Qualified Persons involved in the manufacture of pharmaceuticals Study Guide

Transcription

1 Qualified Persns invlved in the manufacture f pharmaceuticals Study Guide The knwledge and practical experience required by Qualified Persns invlved in the manufacture f pharmaceuticals in the UK February 2017

2 Cntents Preface 1.0 The Qualified Persn invlved in the manufacture f pharmaceuticals: backgrund 2.0 The three fundatin knwledge elements a. Pharmaceutical law and administratin b. The rle and prfessinal duties f the Qualified Persn c. Pharmaceutical Quality Systems 3.0 Additinal knwledge requirements d. Mathematics and statistics e. Medicinal chemistry and therapeutics f. Pharmaceutical frmulatin and prcessing g. Pharmaceutical micrbilgy h. Analysis and testing i. Pharmaceutical packaging j. Active pharmaceutical ingredients k. Investigatinal medicinal prducts 4.0 Practical experience requirements 4.1 Illustratin f requirements 5.0 Rle f the Qualified Persn 5.1 Directives 2001/83/EC and 2001/82/EC 5.2 Directive 2001/20/EC 6.0 Other Eurpean member states 7.0 Summary Reasn fr issue: Minr updates t reflect the latest terminlgy Issue date: February 2017 QP Study Guide 2017 Page 2 f 15

3 Preface The three UK prfessinal bdies, als knwn as the Jint Prfessinal Bdies, administering the Qualified Persns scheme, the Ryal Pharmaceutical Sciety, the Ryal Sciety f Bilgy and the Ryal Sciety f Chemistry, first intrduced a Study Guide fr Qualified Persns in 1978 based n Article 23 f 75/319/EEC. Further revisins were cmpleted in 2000, 2004, 2006, 2008 and This revisin was made effective frm 20 February The three prfessinal bdies require an applicant fr certificatin as a Qualified Persn t demnstrate a thrugh understanding f the fundatin knwledge elements and t be able t apply his r her knwledge f Pharmaceutical Quality System (PQS) principles, and t demnstrate understanding f the additinal knwledge requirements. The applicant will be required t demnstrate this by reference t the prducts and prcesses fr which he r she is claiming his r her qualifying experience, which will apply whlly r in part t the Manufacturer s Authrisatin(s) (may be knwn as a Licence herein) detailed n the applicatin. The three prfessinal bdies have determined that the fundatin knwledge elements are: pharmaceutical law and administratin; the rle and prfessinal duties f the Qualified Persn; and Pharmaceutical Quality Systems (i.e. the basic philsphy and principles f Quality Assurance), which applies t all sectins f this guide. Certificatin f eligibility fr nminatin as a Qualified Persn n a Manufacturer s Authrisatin is dependent upn the demnstratin f bth an apprpriate knwledge f thse activities and disciplines relevant t pharmaceutical manufacturing and Quality Assurance (QA), and apprpriate practical experience. 1.0 The Qualified Persn invlved in the manufacture f pharmaceuticals: backgrund The Medicines and Healthcare prducts Regulatry Agency (MHRA) f the UK Department f Health, and the Veterinary Medicines Directrate (VMD), have interpreted the requirements f the Pharmaceutical Directives 2001/83/EC, 2001/20/EC and the Veterinary Directive 2001/82/EC, and applicable implementing UK legislatin, thrugh a Study Guide, drawn up by a panel f experts, and have given authrity t three prfessinal bdies, (the Ryal Pharmaceutical Sciety, the Ryal Sciety f Bilgy and the Ryal Sciety f Chemistry), t perate an assessment prcedure fr their members. The assessments seek t determine an applicant's suitability fr being named n a cmpany Manufacturer s Authrisatin. The rle f the prfessinal bdies is t certify the eligibility f the applicant fr nminatin as a Qualified Persn n a Manufacturer s Authrisatin. The applicant must be able t demnstrate that he r she can satisfy the knwledge and experience requirements f Articles 49 and 50 f the "Pharmaceutical Directive" 2001/83/EC (amended by Directive 2004/27/EC), Articles 53 and 54 f the QP Study Guide 2017 Page 3 f 15

