Elsanhouty Pharma Notes, Cairo, Egypt.

Standard Operating Procedure

Title: Handling of Change Control

1. OBJECTIVE

1.1. Change control is a quality tool and a management to maintain and keep the records of all
changes as a history. Changes can be related to facility, documentation, system, equipment,
instrument, procedure, layouts and products etc.

1.2. To lay down a procedure to describe the handling of change control which include the procedure
for initiation, evaluation, review, approval/ rejection of proposed change, Implementation of the
approved changes and its post implementation.

2. SCOPE

2.1. This procedure is applicable for handling of change control.

2.2. This procedure covers (but not limited to) the change in product quality / reproducibility, facility,
utilities and / or support systems, process equipment, / instrument including computer data storage
device / software, manufacturing formula, manufacturing / packing process & parameters, process
environment or manufacturing site, standard batch size, specification, analytical methods, vendor /
suppliers, raw / packing material, artworks, process aids, holding period; storage and distribution
of product, documentation including validation master plan, validation reports, qualification protocol
and reports, new material / product introduction, SOP’s, site master file.

3. RESPONSIBILITIES

3.1. Initiator :
 Initiating the Change Control Record and ensuring that change is implemented in accordance with this
procedure and managing the implementation activities in accordance with stakeholders’ review
comments and agreed action items.
 Managing timely execution of activities in conjunction with the stakeholders and Completing risk
assessments.
 Adding action items as required.
 Resolving issues, if any, in coordination with stakeholders and Quality Assurance (QA). Escalating
issues, such as extensions of Change Controls not being closed in a timely manner to higher
management whenever required.
 Initiating variation proposal(s) such as changes being effective (CBE) via CCR, if required, based on
CCR evaluation done by regulatory affairs (if required).

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 Ensuring that all necessary activities related to the implementation of change, including performing a
risk assessment of the change are satisfactory and verified.
 Responsible for discontinuing Change Control Records, as appropriate.

3.2. Regulatory affairs

 Reviewing the proposed change with reference to regulatory impact.

 Communicating the change to the Regulatory Agency/Customer (if applicable) via a variation (CBE,
Prior Approval Supplement (PAS) as examples) or annual report.

 Change Control Record evaluator(s) shall be responsible for reviewing the proposed change
for possible impact on systems and procedures from respective disciplines, such as process
development, validation or material/vendor sourcing.

3.3. Quality head/designee

 Implementing and managing a system for the change control process.
 Ensuring all aspects of the change control process, including management of change proposals,
change evaluations, change approvals, change implementations, and effectiveness checks of
change(s).
 Obtaining the necessary information from other organizational units to comprehensively evaluate the
potential impact of the change(s) on other sites” processes, as appropriate.
 Provide the notification of changes to regulatory affairs (RA), FDD, PDD, ADD, customers, and market
representatives.
 Changing classifications. (E.g. Level (Minor) I, (Major) II & (Critical) III).
 Approving or rejecting the proposed change with respect to the impact on quality/GMP compliance.
 Ensuring the adequacy of action items, approving the Change Control Record, assigning the change level
classification (I, II, & III) to the CCR.
 Performing impact and risk assessment, Identifying and generating action items, as required.
 Approving the extension of Change Control Record closure, performing document assessment, closure of
all action Items, and Performing Trend Analysis of Changes.
 Establishing and maintaining procedures to assure the proposed changes to a system are evaluated
for potential impact on the following:

3.4. Documents:
 Standard operating procedures
 Quality agreements
 Training requirements
 Specifications
 Analytical Methods
 Analytical templates

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  Worksheets
 Master Batch records
 Master packaging record
 Quality manual
 Protocols
 Labeling
 Methods used in manufacture
 Packaging, Testing, release, and distribution of products
 Manufacturing/packaging instructions, including regulatory commitments for global processes, cGMP
engineering drawings.

3.5. Product characteristics:

 Microbial testing
 Identity
 Quality
 Strength
 Purity
 Safety and
 Efficacy of Drug Products.

3.6. Validation Documents:

 Process
 Equipment
 Facilities
 Critical utilities
 Testing analytical methods (chemical, physical, microbiological),
 Cleaning.

4. DEFINITIONS

 Minor change: A change that may not have an impact upon the identity, quality, purity, strength,
stability, safety and efficacy or physical characteristic of the product.
 Major change: A change that may have an impact upon the identity, quality, purity, strength,
stability, safety and efficacy or physical characteristic of the product.
 Critical change: A change that has a significant impact on quality and /or safety of the final
product.
 Cross-Functional Team: A group of people with different functional expertise working towards a
common goal. The team is responsible for the review and implementation of the Change Control
Record.

