Change Control

Dr . K. VENKATESWARA RAJU & Mr. K. T. SUNIL KUMAR

Change control
Change control is a systematic approach managing all
changes made to a product or system.

Purpose:
The purpose is to ensure that no unnecessary changes are
made, that all changes are documented, that services are
not unnecessarily disrupted and that resources are used
efficiently.
 Change control
When a change occurs in any aspect of the materials, equipment
and procedures whether as a planned or unplanned change, the
effect of that change on the process must be properly assessed.

Change control is a formal procedure to (1) ensure through

appropriate evaluation that any changes made will not adversely
affect the quality or validation status of the materials, equipment
or procedures (2) that the change is properly documented and (3)
is made with regard to regulatory compliance’.
PROCEDURE OF CHANGE CONTROL
Documenting the Final assessment
change request

Formal assessment Implementation and

review

Planning Designing and testing

Change control programs
 The example is one way to rate them:
NOT REQUIRING MINOR CHANGE MAJOR CHANGE
CONTROL
No relevance to GMP or Influences a unit requiring Influences product quality or Significance of
authorization control process reliability change
No relevance to GMP or Amendment
 Official license
 Possible
authorization measures
Review
 New approval

(selection)
documentation
 revalidation


Change to working Replacement of apparatus Change of manufacturer: other Examples

times part of the same design synthesis route of a starting
material (other impurities)
Installation of air Change of cleaning agent for
conditioner in floors Removal of processes to
administrative area another site
Change of laundry for work
Change in purchase clothes (non-sterile or Change in the product
procedure antibiotics area) composition
Change to the process
parameters
CASE STUDY
To propose and implement change in the temperature and humidity of the
air in the Fluidized Bed Dryer for Atorvastatin calcium tablets.

1. Documenting the change request:

 When change is required, that request is categorized and recorded,
along with informal assessments of the importance of that change and
the difficulty of implementing it.
IN CASE OF FBD

 The change is categorised into minor as it doesn’t effect the quality of the
final product.
 It is important to implement the change as they effect on the tablet punching
and product stability.
2. Formal assessment:

 The justification for the change and risks and benefits of making/not
making the change are evaluated. If the change request is accepted, a
development team will be assigned. If the change request is rejected,
that fact is documented and communicated to the client.
 IN
CASE OF FBD
 Higher temperature assures high evaporation rate and high drying time.
 Due to the presence of high moisture content of particles, the
evaporation rate decreases.
 Therefore, higher temperature, lower relative humidity are favorable
for drying.
3. Planning:

 The team responsible for the change creates a detailed plan

for its design and implementation, as well as a plan for
rolling back the change should it be deemed unsuccessful.
 IN CASE OF FBD
 The change request is accepted and a development team is
assigned.
 The team created a detailed plan for its design and
implementation, as well as a plan for rolling back the change if
it deemed unsuccessful.
4.Designing and testing:

 The team designs the program for the change and tests it. If the
change is deemed successful, the team requests approval and a
date for implementation.
 IN CASE OF FBD
 The program for implementation of change i.e., increase in
temperature and lower humidity rate is designed and tested for its
conformance.
 The test result shows that the change is successful.
 We requested the approval for implementing the change and the date
for implementation.
5. Implementation and review:

The team implements the program and stakeholders review the change.
IN CASE OF FBD
The increase in temperature and lowering relative humidity is implemented and the
change is reviewed by the stakeholders.

6. Final assessment:
If it is satisfied that the change was implemented satisfactorily, the change request is
closed. If the it is not satisfied, the project is reassessed and steps may be repeated.
IN CASE OF FBD
The change was implemented satisfactorily.
Hence, the change request is closed.
 Other
classifications
are possible
Documentation
 Change control procedure: flow chart (example 2)
Change Request
More
Submission
information
required
Evaluation of
Change Impact

Change Activities Validation

Change Request

Change Activities

Approval Approval

Activities Activities
Completion Completion

Change Closed
 Documentation
Change control logbook (year:________) ____ Page:__ of
Closing Actions and Approval Description Item Requester / Request Nb.
date time limit date department date

_______QA Manager signature _________ Date

Examples of changes
 Changes to the cleaning procedure
 use of a new cleaning agent
 change in concentration / volumes of cleaning agent
 change in volumes of rinsing water
 change of cleaning process parameters
 Changes to the production equipment
 changes to the CIP equipment
 changes to / replacement of equipment parts (difficult to give
detailed examples as these changes are too diverse)
 change of process parameters
Examples of changes
 Changes to the product
 changes to composition (reformulation with different excipients)
 changes to the manufacturing process (i.e. transfer of a product)
 Changes to HVAC system / unidirectional flow
 Changes in lay-out (i.e. implementation of a pass-box)
 Technical Changes
Site of manufacture
Raw material source/grade
Facility
Equipment
Process
Formulation
Test Methods, specifications…
Critical systems e.g... utilities
 Raw Material Changes
New Manufacturer
Manufacturer Site
Manufacturer Name (e.g. due to merger)
Specifications
Test methods
Storage pack & conditions
Dispensing
 Process Changes
Batch Size
Temperature
Cooling/Heating rate
Speed Agitation/Homogenisation
Filtration
Process Change API (Particle size, Specific Surface Area, Morphology)
 Non Technical Changes
• Packaging artwork
• Information systems, e.g. MRP
• Shipping specification
The Change Control System Purpose
• Ensure that change does not adversely impact product quality
• Maintain validated state
• Maintain regulatory compliance
• Ensure proper communication of change
• May also include other considerations e.g. safety

Formal system to evaluate changes that may affect

- product quality
- customer satisfaction
- regulatory compliance
Change Control Considerations

• Significance of change
• Potential effect on product quality
• Potential effect on compliance with Manufacturing Authorization
• Need to inform users/customers
• Need to revalidate process
• Also cost benefit, health & safety, technical desirability
Regulatory Requirements
EU - Regulations 1084/2003 and 1085/2003
- Changes classed as Type IA/1B or Type II
- data requirements specified

FDA - SUPAC-IR
- Level 1, 2 or 3 change
- data requirements specified
Note: If internal requirements are more stringent than
regulatory, these should be used
Benefits
• Maintain validation status
• cGMP/Regulatory status
• Greater understanding of process
• Quality unit input
• Embed compliance into operations
• Plan before you start
Principles of change control

In the American
Code of Federal
In the EU
Regulation CFR, the
regulations, the
responsibility for the
responsibility is
verification and
assigned to Quality
authorization of
Unit
changes is task of the
quality control unit

As the change control is considered an

essential element of the pharmaceutical
quality assurance system, it is logical the
person responsible is quality assurance (QA
representative, QA head)
Principles of change control

Change control is not department-specific, rather the

task of the whole company

The change control monitors all types of changes

which can influence the process or product quality and
states the measures necessary for implementing the
change or decides that a change should not be
implemented
Change control programs
 When a change control program has been introduced, the
effectiveness of the system can be reviewed using data
which is easy to determine
 Total number of changes request /year
 Number of completed change requests / year
 Change type / department involved
 Duration of procedure: from application to closing
 Number of deviations/year
 Number of internal or external complaints /year
 Number of OOS /year
Thank you