4 "Veterinary Directive" 2001/82/EC (amended by 2004/28/EC), r Article 13 f the Clinical Trials Directive 2001/20/EC. Acceptance f a persn, certified as eligible fr nminatin, n a Manufacturer s Authrisatin is a matter fr the Licensing Authrity. The certificatin prcess includes submissin f a cmpleted applicatin frm, the spnsrship f an applicant by a Qualified Persn wh is als a member f ne f the prfessinal bdies (the Ryal Pharmaceutical Sciety, the Ryal Sciety f Bilgy r the Ryal Sciety f Chemistry), the payment f an applicatin fee, and fr applicatins under the permanent prvisins, an ral assessment f the applicant's knwledge and experience. Applicatins under the transitinal prvisins f Article 50 f 2001/83/EC d nt nrmally invlve an ral assessment. Since the change in veterinary legislatin in 2005, applicatins can n lnger be made under the transitinal prvisins f 2001/82/EC. The VMD has the capacity t appint QPs independently f the prfessinal bdies. Since 1992 the ral assessments have been cnducted by a panel f assessrs drawn frm all three prfessinal bdies, wh are themselves well acquainted with the rle f the Qualified Persn. The prfessinal bdies have agreed with the MHRA and VMD that, in principle, an individual wh has been certified as eligible fr nminatin as a Qualified Persn is als ptentially eligible fr transfer frm ne Manufacturer s Authrisatin t anther, althugh the final decisin fr accepting a persn as a Qualified Persn n a Manufacturer s Authrisatin rests with the Licensing Authrity in the UK. In cnsequence the assessrs must be satisfied that an applicant, after a suitable inductin perid, will be able t functin as a Qualified Persn in any licensed undertaking. Appeals can be made by applicants t their prfessinal bdy as apprpriate. A guide t the bdy f knwledge required by the Qualified Persn is set ut in the fllwing pages. This dcument shuld be studied in cnjunctin with the current editin f the Medicines and Healthcare prducts Regulatry Agency s (MHRA) "Rules and Guidance fr Pharmaceutical Manufacturers and Distributrs (knwn as "the Orange Guide") and EU legislatin defined in EudraLex Vlume 4, Guidelines fr gd manufacturing practices fr medicinal prducts fr human and veterinary use. The prfessinal bdies n lnger issue a Surces f Reference dcument. Frequent legislatin changes result in the dcument rapidly becming ut-f-date. Applicants are reminded that a thrugh knwledge and understanding f current legislatin is required t meet the requirements f this Study Guide. 2.0 The three fundatin knwledge elements a. Pharmaceutical law and administratin T assure patient safety, the manufacture and distributin f pharmaceutical prducts is highly regulated within the Eurpean Unin. The Qualified Persn, in particular, must ensure that all legislative bligatins are fully satisfied befre any prduct is released fr sale r supply. A Qualified Persn must have a cmprehensive knwledge f all Eurpean and Natinal legislatin relating t the manufacture, strage and supply f licensed medicinal prducts and the interpretatin f the law as exemplified in the current editin f the MHRA's "Rules and Guidance fr Pharmaceutical Manufacturers and Distributrs ", ("the Orange Guide"). Applicants will be expected t demnstrate a thrugh understanding f the fllwing: Eurpean pharmaceutical directives (including but nt limited t 2001/83/EC, 2001/82/EC, 2001/20/EC, 2003/94/EC, 2004/24/EC, 2004/27/EC, 2004/28/EC); QP Study Guide 2017 Page 4 f 15

