Qualification and Validation have big Weightage in the Regulatory Compliance and GMP. Qualification and Validation only can guarantee about the Product Safety, Integrity, Strength, Purity and Quality assurance.

1. Hardik Mistry
Quality Assurance
Date : 12/06/2019

2. o What is Qualification & Validation ?
o Benefits of the Qualification and Validation.
o V Model approach
o Types of Validation
o Life Cycle of the Equipment
o Definitions
o Procedure for Qualification & Validation
o Q & A
Index

3. Why Qualification/Validation ?

4. Cont…
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WHO : Normally Qualification Should be completed before process Validation is performed

5. Benefits of Qualification/Validations
o Make process better understood
o Reduce the risk of problems
o Assure the smooth running of the processes
o Control of the product quality
o Reduce the variation of outcome
o Reduce the defect and Maintenance cost
o Easy Maintenance and safety
o To improve the overall production reliability and availability
o Reduce the chances of failure and product recall
o Result in reduced time to market for new products
o It saves the noncompliance of the regulatory audits.

6. The act of planning, carrying out and recording the
results of tests on equipment/system/utility/facility to
confirm its capabilities and to demonstrate that it will
Design, Install, operate and perform as intended is
referred to as Qualification.
Qualification

7. Documented evidence that provides a high degree of
assurance that a specific
equipment/utility/facility/system/process will
consistently produce a result of a certain predetermined
quality as intended.
Validation

8. Relationship Between Validation and Qualification
In general qualification and Validation follow similar underlying
principles. The term “Qualification” is normally for new
equipment and utilities and “Validation” for system, method and
process.
Qualification normally precedes Validation

9. USER REQUIREMENT SPECIFICATION
(URS)
PERFORMANCE QUALIFICATION (PQ)
FUNCTIONAL SPECIFICATION (FS) OPERATIONAL QUALIFICATION (OQ)VERFIFICATION
VERFIFICATION
DESIGN SPECIFICATION (DS) INSTALLATION QUALIFICATION (IQ)VERFIFICATION
SYSTEM CONSTRUCTION
DQ FAT
Life cycle development “V” Model approach

10. Prospective Validation
1. Prospective validation is performed for all new equipments, products, and
processes.
2. It is a proactive approach of documenting the design, specifications and
performance before the system is operational.
3. Prospective validation is carried out during development stage to identify
those individual steps and equipment settings or process timing, which
can prove to be critical in the overall impact of product quality.
4. All these steps, equipment setting and process timing are evaluated to
finalize the setting parameter, which can form the basis of giving
acceptable, reproducible results.

11. Concurrent Validation
1. Validation carried out during routine production intended for sale.
2. This validation comprises of determination and evaluation of process
parameters applicable from scale up to final batch size of the product.
This should be performed on 3 process batches.
3. The tests are finalized based on evaluation of the results of these batches.
4. These batches should be monitored for stability and quality trends.
Matrix approach can be applied to process validation.
5. The matrix approach means a plan to conduct process validation on
different strength of same product manufactured by the same process and
similar type of equipment.
6. This approach should be in accordance with cGMP and should
demonstrate that the process is consistent for all the strength.

12. Retrospective Validation
1. This is establishing documented evidence that the process has performed
satisfactorily and consistently over time based on review and analysis of historical
data. The source of such data is Production, QA and QC records.
2. Retrospective validation is historical trending of results of testing and IPQC
evaluation on products manufactured by same process to demonstrate that
3. Critical quality attitudes and critical process parameters are still valid as they
give consistent results.
4. IPQC and in process controls are appropriate for the given product.
5. Majority of the batches should meet the processing steps, equipment process
timings, manufacturing environment and demonstrate consistency to
specifications.
6. All results except “OOS’ results proven to be caused by analyst/operator error,
should be included in the study.
7. Minimum 10 batches should be included in the study. Any gaps in the
chronological order of the batches used for the study should be documented and
explained.

