2. Contents
• Definition
• Change in specification and method of analysis
• Scope
• Other product specific changes
• General changes
• Change control procedure-Flow chart
• Classification of change control
• Types of Change control
• Evaluation & Action Plan
• Parameters to be considered for impact and risk assessment for change control evaluation
• Approval
• Closing of Change control
• Trending of change controls
• Determination of Notification to the Agency
• Reference Guideline
3. Definition
• Change – Any addition to, deletion of, or modification to any approved /
authorized procedures, process, materials or product is defined as a change.
• A formal system to evaluate, document, approve and implement changes that
might affect the validated status of facilities, equipment and process.
• A change is a permanent planned alteration to any approved process or
procedure that may affect the safety, quality and efficacy of blood component.
• CCF is a process that ensure changes to material, method, equipment, process,
facility are properly documented, validated, approved & traceable.
4. Scope
• Master Documents
• Specifications
• Test Procedure
• Master Formula
• Manufacturing Process
• Facility, Equipment, Area
• Other Documents
• Software, PLC, Instruments, Server
• SAP, ERP
• Planned Deviation (Temporary Changes)
• SOPs
5. Change in specification and method of analysis:
Revision of specification limits
Change in analytical procedure
Pharmacopoeial changes
Tightening or relaxation in manufacturing specification
Addition or deletion of test
Change in document template
Inclusion of additional instruction/ simplification or editorial changes without changing actual method of
analysis and specification limit
Other product specific changes
New-product introduction
Change in vendor of product specific starting materials
Change in starting material manufacturing process
Change in customer of product
Change in storage condition based on destination market
Change in master formula records
Addition or deletion of stability study condition
Extension or reduction of product shelf life
6. 2. General changes:
Change on Standard Operating Procedure (SOP)
Facility change
Equipment change
Modification of equipment
Upgrade equipment or system software
Permanent change in working shift timing
Change in layouts and drawings
Modification of facility
Heating Ventilation and Air Conditioning (HVAC) system modification
Revision of documents, such as, Site Master File, Validation Master Plan, Quality
Manual, Protocols, or any other GMP documents
8. Classification of change control
• Major : A change that would be likely to have a significant impact on quality
attributes of a process, material, product, procedure, and registration
requirements.
• Major changes are those changes that have a direct impact or potential impact
on the product quality, safety, strength, identity, efficacy, and purity of a
product, validation status of the process, equipment, utility, facility or GMP
compliance, procedures, systems or regulatory filings.
• Minor : Minor changes are those changes that do not have a direct impact
or potential to have a direct impact on the product quality, identity, safety,
strength, purity, and efficacy of a product or validation status of the
process, equipment, utility, facility or GMP compliance/ procedures, and
systems or regulatory filings.
9. Table: 1 – Classification of change control
Major changes Minor changes
Changes do not require
change control
Modification of manufacturing
facility
Introduction of new product
Change in batch size
Change in manufacturing
equipment
Change in specification of
product or product component
Change in HVAC design
Modification of equipment or
change in critical component of
equipment e.g. change in motor or
Rapid Mixture Granulator,
modification of RABS in the
aseptic area
Change in document template
Periodic review of Standard
Operating Procedure or any other
documents
Adding additional instruction in
the batch record or analytical
method without changing core
process
Modification of lifting device
Change of laundry for work in
non-sterile and non-potent drug
manufacturing facility
Facility modification outside
manufacturing area, e.g.
modification of office area
furniture, pipeline modification in
garden, modification of road
surrounding the building
Replacement of change part of
equipment (like to like)
Replacement of HVAC motor
with similar capacity
Installation of air conditioning
system in staff room
10. Types of Change control
1. Permanent changes:
Permanent changes mean the changes that remain in effect till the next required
revision or modifications.
2. Temporary change controls:
A change that is implemented for a specific predetermined period. Temporary change
controls are also called planned deviation by some of the organizations.
Evaluation & Action Plan
Evaluation of impacted areas done by respective departments.
Evaluation of impacted documents.
Identify action plan related to impacted areas.
