Pharmaceutical Inspection - PowerPoint Presentation

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Pharmaceutical Inspection - PPT Presentation

Cooperation Scheme PICS Mrs Helena Paula Baião PICS Former Chairperson helenabaiaoinfarmedpt httpwwwinfarmedpt PICS 2014 Good Manufacturing ID: 319239

2014 pic reserved rights pic 2014 rights reserved gmp amp inspections deficiencies observations api related trends training quality manufacturing committee guide facilities

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Slide1

Pharmaceutical Inspection Co-operation Scheme (PIC/S)

Mrs. Helena Paula Baião PIC/S Former Chairperson helena.baiao@infarmed.pt http://www.infarmed.pt/© PIC/S 2014

Good Manufacturing Practice - GMPs Trendsin Pharmaceutical Inspections Cooperation Scheme (PIC/S)Brasilia – August 2014

Bom dia Good MorningMrs. Helena Paula Baião PIC/S Chairperson helena.baiao@infarmed.pt http://www.infarmed.pt/Slide3

Overview

About PIC/S & Mission & Goals & Quality Systems & Guides & Recommendations & Seminars & Expert Circles & JVP & JRP & training activities &Liaison with other organisationsTrends and Observations related to GMP inspectionsPIC/S Future & Philosophy Final RemarksAcknowledgementAll rights reserved PIC/S 2014 Slide4

All

rights reserved PIC/S 2014 PIC/S is ...an international organisationa non-profitable organisation a non-political organisationmade up of regulators (inspectors)The convention was signed in Geneva on 8 October 1970Slide5

All

rights reserved PIC/S 2014 PIC/S Mission “To lead the international development, implementation and maintenance of harmonised GMP standards and quality systems of inspectorates in the field of medicinal products”.“成立的宗旨領導,擴展,實施, 藥品GMP法規標準協和、藥品稽查管理體系(稽查品質)一致化, 國際化和全球化. “ While adapting to its growth and needs as well as to a constantly changing GMP environment, PIC/S remains focused on what has made its success to this day. Slide6

Original GoalsHarmonised GMP requirements (*)Mutual recognition of inspectionsUniform inspection systemsTraining of InspectorsMutual confidence (Trust) (*) The difference is not so much in different GMP standards being used around the world but in the interpretation of standards Slide7

Achievement of PIC/S GoalsDeveloping and promoting harmonised GMP standards and guidance documentsAssessing (and reassessing) GMP InspectoratesTraining competent authorities, in particular GMP inspectorsFacilitating the co-operation and networking for competent authorities and international organisationsSlide8

Quality Systemrequirements for Pharmaceuticals Inspectorates Reference document : PI 002-3 Purpose : adopt a common standard for quality system requirements in order to achieve consistency in inspection standards between National Pharmaceutical Inspectorates and thus to facilitate the equivalence of InspectoratesSlide9

Obligations as a PIC/S MemberPayment of annual membership fee(2) To attend PIC/S Committee Meetings – twice a year – one in Geneva and the other one in a member country (together with the annual seminar)(3) To host or participate in the annual PIC/S Seminar(4) To host or participate in PIC/S Expert Circles & JVP & JRP(5) To participate in PIC/S Sub-Committees (SC).Active participation and contribution is the only way forwardSlide10

Information sharing inside PIC/SReports of GMP inspections List of planned foreign inspections List of inspectors List of competencies within each inspectorateTraining events arranged by inspectoratesRapid alerts and drug recallsSurveillance activities Slide11

PIC/S Members (as of 1 July 2014)10 PIC/S Applicants & Pre-ApplicantsAll rights reserved PIC/S 2014 Slide12

PIC/S Members (Europe

)AUSTRIABELGIUMCZECH REP. (Human & Vet)CYPRUSDENMARKESTONIAFINLANDFRANCE (Human & Vet)GERMANYGREECEHUNGARYICELANDIRELANDITALYLATVIALIECHTENSTEINLITHUANIAMALTANETHERLANDSNORWAYPOLANDPORTUGALROMANIASLOVAK REPUBLICSLOVENIASPAINSWEDENSWITZERLANDUKRAINEUNITED KINGDOM (Human & Vet)All rights reserved PIC/S 2014 Slide13