13. VMP
A summary document that describes overall philosophy, approaches, and
objectives to all aspects of validation. The document defines responsibilities and
expectations for the various components of the validation exercise.
Regulatory Requirement

14. Sr. No. Title Page No.
NA Title page
1 VMP approval sheet
2 Table of Content
3 Purpose of VMP 4
4 Scope of VMP 5
5 Types of products manufactured at the Plant. 6
6 Roles and Responsibility 7
7 Definitions 8
8 Validation/Qualification Approach 10
9 Validation Policy 15
10 Description of the Plant 16
11 Equipment Validation 17
11.1 List of all equipment with validation schedule attached as Annexure - I.
11.2 Manufacturing Processes Validation
11.3 System Validation
11.4 Analytical Test Method Validation
11.5 PLC/SCADA/Software qualification/validation
11.6 Vendor or Supplier qualification
11.7 Personnel qualification
11.8 Shipping Validation
Content of VMP

15. Sr. No. Title Page No.
12 Acceptance Criteria 19
13 Frequency 20
14 Validation Protocols 21
15 Validation Report 22
16 Calibrations 23
17 Preventive Maintenance 24
18 Modification of Equipment, Utilities and Buildings 25
19 Standard Operating Procedures 26
20 Training 27
21 Document Management 28
22 Document Control 29
23 Document Identification 30
23 Deviations 31
25 Re – validation 32
26 Periodic Review 33
27 Abbreviations 34
28 References 35
29 Annexures 36
30 Revision History of VMP 37
Content of VMP

16. Responsibilities
1. The primary responsibility of qualification/validation activity lies with the
department section to which the equipment/ process belongs.
2. This overall exercise is coordinated by a validation team, comprised of
qualified internal personal and external consultants as required for the
specific validation activities, preparation of documents and coordination
of the approval processes, establish the extent of the verification and tests
to be included in the validation program and evaluate the progress of the
program, review the collected data and prepare the final summary.

17.  Respective
Department
head/Designee
(Production, QC,
Engineering, QA)
 Preparing validation protocols, reports, change control
documents and validation SOPs.
 Allocate suitably trained personnel to perform activities
during validation.
 Provide technical advice to support the preparation and
execution of validation protocols.
 Participate in the resolution of non-conformances.
 Implement corrective actions arising from validation exercises
 Head
QA/Designee
 Review and approve the Validation Master Plan, validation
protocols, task reports, protocol deviations, change control
documents and SOPs for
 Consistency with cGMPs, Company policies and procedures.
 Participate in and approve the resolution of non-
conformances.
 Ensure all GMP critical equipment and processes are
validated maintain this Validation Master Plan.

18. Definitions
Validation Master Plan
A summary document prepared as part of project planning that describes overall
philosophy, approaches, and objectives to all aspects of validation. The document
defines responsibilities and expectations for the various components of the validation
exercise.
Equipment
Equipment is the apparatus needed for manufacturing, processing, packaging,
holding, or supports of products.
Utility
Supportive services including the generation and distribution of the services as well as
services within a building to the point of use, which Includes, but not limited to steam,
compressed air, types of water, process cooling, nitrogen.

19. Qualification
The action of proving and documenting that equipment, utility or facility are properly
installed, work correctly and actually lead to the expected results.
GMP equipment
Equipment, which is used in manufacturing, processing, packaging, holding, or
supports of products. GMP equipments are classified as critical equipment and non
critical equipment.
Facility
The built environment within which the clean area installation and associated
controlled environments operate together with their supporting Infrastructure.
GMP utility
A utility which has the potential to impact the SISPQ (Safety, Integrity, Strength, Purity
& Quality) during the manufacturing, processing, packaging, testing or holding of a
drug product.

20. Critical equipment
Critical equipment is that equipment needed for processing, packaging, holding, or
supports of products and those unit operations that have the potential to impact
critical process parameters and quality of the product.
Non critical equipment
Non critical equipment is that equipment needed for processing, packaging, holding,
or supports of products but those unit operations that do not have the potential to
impact critical process parameters and quality of the product.
User Requirement Specification
Documented requirement of the equipment, utility and facility for its intended purpose.
Functional design and specification according to cGMP and regulatory requirements.

