This presentation describes approaches for software validation used to automate laboratory research procedures, consolidate data collection and analysis and/or run sophisticated QC or manufacturing operations.
Several approaches to software validation exist and may be appropriate for a specific project.
The scope of any validation effort depends upon a number of factors
Size and complexity of the software,
Origin of the software (custom vs. off-the-shelf) and
Whether the functions are critical or non-critical in nature.
By effectively planning the process, validation time and resources can be reduced while meeting regulatory requirements.
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Computer System Validation
1. This presentation is compiled by “ Drug Regulations” a
non profit organization which provides free online
resource to the Pharmaceutical Professional.
Visit http://www.drugregulations.org for latest
information from the world of Pharmaceuticals.
1/9/2014
1
2. This presentation is compiled from freely
available resources like the websites of FDA,
EMA, WHO.
“Drug Regulations” is a non profit
organization which provides free online
resource to the Pharmaceutical Professional.
Visit http://www.drugregulations.org for
latest information from the world of
Pharmaceuticals.
Drug Regulations : Online
Resource for Latest Information
1/9/2014
2
3.
This presentation describes approaches for software validation used
to automate laboratory research procedures, consolidate data
collection
and
analysis
and/or
run
sophisticated
QC
or
manufacturing operations.
Several approaches to software validation exist and may be
appropriate for a specific project.
The scope of any validation effort depends upon a number of factors
Origin of the software (custom vs. off-the-shelf) and
Size and complexity of the software,
Whether the functions are critical or non-critical in nature.
By effectively planning the process, validation time and resources
can be reduced while meeting regulatory requirements.
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Information
1/9/2014
3
4.
When equipment breaks, there are typically obvious and immediate
symptoms. Catastrophic results can often be avoided
Computer system defects can typically be very difficult to recognise
and severe problems may result without being detected until well
after the problem started
Drug companies, the airline industry, public utilities, nuclear power
plants and other industries where quality is critical have seen very
expensive consequences from improper computer system operation
Many of these consequences cost far more than the cost of
Computer Validation
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4
5.
Significant increase in the use of computer-
related systems in the Life Sciences industries.
These systems must satisfy cGMP requirements
Legitimate questions have been raised
concerning the scope and methods which should
be employed in validations.
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5
6.
Responsibility of the end-user to assure that
systems
used
are
in
compliance
with
applicable regulations.
Many users rely too heavily upon vendorsupplied information and test data to support
their system validation.
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7.
The extent of testing and the type of documentation
required to support validation is unclear
Difficult to delineate vendor and user responsibilities
when validating vendor-supplied systems.
Validation of computer-related systems is often
complex, and any number of alternate approaches
can be utilized.
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8. In general, a combination of hardware, software,
people, documents, inputs, processing, and outputs
working together
Inputs
Software
Hardware
Controlling System
Controlled process
outputs
Equipment
Operating Procedures &
Documentation
People and Training
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9. • MRP/ERP system?
• LIMS system?
• Laboratory Instruments (e.g. Chromatography)?
• Automated manufacturing or packaging equipment?
• IT systems, including those supporting network and
infrastructure?
• Spreadsheets or databases?
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10.
FDA approach is based on three main elements: (Guidance)
◦ Part 11 will be interpreted narrowly
◦ Fewer records subject to part 11
◦ For those records that remain subject to part 11, FDA intends to exercise
enforcement discretion with regard to part 11 requirements for
Validation
Audit trails
Record retention
Record copying
Systems that were operational before the effective date of part
11 (also known as legacy systems)
◦ FDA will enforce all predicate rule requirements, including predicate rule
record and recordkeeping requirements.
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11.
FDA's exercise of enforcement discretion as
described in this guidance is limited to specified
part 11 requirements
FDA intends to enforce all other provisions of
part 11 including, but not limited to, certain
controls for closed systems in § 11.10.