Accession & Pre-accession procedure

Useful DocumentsPharmaceutical Inspection Cooperation Scheme (PIC/S 1/95)Guidelines for Accession to PIC/S (PS/W 14/2011)Questionnaire for Competent Authorities (PS/W 1/2011)Audit Checklist (PS/W 1/2005)Recommendations on quality system requirements for pharmaceutical inspectorates (PI 002)All rights reserved PIC/S 2014 Slide14

Accession &+ Pre-accession

Applicants being assessed for membershipBrazil / ANVISAHong-Kong SAR / PPBHKIran / MoHPhilippines / PFDATurkey / TMMDA Applicants for Pre-AccessionArmenia / SCDMTEBelarus / MoHChile / ISPKazakhstan / CCMPAMexico / COFEPRIS interest in joining PIC/SChina / CFDACroatia / HALMEDNigeria / NAFDACRussia / RoszdravnadzorSaudi Arabia / SFDAAll rights reserved PIC/S 2014 Slide15

PIC/S Training for GMP Inspectors Annual Training SeminarsTraining Courses for New InspectorsExpert CirclesJoint Visits Programme (JVP) and Coached Inspections Programme (CIP)PIC/S - Industry WorkshopsAll rights reserved PIC/S 2014 Slide16

Upcoming PIC/S Training ActivitiesPIC/S – IMB New Inspector Training Course which will be hosted and run by Ireland / IMB from 16-19 June 2014 in Dublin (Ireland), followed by a Train the Trainer course on 20 June 2014 (http://www.picscheme.org/various.php);PIC/S – PDA (Parenteral Drug Association) Q7 Training Course, part of the PIC/S International API Training Programme set up by the PIC/S Expert Circle on API, which regularly delivers general API training in several locations around the world. The next training courses, open to inspectors and industry, will be held in Brussels (Belgium), on 18-19 September 2014 and in Brasilia (Brazil), in October 2014, in co-operation with Brazil / ANVISA (http://www.picscheme.org/various.php)PIC/S Advanced QRM Training Course for GMP inspectors, which will be hosted by Japan / PMDA in Tokyo (Japan), on 8-10 December 2014, organised by the PIC/S Expert Circle on Quality Risk Management (http://www.picscheme.org/expert-circles.php).Slide17

PIC/S SeminarsQualification and Validation Ukraine, 2012Global Supply Chains and Canada, 2013 GMP Compliance“Dedicated facilities or not ?” France 2014“Biopharmaceutical and biosimilars, how to inspect?” Indonesia, 2015 Slide18

Development of GMP Guidance Documents

Usually initiated at end of PIC/S SeminarsPIC/S Working Group formedAuthor prepares draftComments from Working GroupComments from PIC/S InspectoratesComments from IndustryEndorsed by PIC/S Committee for general distributionSimultaneous distribution by EMA (& vice versa)All rights reserved PIC/S 2014 Slide19

Relationship with EMA歐洲藥物管理局 (European Medicine Agency, EMA)Associated Partnership negotiated in 2007 (renewed in 2010)EMA attends PIC/S Committee as a Associated Partner organisationA Harmonised Consultation Procedure Since 8 May 2012 EMA and PIC/S signed an agreement to “Harmonize the Consultation Procedure “ for all GMP documents.PIC/S-EU liaison officer attends Inspectors meetings at EMA as an observerSlide20

PIC/S Guides & RecommendationsPIC/S GMP GuideVirtually identical to EC GMP Guide(main difference = “Qualified Person” vs. “authorised person”)Basic GMP Guide (Part I)The PIC/S GMP Guide – PE 009-11 , into force on 1 March 2014.Geneva, 31 January 2014: the PIC/S Committee has adopted by written procedure the revision of the PIC/S GMP Guide (PE 009-11). The following parts have been amended:- Part II of GMP Guide (Q7A): Introduction of risk management principles- Annexes:* Revised Annex 2 (biological medicinal products for human use)* Revised Annex 14 (products derived from human blood or human plasma)All rights reserved PIC/S 2014 Slide21