21. Design Qualification
Documented verification that the proposed design of the equipment, utility and facility
is suitable for the intended purpose.
Factory Acceptance Test
Documented verification that the equipment or system meets design specification and
conforms to agreed performance intent at manufacturer site before dispatch of the
machine.
Site Acceptance Test
Documented Verification that the receipt of the item at site confirms with the standards
laid down in the packing material List, FAT, purchase order and manufacturer
specification.
A SAT is Site Acceptance Test where /equipment/instrument/ system is tested in
accordance to client approved test plans and specifications to show the system is to be
installed properly and interfaces with other systems and peripherals in its working
environment.

22. Installation Qualification
Documented verification that the equipment, utility and facility as installed or
modified, comply with the approved design, the manufacturer’s recommendations and
user requirement.
Operational Qualification
Documented verification that the equipment, utility and facility operate as intended
throughout the anticipated operating ranges.
Performance Qualification
Documented verification that the equipment, utility and facility is performing
effectively and reproducibly based on approved method and specifications.

23. Facility (Area) Qualification
Documented verification that the area is constructed and commissioned to meet the
predefined specification.
Preventive Maintenance Program
A comprehensive plan for preventive maintenance which is taken prior to equipment,
utility failure to maintain a piece of equipment / utility within design operating
conditions and extend its life.
Major Breakdown
Where equipment is repaired to bring it back to its original working condition. This may
include modification/replacement of important component of equipment/utility/facility
which might have potential impact on qualification status of equipment/utility/facility.

24. Requirement of Qualification
 Whether or not specific equipment, systems, require qualification depends
on its application. Qualification is performed for new
equipment/utility/facility.
 After major breakdown in equipment/facility/utility,
 After Modification in equipment/facility/utility,
 For change /extension of qualification range
 Periodic requalification.

25. The sequence of events
Protocol Schedule
Coordination &
Training
Execution
Review of
Collection of Data
Review and Approval
of Deviation
Compilation of Report
Preparation of
Qualification
Summary
Approval of the
Executed report
Updation of the
Status Label and
Schedule

26.  Based on their impact on the SISPQ (Safety, Integrity, Strength, Purity &
Quality).
 Critical and Non-critical equipment
 If it has direct impact on SISPQ then its critical and if it has no impact or not
direct impact then Non critical.
 Frequency of the Critical equipment defined based on their usage, Risk
Assessment or as per any regulatory recommendations.
GMP Equipment Classification

27. GMP Equipment Non GMP Equipment
Equipment
Critical Equipment Major Equipment Minor Equipment
Risk Assessment
Equipment Master List
Validation Schedule
Calibration Schedule
Preventive Maintenance
Schedule
FAT
DQ
URS
Periodic Validation
SAT
Life cycle for Equipment
Case by Case basis

28.  GMP Equipment : Equipment/Utility/Facility/ System related to the any
aspect of the Manufacturing, Testing or Distribution.
 For all the critical equipments all qualification documents including the URS,
DQ, FAT, SAT, IQ, OQ and PQ are required.
 For the noncritical Equipment, System or Utility Qualification documents are
not mandatory but only commissioning or installation reports are to be taken
as record.
 For periodic validation of critical equipment/utility, operational and/or
performance qualification shall be done as per predefined procedure
mentioned in the protocol.

