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תגית: 21 CFR Part 11

ולידציה – 3 Validation case study – part

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ולידציה – 3 Validation case study – part

 This article was written by Iian Shaya, validation,automation and control expert

אילן שעיה Ilan Shaya
Ilan Shaya CEO , control and automation specialist and designer

Documentation for IQ and OQ – to be checked at PDI/FAT

Welding reports

Surfaces finishing test reports

PDI and FAT results

As-built drawings, 3 sets in nominated project language, plus 1 set in English

As-installed versions of all documentation submitted for design review

Back-up software on diskette/CD-ROM, as appropriate, ready for re-installment

Machine configuration/start up, set-up and commissioning data, including tabulation of all change parts and identifications

Full machine parts list

Complete documentation (protocols and method statements) required for equipment DQ, calibration, IQ and OQ specified for manual and automatic operations

Calibration certificates for all required instruments to NIST

Specification for all parts manufactured by sub-contractors

Full identification of all parts according to the P&ID, including valves, regulators, instruments, pipes, media and flow direction arrows

Tags for electrical and pneumatic wiring

Documentation to ensure qualification in compliance with FDA and EMEA, as outlined above

DQ Protocols Including PC/PLC

Approval

Statement of purpose

System description

Traceability matrix

IQ Protocols Including PC/PLC

Approval

Statement of purpose

System description

Specifications

Materials in product contact

Engineering drawings

Subsystem inspection

Components

Piping

Valves

Instrumentation and calibrations

PC/PLC requirement definition

Software development documentation

Manual / technical literature

Test equipment data sheet

Component data sheets

Utility requirements

Exceptional conditions, if required

Summary

OQ Protocols Including PC/PLC

Statement of purpose

System description

Manual and automatic control over all modules through HMI

PC/PLC validation protocols

Step-by-step checking of schedule of system operation – SSO

Alarm and message reaction

HMI synoptic screen vs. P&ID

System operation tests

Operation tests for HMI to ensure compliance with 21 CFR part 11

Application software certification

HW documentation

SW code

SW components data sheets

HW components data sheets

PLC configuration

Graph printout

Synoptic screen list and printout

Operation screen list and printout

Parameters list screen

Messages and alarms list, and printout

HW inspections

SW inspections and application

Approved schematic description

Ladder diagram validation

PLC capabilities

PLC accuracy

SW development documentation

List of control devices

Exceptional conditions

Reports – verification of authorization inspection

PQ Protocols Including PC/PLC

Statement of purpose

Analysis procedures

Staff instruction

Plan for sampling

Criteria for acceptance

 This article was written by Iian Shaya, validation,automation and control expert

ולידציה – Validation case study – part 2

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ולידציה – Validation case study – part 2

 This article was written by Iian Shaya, validation,automation and control expert

Validation Requirements

Documentation for Initial Tender

Project schedule and milestones design and construction detail

Project quality plan

Supplier’s local subsidiary/agent

Supplier’s documentation that the system / configurable software versions are released to the market and are FDA/EMEA compliant

Compliance to the 21 CFR Part 11 operational requirements – the contractor should ensure covering of all the requirements described below

Contractor to state the system/product status and implementation planned for each requirement – User's approval pre-delivery

Documentation for Design Review

PID for the system

Electrical and pneumatic schematics

:Installation data

General arrangement drawings

Floor loading

Utility requirements

Details of electronic records and approvals that may be subject to regulatory controls under CFR Title 21 part 11

Instrumentation documentation

:Main components specification

Equipment

Instrumentation

Valves

Piping

Control system

Pipe welding documentation

General installation book

Procedures

User guide

Security

Preventative maintenance + spare parts list

Operation procedure

Pressure test procedure

Leak test procedure

Passivation procedure

Calibration

:Functional Design Specifications for

Complete manufacturing system

Software – SW and hardware –HW

Functional Design Specifications

System Detail Design Specifications for HW and SW.

SW source code, with comments, for customized SW

SW complete version history

HMI alarm list, message list and graphical displays

I/O list

:List of materials

Product contact materials

Potential product contact lubricants

Welding procedures for product direct and indirect contact parts

Pre-delivery Inspection and Factory Acceptance Test (FAT) protocols

Steel certificates and gasket certificates

Documentation Prior to FAT or Pre-Delivery Inspection – PDI

:Progress visit report which will include

Mechanical and technical development

Automation and SW development

:Supplier’s factory test results for

Unit tests – The test protocols shall be traced to low level design document and will be approved by the user prior to execution. The approval of the report shall be performed by representatives of the user's validation team, IT QA.