PIC/S Guides & RecommendationsPIC/S GMP Guide (similar to EU GMP Guide)PIC/S GMP Guide for Blood EstablishmentsPIC/S Guide to Good Practices for the Preparation of Medicinal Products in Healthcare EstablishmentsValidation (master plan, IQ/OQ, process, cleaning)Validation of Aseptic ProcessesInspection of Isolator TechnologyQuality Systems for InspectoratesValidation of Computerised SystemsPIC/S Aide –Memoire ON ASSESSMENT OF QRM IMPLEMENTATION PI 038-1PIC/S RECOMMENDATION ON RISK-BASED INSPECTION PLANNINGPI-037-1Slide22

PIC/S Liaison with other organisationsThe European Department for the Quality of Medicines (EDQM 歐洲药品质量部) : Associated Partnership negotiated in 2007 (renewed in 2010)United Nations International Children‘s Emergency Fund (or known as United Nations Children’s Fund, UNICEF, 聯合國儿童基金会（舊称聯合國國際兒童緊急救援基金會 : Associated Partnership negotiated in 2008World Health Organisation, WHO 世界衛生組織 : Co-operation Arrangement negotiated in May 2009International Conference on Harmonization,ICH (國際協调會)European Commission (DG Health & Consumers) 歐盟執委會Association of South East Asian Nations (ASEAN);Slide23

PIC/S liaises with major Professional OrganisationsPIC/S liaises with major professional organisations such as ISPE and PDA, active in the field of interpretation & guidance documents as well as training;The support of industry associations and professional organisations to the goals of PIC/S is crucial.Slide24

PIC/S Liaison with other organisationsIn the PIC/S Blueprint, Co-operation between PIC/S and other organisations should be based on the principle of complementarity. Where PIC/S Participating Authorities are already actively co-operating, PIC/S as an organisation should not duplicate Members’ efforts.Slide25

PIC/S's perspectives Trends and Observations related to inspectionsUS/FDA makes their inspection results available to the public due to the Freedom of Information Act (FOI). However, very rarely, inspection results of European supervisory authorities are accessible in any public domain except analysis of regulatory / GMP inspection findings that are periodically published by UK/MHRA and European Medicines Agency (EMA). All rights reserved PIC/S 2014 Slide26

PIC/S's perspectives Trends and Observations related to inspections At PIC/S level, a similar exercise has never been done before in spite of the fact that PIC/S is an international organization with membership spread across all the 6 continents globally but as part of the PIC/S Seminar 2011 on “Good Pharmaceutical Inspection Practices”, developed a worshop “Similarities and differences for top 10 deficiencies cited by PIC/S Members; Hans Smallenbroek (Netherlands/IGZ) and Boon Meow Hoe (Singapore/HSA)Slide27

PIC/S's perspectives Trends and Observations related to inspectionsMethodologyQuestionnaire invite all PIC/S Participating Authorities and applicants to offer data. 1. Top ten & most frequently cited categories of GMP deficiencies2. Top five &f most severe GMP deficiencies (critical and/or major)The scope of the survey was defined for GMP inspection findings of finished product dosage form manufacturers only, including medicines for veterinary use and investigational medicinal products, if applicable. Inspections of Active Pharmaceutical Ingredients (API) were out of the scope of this survey.Slide28

PIC/S's perspectives Trends and Observations related to inspectionsPIC/S did not have a formal model “Categories of GMP Deficiencies”, the model of “Categories of GMP Deficiencies” used by UK/MHRA was used as a standard template. However, flexibilities were given to PIC/S Participating Authorities and applicants which might wish to use their own model of “Categories of GMP Deficiencies”. Inspection findings were classified into the categories “critical:”, “major” and “others or minor”Slide29

