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Unless a very simple control system (PLC and HMI) there is likely to be some elements of infrastructure software.

Infrastructure software in its most simple form is the operating system which the application software resides.

Additional software for managing the infrastructure the process control system includes:

• Operating Systems
• Anti-virus Software
• Active Directory / Domain Controller
• Database Software (SQL / Oracle)
• Server and Network Hardware
• Virtual Environments
• Firewalls, including configuration
• Server and Network Monitoring Tools
• Backup Systems

Configured software for a process control system is software applications that are configured to meet specific business needs (see above GAMP Category 3).

GAMP Category 4 – Configured Software range in complexity from simple configuration of SCADA system graphics to complex process control within a DCS or PLC (linking standard library objects to control the process).

Examples of configurable software for a Process Control System includes:

• DCS / SCADA Mimics
• DCS / SCADA Databases (Alarms, Tags, History)
• PLC / DCS programs configured from Standard functions library / IEC61131-3

For GAMP Category 4 software the approach to the computer systems validation may be to use the supplier’s documentation and verification to demonstrate the suitability of the standard modules and limit the regulated company’s verification to the critical functions of the business process and functions to support regulatory compliance (security, electronic records, etc.).

Custom application is software that is generally written from scratch to fulfil the business need. As this software is going the full development lifecycle there is a higher level of risk of errors within the application code.

In terms of a Process Control System GAMP Category 5 software may range from PLC logic (Ladder, Sequence Flow Chart, C++, etc.) to custom scripts written within the SCADA / DCS system.

As GAMP Software Category 5 the level of verification through software testing (FAT, SAT, IQ, OQ, etc.) will be increased. The level and formality of performing and documenting this testing will be determined on the GMP Impact (Product Quality, Patient Safety, Data Integrity and GMP regulatory requirements).

The GxP impact assessment is carried out to determine if the computer system has an impact on product quality, patient safety, or data integrity. All GxP impact computer systems must comply with applicable regulatory requirements.

Perform GxP assessment using the below Questioners.

1. Is the system used to generate data used in support of a regulatory submission?

2. Is the system is used to monitor, control or supervise a GxP manufacturing or packaging process and has the potential to affect Product Quality, Safety, Identity, or Efficacy?

3. Is the system used to hold and/or manipulate clinical study data?

4. Is the system used to monitor, control or supervise packaging and labeling operations?

5. Is the system used to create critical study control data?

6. Does the system hold electronic records that are or could be used in the electronic form to make GxP decisions?

7. Is the system used to transmit e-data/ records to other systems for the execution of GxP activities?

8. Is the system is used for GxP analytical quality control?

9. The system manipulates data or produces reports, to be used by GxP quality-related decision authorization/approval processes, where the data supports the decision process or the electronic record constitutes the master record.

10. Is the system is used to maintain compliance with a GxP requirement?

11. Is the system is used to monitor, control, or supervise warehouse or distribution within a GxP requirement?

12. Is the system is used for GxP batch sentencing or batch records?

13. Is the system used to store GxP documents for example SOPs, Specifications, BMR, BPR, DMF

14. Is the system used for GxP data backup, restore, archival or storage, data security, or access/domain control?

15. Is the system used for physical access to GxP to the environment (i.e. area or location)?

16. Does the system support a GxP application i.e. LAN/WAN?

If any of the above questions are answered “Yes” then the system has a GxP impact and the system requires a level of Validation and control through the Computer Systems Validation.

If all the questions are answered “No” then the system may be deemed not to have a GxP Impact. This should be documented to support the decision not to perform formal validation.

Electronic Records and Electronic Signatures (ERES) Assessment

An assessment is carried out to establish if the system needs to meet the requirements of electronic records and electronic signatures by determining what electronic records are created by the system, how those records are maintained, and how the records will be signed, either by hand or electronically.

The system supplier must be assessed to determine their suitability to provide a quality system that meets all requirements. Confidence will be gained through their adherence to a documented Quality Management System and Software Development Life Cycle (SDLC). The assessment may take the form of a basic checklist, a postal questionnaire, or an onsite audit, depending on the outcome of the risk assessment. Supplier selection should then be documented in a report, along with whether the supplier documentation will be leveraged or not.

Risk assessments should be performed at various key stages of the validation process by a multidisciplinary team so that a full understanding of all processes and requirements are covered and taken into account. This helps to identify and manage risks to patient safety, product quality and data integrity.

An initial risk assessment is conducted early on in the project phase so that the results can be used in the validation plan, along with the outcome of activities in the concept phase, to define the depth and rigor of required activities and compile a list of deliverables. This produces a validation approach which is commensurate with the level of risk the system poses.

A functional risk assessment is performed following approval of the functional specification to identify potential risks. Mitigation activities are then planned to manage the identified risks and allow focusing on critical areas, e.g.by modifying functionality, detailed testing, procedural controls or training.

Further risk assessments can be performed during the course of the project such as testing and deployment, and for other activities throughout the life of the system.

A risk assessment uses a simple scoring system documented in a matrix to produce the level of risk. A maximum scoring of 1 to 3 and low, medium and high are used to judge the severity of the risk, likelihood of occurrence and the probability of detection to attain an overall risk level.

