Validation of Computer Systems in a Global Environment

Validation of Computer Systems in a Global Environment

June 2012

Presented at the National Validation Forum

Presented by: Andrew Giles

on 27 June 2012

This Presentation• Definitions

• Validations of computer systems in a global network environment. Examples of global systems and deficiencies

• When is a computer system required to comply to the code of GMP?

• Is there more to the inspection of computer systems than validation?

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What first?

Understand the terms used in computer systems validation

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Definitions

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Acronym Full Name What & Where?

LAN Local Area Network

A computer network that connects computers and devices in a limited geographical area such as computer laboratory, office building or manufacturing site

WAN Wide Area Network

A computer network that covers a broad area (i.e., any network whose communications links cross metropolitan, regional, or national boundaries).

Definitions

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Acronym Full Name What & Where?

MRP I or MRP II (MRP 2)

Material Resource Planning

Purchasing, warehouse and stock control systems. MRPII systems have simulation capability to answer "what-if" questions

ERP Enterprise resource planning

Is a company-wide computer software system used to manage and coordinate the resources, information, and functions of a business from shared data stores.

ERP Systems as an Example of a Global Network System

To follow is an example of where an ERP system can be a globally networked system

IssueCompanies regularly merge

To gain efficiencies group management merge computer systems from different sites

Sites that have been operating independently are often faced with corporate policies that require they will use particular software as specified by the corporate IT department or link existing systems with corporate systems

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ERP Systems Example

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SITE 2

SITE 1

Supplier Warehouse

Corporate Head Office

MRP SYSTEM A

MRP SYSTEM B

ERP Systems Example

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IssueThe TGA inspects a manufacturing site by geographical location

That is in Australia Inspectors can legally enter the premises of the company named on the TGA Licence at the address specified on the TGA Licence, for purpose of conducting a GMP inspection

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ERP Systems Example

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SITE 1

Supplier Warehouse MRP SYSTEM A

SITE 2

Corporate Head Office

MRP SYSTEM B

TGA LICENSED SITE

Not Licensed or Inspected by the TGA

Issue

The concept is similar for an overseas site that is being certified by the TGA although the legal authority to enter the premises is different

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If a manufacturer uses a computer system for GMP purposes then the inspector must be able to inspect all aspects of the systems to ensure that the system complies to the relevant parts of the code of GMP (including cGMP Medicinal Products part I clause 4.9 & Annex 11 and for API’s part II section 5.4)

If a GMP system is not physically located on the site that is being inspected and/or the staff maintaining the system are not located on the site, this does not change the manufacturer's obligation to ensure and demonstrate that the system meets all the code requirements relating to the system

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Often inspectors find that computer systems are not on the site that is being inspected and the systems are controlled by the corporate head office or a third party

It is also very common for the company name of the corporate head office to be different to that on the licence/certificate and it is common for the corporate head office to be registered and located in a different country to the one that is being inspected

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If a GMP related computer system is located/maintained on a site that is not licensed/certified by the TGA then the system will be considered deficient if the manufacturer asserts that “the computer system is controlled by the corporate head office or other site” but does not have evidence to demonstrating that the system meets the requirements of the GMP code available for inspection on the site that is being inspected at the time of an inspection.

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The manufacturer can then either make all aspects required for the demonstration of compliance available on the site being inspected at the time of the inspection

or

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or The manufacturer can treat the site in which the computer system is located as an outside agency. This would be required even if the none licensed site was the corporate head office and considered by the manufacturer to be part of the group of companies to which they belonged.

The company would then need to comply with all aspects of cGMP Med Annex 11 section 18: "When outside agencies are used to provide a computer service, there should be a formal agreement including a clear statement of the responsibilities of that outside agency (see Chapter 7)." Note: chapter 7 now applies. 17

Note: chapter 7 now applies.

7.1 “There should be a written contract covering the manufacture and/or analysis arranged under contract and any technical arrangements made in connection with it.”

7.2 “All arrangements for contract manufacture and analysis including any proposed changes in technical or other arrangements should be in accordance with the marketing authorisation for the product concerned.”

7.14. “The contract should permit the Contract Giver to visit the facilities of the Contract Acceptor.”

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Note: chapter 7 now applies.

The site that is being inspected must hold evidence demonstrating that the contracted third party is capable of meeting the cGMP requirements for computer systems

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Deficiency Example

During an initially inspection of an Indonesian site the following was found:

The site used an ERP system that was a customised system based on SAP.

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ExampleThe manufacturer claimed that the system had been designed in

Australia by the corporate head office and installed on many sites that were authorised by several different regulatory authorities.

The global group of companies had a site with a TGA licensed site in Australia but the computer systems was not located or maintained from the licensed site.

There were also several other sites linked to the system that had not been inspected by the TGA.

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Example

The Enterprise Resource Planning (ERP) system was installed, controlled and maintained by the South East Asian corporate head office.

At the time of the inspection, evidence of completed validation was not available on the Indonesian site.

The manufacturer indicated that the ERP system’s validation documentation were held at a Singaporean site as the systems was relevant to many sites controlled by the parent company in multiple different countries.

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ExampleThe company relied on the ERP system to prevent the

duplication of batch numbers.

It was noted by the Inspector that the ERP system would accept a space in front of a batch number, which then allowed duplicate batch numbers to be entered into the system.

As all records of validation and maintenance of the SAP system was not available at the Indonesian site it was not possible for the inspector to investigate this discrepancy any further.

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ExampleThere were no agreements or procedures defining

responsibilities for design and maintenance of the system.

There were no SOP’s, agreements with corporate IT, policies or validation documents on the Indonesian site.