Trends and Observations related to inspections Analysis and summary of raw dataSummary of top 10 most frequently cited categories of GMP deficiencies(1) Documentation - manufacturing 24(2) Design and maintenance of premises 22(3) Documentation - quality systems elements / procedures 20(4) Personnel issues - training 19(5) Design and maintenance of equipment 18(6) Cleaning validation 14(6) Process validation 14(6) Product Quality Review 14(7) Supplier and contractor audit 13(8) Calibration of measuring + test equipment 12(9) Equipment validation 11Slide30

TOTAL NUMBER OF DEFICIENCIES PER GROUP OF TOP TEN MOST FREQUENTLY CITED DEFICIENCIESSlide31

Total number of deficiencies per group of top ten most frequently cited deficienciesSlide32

Trends and Observations related to inspections Analysis and summary of raw data Total number of deficiencies per group of top five most severe deficiencies(1) Production 44 (27%)(2) Quality system 32 (20%)(3) Premises and equipment 28 (17%)(4) Validation 22 (14%)(5) Quality control 14 ( 9%)(6) Regulatory issues 9 ( 6%)(7) Materials management 8 ( 5%)(8) Personnel issues 5 ( 3%)Slide33

Summary of top 5 most severe GMP deficienciesSlide34

Summary of top 5 most severe GMP deficienciesTOTAL NUMBER OF DEFICIENCIES PER GROUP OF TOP FIVE MOST SEVERE DEFICIENCIESSlide35

Trends and Observations related to inspections Review similarities and differences for the top 10 deficiencies Comparison between summary of groups Most frequently cited deficienciesProduction 24% Quality system 20%Quality control 14% Premises + equipment 14% Validation 12% Personnel issues 8% Materials management 7% Regulatory issues 1%Most severe deficienciesProduction 27%Quality system 20%Premises + equipment 17%Validation 14%Quality control 9%Regulatory issues 6%Materials management 5%Personnel issues 3%Slide36

Trends and Observations related to inspectionsGENERAL OBSERVATIONSDifferences PIC/S Participating Authorities use different GMP deficiencies classification model:Some used the model developed by UK/MHRA;Some use the PIC/S GMP Part I model i.e. in according to the 9 Chapters and Annex 1.Some have their own classification methodology.Some members did not have formal analysis trending on such GMP deficiencies.Slide37

Trends and Observations related to inspections Review similarities and differences for the top 10 deficiencies GENERAL OBSERVATIONSSome of the most frequently cited GMP deficiencies may due to easy detection as part of the inspection process. (E.g. Documentation – manufacturing -- #1 most frequently cited deficiency).The design and maintenance of premises ranked as #2 most frequently cited deficiency may relate to aged buildings or saving on maintenance budget.Slide38

Trends and Observations related to inspections Review similarities and differences for the top 10 deficiencies GENERAL OBSERVATIONS The 10 most frequently cited GMP deficiency classes meant that the industry is weak in these areas and inspectors should communicate moreeffectively and efficiently to the industry on suchweaknesses.Different level of details of the deficiency classes model observed. A model that could be accepted by most PIC/S PAs may be requiredSlide39

Trends and Observations related to inspections Common model recommendation Adopt this exercise at PIC/S level in an annual basis. Output may be used as a Training Need Analysis to identify common specific GMP areas to be focused on training and to pull all resources together within PIC/S.PIC/S may wish to consider to develop a PIC/S common GMP deficiencies classification model May 2013, established Working Group coordinated by TGA (...)Slide40

Trends and Observations related to inspections Data trending recommendation All PIC/S Participating Authority (PA) should consider to implement and put in place such exercise for analysis and trending within a defined period (e.g. annually) and subsequently, for trending across different years.Slide41

Trends and Observations related to inspections ConclusionThere is a correlation between the most frequent GMP Deficiencies Classes and the most severe GMP Deficiencies Classes. There is no significant differences among regionsThis implies that there is harmonisation across all PIC/S Participating Authorities.Slide42

Trends and Observations related to inspectionsPIC/S reviews deficiencies found during inspections of API manufacturing facilitiesPIC/S facilitates international technical training on relevant topics of interest. One of the most active bodies within PIC/S is the API Expert Circle.Slide43