◦ For example, FDA intends to enforce provisions related
to the following controls and requirements:
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12. ◦ Limiting system access to authorized individuals
◦ Use of operational system checks
◦ Use of authority checks
◦ Use of device checks
◦ Determination that persons who develop, maintain,
or use electronic systems have the education,
training, and experience to perform their assigned
tasks
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13. ◦ Appropriate controls over systems documentation
◦ Controls
for
open
systems
corresponding
to
controls for closed systems bulleted above (§
11.30)
◦ Requirements related to electronic signatures
(e.g., §§ 11.50, 11.70, 11.100, 11.200, and 11.300)
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14. ◦ FDA intends to exercise enforcement discretion
regarding
specific
part
11
requirements
for
validation of computerized systems (§ 11.10(a) and
corresponding requirements in § 11.30).
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15. ◦ Take into account the impact the systems have on
ability to meet predicate rule requirements.
◦ Consider the impact those systems might have on
the accuracy, reliability, integrity, availability, and
authenticity of required records and signatures.
◦ Even if there is no predicate rule requirement to
validate a system, in some instances it may still be
important to validate the system.
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16. ◦ Base validation approach on
A justified and documented risk assessment
A determination of the potential of the system to affect
product quality and safety, and record integrity.
◦ Validation would not be important for a word
processor used only to generate SOPs.
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17.
Audit Trails
◦ Enforcement discretion related to computer-generated, timestamped audit trails (§ 11.10 (e), (k)(2) and any corresponding
requirement in §11.30).
◦ Also comply with all applicable predicate rule requirements
related to documentation
Date (e.g., § 58.130(e))
Time, or sequencing of events
Requirements for ensuring that changes to records do not obscure
previous entries
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18.
Audit Trails
◦ Have them even if there are no predicate rule
requirements
(for date, time, or sequence of events)
◦ Alternatively
have
other
physical,
logical,
or
procedural security measures in place.
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19.
Audit Trails
◦ Base your decision on
The need to comply with predicate rule requirements
A justified and documented risk assessment
A determination of the potential effect on product
quality and safety and record integrity
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20.
Audit Trails
◦ Apply appropriate controls based on such an
assessment.
◦ Audit trails appropriate when records are
Created
Modified
Deleted
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21.
Legacy Systems
◦ FDA to exercise enforcement discretion for systems
that otherwise were operational prior to August 20,
1997
◦ FDA not to take enforcement action if all the
following criteria are met for a specific system:
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22.
Legacy Systems …..contd
◦ The system was operational before the effective date.
◦ The system met all applicable predicate rule requirements before
the effective date.
◦ The
system
currently
meets
all
applicable
predicate
rule
requirements.
◦ You have documented evidence and justification that the system is
fit for its intended use (including having an acceptable level of
record security and integrity, if applicable).
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23.
Applies to all forms of computerised systems used as part of a
GMP regulated activities.
A computerised system is a set of software and hardware
components which together fulfil certain functionalities.
The application should be validated;
IT infrastructure should be qualified.
Where a computerised system replaces a manual operation, there
should be no resultant decrease in product quality, process
control or quality assurance.
There should be no increase in the overall risk of the process.
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24.
Validation
◦ Documentation and reports should
Cover life cycle.
Include change control
Deviations during validation process
◦ Justify
standards,
protocols,
acceptance
criteria, procedures and records based on their risk
assessment.
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25.
Validation
◦ List all relevant systems and their GMP functionality
◦ For critical systems prepare
System description
Physical and logical arrangements
Data flows
Interfaces with other systems or processes
Hardware and software pre-requisites
Security measures
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26.
Validation
◦ Prepare user requirements Specifications
Describe the required functions
Base it on documented risk assessment and GMP
impact
Make it traceable throughout the life-cycle
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27.
Validation
◦ Ensure that the system has been
developed in
accordance with Q M S
◦ Assess the supplier appropriately
◦ Ensure formal assessment and reporting of quality
& performance measures of bespoke or customised
computerised systems for life cycle.