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ExampleA deficiency was raised against Annex 11 sections 2

(Validation) and 18 (When outside agencies are used to provide a computer service).

It was expected that the company would investigate the adequacy of their Service Level Agreements (SLA) and validation of the SAP system in light of the above observations.

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Cases: System is Located Another Licensed Site

If the corporate head office/corporate IT that is controlling GMP computer system(s) is on a site that is licensed/certified by the TGA then the TGA inspectors can include the inspection of the computer system during the inspection of the head office/other licensed site and the site that is being inspected only need to have procedures/SOP's that define their responsibilities with respect to the usage of the system available at the point of use.

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on

Cases: System is Located on Another Licensed Site

However, be aware of site specific configurations or adaptations that may not be covered by the controlling site

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When is a Computer System Required to Comply to the cGMP?

Whenever all or part of a computer system is used in manufacturing, quality control, quality assurance or release for supply as defined in the code

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When is a Computer System Required to Comply to the cGMP?Only the parts related to GMP functions are

required to comply with the code but be aware some items like security can not be separated by GMP and Non GMP parts

Remember GMP computer systems also consist of modules, operating systems and networks

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When is a computer system required to comply?

Does Med Prod P1 Clause 4.9 Apply?

Data may be recorded by electronic data processing systems, ......... Batch records electronically stored should be protected by back-up transfer on magnetic tape, microfilm, paper or other means. It is particularly important that the data are readily available throughout the period of retention,.

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Does Med Prod P1 Clause 5.29 Apply?

[5.29] Starting materials in the storage area should be appropriately labelled (see Chapter 5, Item 13). Labels should bear at least the following information:

...........When fully computerised storage systems are used, all the above information should not necessarily be in a legible form on the label.

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Considerations

Possible questions to ask about the system

Do any outputs from the system form part of the batch record? [4.18]

Is any part of the system used in place of GMP documentation? [4.9]

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Considerations

QuestionsHow do stores personnel know which stock is released supply? [1.3 vii, Annex 11.19]

for

How is quarantine/hold stock controlled? • [3.21] Where quarantine status is ensured by storage in separate

areas, these areas must be clearly marked and their access restricted to authorised personnel. Any system replacing the physical quarantine should give equivalent security.

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Considerations

Questions

How is stock rotation controlled? [5.7]

In the case of a recall how would materials be reconciled and returned materials isolated? [Chapter 8.12, 8.13, 8.14]

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Considerations

Questions

How is the sampling and re-sampling of quarantined materials controlled?

What control systems are in place to remove reject materials from the warehouse for destruction?

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Considerations

Questions

How are batch records generated?

Where are the formulations stored that make up a Bill of Material (BOM)?

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Considerations

Questions

Where are results from laboratory equipment first stored?i.e. are chromatograms or other results first collected on a hard drive or other computer based durable media?

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Considerations

If the answer to any of the above questions indicate that a computer system is implicated in the GMP processes then the computer system forms part of the GMP quality system and could be subject to inspection.

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Is there more to a inspecting computer systems than validation?

Validation is only a small part of what computer systems need to comply with

Annex 11 refers to items such as security, change control, validation, back-up, archiving and audit trails

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Validation

Inspectors will check that the manufacturer’s Validation Master Plan (VMP) includes computer

systems

There maybe a separate validation master plan for computer system or they maybe embedded in area VMP’s

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Annex 11 Section 2 on Validation

(A 11- S 2) 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, commissioning, documentation, operation, monitoring and changing.

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Systems Development Life Cycle (SDLC)

The codes do not restrict manufacturers in which SDLC a manufacturer may use

The manufacturer needs to define the SDLC and ensure that it is appropriate for the application

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Systems Development Life Cycle (SDLC)

The most common SDLC is the V model

Some of the alternative SDLC’s that might be used are:Classical WaterfallPrototypingJoint Application Development (JAD)Rapid Application Development (RAD)

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GAMP V Model SDLCURSUSER REQUIREMENT SPECIFICATION

FRSFUNCTIONAL REQUIREMENT SPECIFICATION

DSDESIGN SPECIFICATION

PQPERFORMANCE QUALIFICATION

OQOPERATIONAL QUALIFICATION

IQINSTALLATION QUALIFICATION

CODE

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Classic GAMP V Model SDLCURSUSER REQUIREMENT SPECIFICATION

FRSFUNCTIONAL REQUIREMENT SPECIFICATION

DSDESIGN SPECIFICATION

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PQPERFORMANCE QUALIFICATION

OQOPERATIONAL QUALIFICATION

IQINSTALLATION QUALIFICATION

CODE

MISSING MAINTENACE AND DECOMMISSIONING

Validation vs. versionValidation should be considered as part of the entire

life cycle

Check that the version that is validated matches the version of the live system

There maybe multiple levels of version number. Are they covered in the IQ?

Is configuration version controlled?

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Validation vs. version

Operating system

DATABASE

BASE APPLICATION

Configuration settings

ModularAdd-Ons

User Interface Interface version number

Configuration version number

DB version number

Base application version Number + service packs

Version number of each add-on

OS version number

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Examples of components

Operating system

DATABASE

BASE APPLICATION

Configuration settings

ModularAdd-Ons

User Interface Remote access (eg. Citrix), Web access or

direct access

e.g. security settings and audit trails

e.g. Oracle, SQL or proprietary databases

Also table field settings

Purchased base software, customised

components and patches

e.g. quality packages, LIMS packages and

accounting packages

OS is both at the server and at the client

Thank you for your attention

Questions?

Validation of Computer Systems in a Global Environment

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