Trends and Observations related to inspectionsPIC/S reviews deficiencies found during inspections of API manufacturing facilities PIC/S reviews deficiencies found during inspections of API manufacturing facilities, harmonizes GMP standards, and provides training for inspectors worldwide.Carmelo Rosa chair of the PIC/S API Expert Circle, othersSlide44

Trends and Observations related to inspectionsPIC/S reviews deficienciesfound during inspections of API manufacturing facilities Efforts and strategic plan are focused in 4 key areas: identifying regions and countries where the inspectorate and industry have greater needs of GMP training in APIs; providing the inspectorate with up-to-date information on advanced or complex APIs manufacturing processes; through partnership with technical organizations and established procedures, ensuring that the inspectorate is exposed to new technologySlide45

Trends and Observations related to inspectionsPIC/S reviews deficienciesfound during inspections of API manufacturing facilitiesFive API Expert Circles have been held,in September 2012, in Washington DC, where approximately 130 inspectors were trained on sterile APIs and biotechnology manufacturing. The 6th Expert Circle on APIs will be held in Rome on May 19-21, 2014 on the topic of API process validation and contemporary issues. (…)Slide46

Trends and Observations related to inspectionsPIC/S reviews deficienciesfound during inspections of API manufacturing facilities Since the implementation of Q7, most API manufacturers appear to have a better understanding of GMP principles. Many firms have good quality systems, process understanding, seek opportunities for optimization, have robust change-controls systems, and have good laboratory controls and procedures to facilitate knowledge management. On the other hand, inspections also reveal that some API manufacturers continue to struggle with achieving sustainable compliance with GMP requirements. Slide47

Trends and Observations related to inspectionsPIC/S reviews deficiencies found during inspections of API manufacturing facilities Inspections of API facilities, conducted by PIC/S members, have recently been reporting critical deficiencies related to laboratory controls, records/investigations, quality systems, equipment cleaning/maintenance, and process validation. Slide48

Trends and Observations related to inspectionsPIC/S reviews deficienciesfound during inspections of API manufacturing facilitiesData integrity issuesPIC/S members and partners have also noted an increase in findings of data-integrity practices during inspections of API sites. These deficiencies include: recording data in logbooks, falsification of batch records and test results, pretesting samples and ignoring or not investigating out-of-specification results, blending or mixing API batches that failed to meet the established released specifications with batches that met the required final specifications, lacking the necessary controls in handling and managing critical data, and entering manufacturing activities on records before they had occurred.Slide49

Trends and Observations related to inspectionsPIC/S reviews deficiencies found during inspections of API manufacturing facilitiesOutsourced operations and the changing face of API manufacturingWith the increase in the outsourcing of APIs by sponsors/drug applicants/finished drug product owners/contract givers (party that purchases APIs), there is more concern about how the roles and responsibilities of each party are established and managed.Slide50

Trends and Observations related to inspectionsPIC/S reviews deficiencies found during inspections of API manufacturing facilities.During PIC/S’ API Expert Circles, inspectors are trained on new technology, quality trends, and critical deficiencies and how to detect problems that may affect the quality of the APIs produced and that may impact the finished drug products, and subsequently affect the patients who consume these medicines. Slide51

Trends and Observations related to inspectionsPIC/S reviews deficienciesfound during inspections of API manufacturing facilities Conclusion A regulator’s role is to determine whether firms are operating in sustainable compliance with GMP for APIs, pursuant to ICH Q7.Bearing in mind that inspections are limited by time and other resource constraints, regulators rely heavily on manufacturers to implement and maintain appropriate quality systems and processes to ensure that all APIs produced meets the required quality standards.Slide52

Future of PIC/S & New ProjectsExpansion to cover Good Distribution Practices - GDP PIC/S adopted a Guide on Good Distribution Practice (GDP), into force since 1 June 2014; Good Clinical Practices - GCP and Good Pharmacovigilance Practices - GVP (new Working Group);PIC/S Inspectorates Academy;Other needs of Agencies (e.g. biosafety, medical devices, etc.). Slide53