Automation and SW development

:Integration Tests  – Simulation Testing

Approved PDI and FAT protocols

Commissioning

MCCR

Purpose

Scope

Responsibility

Execution instructions

System scope

System description

Drawing verification

Equipment verification

Valve verification

Instrument installation and calibration

Utility verification

Documentations verification

Piping Verification

Sample Point Verification

Safety, health and environment verification

Slopes verification (if relevant)

Electrical and communication activities

Pump installation verification, if relevant

Heat exchanger installation verification, if relevant

Air break verification, if relevant

Dead leg verification, if relevant

CE

Purpose

Scope

Responsibility

Execution instructions

System scope

System description

System startup

Equipment verification

Main equipment operation checks

System FDS (SSO) verification

System performance testing

 This article was written by Iian Shaya, validation,automation and control expert

ולידציה – FRS – Regulatory & HMI Requirements

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ולידציה – FRS – Regulatory & HMI Requirements

 This article was written by Iian Shaya, validation,automation and control expert

Regulatory Requirements

These requirements cover all the FDA specifications regarding the system compliance with the 21 CFR Part 11 definitions, and also with usual validation documentation demands

Method to provide a computerized system that complies with 21 CFR Part 11 definitions, such as the system access control by the user's managing personnel, who shall be responsible for the content of the electronic records (ERs) contained in the system

Method to restrict logical access to the system according to specified authorization levels

Method to restrict logical access to the system only to specific user ID and password

Method to provide system capability to record the values, alarms, user changes and any other events, and provide readable forms and reports of ER data

Method to allow storage of historical events, current alarms and historical alarms data records on the computerized system database

Capability of data display to the user in "view only" mode, so the user cannot alter or delete data/records

Provision of user's capability to backup data daily, weekly and monthly, according to his procedures, to ensure protection of the records and to enable their accurate and ready retrieval throughout the records retention period

Provision by the supplier of a project plan and quality assurance (QA) processes during development and the testing stages as part of his QA systems

Provision by the supplier of the following documents

Functional Requirements Specification – FRS

Functional Design Specification- FDS

IO List

Schedule of System Operation – SSO

Installation Qualification (IQ) protocol

Operation Qualification (OQ) protocol

Performance Qualification (PQ) protocol

HMI Requirements

These requirements are intended to provide the URS demands from the HMI screens, regarding proper graphic design and functionality for controlling and monitoring the system, as specified in customer's contract with the supplier. The HMI screens provided usually are of the following types

Main Screen

Synoptic screens for displaying online values and status

Parameters screens for displaying temperature, humidity and pressure parameters values

Data logging and storage of historical trends, alarms and events

Tabular screens for displaying alarms

Graphical screens for displaying trends

 This article was written by Iian Shaya, validation,automation and control expert

ולידציה – URS – Regulatory & HMI Requirements

Posted on by אביב צברי

ולידציה – URS – Regulatory & HMI Requirements

 This article was written by Iian Shaya, validation,automation and control expert

Regulatory Requirements

These requirements cover all the FDA specifications regarding the system compliance with the 21 CFR Part 11 definitions, and also with usual validation documentation demands

Computerized system compliance with 21 CFR Part 11 definitions, such as the system access control by the user's managing personnel, who shall be responsible for the content of the electronic records (ERs) contained in the system

System capability of restricting logical access to the system according to specified authorization levels.

Access to the system allowed only by user ID and a specific password

System capability to record the values, alarms, user changes and any other events, and provide readable forms and reports of ER data

Storage of historical events, current alarms and historical alarms data records on the computerized system database

Data display to the user in "view only" mode, so the user cannot alter or delete data/records

Provision of user's capability to backup data daily, weekly and monthly, according to his procedures, to ensure protection of the records and to enable their accurate and ready retrieval throughout the records retention period.

Provision by the supplier of a project plan and quality assurance (QA) processes during development and the testing stages as part of his QA systems

Provision by the supplier of the following documents

Functional Requirements Specification –FRS.

Functional Design Specification – FDS

IO List

Schedule of System Operation – SSO

Installation Qualification (IQ) protocol.

Operation Qualification (OQ) protocol

Performance Qualification (PQ) protoco

HMI Requirements

These requirements cover the provisions demanded from the HMI screens, regarding proper graphic design and functionality for controlling and monitoring the system, as specified in customer's contract with the supplier

:Note

The final contents of the URS and FRS are tailored according to the type and size of the system under validation. Since the URS and FRS regarded herein are generic, they include requirements that may not be necessary in small or simple systems

 This article was written by Iian Shaya, validation,automation and control expert

ולידציה – URS and FRS Preparation Overview

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ולידציה – URS and FRS Preparation Overview

 This article was written by Iian Shaya, validation,automation and control expert

User Requirements Specification (URS) and Functional Requirements Specification (FRS) are the first and starting points of a validation process and a validation documentation file

  – The validation process must comply with regulations issued by the United States Food and Drug Administration FDA

:The FDA regulations that are most relevant to the validation process are

Good Manufacturing Practice  – GMP.