11. Table: 2 – Parameters to be considered for impact and risk assessment for change control
evaluation
Sr. no Impact of change to be evaluated for Sub sections
1 Facility approvals
Site approval status
Approvals for additions of facility or expansions
Layout approvals
Any other legal approvals
2 Buildings and facilities
Facility concept design
Building design approval
Validation master plan for the facility
Direct impacting utility requirements and design
Layout design for material movements, AHU distribution, pressure zoning,
classification layouts, HVAC ducting layouts
Service area design
Environment/ classification requirement
Rodent and pest control design
Drainage layouts
Facility blue print
Facility qualification
12. 3 Equipment/ instrument
Identification of equipment/ instrument
Requirement of vendor support for list of activities
User Requirement Specification (URS)
Design Qualification (DQ)
Factory Acceptance Test (FAT)
Site Acceptance Test (SAT)
Installation Qualification (IQ)
Operation Qualification (OQ)
Performance Qualification (PQ)
Preventive maintenance program and schedule
Calibration of instrument and schedule
Equipment list
List of spare parts
Supporting utility requirement
Annual Maintenance Contract
Re-qualification/ re-validation program
Passivation of equipment
Data backup
User rights
Discontinuation of equipment
Data archival
Process validation
Cleaning validation
13. 4
Components and drug product
containers and closures
Vendor approval
Supplier approval
Specification
Method of analysis
Legal requirement of storage
Facility for material receipt, handling and storage
Toxicological assessment
Safety assessment
Technology transfer
New artwork
Process validation
Packing validation
Material code generation
Working standard
Reference standard
New instrument for analysis
Contract testing laboratory requirement
14. 5 Production and process controls
Master formula record
Batch manufacturing record
Process validation
Cleaning validation
Manufacturing area and facility
Utility requirements
Gowning requirements
Dedicated facility
Dedicated equipment
Sampling tools
Regulatory submission
Stability studies
Hold time studies
Annual product quality review
Continuous process verification
6 Packaging and labeling control
Batch packing record
Artwork approvals
Packing validation
Track and trace
Temper evident
Equipment and facility
Product price tag
Serial number generation requirement
Label approval
Change part validation
Packing configuration trails
15. 7 Holding and distribution
Storage facility
Data logger placement requirement
Transportation requirement
Transport validation
8 Laboratory controls
Specification
Method of analysis
Method validation
Method transfer
Method verification
Contract laboratory
Stability studies
Worksheets
Working standard
Reference standards
Primary standards
Instrument requirement
Instrument capability
16. 9 Records and reports
Standard operating procedure
Master lists
Batch manufacturing record
Batch packing record
Site master file
Validation master plan
Training
Documents to be made obsolete
Bill of material
Formats
Logbooks
Protocols
10 Electronic system
Use requirement specification
High level risk assessment/ preliminary risk assessment
Validation plan
Vendor assessment
Design specification
Functional specification
Risk assessment
Installation qualification
Operation and performance qualification
Traceability matrix
Validation summary report
Application of system policies and restrictions at OS level
Antivirus requirement
Allocation of user rights
Backup policies
17. 11 Aseptic processing
Media fill
Environmental monitoring
Media fill matrix
Media fill protocol
Media fill batch record
Visual inspection qualification
Approval
Evaluation & action plan of impacted verification by QA.
Change control approval by QA Head.
After approval of change control submit to QA.
18. Trending of change controls
Trending of changes in the facility is very important to monitor and control the changes. Changes
which were rejected, cancelled, major changes, open changes etc. are required to be closely
monitored and trended. During regulatory inspections, primary focus are major changes, facility
related changes, rejected changes etc.
Closing of Change control
Implementation of identified action plan within TCD.
Submit all implemented documents to QA for verification.
Close the change control by QA Head.
19. Determination of Notification to the Agency
PAS:
• A change in a regulatory analytical procedure that does not provide the same or increased assurance
of the identity, strength, quality, purity, or potency of the material being tested as the regulatory
analytical procedure described in the approved application.
CBE-30:
• Any change in a regulatory analytical procedure other than those identified as major changes or
editorial changes.
CBE-0:
• A change in an analytical procedure used for testing components, packaging components, the final
intermediate, in-process materials after the final intermediate, or starting materials introduced after
the final intermediate that provides the same or increased assurance of the identity, strength, quality,
purity, or potency of the material being tested as the analytical procedure described in the approved
application.
Annual Report:
• For drug substance and drug product, the addition or revision of an alternative analytical procedure
that provides the same or increased assurance of the identity, strength, quality, purity, or potency of
the material being tested as the analytical procedure described in the approved application or deletion
of an alternative analytical procedure.
20.
21. Reference Guideline
• ICH 10 PHARMACEUTICAL QUALITY SYSTEM
• Eudralex Volume-4, annexure-15
• 21 CFR, 211.100 (Production & process control)
• 21 CFR, 211.160 (specifications, standards, sampling plans, test procedures,
or other laboratory control)
• PICS: PI 002-3
• APIC-Guideline Technical Change Control revised Nov 2018