The Validation Plan (VP) is produced to define the validation approach, describe the required activities, detail the acceptance criteria and list the deliverables and responsibilities. The VP specifies how flexible and scalable the validation approach will be which is derived from the outcome of activities in the concept phase.

The system overview is a brief description of the system and includes:

• System identification
• Business processes the system supports
• Data managed by the system
• High level functionality of the system
• High level schematic diagram of system architecture/hardware
• All interfaces to external systems
• How data is secured by physical or electronic means

The system overview may be incorporated into a section of the VP.

The User Requirements Specification (URS) clearly and precisely states what the user wants the system to do, what attributes it should have and details any non-functional requirements and constraints. The following areas should be considered:

• Operational and data requirements
• Regulatory requirements including ERES
• Interfaces
• System access & security
• Data handling and reporting
• System capability
• Environmental health and safety
• Supplier support – documentation and testing

The Functional Specification (FS) defines the full system functionality including how the user and business requirements are satisfied. It is the basis for system design, customization, development and testing. Supplier documentation should be leveraged wherever possible or referenced from the FS. It must be clear how the requirements are met from the URS and provide sufficient information to allow the design specification to be written. The FS may be combined with the URS as a Functional Requirement Specification (FRS)

The Configuration Specification details the configuration parameters and how these settings address the requirements in the URS. This may be a standalone document or detailed in the FS.

This activity involves documenting both the hardware and software as a combined document (DS) or for larger systems as two separate specifications, Hardware Design Specification (HDS) and Software Design Specification (SDS). It can be merged with the Functional Specification as the Functional Design Specification (FDS).

Design Reviews are conducted to verify that the design conforms to required standards; the FS meets the requirements defined in the URS and that the requirements can be traced through the design documents in preparation for testing. The output from the risk assessment is also considered in the review process. A design review report documents the outcome of the design review process.

This is a process where source code is planned and written in accordance with pre-defined programming standards.

If applicable, a code review is performed to detect and fix coding errors before the system goes into formal testing. It verifies that the software has been developed in accordance with the design and programming standards have been followed.

A Data Migration Plan is created when a system requires data loading from an existing system. It describes the activities and deliverables required to select, remove, cleanse, migrate and verify all data to assure its security and integrity. Data can be manually or automatically loaded/migrated, however if any critical data has been manually entered, an evaluation should be carried out to ensure its correctness.

Testing is carried out to verify that installation and configuration has been conducted in line with specifications and that the functionality is challenged at subsystem and system level. This verifies that system components perform their tasks separately, that the subsystems integrate correctly and that the system meets the requirements and expectations of its users. The testing approach is described in a test plan as either a section within the validation plan or as a standalone document. Where possible at each stage, any previous testing should be leveraged, which is defined in the plan. The plan also defines the different types and details the level of testing (e.g. installation, unit, system, acceptance) that will be required for a project. The results from the outcome of the risk assessment will define how precise the depth and rigor of testing shall be and the level of testing will be scaled appropriately. The plan will specify the test environment (development, test, or production) in which testing shall be performed, the use of any tools to be employed for testing and test data requirements.

The installation verification, functional verification and requirements verification testing documents are generated against pre-approved specifications. Test cases are written in test steps as instructions to be followed to test whether the system satisfies the defined acceptance criteria appropriate for the test level. The test steps are written in sufficient detail so that testing is repeatable with consistent results. A printed copy of the approved test case document is executed and the test steps annotated to record the test results. Verification against the expected result defines whether the test step is a pass or fail. Evidence produced during test execution (e.g. reports or screen prints) is attached to allow an independent review and approval of the results. Test results are reviewed, summarized and approved as a standalone test report or as part of the executed document.

System Operating Procedures should be written to provide clear unambiguous instructions to personnel as to the accepted process of completing a particular operation in a systematic, consistent and safe manner. User manuals should be leveraged wherever possible.

Key users must be trained in the use of the system software, applications and procedures as necessary for the development, maintenance, testing and support of the system.

A System Support Plan defines the supporting organizations and procedures to support and maintain the quality/validation of the system during its operation phase.

A Service Level Agreement (SLA) documents a mutual agreement for the service provided between all parties. It should clearly define service, document and data ownership and ensure accountability, roles and responsibilities are established. The escalation process should be fully described along with the service performance criteria.

A plan should be written to define when the application will transition into the operation phase and how any disruption will be managed. The risk management process could be used in this process together with a back out plan. It should ensure that project and validation / verification deliverables are complete prior to handover.

When the system is ready to be released for routine use, a certification statement is created detailing the following:

• System name and version
• Date of release
• Department using the system
• The activities and deliverables relating to the release
• Restrictions on use (if any)
• Open incidents (if any)

Deployment activities include the installation, configuration, data migration and testing of the system and components on the final operating environment (production).

The Validation Report (VR) summarizes the activities carried out during the project, describes any deviations, with justification, from the Validation Plan (VP), lists any limitations or restrictions on use, summarizes any incidents and details any outstanding and corrective actions.

A certification statement concludes whether the validation was successful or not and approves or declines the system for its intended routine use.

An Interim Validation Report may be issued if all post go-live activities are not complete.