Current Good Manufacturing Practice – cGMP

Good Automated Manufacturing Practice – GAMP

The validation process includes design, installation and operation of a monitoring and control system for a production facility, as well as planning and execution of test procedures, to verify that a monitoring and control system meets the FDA standards

Validation documentation is part of the validation process that includes written and/or electronic records regarding the installation and operation of the monitoring and control system, and the corresponding test procedures for this system

Electronic records are often required to fulfill regulations set by the FDA. These regulations regard the scope and application of Part 11 of Title 21 of the Code of Federal Regulations; Electronic Records; Electronic Signatures (21 CFR Part 11). Electronic Records may contain any combination of text, graphics, audio, pictures, or other information represented in electronic form, which are created, modified, maintained, archived, retrieved or distributed by a computer system

Electronic Signatures may contain computer data compilation of any symbol or series of symbols executed, adopted or authorized by an individual to be legally binding equivalent of the individual's handwritten signature

Electronic records and signatures are generally used in Closed Systems, in which the system access is controlled by personnel responsible for the contents of the system electronic records

The responsibility for writing and approving the URS and FRS is shared in practice by the user, who operates the production facility, and the supplier or vendor, who provides the monitoring and control system for ensuring the proper operation of the production facility. Usually, the URS is written by the user and the FRS by the supplier

:Note

The final contents of the URS and FRS are tailored according to the type and size of the system under validation. Since the URS and FRS regarded herein are generic, they include requirements that may not be necessary in small or simple systems

 This article was written by Iian Shaya, validation,automation and control expert

ולידציה – DQ – Design Review

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 ולידציה – DQ – Design Qualification / Design Review

DQ  – Design Qualification is for Design Review by verifying that the system has been designed as specified in the URS (User Requirements Specification), FDS (Functional Design Specification), and relevant equipment specifications satisfying all GMP requirements. The Process User Requirements in the URS have been identified by the Quality Risk Assessment. Since the Quality Risk Assessment is an iterative process, it may be performed again, whenever necessary, during the DQ and subsequent lifecycle qualifications.  For  hardware and software of the control system, verification data will be collected to prove that the system has been designed in accordance with the URS and FDS including the requirements of 21 CFR Part 11. As DQ is the final step to formally review and document the proper design of the system, the protocol must enable the reviewers to verify that all quality-critical attributes and essential technical attributes of the system have been incorporated in the design. When the DQ report is approved, the system is ready for fabrication and construction.

DQ PROTOCOLS
PROCESS EQUIPMENT AND SYSTEMS
Media Preparation and Hold Tanks
Buffer Preparation and Hold Tanks
Process Tanks
Reactors – Organic Synthesis
Bioreactors
Evaporator Systems
Distillation Tower Systems

CLEAN UTILITY SYSTEMS
USP Purified Water Storage and Distribution Systems
WFI Storage and Distribution Systems
Clean Steam Generation and Distribution Systems
Process Air Systems
Nitrogen Gas Systems

SUPPORT SYSTEMS
CIP Systems
Biowaste Kill Systems – Continuous
Biowaste Kill Systems – Batch
Autoclaves

HVAC SYSTEMS AND CLEANROOMS
HVAC Systems
Cleanrooms – Aseptic
Air Locks – Gowning

LABORATORY EQUIPMENT
Incubators
CO2 Incubators
Water Bath Incubators
Ultra-Low Temperature Freezers
Refrigerators

ולידציה – FRS for Compliance with 21 CFR Part 11

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Functional Requirements Specification -FRS Regarding Requirements for Compliance with 21 CFR Part 11

This FRS presents SmarLogic's functional requirements in response to the User Requirements Specification (URS) . These functional requirements should be met in order to ensure  Control and Monitoring System complies with 21 CFR Part 11.

This FRS must be considered for the system design, build, installation, operation and testing requirements, and for traceability purposes along the product life cycle up to the Operational Qualification (OQ) stage.

                              Responsibility

The Validation Engineer is responsible for writing this protocol. The Control, Automation & Validation Engineer is responsible for ensuring the preparation and approval of this protocol.

The Control Engineer, Division Process Engineer and QA Manager are responsible of approving this document before development and on-site implementations.

