharmacvigilance systems, prcesses and prcedures during their inspectins f a MAH, this means that the activities undertaken by a particular pharmacvigilance cntract service prviders may underg review by the MHRA multiple times, Page 2 f 5
depending n the number f MAHs wh have subcntracted activities t that cmpany. The cst f inspecting a cntract service prvider is cvered by the fee charged t a particular MAH and the repeated inspectin f a cntract service prvider invlves repeated csts. By implementing fee-bearing pharmacvigilance inspectins f service prviders this culd benefit bth the service prviders and the MHRA by: Pssibly reducing the number f times a service prvider wuld be inspected Reducing the frequency fr each MAH t individually audit their service prviders, as part f the MAH s risk-based audit prgramme Pssibly allcate MHRA resurce where required in a risk-based fashin it may be pssible t cver the activities that supprt multiple MAHs at a single inspectin f that service prvider, which may result in a reduced inspectin scpe f MAH inspectins, where a service prvider had previusly been evaluated as part f a stand-alne inspectin (althugh an evaluatin f interfaces and versight by the MAH may still be required). In Octber 2014 the MHRA cntacted 22 cntract service prviders and ffered them the pprtunity t cmplete a survey aimed at helping the MHRA assess the feasibility f cnducting stand-alne inspectins f pharmacvigilance cntract service prviders. As part f the survey vlunteers were requested t participate in a pilt phase f fee-bearing inspectins, planned fr the financial year f 2015/2016. Of the 22 cntract service prviders cntacted, 10 respnded t the survey and f these 7 vlunteered t participate in the pilt phase. Currently 2 rganisatins have been cntacted fr inspectin by the MHRA s GPvP inspectrate. These inspectins are due t take place in Q2 and Q3 2015/2016. https://mhrainspectrate.blg.gv.uk/2015/08/11/gpvp-inspectins-f-cntract-service-prviders/ MHRA Enfrces EC Decisin in Relatin t GVK Bisciences In line with the Eurpean Cmmissin s (EC) decisin (16 Jul 2015), the MHRA has suspended a number f prducts fr which authrisatin was based n clinical studies cnducted at GVK Biscience s site in Hyderabad, India. Only generic medicines are affected, therefre alternatives t suspended prducts are readily available. The prducts which have been suspended are deemed nncritical t cntinuity f supply t the UK market. Prducts necessary fr cntinuity f supply and thse nn-critical prducts fr which further data in supprt f the marketing authrisatin has been prvided, have nt been suspended. The EC endrsed the recmmendatin f the Eurpean Medicines Agency s (EMA) Cmmittee fr Medicinal Prducts fr Human Use (CHMP) t suspend a number f licenses fr generic medicines, fr which authrisatin was based n clinical studies cnducted at GVK Bisciences site in Hyderabad, India. The actin t suspend a number f prducts is a precautinary measure and there is n evidence f safety cncerns r lss f efficacy f these prducts. https://www.gv.uk/gvernment/publicatins/mhra-enfrces-eurpean-cmmissin-decisin-tsuspend-medicines-fr-which-authrisatin-based-n-clinical-studies-cnducted-at-gvk-bisciences Page 3 f 5
EMA Launches Pilt in Relatin t Pst-Authrisatin Safety Studies The EMA is launching a 12-mnth pilt t encurage cmpanies t seek scientific advice fr pstauthrisatin safety studies (PASS) fr medicines. This vluntary, ptinal prcedure will help t imprve the design f studies meant t cllect further infrmatin n a medicine s safety nce it is n the market. The main fcus f the pilt will be n PASS studies which are nt a cnditin t the marketing authrisatin. By requesting scientific advice, this shuld assist develpers in putting tgether high-quality safety studies that can prvide useful infrmatin n a medicine in a real-life setting, in the interest f patients. The EMA is publishing updated questins and answers t give mre details n this prcedure, as well as a letter f intent cmpanies shuld send t the EMA t submit a request fr scientific advice. http://www.ema.eurpa.eu/ema/index.jsp?curl=pages/news_and_events/news/2015/07/news_det ail_002382.jsp&mid=wc0b01ac058004d5c1 EMA Revises Guidelines n Implementatin f Fast Track Rutes fr Medicines that Address Unmet Medical Needs The EMA has revised its guidelines n the implementatin f accelerated assessment and cnditinal marketing authrisatin. These are tw key tls in Eurpean legislatin which are intended t accelerate patients access t innvative medicines that target a disease fr which n treatment is available r that prvide patients with a majr therapeutic advantage ver existing treatments. The EMA s accelerated assessment prcedure allws fr a faster assessment f eligible medicines by EMA s scientific cmmittees. Cnditinal marketing authrisatin allws fr the early apprval f a medicine n the basis f less cmplete clinical data than nrmally required, if the medicine addresses an unmet medical need and targets a seriusly debilitating r life-threatening disease, a rare disease r is intended fr use in emergency situatins in respnse t a public health threat. While less cmplete, the available data must still demnstrate that the medicine s benefits utweigh its risks and the applicant shuld be in a psitin t prvide the cmprehensive clinical data after authrisatin within a timeframe agreed with the CHMP. In additin, the benefit t public health must utweigh the risk due t limited availability f clinical data at the time f marketing authrisatin. The main changes in the prpsed revisin t the guideline are as fllws: Accelerated Assessment Mre detailed guidance n hw t justify fulfilment f majr public health interest, which is the basis fr a request fr an accelerated assessment Optimisatin f the assessment timetable by better balancing evaluatin phases t reach a CHMP pinin within the 150 days after the start f marketing authrisatin applicatin prcedure (cmpared t 210 days in nn-accelerated prcedures) Emphasis n the imprtance f early dialgue with EMA s that accelerated assessment can be planned well ahead f the submissin. The EMA highlights that the eligibility criteria laid dwn in the accelerated assessment guideline are als being cnsidered fr a new scheme, currently under develpment, that is designed t facilitate the develpment and accelerated assessment f innvative medicines f majr public health interest, in particular frm the viewpint f therapeutic innvatin. Cnditinal Marketing Authrisatin Page 4 f 5
Clarificatin n fulfilment f unmet medical needs, i.e. medicines prviding majr imprvements in patient care ver existing therapies can be legible in certain cases Clarificatin f hw a psitive benefit-risk balance is t be substantiated where there are less cmplete data, with further guidance n the level f evidence that must be prvided at the time f authrisatin and the data that can be prvided after authrisatin Updated guidance n the extent and type f data required t be included in annual renewal submissins. An verview f the prpsed changes is available n the EMA website. Public cnsultatin n the revised guidelines is pen until 30 Sep 2015. http://www.ema.eurpa.eu/ema/index.jsp?curl=pages/news_and_events/news/2015/07/news_det ail_002381.jsp&mid=wc0b01ac058004d5c1 Page 5 f 5