010 Change Control1

Management of Change
Control
Overview
Changes Good or bad? Forced or voluntary?
The Importance of Change Control
Major Changes to both legacy company documents
Scope and Responsibilities according to our new Directive
General Requirements
The Process with the detailed Requirements
Changes - Good or Bad?

A pharmaceutical company is built on both Quality and
Consistency
To always get the right product quality
To follow the established process
But a successful firm has also to perform changes

To make continuous improvements and implement innovations
To remain competitive and ultimately stay in business
Changes - Forced or Voluntary?
Some items must be changed where you have no option

Supplier cannot deliver the material
Raw material no longer available
Other items can be changed where we do have an option

Change of site, scale, or equipment
Change of QC test method
We need to consider the risk versus benefit of each change
But the biggest risk by far is an uncontrolled change
Even the smallest changes can cause very high risk if not
properly controlled
The Importance of Change

Control
Changes must be controlled, managed and followed
up to ensure that they are processed according to
GMP requirements and Health Authority regulations
This includes changes initiated by site or other
company internal decisions as well as changes
resulting from regulatory requests
The change control process must ensure quality,
efficacy and safety of the product throughout its life
cycle and updated regulatory files.
In other words : Change

Control
Process has
To evaluate the impact of proposed changes on the quality,

efficacy and safety of the final product
To evaluate the equivalence of changes of facilities,

equipment, manufacturing process, and technical transfer
To assess the impact on changing specifications and/or

analysis methods of all materials used
To determine appropriate actions before the change is

implemented
Scope
This scope applies to all manufacturing sites, affiliates and

subcontractors
It applies to all modifications of a product or a process

covering the following not limited to :
Raw materials (Change of suppliers, process, specs.)

Formula of drug products
Manufacturing process
Specifications and control procedures of components,
bulk and finished product
Primary packaging, storage and labelling
Medical devices
Equipment (incl. computerized automated systems)
Facilities, utilities and environment
GMP documentation (e.g., SOPs, MBR, batch records)
Responsibilities (1)
Site Management is responsible for ensuring that
any modification to their operations is
documented, evaluated and approved from a
technical, scientific, quality and regulatory point of
view
Site Quality Management along with other appropriate
functions are responsible for coordinating change
control activities in their respective areas to ensure
that there is an assessment of all proposed changes
and that approved changes are communicated to all
affected parties.
The site Quality Head is responsible for
ensuring that there are systems and
procedures to comply with applicable
Directives
The site Quality Head is responsible for
approving or rejecting a proposed change
at site level following an assessment by
the site Change Control Committee.
It is the responsibility of site Quality Management (QM) to ensure
that the regulatory evaluation assesses any potential impact the
change may have on the registration file
If the change has a potential regulatory impact, it is the
responsibility of the Regulatory Site Officer (RSO) to involve the
appropriate functions for further activities
If the change has a no regulatory impact, the implementation
/closing is handled by the site QM/RSO
For non-local products (i.e. products under the responsibility of
Corporate), the RSO is responsible to initiate the assessment of the
proposed change via the Corporate Change Control Committee
QM Responsibilities for Change

Control
QM is responsible for ensuring a robust
and easy to handle Change Control system
Defining clear roles and responsibilities
(initiator, reviewer, approver)
Creating a simple procedure with flow-charts
Defining the needed activities (internally and
externally)
Ensuring that all needed functions are involved
Training and education of all employees
involved
Change Control Management

needs Training
QM is responsible for managing the site Change Control

system
Change control is a topic in which every employee involved

in the manufacturing process needs to be trained
Good change control will be as good as the training and

education received
Focus the training on the serious potential for negative

impact of any uncontrolled change
We do not want anyone making unauthorised changes to

any activity that has Quality and/or Compliance impact
A Strong Reminder
Change made and intended to improve can result in a
worse situation or even in a disaster. Therefore, all
consequences must be considered
With a good change you can create other related
problems and also high amount of costs
Even minor changes or those that are considered to be
minor, can have a big impact to product quality and
regulatory compliance
And finally, all changes need to be closed-out.
General Requirements (1)

Any change, which can affect a product with
respect to its qualitative and/or quantitative
composition, quality (including bioavailability,
tolerance), purity, appearance, functionality
and/or stability must be assessed for its potential
impact prior to its implementation and processed
according the result of the assessment
There must be a procedure in place at the site for
periodic assessment that incremental changes
have not altered the overall process.
General Requirements (2)

The Corporate Change Control Committees must address all
changes with regulatory impact, evaluate all technical, quality
and regulatory aspects and decide
The Corporate Change Control Committees must decide on the :
Worldwide strategy based on the technical and/or scientific, quality and
regulatory information available at the Corporate Change Control
Committee level
Identification of Department/Person in charge of writing the dossier
Action plan including timelines until submission
More details later !
Initiation of the Change

Control
Request at the Site Level (1)
For an effective primary technical, scientific, quality and

regulatory evaluation, the following systems and
processes must be implemented :
An evaluation system which allows the assessment of all
changes proposed by the site on a regular basis. This
must include the creation of a change control committee
at site level involving appropriate site functions/experts
Use of a Change Control Request Form (CCRF) and followup tool (e.g. via electronic mails) as described in the
company procedure on change control.