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  Change: The creation, revision, or discontinuance of a process, software, equipment, facility, utility,
product, or document.
 Corrective and Preventive Action: A concept with current Good Manufacturing Practice (cGMP)
that focuses on the systematic investigation of root causes of unexpected incidences to prevent
their recurrence (corrective action) or to prevent their occurrence (preventive action).

 Closure Date: The date on the proposed changes is implemented and evaluated is the
closure date of Change Control.

5. PROCEDURE

5.1. Initiation of change control record (CCR):

 The Initiator shall discuss the proposed change with the Department Head and key stakeholders,
including, Quality Assurance and Regulatory Affairs to reach a consensus that the change is
necessary, feasible, and supportable whenever required.
 Once the agreement is reached regarding the proposed change, the Initiator shall initiate a Change
Control Record (CCR).
 QA shall issue the Change Control Record to the concerned department & shall assign the change
control number on the form with signature and date for issuance.

5.2. Numbering system for changes

 All changes shall be numbered as a specific numbering system, as example it shall be CC/XXX/YYYY
demonstrated as: CC denotes to change control, XXX denotes to sequential number and YYYY
denotes to year, E.G. CC/001/2017: this shall be the first change control in year 2017.

5.3. Approval and review of change control

 After approval on change initiation form user shall give the intimation for change control form, QA
issued the form by assigning change control number.
 User shall fill the form and make available all documents related to proposed changes; all attachments
shall flow with the form to HOD than QA.
 QA head review the form, as per assigned category, review all attached documents and planned
programs related to changes.
 After a successful review QA shall approve the form. This shall be entered in log book of change
control by QA personnel.
 In case change control related to regulatory shall be approved by regulatory in consultation with Head
QA

5.4. Evaluation and implementation

 Head QA shall assign the effective date of implementation of the changes and the originating
department shall plan for any necessary training and shall update the relevant documents with

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 corrective actions jointly with QA. The status of completion of action shall be mentioned in the change
control form by the originating department and shall be forwarded to QA.
 Implemented change control shall be further reviewed by Head QA. After finding all correct the
documents undergoing for changes / revisions shall have revised as per the procedure.
 Approved and closed change control forms are then filed and maintained by QA.

5.5. Closing of Change control

 Change control must be close within a specified period in exceeding a proper justification to be done.

5.6. Timeline for change closure

 Product, document, and system-related change controls should be closed within 90 days and
facility/equipment related change controls should be closed within 180 days if all impacted actions are
completed.
 If any impacted action is not completed within the time limit, then such change controls should be kept
open till completion of all impacted actions and fill the “Extension of change control” format for the
extension of change control.
 Fill the required details of the form by the user department and HOD give the justification for the
extension with a tentative date for closure of change control.
 Reason for the extension should be reviewed and approved by Head QA after consulting the User
Department.
 After approval by Head QA for an extension, Quality Assurance person should monitor the status of
change controls pending for closure and record every month.

6. Examples on change types

6.1. Level I:

 No impact on control system ensuring SISPQ of product. e.g.

6.1.1. Reduction in Hold time,

6.1.2. Tightening IP / FP limits,

6.1.3. Increased frequency of monitoring and in-process checks.

6.2. Level II:

 The changes do not have a significant impact on the control system however that triggers
validation/qualification/stability study etc. e.g.
6.2.1. Establishment/increase of hold time
6.2.2. Introduction of new count / new pack
6.2.3. Change in SOP/Template/Protocol/LIMS documents
6.2.4. Change in Machine/Equipment
6.2.5. Release limit change (e.g. from IH to USP, etc.)

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6.2.6. Change in In-process parameters
6.2.7. Change in Pack style/Pack count.

6.3. Level III:

 The changes have a potential impact on product quality/regulatory bodies according to respective
guidelines i.e. Changes except for annual notification requirements. e.g.,
6.3.1. Change in Calibration/Stability frequency,
6.3.2. Change in FP limits (Dissolution / Average Wt. etc.)
6.3.3. Batch size change
6.3.4. Updating of pharmacopoeia change
6.3.5. Change in the strength of RM (e.g. Pellets)
6.3.6. Change in Manufacturing formula
6.3.7. Relaxation of FP limit
6.3.8. Launch of new product/system
6.3.9. Change in Storage condition
6.3.10. Change in Primary Packing Material
6.3.11. Product Shelf Life Extension
6.3.12. Deletion and Up-gradation, and repair, replacement of equipment, facility, area, or utility.

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