5 UK Medicines Act (1968) and ther UK natinal medicines legislatin eg Statutry Instruments, and the Veterinary Medicines Regulatins, including amendments; marketing, Manufacturing and Whlesaler Authrisatin structure, cntent, applicatin and apprval prcedures, and respnsibilities; the rle, legal status and structure f bth the Eurpean and British Pharmacpeias, including the Certificatin prcedure f the EDQM; the rganisatin f the UK MHRA, the rle f the Eurpean Medicines Agency (EMA), and the rle f the Veterinary Medicines Directrate (VMD); prcedures fr dealing with cmplaints and prduct recalls, the rle f the MHRA s Defective Medicines Reprt Centre, the EMA s CHMP/ CVMP guidelines n quality and the VMD s defect reprting prcess; pharmacvigilance regulatins and requirements; hw t interpret and apply the varius Internatinal Cnference n Harmnisatin (ICH and VICH) guidelines; the applicatin and scpe f Mutual Recgnitin Agreements (MRAs) between the Eurpean Unin and Third Cuntries; hw t interpret and apply the regulatins cncerning imprtatin f pharmaceutical medicinal prducts frm utside f the Eurpean Unin; and Pharmaceutical Inspectin C-peratin Scheme (PICS). b. The rle and prfessinal duties f a Qualified Persn It is incumbent upn all Qualified Persns, whether r nt members f ne f the three prfessinal bdies, that they discharge their prfessinal duties in accrdance with the Cde f Practice fr Qualified Persns. The Cde f Practice was prduced by MHRA, VMD and the three prfessinal bdies and defines the standards f cnduct and gd practice fr the Qualified Persn. It is the respnsibility f the Qualified Persn t certify that a prduct has been manufactured in accrdance with its Marketing Authrisatin, Clinical Trial Authrisatin (where apprpriate) and with Gd Manufacturing Practice (GMP). The Qualified Persn might nt have direct line respnsibility fr many f the activities which culd affect cmpliance with GMP r the Marketing Authrisatin. Hwever, they must be aware f any infrmatin, incidents r deviatins which may influence their decisin t certify whether a batch is suitable fr release fr sale. Applicants will be expected t demnstrate a thrugh understanding f the fllwing: the rutine legal duties f a Qualified Persn, the level f versight required; including detailed knwledge n the principles and applicatin f risk management within the pharmaceutical industry; batch review and decisin making n dispsitin f batches f pharmaceutical prducts i.e. whether t release fr sale r, in the case f nn-cmpliant r defective material t decide n its rejectin r rewrk/reprcessing; QP Study Guide 2017 Page 5 f 15

6 the key factrs, infrmatin r metrics that cnfirm that a batch f pharmaceutical prduct has a suitable pedigree demnstrated thrughut the manufacturing supply chain and has been made t GMP; the principles and practice f current GMP and QA as given in Eurpean Directives and Guides n Gd Manufacturing Practice including relevant Regulatins made under the Medicines Act 1968 and the current editin f the MHRA s Rules and Guidance fr Pharmaceutical Manufacturers and Distributrs, (the Orange Guide"); the cnduct and bligatins f Marketing Authrisatin (MA) and Manufacturer s / Imprter s Authrisatin (MIA) hlders (and the equivalent fr Veterinary Medicines); the GMP requirements fr Imprt and Exprt f medicinal prducts within the brders f the EU and between the EU and Third Cuntries ; the cnduct and bligatin f Clinical Trial Spnsrs and IMP prviders; the preparatin fr and management f Regulatry Inspectins; the requirements and respnsibilities f the QP regarding API certificatin; the tls and methds used fr risk management and their interface with regulatry requirements; and the requirements fr QPs when acting as independent cntractrs r n behalf f third parties. c. Pharmaceutical Quality Systems The manufacture f pharmaceutical prducts requires the establishment and implementatin f an effective Pharmaceutical Quality System (PQS). The cncepts f QA, GMP and Quality Cntrl (QC), which are inter-related, frm the basis f such a system fr the manufacture f pharmaceutical prducts frm initial develpment, thrugh clinical phases t cmmercial and supply. Applicants will be expected t demnstrate a thrugh understanding f the fllwing: the philsphy and basic principles f QA; the design criteria fr an effective PQS including but nt limited t; auditing and self-inspectins; management f quality and GMP at apprved vendrs and cntractrs; deviatins, rt cause analysis, crrective and preventive actins; change cntrl; dcumentatin and recrd keeping; quality risk management; cmplaints and recalls; the interpersnal skills (leadership, delegatin, cmmunicatin, etc) necessary t implement an effective PQS; the principles f design, selectin, qualificatin and maintenance f premises, equipment, utilities, and services; calibratin, preventative maintenance and training; QP Study Guide 2017 Page 6 f 15

