Validation of Automation Systems

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GAMP5

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Different Terminology

Computerised Systems Automation Systems Control Systems Control Equipment

www.chinapat.com Data Management systems Computerised System: A system including the input of data, electronic processing and the output of information to be used either for reporting or automatic control : SFDA: Good Manufacturing Practice for pharmaceutical products
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US FDA
Automated processes. When computers or automated data

processing systems are used as part of production or the quality system, the manufacturer shall validate computer software for its intended use according to an established www.chinapat.com protocol. All software changes shall be validated before approval and issuance. These validation activities and results shall be documented.

PART 820 QUALITY SYSTEM REGULATION

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EMEA
Validation: The extent of validation necessary will depend on

a number of factors including the use to which the system is to be put, whether the validation is to be prospective or retrospective and whether or not novel elements are incorporated. Validation should be considered as part of the complete life cycle of a computer system. This cycle includes the stages of planning, specification, programming, testing, www.chinapat.com commissioning, documentation, operation, monitoring and modifying.

Commission Directive 3003/94/ECAnnex 11 Computerised system

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SFDA

Where automated and monitoring systems are used

for these applications they should be validated to ensure that critical process requirements are met.

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Good Manufacturing Practice for pharmaceutical products, Part II Annex Chapter 12 Terminal Sterilisation:

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Functional Hierarchy, ISA-S95

Business Logistics Systems
Level 4 Plant Production Scheduling and Operational Management

Level 3

www.chinapat.com Manufacturing Control Systems Area Supervision, Production

Scheduling, Reliability Assurance

Batch
Levels 2,1,0 Control Systems

Continuous
Control Systems

Discrete
Control Systems

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Process Control Systems Level 1 & 2

Process Control systems

Configurable

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Embedded

Standalone

Controllers, Analysers

Machine+ PLC+ HMI

PLC+ SCADA

DCS

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Examples of Process Control System

Standard hardware, Configurable (no programming only

parameterisation)
pH

HPLC Controllers (Temperature Controller, pH Controller, etc.)

Embedded: Generally standard hardware, Software may include just

Freeze Dryer control system, Autoclave control system, etc.

www.chinapat.com parameterisation, partial programming or full programming

Standalone: Requires custom hardware, and software requires

BMS & EMS system API Control system Plant SCADA systemSCADA
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programming SCADA + PLC, DCS SCADAPLC,DCS

Validation of Automation System

GAMP5
(Good Automated Manufacturing Practice) www.chinapat.com A RisK Based Approach to Compliant GxP Computerised System GxP

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GAMP5 V Model (1)

Planning URS Risk Assessment Vendor Assessment & Selection Quality Plan Specification www.chinapat.com Functional Specification Hardware Design Specification Software Design Specification Software Module Specification Risk Assessment Design Qualification
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GAMP5 V Model (2)

Configuration & Coding Build system hardware Configure system software Integrate hardware & software Verification www.chinapat.com Code Review FAT Protocol & Execution FAT SAT Protocol & Execution SAT Reporting Final Documentation Final Quality Report and handover
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Computerised System Life Cycle

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What GAMP5 Is and Isnt? GAMP5

It is not about making documents GAMP5 is a Guideline which is accepted by major regulatory

bodies as a methodology for the development and operation of Control Systems GAMP5 It is about ensuring the Brain of a Machine or a Process work properly and is fit for its intended use. www.chinapat.com It is about Building Quality onto a Control System throughout its Life Cycle. It defines the steps to be taken at each stage of Control System Life Cycle It defines Roles and Responsibilities of User and Suppliers

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Key Personnel

Process Owner: The person ultimately responsible for the

business process or processes being managed

System Owner: The person ultimately responsible for the

availability , support, and maintenance of a system and for the security of the data residing on that system

Subject Matter Expert: Those individuals with specific

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expertise in a particular area or field. SME should take the lead role in the verification of computerised systems. SME responsibilities include planning and defining verification strategies, defining acceptance criteria, selection of appropriate test methods, execution of verification tests and reviewing results

SME SME

Scalable Life Cycle Activity

Life cycle activities should be scaled according to:

System impact on patient safety, product quality and

data integrity www.chinapat.com

GxP Assessment GxP Impact Assessment

System complexity and novelty Software category Hardware Category

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GxP Assessment, GxP

Does the system generate, manipulate or control data supporting regulatory safety and efficacy submissions? Does the system control critical parameters and data in preclinical, clinical, development, or manufacturing? www.chinapat.com Does the system control or provide data or information for product release? / Does the system control data or information required in case of product recall? Does the system control adverse event or compliant recording or reporting? Does the system support pharmacovigilance? ()
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Yes / No

