2. Table of content
1. Definitions ( Change and Change Control) 3
2. Tasks of Change Control 4
3. Principles of Change Control 5
4. Regulatory requirements 6
5. Elements of Change Control 7
6. Steps of Change Control 8
7. Classification of Change Control with example 9-10
8. Motives for Change Control 11
9. Documentation 12-13
10. Challenges of Change Control 14-16
11. Examples of Changes 17-18
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3. CHANGE CONTROL
• Change refers to any modification in equipment, manufacturing
materials, facilities, utilities, design, formulations, processes,
packaging/labeling, computer systems, and all associated
documentation (SOPs, quality manual, etc.).
• According to WHO
“Change control is a formal system by which qualified representatives of
appropriate disciplines review proposed or actual changes that might
effect a validated status. The intent is to determine the need for the action
that would ensure that the system is maintained in a validated state”.
OR
• Change Control within a QMS is a formal process used to ensure
that a change to a system is introduced in a controlled and
coordinated manner.
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4. TASKS OF CHANGE
CONTROL
• Change control minimizes the risk that changes can have on
the quality or process characteristics
• Each change to previously approved requirements requires a
review and authorization to keep the system in its original
state of “proven suitability”
• Formal change control guarantees that all changes are
evaluated for their effect on product quality or validation
status
• Change control programs have become recognized as essential
element of the pharmaceutical quality assurance system
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5. PRINCIPLES OF CHANGE
CONTROL
• 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)
• 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
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6. REGULATORY
REQUIREMENTS
• Any changes in the production and processes must be controlled-meaning
recorded, reviewed and approved by the QC unit.
• Manufacturers certified to ISO 9000:2000 and ISO 13485 standards are
required to ensure that any changes affecting QMS ( including product
requirements, deign and development changes) should be controlled.
• All changes should be made according to approved (approval implies
successful testing or thorough review/investigation) written company
policies and procedures.
• Change control procedures have to be written as a way of standardizing
instructions.
• In FDA and ISO environments, strict adherence to approved policies and
procedures is a key factor in keeping manufacturing operations in a state of
control and it is what makes change control crucial.
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7. ELEMENTS OF CHANGE
CONTROL
• INITIATOR
Change is typically introduced by a initiator or originator. Initiating a changes
involves filling out a change request form which them moves through a process or
system of review and approval.
• CHANGE CONTROL COMMITTEE
May be a single entity for the whole company or may be one for the company’s
manufacturing site. It usually includes representatives from different departments
involved in production such as quality, manufacturing, regulatory affairs and
engineering. Depending on the change, committee may include legal, sales and
marketing departments.
• CHANGE ADMINISTRATOR
In pharmaceutical companies, cGMP requires that all changes must be reviewed
and approved by quality unit. In such companies, there must be a “Change
Administrator”, a role usually assumed by quality unit.
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8. STEPS OF CHANGE
CONTROL
• Record / Classify ( Initiator initiates a change by filling a change request form. The
change control team then records and categorize it).
• Assess (Assessors then make their risk analysis typically by answering a set of
questions concerning risk, both to the business and to the process, and follow this
by making a judgment on who should carry out the change, then it is sent for
planning ).
• Plan ( Planning team plans the change in detail as well as construct a regression
plan in case if the change is backed out).
• Build / Test ( team then make solutions, which will then be tested. They will then
seek approval and request a time and date to carry out the implementation phase) .
• Implement ( In this phase, finalized solutions or changes are implemented).
• Evaluation ( after change has been implemented, it should be evaluated)
• Close / Gain Acceptance ( when change is implemented correctly then it will be
closed).
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9. CLASSIFICATION OF
CHANGES
• A classification procedure nay help in determining the level of
testing, validation and documentation needed to justify the
changes of validated process.
• Changes may be classified as Major or Minor, depending on
the nature and extent of changes or the effect these changes
impart on process.
• They can also be categorized as specification changes, raw
material changes, equipment changes.
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10. EXAMPLES OF CHANGES
Major change Minor change
Not requiring
control
Significance change
Influences product
quality of process
reliability
Influencing a unit
requiring control
No relevance to GMP or
authorization
Possible measures
(selection)
• Official licence
• Approval
• Revalidation
• Amendment
• Review
• Documentation
No relevance to GMP or
authorization
Examples
• Changes of
manufacturers:
other synthesis
route of a starting
material (other
impurities)
• Removal of
processes to other
site
• Change in the
product
composition
• Change to the
process parameters.
• Replacement of
apparatus part of the
same design
• Change of cleaning
agent for floors
• Change of laundry
for work clothes
(non-sterile or
antibiotics area)
• Change to working
times
• Installation of air
conditioner in
administrative area
• Change in purchase
procedure
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11. MOTIVES FOR CHANGE
CONTROL
• Experiences from developmental and transfer phases.
• Results of process monitoring and statistical process control.
• Finding from quality control and stability results.
• Continuous improvement processes and processes
optimization.
• Strategic consideration ( changing suppliers, product transfer)
• CAPA processes
• Customer requests
• Regulations ( legal changes and official requirements)
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13. DOCUMENTATION
• Change control requires a written procedure to establish at least the following steps:
– What type of changes does change control take into account?
– What are the requirements for urgent changes?
– For which areas does this operating procedure apply?
– Who can suggest changes?
– How are changes requested (forms, method of communication)?
– How are changes graded and who is responsible for the rating?
– How are the measures for carrying out the change established?
– Who is responsible for the implementation and monitoring of all measures?
– Who is included in the change control team?
– What are the duties of the change control team?
– How is the change documented (format, content, storage)?
– Who is responsible to authorize changes?
• All quality-relevant changes should be documented
• All actions to be taken, including the need for and extent of qualification or validation, should be
described
• The records can be archived in paper form or electronically
• When storing documents, raw data and other relevant documents for change should be kept accessible
• The documentation for the change procedure should show that the change was evaluated (risk analysis)
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15. CHALLENGES IN CHANGE
CONTROL
There are many factors, but the following are the most common issues:
• Poor Communication - Lack of communication between departments, failure to
follow up or escalate change requests and delayed or inappropriate notification of
changes made by suppliers etc.
• Poor Turnaround - Timeliness can make or break a product's chances of
succeeding in the market. Companies that rely on a manual system to generate
data and to route and track submissions and change orders are likely to have poor
turnaround for change implementation because the system requires more time
and effort. The problem becomes worse when there is an unexpected change—a
deviation—and supporting data is not generated in a timely manner. Delays may
also result because of failure to recognize the urgency of a change and the
absence of a contingency plan for certain types of changes.
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16. • Ineffective Documentation - A manual system makes it more difficult to update
documentation, including revision history, and to find/retrieve necessary data to
support a change. The proposed change may be delayed when an outdated record
does not show revision history, or testing may be duplicated because
documentation has not been updated with results of a previous testing.
• Training not integrated with Change - Adequate training of personnel is a
prerequisite in both FDA and ISO environments. When training control is not
connected to the rest of the quality process, such as in manual systems, keeping
training current with procedures that have changed can be difficult. Training tasks
can easily fall through the cracks if employees are not vigilant in seeking them.
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18. 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
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-box07/15/13 18