7 the principles f purchasing and supplier certificatin, including knwledge f supply chains and material cntrl including but nt limited t the rles f brkers, distributrs and repackagers preventin f cunterfeiting and illegal activities prcesses t supprt and verify the supply chain pedigree mnitring and cntrl f bth prduct and raw material transprt and distributin prcesses. prductin planning, scheduling, and inventry cntrl; prduct quality reviews; the interface between QA and the planning, prductin, quality cntrl, purchasing, pharmaceutical develpment, regulatry affairs, medical, pharmacvigilance and marketing departments; the skills and cmpetences needed t prvide effective Gd Pharmaceutical Manufacturing Practice training; rganisatinal structures and reprting relatinships; and technical agreements and auditing in cntract giving and acceptance. 3.0 Additinal knwledge requirements fr the Qualified Persn d. Mathematics and statistics The practical applicatin f basic statistical tls in pharmaceutical prductin and QA is essential in demnstrating the capability f prcesses r the acceptability f materials. Applicants will be expected t demnstrate an understanding f the fllwing: the underlying principles and applicatin f Statistical Prcess Cntrl t pharmaceutical manufacturing, testing and cntrl prcesses; the underlying principles and applicatin f ISO2859 Sampling by Attributes and ISO 3951 Sampling by Variables, including the use f Sampling plans and Acceptable Quality Levels (AQLs); the interpretatin f stability data fr mdelling prduct perfrmance and quality; apprpriate data mnitring tls used t verify that apprpriate strage and distributin cnditins have been maintained; simple and statistical trending methds including but nt limited t the underlying principles and applicatin f Prcess Cntrl Charts, Shewhart Charts, Cusum Charts, Paret Analysis and prcess capability (Cpk); statistics used in the planning and interpretatin f prcess, facilities, utilities and equipment validatin and analytical testing; and statistics applied during analytical methd validatin including, precisin, accuracy, linearity and range, Specificity / Selectivity, LOD / LOQ, Ruggedness, Slutin Stability, Rbustness and statistical tls fr cmparing data sets. QP Study Guide 2017 Page 7 f 15

8 e. Medicinal chemistry and therapeutics The Qualified Persn must have an understanding f the actins and uses f medicines in clinical practice in rder t judge their significance fr the manufacture f sales material r clinical trial supplies. Evaluating the significance f crss-cntaminatin hazards r prduct cmplaints are examples where such knwledge is imprtant. Applicants will be expected t demnstrate an understanding f the fllwing: basic physilgy; utline knwledge f the autnmic nervus system and sme general aspects f chemical structure/pharmaclgical actin relatinships; summary f key therapeutic drug classificatins with examples; examples f disease states and their treatment with medicinal prducts; general absrptin, distributin, metablism and excretin f drugs; principal rutes f drug administratin; rle f the cmpany medical department; principles f Gd Pharmacvigilance Practice; general implicatins f clinical knwledge f drugs upn facility design, plant segregatin/islatin, cleaning verificatin and prductin scheduling; and general implicatins f clinical knwledge f drugs in relatin t cmplaint investigatin, incidents and deviatins. f. Pharmaceutical frmulatin and prcessing The frmulatin and prcessing cnditins emplyed in the manufacture f medicinal prducts have a significant effect upn their safety, quality and efficacy. Even subtle changes t the input materials and/r prcessing cnditins can have a prfund adverse effect n cntent unifrmity, stability, biavailability, and ther attributes which are nt detectable by rutine QC testing. It is vitally imprtant that the Qualified Persn understands the principles f frmulatin and pharmaceutical prcessing t ensure that infrmed release decisins are made. Applicants will be expected t demnstrate an understanding f the fllwing: the majr prcessing techniques, their limitatins and critical cntrl parameters; the factrs that culd ptentially affect purity, cntent unifrmity, stability (chemical, physical and micrbilgical) and biavailability in manufacture; the principles f prcess validatin and cntrl; the principles f technlgy transfer and prductin scale-up; pre-frmulatin studies and prduct develpment; and the strage and distributin f materials and finished prducts. QP Study Guide 2017 Page 8 f 15