PIC/S Future Recent Developments

Accession of Japan’s MHLW, PMDA & Prefectures and of South Korea’s MFDS (July 2014)New PIC/S GDP Guide, based on EU GDP Guide (June 2014)Revision of PIC/S GMP Guide (Part II of GMP Guide (Q7A), Annex 2 and 14) (March 2014)Revision of PIC/S Guide to Good Practices for the Preparation of Medicinal Products in Healthcare Establishments (new Annex 3 on radiopharmaceuticals) (March 2014)New PIC/S Organisational Sub-Committee Structure (Jan 2014)Accession of United Kingdom’s Veterinary Agency VMD (Jan 2014)Accession of Chinese Taipei’s TFDA and New Zealand’s Medsafe (Jan 2013)All rights reserved PIC/S 2014 Slide54

PIC/S Future New PIC/S Organisational

Sub-Committee StructureTo reply to PIC/S’s growing membership, a new Sub-Committee structure has been developed and come in force 1st January 2014, in order to:Favour the participation of all PIC/S Participating AuthoritiesEstablish a more participative and efficient organisation of PIC/S, where each Sub-Committee will be responsible for its respective core areas and will take the lead in developing policies.Among the Sub-Committee Members, 57% are from non-EU PIC/S Participating Authorities, reflecting the fact that PIC/S has become less of an Eurocentric and an ever more global international organisation.All rights reserved PIC/S 2014 Slide55

PIC/S Future PIC/S new structure

PIC/S Executive Bureau

Joey Gouws (South Africa / MCC), PIC/S Chairperson;Paul Hargreaves (UK / MHRA), PIC/S Deputy Chairman and Chair of the Sub-Committee on Budget, Risk and Audit (SCB);Helena Baião (Portugal / INFARMED IP), immediate former Chairperson;Boon Meow Hoe (Singapore / HSA), Chair of the Sub-Committee on Training (SCT);Alexander Hoenel (Austria / AGES), Chair of the Sub-Committee on Expert Circles (SCEC); Jacques Morénas (France / ANSM), Chair of the Sub-Committee on Strategic Development (SCSD);Anne Hayes (Ireland / IMB), Chair of the Sub-Committee on Compliance (SCC);Paul Gustafson (Canada / HPFBI), Chair of the Sub-Committee on GM(D)P Harmonisation (SCH);Tor Gråberg (Sweden / MPA), Chair of the Sub-Committee on Communication (SC COM).All rights reserved PIC/S 2014 Slide57

Final RemarksTrends and NeedsThere is a need Of Training for regulators and industryfor adequate expertise at National and Global level (at a time of limited resources) There is a need to share knowledge with the network of Assessors and Inspectors (Training & Guidance) incl. discussions before, during & after assessmentFor appropriate continuous dialogue between regulators and industry Slide58

Final RemarksTrends and Needs There is a need better use of international cooperation opportunities in order to achieve a better use of resources through better communication and collaboration in areas of common interest Entails the use of :Science-based Policies and StandardsRisk-based orientationTo ensure Public Health ProtectionSlide59

Final RemarksConclusions“PIC/S is continuously exploring ways to facilitate the harmonization of GM(D)P and to adapt to a beautiful but constantly changing world” Trust & Co-operation & CommunicationReason for PIC/S’ success: mandate & mission still valid todayIncreasingly becoming and acting as a “global player”Slide60

AcknowledgementMr. Boon Meow Hoe (HSA, Singapore) (Chinese version) Chair of the Sub-Committee on Training (SCT)Mr. Hans Smallenbroek (Netherlands/IGZ) PIC/S Former ChairSpeakers, workshop facilitators, participants, “Global Supply Chains and GMP Compliance”, Canada Seminar 2013Mr. Daniel Brunner; Mr. Jeffrey Hodgson PIC/S Secretariat all those who directly or indirectly contribute to PIC/S Goals and make them possibleSlide61

PIC/S Secretariat

The protection of public health and

of the patient is our common goalThanks for the attention