The following sections list the functional requirements determined by the relevant groups of the system upgrading. Each functional requirement number is followed by the corresponding user requirement paragraph number for design qualification purpose

                            Glossary

ER – Electronic Record

DB – Database

FRS – functional requirements Specification

HMI – Human/Machine Interface

HSP – High Set-Point

HW – Hardware

IQ –  Installation Qualification

LSP –  Low Set-Point

OQ – Operational Qualification

OS – Operating System

PLC ָָ*- Programmable Logic Controller

QA – Quality Assurance

SCR – Screen

SOP – Standard Operating Procedures

SP – Set-Point

SSO – Schedule of System Operation

SW – Software

TP – Test Point

URS – User Requirements Specification

Requirements for Meeting 21 CFR Part 11

                        Top-Level Requirements

This section covers the proposed solutions for meeting 21 CFR Part 11 presented in the URS for a new WinCC HMI System. This system must allow the :following five main functionalities

Ensure the system integrity

Control the access to the system by logical security

Audit events that create and modify electronic records

Apply electronic signatures to the system

Backup and archive data to ensure record integrity in case of failure

                      Detailed Requirements

This section describes SmartLogic's solutions that will meet the detailed requirements listed in the URS. These requirements are divided into 6 categories for the sake of clarity:

Electronic Records

Security

Audit Trail

Archive

Backup

* Here are some examples of the PLCs used by smartlogic: 6XV1830-0EH10, 6ES7131-4BF00-0AA0,6ES7193-4CA40-0AA0,6ES7134-4GD00-0AB0,6ES7193-4CA40-0AA0, 6ES7138-4CA01-0AA0,6ES7193-4CC20-0AA0, 6ES7590-1AB60-0AA0, 6ES7511-1AK00-0AB0, 6ES7954-8LP01-0AA0,6ES7155-6AU00-0BN0

ולידציה – Operation Qualification – OQ- part 2

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ולידציה – Operation Qualification – OQ- part 2

Protocol Preparation Overview

This article provide overviews of the main test procedures and verification, and their purposes. This OQ procedure is generic, and relevance of the test procedures and verifications provided below depends on the composition of the system under validation

:Note

As mentioned in the previous artcle on OQ Protocol Contents, the final contents of the OQ protocol are tailored according to the type and size of the system under validation. Since this document is generic, it covers test procedures that may not be necessary in small or simple systems

:Where relevant, the OQ procedure may consists of five main test procedures

HMI Screen Test Procedure – intended to verify that the HMI screens provide the graphic design and functionality required for properly monitoring and controlling the environmental conditions in the user's

Parameters Lists Verification – intended to verify that the system parameters lists comply with the values specified in the SSO

: Two types of parameters are checked

Process parameters

Alarm parameters

System Operation Test Procedure – intended to verify that system monitoring and control components are capable of maintaining the user's facility within specified temperature, humidity and pressure levels

System Alarms Test Procedure – intended to verify that when the specified temperature, humidity and pressure levels exceed its specified limits, an alarm message is displayed, and an SMS or e-mail notification is sent to relevant personnel

Test of HMI Compliance with 21 CFR Part 11 – This test is intended to verify that the HMI meets Valtech Cardio's URS regarding 21 CFR Part 11. These : requirements are divided into 5 categories for the sake of clarity

Security

Electronic Records

Audit Trail

Archive

Backup

 HMI Screen Test Procedure

This section includes specific test procedures for all the relevant HMI screens, where each test procedure serves to verify that the specific HMI screen provides the graphic design and functionality required for its intended purpose within the monitoring and controlling functions

Parameters Lists Verification

:This procedure covers the verifications of two types of parameters

Process parameters

Alarm parameters

Process Parameters List Verification

This procedure is intended to verify that:

The system enables to set the default values of the process set-points of each monitored environmental parameter.

The system provides automatically the corresponding low and high limits of these default values. These limit values are listed in  below

The system rejects all the SP values that exceed their allowed ranges, as specified in the SSO

Alarm Parameters List Verification

:This procedure is intended to verify that

The system enables to set the default values of the alarm set-points of each monitored environmental parameter

The system provides automatically the corresponding low and high limits of these default values

The system rejects all the SP values that exceed their allowed ranges, as specified in the SSO

 System Operation Test Procedure

This procedure is intended to verify that system monitoring and control components are capable of maintaining the user's facility within specified temperature, humidity and pressure levels. For this purpose, it is necessary to temporarily change set-points, in order to activate the control devices

System Alarms Test Procedures

This procedure is intended to verify that, when an environmental parameter value exceeds the specified normal range, the system reacts as specified in the SSO, by providing a specified alarm indication, a relevant e-mail alarm message, and relevant records in the Current Alarms and Historical Alarms screens

Test of HMI Compliance with 21 CFR Part 11

This test is intended to verify that the HMI meets the user's URS regarding 21 CFR Part 11. These requirements are divided into 5 categories for the sake of :clarity

Security

Electronic Records

Audit Trail

Archive

Backup