9 g. Pharmaceutical micrbilgy The Qualified Persn must understand the significance f the presence f bacteria, yeasts, mulds, viruses and txins in pharmaceutical raw materials, prducts and prductin envirnments. In additin, they must understand hw t prevent cntaminatin by gd prduct and facility design, GMP and cntrl ver starting materials, intermediates, finished prducts, prductin plant and prcesses, peple and the envirnment. Applicants will be expected t demnstrate an understanding f the fllwing: surces and types f micr-rganisms as related t pharmaceutical prductin; prductin f sterile and nn-sterile prducts and assciated envirnmental cntrls; bacterial endtxins and pyrgens, their surces, remval and testing; micrbilgy f water, its prductin and distributin systems; including different grades f water, their use, manufacture and cntrl sterilisatin and disinfectin methds; interpretatin f micrbilgical data; validatin f micrbilgical test methds; micrbilgical specificatins; selectin and use f preservatives; micrbilgical test methds used in rutine manufacture and prduct develpment; and rapid methds f micrbilgical testing. h. Analysis and testing The sampling and testing f materials des nt by itself assure prduct quality. It must be seen as ne part f a cmprehensive Pharmaceutical Quality System, including QA and GMP, which must be crrectly implemented and cntrlled. The data generated by labratry testing f samples must be evaluated befre materials are released fr sale. Applicants will be expected t demnstrate an understanding f the fllwing: GcLP (Gd Cntrl Labratry Practice); the underlying principles f and interpretatin f qualitative and quantitative analytical methds in cmmn use fr the analysis f medicinal prducts; the underlying principles, applicatin and interpretatin f bilgical analytical test methds and validatin; the underlying principles, applicatin and interpretatin f analytical methd selectin and validatin; the underlying principles, applicatin and interpretatin f stability testing (prtcls and methds), used during develpment t determine prduct shelf life and supprt nging marketing f the prduct; the significance f degradatin, cntaminatin and adulteratin f pharmaceutical materials; QP Study Guide 2017 Page 9 f 15

10 the underlying principles, methds and types, purpse, significance and management f systems f in-prcess cntrl; the underlying principles, applicatin and design f sampling regimes; the underlying principles, applicatin and design f Analytical methd transfers; the ICH guidelines fr methd validatin, impurities and stability testing; ut f specificatin results and systems/ prcedures fr mnitring and cntrl; and Sample retentin and retesting. i. Pharmaceutical packaging It is a requirement f GMP that hlders f Manufacturer s Authrisatins establish prcedures fr their packaging peratins t minimise the risk f crss-cntaminatin, mix-up r substitutins. The Qualified Persn must understand the imprtance f cntrlling packaging cmpnents (bth primary and printed materials) thrughut the supply chain t assure the quality f finished prducts. Applicants will be expected t demnstrate an understanding f the fllwing: cntrl f packaging cmpnents by suppliers and thrughut prductin; the chain f systems which ensure the integrity and accuracy f textual infrmatin frm riginatr t rutine prductin, including artwrk generatin, text apprvals and regulatry submissin requirements; the testing f packaging materials as part f incming gds checks, including the applicatin f sampling regimes and Vendr Assurance prgrammes; the ptential rt causes f label and ther printed cmpnent mix-ups and hw they can be identified and eliminated; the ptimum layut, rganisatin and cntrl f packaging peratins, different types f packaging and labelling prcesses and equipment, including the cnsideratin f the type f equipment required fr high vlume / high speed peratins and smaller / manual peratins; the underlying principles and applicatin f in-prcess cntrls cnducted during packaging peratins, including line clearance, pack integrity testing, challenge testing, recnciliatin, bar cding and ptical systems; the design and cmpletin f packaging batch recrds, including full traceability f all prduct and materials fr investigatin and recall purpses; effects f packaging materials n prduct stability; and the requirements and desirability f tamper-evidence, anti-cunterfeiting and general supply chain security. j. Active pharmaceutical ingredients The Qualified Persn must understand the influence f manufacturing pathways and assciated physical and physic-chemical attributes, f bth active pharmaceutical ingredients and majr excipients n the quality f the finished dsage frm. QP Study Guide 2017 Page 10 f 15

