GMP Compliance. George Acevedo, CQV Senior Engineer M+W Singapore Pte. Ltd

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1 GMP Compliance George Acevedo, CQV Senior Engineer M+W Singapore Pte. Ltd June 2017

2 Overview GMP Definition and Regulation Our Philosophy and Strategy for Compliance Project Lifecycle Deliverables Master Plan and Flow Qualification Protocols Summary

3 Good Manufacturing Practice (GMP) Manufacturing of medicinal products shall be undertaken in accordance with the principles of Good Manufacturing Practice (GMP) which is governed by the Health Authority within the products market intent. Definition. There should be written procedure and the associated records of action taken or conclusion reached, where appropriate, for validation, equipment assembly & calibration, maintenance PICS PE activities undertaken to demonstrate that utilities and pieces of equipment are suitable for their intended use and perform properly FDA guidance for Industry Process Validation: General Principles and Practices, Jan 2011.

4 GMP Regulation Country / Region Authority GMP Guidelines Australia TGA (Therapeutic Goods Administration) PIC/S Canada Health Products and Food Branch Inspectorate ( HPFBI ) PIC/S China SFDA (State Food and Drug Administration) WHO / SFDA GMP European EMA (European Medicines Agency) EudraLex India CDSCO (Central Drugs Standard Control Organization) Indonesia NA-DFC (National Agency of Drug and Food Control) PIC/S WHO Japan PMDA (Pharmaceuticals Medicines & Drugs Agency) MHLW (Ministry of Health Labor and Welfare) / PIC/S Malaysia NPRA (National Pharmaceutical Regulatory Body) PIC/S New Zealand Medsafe PIC/S Singapore HSA (Health Sciences Authority) PIC/S Thailand Thai FDA ( Food and Drug Administration ) WHO / PIC/S US (United States) US FDA (Food and Drug Authority) 21 CFR / PIC/S UK (United Kingdom) United Kingdom's Medicines and Healthcare Products Regulatory Agency (MHRA) Vietnam Ministry of Health WHO PIC/S

5 What is GMP compliance? The aim of the GMP standard is to ensure medicinal products are consistently produced to the quality standards appropriate for their intended use. This standard is defined as being within specifications of strength, quality and purity and without adulteration. It is designed to minimise the risks involved in any pharmaceutical production that cannot be eliminated through testing the final product. Main risks are : unexpected contamination of products incorrect labels on containers, which could result in patients being prescribed the wrong medicine insufficient or too much active ingredient, resulting in ineffective treatment or adverse effects due to incorrect dosage

6 What is GMP compliance? Common GMP requirements include The establishment and maintenance of an effective quality assurance system Adequate process control. Suitably qualified, trained and supervised employees. Premises and equipment that has been located, designed, installed, operated and maintained to suit intended operations. Maintenance of a documentation system comprising of adequate records which detail all critical aspects of the process. Appropriate measures to minimise the ingress of contamination into the product from any external source, in particular from components, environment, premises and equipment. GMP covers all aspects of production; from the starting materials, premises and equipment to the training and personal hygiene of staff.

7 GMP Compliance Strategies Involve CQV representative from DAY ONE (e.g. RFP stage). Formal documented GMP reviews will be conducted at an early stage of the project Combined commissioning and validation approach that optimises the schedule and integration activities Define process flow, procedure and template with the client. Production of high quality documentation which is complete and compliant to support qualification activities. Development of Quality Audit Programme to monitor compliance throughout the project. Basic Design Detail Design Procurement Construction C&Q

8 Validation Approach A risk-based approach with a combination of Good Engineering Practices (GEP), corporate guidelines and adherence to regulatory requirements. V-Model Risk Based Verification Reference: The V-Model for direct Impact systems From ISPE, V-model for direct impact systems, in Commissioning and Qualification Baseline Pharmaceutical Engineering Guide, Vol. 5 1 st ed. International Society for Pharmaceutical Engineering, March 2001 Reference: The Specification, Design and Verification Process Figure 1 ASTM E Standard Guide for Specification, Design and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment, pg 3 Basic Design Detail Design Procurement Construction C&Q

9 Project Life Cycle / C&Q Deliverables Basic Design Detail Design Procurement Construction C&Q GMP Design 30% and 60% Review System List Boundary Limits Regulatory Statement / Assessment Initial GMP Report GMP Design Review 90% GMP Review Report Risk Assessment Qualification Matrix QMP / VMP URS/ FRS DQ Vendor Audit Vendor Qualification Review / Approve vendor s VDR and PQP FAT SAT Quality Plan Vendor Turn over package Cx execution IQ execution OQ execution PQ execution CQV Reports

10 GMP Design Review The GMP Review is the documented examination/audit at timely interval during the design phase, that the design of the facilities, systems and equipment is suitable for the intended purpose and published GMP. Ensure that compliance requirements are adequately addressed by the proposed design. Topics typically include: - Facility / premises Controlled environment area HVAC Personnel / material flow Waste management Equipment Automation / computerized system Basic Design Detail Design Procurement Construction C&Q