29. Sr.No Parameter/Operation/Function Rating Remark
1
Is the equipment/system directly/indirectly or not impacting the products
Safety, Integrity, Strength, Purity and quality?
2
Is the equipment/system, producing gas/liquid that may come in contact with
the product directly/indirectly or not producing?
3
Would malfunction of the equipment/system directly/indirectly or not
impacting the product quality?
4
Will the equipment/system create data (electronic) that will become part of a
CGMP record or be recorded on cGMP document or the entered as cGMP data
into a computer system?
5
Does the equipment/system contain measuring/controlling deices that
measure or control critical process/steps parameters?
If yes is the measuring/controlling devices contacts the product has
direct/indirect/ No impact on product quality during operation or control and
provides an alarm for a condition that has a direct effect on product quality.
6 Are the equipment part is direct contact with the product?
If question in Sr. No 1 to 6 having rating ≥12 then categorize the equipment/system as direct impact”.
If the questions in Sr.No 1 to 6 having rating >6 and <12 then categorize the equipment/system as “Indirect Impact”.
If the questions in Sr.No 1 to 6 having rating ≤ 6 then categorize the equipment/system as “No Impact”.
Rating Impact
1 No Impact
2 Minor Impact
3 Moderate Impact
4 Serious Impact
5 Hazardous Impact

30.  URS, DQ, FAT, SAT shall be performed for the equipment which are
customized.
 Some equipment (e.g. readily available) shall be qualified only for its
installation/ operation or performance depending on the usage, function and
operation.
 For other equipments (which are available with standard specification)
technical specification data can be collected from manufacture.
 For non-critical and on the shelf (Non customized) equipment IQ, OQ, PQ
shall be done as per predefined procedure mentioned in the protocol. URS,
DQ, FAT, SAT documents may be prepared on need basis.
 For periodic validation of critical equipment/utility, operational and/or
performance qualification shall be done as per predefined procedure
mentioned in the protocol.

31.  Validation Schedule shall be maintained on yearly basis. Yearly schedule
shall be prepared and approved at start of every new year.
 If the qualification documents (FAT/IQ/OQ/PQ) provided by the
manufacturer /supplier then based on URS and DQ/Manufacturer
specification all qualification documents shall be reviewed by user
department, engineering department, QA and finally approved for
qualification purpose.

32. Should be include following but not limited to:
 URS Approval sheet
 Table of Content
 Purpose and Scope of the URS
 Document History
 Description and Overview
 User requirements
 Functional Specifications
 Operational Specifications
 Design Specifications
 Electrical specifications
 Hardware specifications
 Software specifications : HMI/MMI/PLC/SCADA
 Specific Requirements
 Documentation Requirement
 Scope of work (supplier)
 Design shall be submitted to user for review & approval.
User Requirement Specifications

33. Design Qualification
May contain the following type of information but not limited to:
 Equipment drawings and details
 Equipment technical specification .
 Construction materials and details
 Utility requirements
 Operational specifications
 Emergency power or UPS requirements
 Computer, Programmable logic control features
 Communications with other equipment / systems
 Interlocks details
 Recommended spare parts lists
 Electrical drawing.
 Pneumatic & Instrument drawing
 Operating and Maintenance manuals
 Controls descriptions
 Programmable logic controller (PLC) programs
 Compliance details with reference to 21 CFR Part – 11.

34. Minimum Acceptance Criteria
 The items of equipment and systems shall comply with:
 URS/DQ and purchase specification
 Design drawings
 Engineering diagrams (Where it is applicable)
 Safety rules (Where it is applicable)
 Trial run (wherever is applicable)
 Software requirements to meet 21 CFR part 11
Factory Acceptance Test
Limited Tests are included in FAT

35. Minimum Acceptance Criteria
 Major component verification as per FAT report and specifications
 Packing material list
 Physical condition of major component or machine.
 Manufacturer's machine identification code/ Identification No.
 It shall be checked that following documentation is provided:
 User manual
 Maintenance manual
 Electrical schematics
 Process and utility diagram
 Spare part list
 Qualification documents (if provided by supplier/manufacturer)
Site Acceptance Test

36. Minimum Acceptance Criteria :
 Each examined component (equipment, instruments and materials) meets:
 Brand, type or model, range & accuracy
 The items of the equipment and systems shall comply with the IQ Protocol
 Delivered undamaged and as specified.
 Safety provisions (guards, disconnects, fire alarms, smoke detectors, grounding,
explosion protection, etc.)
 Installed correctly according to drawings and specifications and verified.
 Calibrated and supported with documentation of the calibration.
 The following documents shall be a requirement of the IQ:
 User manual
 Maintenance manual
 Electrical schematics
 Process and utility diagram
Installation Qualification

37.  Installation order of components
 Utility connections
 Electrical connections
 Spare part list
 Change part list
 List of lubricants
 Installation layout drawings
 Technical documentation for the components needed for operation and
maintenance
 Documentation to support specified quality of parts (e.g., Materials of
construction.)