11 Applicants will be expected t demnstrate an understanding f the fllwing: the steps cmmnly taken in the manufacture f Active Pharmaceutical Ingredients (API) and excipients including their purpse and limitatins; the requirements f Gd Manufacturing Practice as applied t the prductin f APIs; the underlying principles and applicatin f the EDQM certificate f suitability; the pathways respnsible fr the generatin f impurities r degradatin prducts, analytical methds fr their identificatin, quantificatin, and pssible strategies fr eliminatin f such impurities; the ptential and avidance f cntaminatin and adulteratin f API and verificatin f the supply chain pedigree; the physic-chemical and bilgical prperties f APIs and excipients, and their effect n the attributes f the final dsage frm; the requirements fr API intended fr use in sterile prducts; the principles and technical requirements fr the manufacture and cntrl f bulk bilgical, herbal and bitech prducts; the requirements fr cntrl and declaratins regarding adventitius infectius agents e.g. transmissible spngifrm encephalpathy (TSE); and API audit and Certificatin requirements. k. Investigatinal medicinal prducts The manufacture, packaging and distributin f Investigatinal Medicinal Prducts (IMP) must be cntrlled. There are significant differences between the manufacture and packaging f IMPs and licensed dsage frms. The Qualified Persn must understand these differences tgether with the safeguards required t assure the quality f IMP supply. Applicants will be expected t demnstrate an understanding f the fllwing: the applicatin and interpretatin f specific GMPs assciated with the manufacture f investigatinal medicinal prducts; the underlying principles and applicatin f the manufacture and cntrl, the expectatins arund the level f validatin required fr each phase f develpment, including thse fr analytical methds and thse prcesses, equipment and tests essential t assure the safety and quality f the prduct; the underlying principles and applicatin f the cntrl f packaging peratins including blinding and assciated cntrls; the requirements fr effective batch dcumentatin, cntrl, sampling, testing and batch release/certificatin, including the cntrl and release f imprted IMPs, cmparatrs frm EU/EEA cuntries, MRA cuntries r Third Cuntries ; change cntrl and material traceability; cntrls surrunding the prcurement, strage, distributin and cntrl f IMP, Nn-IMPs, Placeb and licensed and un-licensed Cmparatrs; the underlying principles, interpretatin and applicatin f Gd Clinical Practice (GCP); QP Study Guide 2017 Page 11 f 15