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28.
Validation
◦ Demonstrate evidence of appropriate test methods
and test scenarios
System (process) parameter limits
Data limits
Error handling
◦ Document adequacy of Automated testing tools and
test environments.
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29.
Validation
◦ If data are transferred to another data format or
system, validation should include checks that data
are not altered in value and/or meaning during this
migration process.
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30. New Computer System
Existing Computer System
Def inesy stem
Function Structure
Def ine Sof tware
Def inesy stem
Function Structure
Design/Specif y
hardware
Qualif y Sy stem
Dev elop
Sof tware
I ns t all hardware
Rev iew operating
experience
Verif y Sof tware
Qualif y hardware
Test Indiv idual
Modules (Computer
Sy stem)
Data
Integrate
ComputerizedSy stem
Dataanaly sis
Test Integrated
modules
(Computerized
Sy stem)
Validation
Acceptance
Demonstratetotal
sy stem operation
(Computer-Related
Sy stem)
Ongoings y s t em ev aluat ion
Change
Conduct sy stem
testing (if needed)
F ileD oc um ent at ion
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31.
Users play a key validation role in:
Starting the process for new or existing systems
Performing some major steps (e.g. Requirements)
Writing and following operating procedure
Maintaining the validated state while in use
Developers play a key role in many steps including:
Design, coding, testing, changes, support
Support groups (IT, IR, SCS, Infrastructure):
Maintain proper network environment
Troubleshooting and maintenance
Desktop and infrastructure control
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32.
QA and Validation
Author some major documents
Approve major documents that others write
Provide advice, training, auditing
Senior management for each group decides:
Which systems to buy or build
How much resource to make available
What risks are acceptable
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35.
Have a combination of skill sets in the team
Include individuals who are experienced with
◦
Regulations
◦
Validation approaches
◦
Systems
◦
Processes
◦
Intended users
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36. The level of documentation required depends on
◦
Complexity and intended use of the system;
◦
Origin of the software/system (vendor supplied or
developed internally).
◦
Examples
of
documentation
required
to
support
validation:
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37.
Validation SOPs and Policies
Project Management Plan
Validation Plan
Traceability Analysis
Risk (Hazard) Management
System Topology and
Specification and Documents
Plan
Computerized System Design
Installation Summaries
Configuration Management
Plan
Validation Protocols / Test
Case Procedures
Change Management Plan
IQ/OQ/PQ Reports
System Test Plans
Validation Reports
Computer-Related System
Requirements Specification
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38. 1. PLAN
Validation Activities
4. DESIGN & REVIEW
5. CONSTRUCT & TEST
2. DEFINE
6. INTEGRATE/INSTALL
Requirements
7. QUALIFY
8. EVALUATE
3. SELECT
Computerized System
Vendors
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39.
Write and approve validation policies
Write specific SOPs for validation of Computer Systems
Develop protocols
Review test data
Write summary reports to assure the validation objectives are met
Use validation Project Plan to
Identify the systems to be included
Procedures to be followed
Timeline for a specific validation project
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40. Project resources and budget requirements
Validation Project Plan for
Single system,
Combination of systems
Entire facility.
Establish specific responsibilities
Establish expectations for each validation
activity
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41. Create a document of high level goals of validation
Specify
“what”
at
a
high
level
should
be
accomplished by the CSV
Review available documentation
Conduct interviews with users
Map existing processes
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42. Initial focus on
Functionality
Operational and performance parameters
Overall objectives for the validation effort
Specify the requirement in detail to support testing
that requirement and defining acceptance criteria.
Trace back protocols to each requirement
via a Traceability Matrix
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43. Requirements traceable to Functional Specifications
and testing
Unambiguous, clear, concise
Testable and measurable
Typically written and approved by end-user
Basis for system acceptance testing
Should be approved before the design review
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44. The highest level design document responding
directly to the User Requirements Specification
All system inputs, outputs, and interfaces
All functions and performance requirements
Error definition and handling
Ranges, limits, defaults
Safety considerations
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45. Internal development group or an outside company.