38. Minimum Acceptance Criteria
 Each components / functions should meet following :
 Must be in calibrated state prior to start OQ
 Operate as described in Operations Manual
 Operate as described in draft Standard Operating Procedures
 Operate throughout all intended and worst case operating ranges
 Operate reliably
 Meet all parameters (such as, flow rates, temperatures, speeds, control
sequences)
 All the challenges shall meet acceptance criteria
 Safety operation should be checked.
 Challenge study for power outage should be performed for critical process
equipments.
Operational Qualification

39. Minimum Acceptance Criteria
 Each examined equipment, system or process shall : Perform reproducibly
according integrated systems and its intended use Meet all ranges,
microbiological, chemical, or physical limits, where as applicable.
 Performance Qualification Should be designed based on Risk assessment
and Worst case approach.
Performance Qualification
Three Runs
First Run : By Chance
Second Run : Accidently
Third Run : Consistently

40. • Acceptance criteria are the fundamental component of each respective validation
or qualification protocol. Each protocol must include acceptance criteria by
which the success or failure of the exercise can be assessed.
• The following guidelines should be implemented when determining acceptance
criteria:
 They must be measurable by means of observation, a traceable reference
standard instrument or test method.
 They should demonstrate an appropriate level of reliability and accuracy.
 They should, where possible and appropriate, be derived from user and/or
vendor defined requirements and specifications.
 They should, where possible, be derived from industry recognized specifications.
 They must be clearly defined, unambiguous and readily assessable on
completion of testing.
Acceptance Criteria

41. • Routine revalidation is the scheduled re-testing and certifying of
equipment, products, procedures or methods as required by assessment.
• Company performs routine validation as per frequency mentioned in
respective protocol.
Frequency of the Critical equipment defined based on their usage,
Risk Assessment or as per any regulatory recommendations.
Frequency

42. • Protocols will be drafted and approved prior to execution.
• As a minimum the protocols should include the following significant
background information:
– objectives
– site
– responsible personnel Very Important
– description of SOPs to be followed
– equipment to be used; standards and criteria for the relevant products and
processes
– type of validation
– processes and/or parameters
– sampling, testing and monitoring requirements
– predetermined acceptance criteria for drawing conclusions
• Protocol deviations will be documented within each protocol and reviewed and
approved by the responsible individual and QA. Task reports shall be prepared
to summarize the objectives and results of each qualification phase.
Validation Protocols

43. • As a minimum the report should include the following significant
background information:
– Title
– Objective
– Reference to the protocol
– Responsible person
– details of material, equipment
– procedures and test methods
– results
– Deviations
– Summary and Conclusion
– Approval
Validation Report

44. For the new equipment or system, operating parameters are challenged during
the operational qualification and same are to be build in standard operating
procedure of the respective equipment.
After the completion of the performance qualification, load pattern, approved
or revised parameters shall be built in Standard Operating Procedure.
Standard Operating Procedures
All the Challenged and qualified parameters are to be built in SOP

45. All personnel involved in the performance of qualification and validation
activities must be trained in the tasks they will perform.
Personnel responsible for the maintenance or operation of equipment to be
qualified must be trained and qualified prior to executing the qualification
studies.
After the Qualification and Validation, all the concerned persons must be
trained for the qualified and validated
equipments/utility/facility/system/process.
Training

46. • WHO GMP validation Part -2,validation
• EU GMP Annexure 15 - Qualification and validation
• Guideline for Process Validation : General Principles & Practices
References