12 an appreciatin f the Declaratin f Helsinki; the requirements fr the cntent, management,cntrl and applicatin f the Prduct Specificatin File; the structure and cntents f the Clinical Trial Applicatin (CTA); an understanding f clinical trial design at all phases (I, II, III and IV), including early stage safety and dse ranging studies thrugh t pst marketing studies; an understanding f the requirements fr specific dsage frms and drug types; and an understanding f safety management fr Clinical Trials, including Pharmacvigilance and assciated reprting requirements. 4.0 The Qualified Persn: practical experience requirements The precise wrding used in Article 49 f the Pharmaceutical Directive 2001/83/EC is as fllws: "The qualified persn shall have acquired practical experience ver at least tw years, in ne r mre undertakings which are authrised t manufacture medicinal prducts, in the activities f qualitative analysis f medicinal prducts, f quantitative analysis f active substances and f the testing and checking necessary t ensure the quality f medicinal prducts. The three prfessinal bdies have interpreted this legal bligatin as requiring the applicant t have had at least ne/tw # years f relevant practical experience in assuring the quality f medicinal prducts during their manufacture, including Gd Manufacturing Practice, as defined in the current editin f the MHRA s "Rules and Guidance fr Pharmaceutical Manufacturers and Distributrs ("the Orange Guide"). ( # In the UK, the MHRA and VMD have apprved ne year f practical experience fr pharmacists.) 4.1 Illustratin f requirements Applicants may find the fllwing infrmatin helpful in further understanding the expectatins f the prfessinal bdies and f the knwledge and practical experience requirements which need t be satisfied. The prfessinal bdies will seek demnstratin f the fllwing: 1. The applicant must have had at least ne/tw # years relevant practical experience in ne r mre f thse activities embraced by the term QA (as defined and detailed in the EC Gd Manufacturing Practice Guide, and the EC Directives 2001/83/EC, 2001/82/EC and 2001/20/EC) gained in premises licensed fr the manufacture f medicinal prducts. ( # In the UK, the MHRA and VMD have apprved ne year f practical experience fr pharmacists). The MHRA advises that experience btained in an establishment that has nly a Specials Licence cannt cntribute t the practical experience requirement as described in Pint 1 abve. Experience in manufacture f active pharmaceutical ingredients nly cntributes if the API is made under the prvisins f a Manufacturer s Authrisatin. The applicant must demnstrate a thrugh cre cmpetence in the manufacturing prcesses and the Pharmaceutical Quality Systems invlved in the prductin, testing, batch release and QP Study Guide 2017 Page 12 f 15

13 apprval fr sale f the prducts made under the Manufacturer s Authrisatin(s) under which he r she is claiming his r her qualifying experience. 2. In additin, it is imprtant that the applicant can demnstrate an ability t translate and extraplate the wrking knwledge and understanding gained frm his r her experience. In particular, scenari questins may be used t determine whether an applicant is able t articulate a lgical apprach t a practical situatin with which he r she may be unfamiliar, thereby demnstrating his r her ability t apply his r her knwledge and experience. The applicant can expect detailed questining n his r her knwledge f PQS principles, and will be required t demnstrate this by reference t the prducts r prcesses perating under the Manufacturer s Authrisatin(s) under which he r she is claiming his r her qualifying experience. The assessrs may ask questins pertinent t ther activities r functins which they cnsider relevant. The assessrs must satisfy themselves that the applicant, after a suitable inductin perid, will be able t functin as a Qualified Persn in any licensed undertaking. 5.0 Rle f the Qualified Persn 5.1 Directives 2001/83/EC and 2001/82/EC The functins f a Qualified Persn are set ut in the UK Statutry Instruments and EU Directives 2001/83/EC, 2001/82/EC and 2001/20/EC as fllws: t ensure that each batch f the medicinal prduct t which the licence relates has been manufactured r assembled and checked in cmpliance with the prvisins f the Act and Regulatins made there under and the prvisins f the Manufacturer s Authrisatin and Prduct Licence r Marketing Authrisatin which relates t the prduct; t certify in a register, r ther recrd apprpriate fr the purpse, whether each prductin batch f the medicinal prduct t which the licence r authrisatin relates satisfies the requirements set ut abve and t ensure that such register r ther recrd is regularly maintained, in particular that the apprpriate entries in such register r ther recrd are made as sn as practicable after each such batch has been manufactured; fr medicinal prducts manufactured utside the Eurpean Cmmunity, the Qualified Persn must ensure that each imprted batch has undergne in a Member State a full qualitative analysis, a quantitative analysis f at least all the active substances and all the ther tests r checks necessary t ensure the quality f medicinal prducts in accrdance with the requirements f the Marketing Authrisatin (althugh it shuld be recgnised that there are exemptins t this requirement: batches f medicinal prducts which have undergne such cntrls in a Member State shall be exempt frm the abve cntrls); in the case f medicinal prducts imprted frm a third cuntry, where apprpriate arrangements have been made by the Cmmunity with the exprting cuntry t ensure that the manufacturer f the medicinal prduct applies standards f GMP at least equivalent t thse laid dwn by the Cmmunity and t ensure that the cntrls referred t abve have been carried ut in the exprting cuntry, the Qualified Persn may be relieved f respnsibility fr carrying ut thse cntrls. QP Study Guide 2017 Page 13 f 15