Yes / No Yes / No Yes / No Yes / No Yes / No

System Impact Classification

High = potential for serious injury or death Medium = potential for minor injury Low = potential for little harm to patient = = = Worst case High = potential for release of product which would cause serious injury to a patient impact on Medium = potential for release of product which would cause minor injury to a product patient quality Low = potential for poor quality product which would not be released or would not cause harm to patient = = = Worst case High = loss of data integrity such that product recall could not be carried out or impact on release could be made of product which would cause serious injury to a patient data integrity Medium = loss of data integrity such that release could be made of product which would cause minor injury to a patient Low = loss of data integrity such that product would need to be scrapped or data records not essential to product release or recall might be lost or impaired = = = Worst case impact on patient safety

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GAMP 5 Hardware Categories

Category 1, Standard Hardware Components Typical Approach Document manufacturer or supplier detail, serial number and version number Correct installation to be verified www.chinapat.com Configuration Management and Change control apply 2, Custom Built Hardware Components As per above plus: Design specification Acceptance testing Configuration and Change control apply
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GAMP 5 Software Categories

Category 1, Infrastructure Software Description Layered software Software used to manage the operating environment Typical examples Operating systems Database engines Middleware Programming languages Spreadsheets Version control tools Typical Approach Record version number, verify correct installation by following approved installation procedure

www.chinapat.com Network monitoring tools

3, Non-configured Runtime parameters maybe entered and stored, but the software can not be configured to suit the business process Firmware based applications COTs software Abbreviated Life cycle approach URS Risk based approach to supplier assessment Record version number, verify correct installation Risk based test Procedure in place for maintaining compliance 19 Pharma Bio Solutions Ltd

GAMP 5 Software Categories

Category Description Typical examples Typical Approach

4, configured

Software, often very complex, that can be configured by the user to meet the specific needs of the users business process. Software code is not altered

DAQ systems SCADA DCS BMS HMI LIMS ERP Clinical trail monitoring

Life cycle approach Risk based approach to supplier assessment Supplier QMS Record version number, verify correct installation Risk based testing in a test environment

www.chinapat.com Risk based testing within the business process

Procedure in place for maintaining compliance

5, Custom

Software custom designed and coded to suit the business process

Internally, externally developed IT applications.IT Internally, externally developed process control applications. Custom ladder logic Custom firmware Spreadsheet (macro)()

Same as cat 4 plus 4 More rigorous supplier assessment, with possible supplier audit Possession of full life cycle Design and source code review

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Software Category 3 3

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Software Category 4 4

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Software Category 55

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Example of GAMP5 Categories

Item Configurable (Controllers, weigher, etc) Embedded Standard (PLC + HMI) Embedded Non-Standard (PLC + HMI) Standalone (DCS, SCADA+PLC)

Hardware Category 1

Software Category 3 3 3, 4 ,5 3, 4 ,5

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1 or 2 2

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User Requirement Specification

Most important document Describes what the system is supposed to do Normally written by the end user, maybe also be provided by supplier.

Controlled Document For Cat 3 written for a specific solution 3 www.chinapat.com For Cat 4 & 5 It is written in general 45 Sufficient, Realistic, Measurable, Achievable Testable: Clear, Precise, basis for formal testing Traceable: Design and testing Define priority: Mandatory, Beneficial, Nice to have

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Functional Specification
A Functional Specification is a key document in defining how the customer functional requirements, as defined in the user requirements specification, are to be met.

Functional Specification is the responsibility of the supplier www.chinapat.com It is written in response to URS URS It provides the main basis for FAT FAT It needs to be approved by User. Generally may require further revision during the project life cycle.

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Test Phases
A system test phases depends on its size and complexity

Typical test phases include Software Module testing Internal integrated testing Hardware www.chinapat.com Software FAT test FAT Hardware Software SAT test SAT Hardware (IQ) IQ Software (OQ) OQ
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Test Protocols
A Test 'protocol' or 'specification' defines the testing to be carried out to verify that the system (or its individual elements) meets pre-defined requirements.

A project may include Software Module Test Protocol, FAT protocol, SAT protocol FATSAT www.chinapat.com Depending the size of the project there maybe a separate Hardware Test protocol Test Protocols are the responsibility of the supplier They should be approved by User. Generally may require further revision during the FAT. FAT

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Supporting Processes

Risk Management

Change & Configuration Management

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Design Review

Traceability

Document Management

On-going Operation
Maintaining compliance and fitness for intended use

of GxP Validted system throughout its life cycle GxP Users of the system must be able to demonstrate that www.chinapat.com they have considered and reviewed maintenance requirement and supports needs for the system and decided what procedures and records should be established and maintained.
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On-going Operation activities

Performance Monitoring Incident Management Corrective and Preventive Action Repair activity www.chinapat.com Periodic Review Backup & Restore Security Management Archival and Retrieval

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Project Stages

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