Consider vendor‟s ability to provide a system which can
be validated
Selection Criteria
Technical competency
Qualified to supply
Support for the proposed system
Knowledge of validation requirements
Experience in providing systems for cGMP applications
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46. Type of software being evaluated
Type hardware being evaluated
For off-the-shelf software and standard hardware
History of customer satisfaction is of importance
For custom developed systems
Vendor‟s Quality Assurance System
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47. Primary Responsibility
for Specification
Primary Responsibility
for Testing
Testing of the URS
More User involvement for custom
systems, less for packaged
Supplier
Functional
Specification
Performance
Qualification
Testing of the
Functional Specification
Design
Specification
Testing of the
Operation
Qualification
Installation
Qualification
Design Specification
Build System
Design
Specification
Unit Testing
Requirement Specification
System Testing
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User
More Supplier involvement for custom
systems, less for packaged
User Requirements
Specification
User
Supplier
48. Computerized System Design Specification
Document or a collection of documents
Describes clearly and completely
How the computerized system will Operate
Satisfy Computer-Related System Requirements
Specification
Both normal and abnormal operating conditions
Information about the interfaces between the
computerized system and its operating environment
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49. Applies to both the computer system and the controlled
function/process
joint responsibility of the vendor and user.
Interfaces between the computerized system and its
operating environment.
The Design Specification can not be developed until
the vendors and the specific hardware and software
have been selected.
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50. Defines how the system should meet the
requirements, including…
Architecture AND interfaces
All functions
Data processing and integrity
Security
Backup, archive, and restoration
disaster recovery
Data definition
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51. Activity performed to verify that all deliverables
from Requirements and Design Phases are
produced and…
are clear and concise
are complete, current, and traceable
electronic record and signatures addressed
are testable
show system fit for purpose
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52. Complete Design Review before starting
Perform in accordance with written Programming
Standards
Programming Standards should define appropriate
rules for writing source code (e.g. dead code,
structure, naming)
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53. The computerized system may be constructed by
developing custom software and hardware for the
application - or purchasing established products - or a
combination of both.
From a validation perspective, custom developed
software and hardware require the greatest amount of
testing since they have never been proven effective.
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54. Three categories of software can be defined:
System software
Configurable software
Application specific software
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55. GAMP Classification
No
GAMP 4
GAMP 5
1
Operating Systems
Infrastructure Software
2
Firmware
No longer used
3
Standard Software Packages
Non configured Products
4
Configurable Software
Packages
Configured Products
5
Custom (bespoke) Software
Custom Applications
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56. These categories are not intended to be rigid but
they allow distinctions to be made so that
validation approaches are appropriate.
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57. Efficient Environment
Defined processes
Assigned responsibilities
Planned audits
Structured reviews
Management controls
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58. Should be completed before formal testing
Verify code complies with Programming Standards
Check to ensure all pre-defined system
specifications are addressed
Check for coding errors
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59. „White Box‟ *
●
Unit Testing/Structural Testing
●
Low level
out
in
„Black Box‟ *
●
System & Acceptance testing
●
Functional Testing
●
Higher level
in
out
Manual Calculation
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60. Define and justify the how the system will be
tested and how much
Address how tests are traceable to specifications
Testing approach should address
Normal operation
Entire design range, boundaries, stress
Failure modes, including power failure
Should be approved before testing starts
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61. Lists the test objective
Traceable to specifications
Lists test pre-requisites
Reproducible test steps
Clear acceptance criteria
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62. Record all raw data and derived results
Ticks, „ok‟, „yes/no‟, „Pass/Fail‟ or similar are not valid
results
Record a „Pass/Fail‟ conclusion of whether results met
acceptance criteria
Signature and date of test performer
Signature and date of test result approver
References to incident log for failures
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63. Used to…
Collate test result documentation
Conclude each phase of testing
Authorise subsequent testing phases
Summarises the testing outcome, addresses test
failures
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64. Unit Testing
Focuses verification effort on the smallest unit of software
design – the software component or module
Integration Testing
“If they all work individually, why do you doubt that they‟ll work
when we put them together?”