14 5.2 Directive 2001/20/EC The functins f a Qualified Persn as set ut in the Clinical Trials Directive 2001/20/EC. are as fllws: Fr IMP manufactured in the Member State cncerned, that each batch f medicinal prduct has; been manufactured and checked in cmpliance with the requirements f Directive 2003/94/EC laying dwn the principles f gd manufacturing practice fr medicinal prducts fr human use and investigatinal medicinal prducts fr human use, the prduct specificatin file and the infrmatin ntified pursuant t article 9(2) f Directive 2001/20/EC; in the case f an investigatinal medicinal prduct manufactured in a third cuntry, that each prductin batch f prduct has been manufactured and checked in accrdance with standards f Gd Manufacturing Practice at least equivalent t thse laid dwn in Directive 2003/94/EC, in accrdance with the prduct specificatin file and that each prductin batch has been checked in accrdance with the infrmatin ntified pursuant t article 9(2) f Directive 2001/20/EC; in the case f an investigatinal medicinal prduct which is a cmparatr prduct frm a third cuntry and which has a Marketing Authrisatin, where the dcumentatin certifying that each prductin batch has been manufactured in cnditins at least equivalent t thse laid dwn in Directive 2003/94/EC cannt be btained, that each prductin batch has undergne all relevant analyses, test r checks necessary t cnfirm its quality in accrdance with infrmatin ntified pursuant t article 9(2) f Directive 2001/20/EC. The rle f the Qualified Persn is thus f cnsiderable imprtance within the industry and this shuld be reflected in the calibre f applicant appinted t such a psitin. Althugh every persn included in the Register meets, in the pinin f the prfessinal bdy cncerned, the statutry requirements t becme a Qualified Persn, it is up t individual cmpanies t satisfy themselves f the suitability f any individual applicant fr a particular pst. The Licensing Authrity is the final arbiter f wh can be named as a Qualified Persn n a Manufacturer s Authrisatin. 6.0 Other Eurpean Member States Applicants frm ther EU Member States, wh are nt members f any f the three afrementined prfessinal bdies, but wh hld an apprpriate qualificatin as defined in Article 49 f 2001/83/EC and Article 53 f 2001/20/EC, will be cnsidered by the Licensing Authrity n nminatin by a cmpany, as a QP fr a Manufacturer s Authrisatin. The Ryal Sciety f Chemistry (RSC) has an agreement with the Institute f Chemistry f Ireland (ICI) that Irish applicants will be assessed by a team f assessrs that will include an Irish assessr, wh is a member f bth the RSC and ICI. QP Study Guide 2017 Page 14 f 15

15 7.0 Summary In summary, the applicant must demnstrate: the relevant practical experience in ne r mre licensed facilities; an in-depth wrking knwledge f the fundatin elements and understanding f all the requirements described in this Study Guide; a thrugh understanding f the principles and requirements laid ut in "the Orange Guide" and ther dcuments issued by the Health Authrities and relevant rganisatins (e.g. PICS, WHO, ICH, etc.); an ability t translate thse principles and requirements t ther situatins currently utside his r her direct experience; an endrsement f his r her credentials, including qualificatins and experience, frm a Spnsr wh meets the requirements described in the Guidance Ntes fr Applicants and Spnsrs issued by the three prfessinal bdies. QP Study Guide 2017 Page 15 f 15