Control
The CCRF must be submitted to the sites change control
committee
Proposed changes must be justified by adequate and
sufficient supporting data and documentation must allow
complete understanding and the implications of the
planned change to ensure adequate assessment
The technical and/or scientific evaluation of the change is
under the responsibility of the concerned departments
(Technical, Production and/or Development departments)
at the site level.

Control
The quality and regulatory evaluation is under the

responsibility of the Head of Quality and the site regulatory
officer. Advice provided by experts such as the regulatory
representative responsible for the product may be
requested
If the proposed change has a regulatory impact and is

approved by the Head of Quality, the completed CCRF must
be routed by Quality Management and site regulatory
officer to other appropriate functions outside the site for
coordination of a complete assessment of the technical
and/or scientific, quality and regulatory actions required to
enact the change, including timing of implementation.
Processing of the Change

Control
Request after Site Approval
(1)
Changes approved by the Head of Quality must
be supported by a detailed time and events
schedule that has been agreed upon by the
Change Control Committee or directly with
affiliate RAs
The Change Control Committee (CCC) addresses

all changes with regulatory impact for all active
pharmaceutical ingredients and all quality
changes that may have an impact for the
pharmaceutical product (ex: crystallography)

Control
(2)
In all cases, the Committee must involve representatives of
appropriate functions competent to assess the proposed

change request with regards to technical and/or scientific,
quality and/or regulatory aspects in order to approve or to
reject the proposed change or to put the proposed change on
hold until supplementary information is made available
The Corporate Change Control Committees must decide on the

Worldwide strategy based on the technical and/or scientific, quality
and regulatory information available at Corporate Change Control
Committee level.
Identification of Department/Person in charge of the writing of the
dossier
Action plan including timelines until submission

Control
(3)
Any modification of the change must
be
reported to the Committee through an
addendum of the initial CCRF for new
assessment
The Corporate Change Control Committees

decision should have a validity period of
typically 6 months. If a change is not
processed during this period, a new CCRF
must be initiated for re-assessment
Compilation of Documentation
Supporting
Changes with Regulatory Impact
On receipt of filled-in and signed-off CCRF from either Corporate
Change Control Committees or local Change Control Committees ,
the Affiliate Regulatory Affairs or regulatory site officer must prepare
or support the preparation of submission ready documents based on
the agreed regulatory assessment of the change and must provide
them to the appropriate regulatory function for review and approval
for file ability
The appropriate regulatory function must submit the provided
documentation to the appropriate Health Authorities
The Affiliate Regulatory Affairs or the site regulatory officer must
inform the change control committee, as applicable, of the receipt of
regulatory notification or approval or rejection of submitted changes.
Implementation of Changes
at Site Level (1)
For changes without regulatory impact, the site Change
Control Committee must decide about the prerequisites
and implementation timelines as well as informing the
respective unit in which the change will occur. A change
must only be implemented after receipt of the written
approval documented on the CCRF
For changes with regulatory impact, the release of the
batch after implementation of the change must only be
made after notification or approval of the submitted file
by the respective Health Authorities (except in case of
an annual reportable change for the US).
Implementation of Changes
at Site Level (2)
The regulatory site officer must
inform affiliate regulatory affairs of
the date of implementation of such a
change with the specific batch
number reference
The change request form must be
archived by site Quality Management.
Conclusion and Summary
Changes need to be traceable

Who changed, What, Where, When, Why, and How
What are the consequences with respect to risks and
costs, to validation status and submission to Authorities
Changes need to be planned in advance, evaluated,

approved, implemented and followed-up
The required experts need to be involved. Dont forget

engineers and IS people!
Documentation should be clear, accurate and complete
Keep you manufacturing process in the validated state/

state of control when you perform changes !
Thank You
Any Questions

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What are the different types of changes discussed in the document?

What are the different types of changes discussed in the document?

What factors need to be considered when evaluating a proposed change?

What factors need to be considered when evaluating a proposed change?

Management of Change

Changes - Good or Bad?

But a successful firm has also to perform changes

Changes - Forced or Voluntary?

Some items must be changed where you have no option

Other items can be changed where we do have an option

We need to consider the risk versus benefit of each change

But the biggest risk by far is an uncontrolled change

The Importance of Change

In other words : Change

To evaluate the impact of proposed changes on the quality,

To evaluate the equivalence of changes of facilities,

To assess the impact on changing specifications and/or

To determine appropriate actions before the change is

This scope applies to all manufacturing sites, affiliates and

It applies to all modifications of a product or a process

Raw materials (Change of suppliers, process, specs.)

QM Responsibilities for Change

Change Control Management

QM is responsible for managing the site Change Control

Change control is a topic in which every employee involved

Good change control will be as good as the training and

Focus the training on the serious potential for negative

We do not want anyone making unauthorised changes to

General Requirements (1)

General Requirements (2)

More details later !

Initiation of the Change

For an effective primary technical, scientific, quality and

Initiation of the Change

Initiation of the Change

The quality and regulatory evaluation is under the

If the proposed change has a regulatory impact and is

Processing of the Change

The Change Control Committee (CCC) addresses

Processing of the Change

appropriate functions competent to assess the proposed

The Corporate Change Control Committees must decide on the

Processing of the Change

The Corporate Change Control Committees

Conclusion and Summary

Changes need to be traceable

Changes need to be planned in advance, evaluated,

The required experts need to be involved. Dont forget

Documentation should be clear, accurate and complete

Keep you manufacturing process in the validated state/

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