The problem is “putting them together” – interfacing
Data may be lost
One module can have an inadvertent, adverse effect on
another; sub-function when combined
Global data structure can present problems
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65.
Regression Testing
Each time a new module is added as part of integration
testing, the software changes
New data flow paths are established
New I/O and control logic is invoked
Regression testing is the re-execution of some subset of tests
that have already been conducted to ensure that changes have
not propagated unintended side effects
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66.
Smoke testing
An integration testing
Software components that have been translated into code are
integrated into a “build” – data files, libraries, reusable modules,
and engineered components that are required to implement one
or more product
The intent of testing here is to uncover show stoppers – errors
that have the highest likelihood of throwing the software project
behind schedule
The build is integrated with other builds and the entire product is
smoke tested daily
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67.
Unit Testing
An encapsulated class is the focus of unit testing
Operations within the class are, however, the smallest unit
Integration Testing
Thread based testing
Integrates a set of classes required to respond to one input or event for the
system
Used based testing
Begins the construction of the system by testing independent classes – use
very few if any server classes
Testing dependent classes – which use independent classes
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68.
Integration Testing
Cluster Testing
A cluster of collaborating classes (determined by
examining the CRC) to uncover errors in
collaboration
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69. Proper integration, installation and commissioning
of a computerized system is essential to the
successful qualification of the system.
A packaged system may be integrated at the
vendors site
More complex systems may be integrated at the
users site
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70. Data Load
Operational and Support Plans (e.g.
SOP, training, service contracts, security, support
processes)
Specify procedures employed in the Validation Plan.
Specify responsibility for all tasks in the Validation Plan.
Demonstrate proper installation of hardware & software
in Installation Qualification (IQ)
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71. Qualification is a procedure of testing and collecting data
to provide a high level of assurance that a computerized
system operates in accordance with the system
specification.
Write & approve protocols in advance
Protocols should specify the following
Goals of testing
Test methods
Acceptance criteria
Who is responsible for testing
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72. IQ (Installation Qualification) verifies that all aspects of
installing hardware and software meet specifications
and that user manuals, SOP‟s and backup procedures
are in place.
OQ (Operational Qualification) verifies that the system
operates throughout its anticipated ranges according to
its specifications and identifies all important
parameters.
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73. PQ (Performance Qualification) verifies that a
system performs its intended function in
accordance with its specifications.
Testing is completed on the entire system while
operating in its normal environment.
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74. In order to assure that the system remains in a validated state,
Performance Monitoring is required to continually test a system‟s
performance in executing defined processes:
Periodic calibration and maintenance
Continuous monitoring of critical parameters
Confirmation of security measures
Provisions for contingency planning, disaster recovery and personnel
training
Change Control procedures must be established to keep a CRS in
a validated state during planned and unplanned changes.
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75. Summary: Validation requirements for Software
Programme
overrides
Edits,
input
manipulation
Language
Name,
function
Software
identification
Fixed and
Variable
Set points
Input,
output
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76. Summary: Validation requirements for Software
Key aspects
Software
development
Software
security
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77. Summary: Validation requirements for Software
Function
Worst case
Documentation
Validation
Revalidation
Repeats
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78.
This presentation was compiled from freely
available resources like the websites of FDA,
EMA, WHO.
“Drug Regulations” is a non profit
organization which provides free online
resource to the Pharmaceutical Professional.
Visit http://www.drugregulations.org for
latest information from the world of
Pharmaceuticals.
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