11 Validation Master Plan (VMP) The purpose of this is to define the format for the preparation of the Validation Master Plan (VMP) that summarises the firm's overall validation philosophy, intentions and approach to be used for establishing performance adequacy. Common Content: Validation team organisation / Responsibility Qualification/Validation Documents Required Facility/Product/Process Description Qualification / Validation Approach Risk Assessment General Acceptance Criteria Change Control procedure Revalidation consideration Quality support program Engineering support program Regulatory Requirement and Standard Basic Design Detail Design Procurement Construction C&Q

12 Design Qualification Documented verification that the design of the utilities, equipment or systems is suitable for the intended purpose. Deliverables Samples: User Requirement Specification Design Specification Functional specification Block Diagram Process Flow Diagram Job Specification (Automation) Hardware Design Specification Software Design Specification Equipment Layout Room Data Sheets Personnel Flow Plan Material Flow Plan Architectural Plan GMP Zoning Plan Basic Design Detail Design Procurement Construction C&Q

13 Project Flow Basic Design Detail Design Procurement Construction C&Q

14 Commissioning and Qualification Phase Basic Design Detail Design Procurement Construction C&Q

15 Installation Qualification Documented verification that a system is installed according to written and pre-approved specifications. Deliverables Samples: Installation Verification Design Verification Critical Instrument List Non-Critical Instrument List Drawings Manuals Recommended Spare Parts and Consumable List Purchase Orders Environmental Conditions Safety Inspection Calibration Preventive Maintenance Documentation Wiring Basic Design Detail Design Procurement Construction C&Q

16 Operational Qualification Documented verification that a system operates according to the written and pre-approved specifications throughout all specified operating ranges. Test Samples: Written Procedure Verification Training Documentation Validation Test Equipment Calibration Utilities Testing Operator panel Verification Environmental Test Alarm Verification Security and Access Electromagnetic Interference Test Radio Frequency Interference Test Power Failure and Recovery Test Back-up Procedure Verification Operational Testing Protocol Deviation Investigation Form Basic Design Detail Design Procurement Construction C&Q

17 Vendor Turn Over Package Production Data Book (PDB) Mechanical Catalogue (MC) Quality Control Dossier (QCD) Mechanical Construction and Commissioning Dossier(MCCD) Basic Design Detail Design Procurement Construction C&Q

18 GMP Audit Purpose is to evaluate GMP compliance status of the manufacturer in accordance with the current GMP requirements On-site assessment using systematic, independent and documented process for obtaining evidence and evaluating it objectively to determine the extent to which criteria are fulfilled. Benefits : Effective assessment of GMP Compliance Reduced costs Improved performance Facilitate harmonised guidelines for auditing Increased external confidence Inspection readiness

19 GMP Audit General Org & Management responsibilities, Employee orientation and training, Plant safety and security, Internal quality program Facility Design and Layout, Environmental control, Maintenance and Good Housekeeping Program, External contractor Control Equipment Design and Placement, Identification, Maintenance and Cleaning, Calibration program, Qualification program Material / Component Specification and Purchasing control, Receipt, Inspection, Sampling and Lab Testing, Storage and Handling, Inventory Control, Supplier Control Operational Material/ Component / Label Verification, Storage and Handling, Equipment/Line/Area Cleaning, Preparation and Clearance, Operational Process Validation and Production Change Order Control, In-process Inspection, Sampling and Laboratory Control, reprocessing/disposition of materials Finished Products Verification, Storage and Handling, Inspection, Sampling, Testing and release for distribution, Distribution control, Complaint handling and customer satisfaction program

20 Summary Basic Design Detail Design Procurement Construction C&Q GMP Design 30% and 60% Review System List Boundary Limits Regulatory Statement / Assessment Initial GMP Report GMP Design Review 90% GMP Review Report Risk Assessment Qualification Matrix QMP /VMP URS / FRS DQ Vendor Audit Vendor Qualification Review/ Approve vendor s VDR and PQP FAT SAT Quality Plan Vendor Turn over package Cx execution IQ execution OQ execution PQ execution CQV Reports GMP Compliance must be incorporated in the project from Day 1 M+W has the in house ability to assess these requirements and ensure compliance. We offer a one stop solution.

21 What we can offer Consulting Design Construction Operation Auditing GMP Compliance Review Qualification/Validation Design Review Design Qualification Project / Construction- Management Schedule QA / QC Commissioning & Start-up Process Support / Operational Qualification Performance Qualification Installation / Operational Qualification Additional Consultancy and Support Service: GMP Training and Audits Quality Management System preparation Cleaning Validation Support for Process Validation Preparation of SOPs and delivery of associated training

22 M+W Life Sciences Capabilities We deliver one stop shop solutions for the Life Sciences Industry - from initial Site selections and Feasibility studies, to Concept/ Basic/ Detail Design moving into Construction and last but not least Commissioning/ IQ/ OQ as well as Validation - in short the whole project Life cycle Qualification / Validation Project Management & Construction Consultation / Engineering

23 If you think compliance is expensive, try noncompliance. -Former Deputy US Attorney General Paul McNulty

24 Thank You. George Acevedo CQV Senior Engineer M+W Singapore Pte. Ltd. A Company of the M+W Group 16 International Business Park #02-00 Singapore DID: SG Mobile: george.acevedo@mwgroup.net