SOP on Change Control

 Pharmaceutical Guidanace
 April 4, 2016  QA & QC, Quality Assurance, SOP
 9,069 Views

SOP on Change Control

Objective :To establish a procedure for controlling and documenting changes. Through the provisions of

this procedure, a proposed change shall be evaluated and approved internally on its scientific merit and
appropriate external authorization shall be sought for those changes that impact on regulatory submissions.

Scope:This procedure shall apply to formulation plant of (Pharmaceutical Company Name) that

manufacture, package, test, and store or distribute drug products.

Responsibility

All concerned personnel shall responsible to follow the procedure mention in this SOP.

Concerned Department Heads shall be responsible for compliance of the procedure.

Head QA shall be responsible for final approval & closure of change control.

Accountability

Department Head & QA Head shall be accountable for implementation of this SOP.

Abbreviations and Definitions

QA : Quality Assurance

SOPs : Standard Operating Procedure

ROW : Rest of World

VMP : Validation Master Plan

STPs : Standard Testing Procedures

GTPs : General Testing Procedures

PMS : Packing Material Specifications

HVAC : Heating ventilation Air-Conditioning

Formal review, evaluation and approval of changes to processes, procedures,

Change Control :
specifications, analytical methods, vendors, machines, facilities and utilities 
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 “Critical signifies the category of the change”. A critical change is a change         
that has a substantial potential to have an adverse effect on the identity,
Critical :
strength, quality, purity, or potency of a product as they may relate to the  safety
or effectiveness of the product

Major signifies the category of the change” A major change is a change that has
a moderate potential to have an adverse effect on the identity, strength, quality,
Major :
purity, or potency of the product as they may relate to the safety or effectiveness
of the product.

“Minor signifies the category of the change” A minor change is a change that has

minimal potential to have an adverse effect on identity, strength, quality, purity, or

Minor :
potency of the product as they may relate to the safety or effectiveness of the
product.

“Level -1 signifies level of approval required to approve a change” Initiator

department and the quality assurance department only e.g. SOPs related to
Level-1 :
single department like operating procedure of equipment’s, cleaning procedure
of equipments, etc.

“Level -2 signifies level of approval required to approve a change” Initiator

Level-2 : department and all other interlinked departments within the plant e.g. Change in
SOPs which are being followed at different departments at plant level.

“Level -3 signifies level of approval required to approve a change” Initiator

department and all other relevant departments (within plant or outside the plant)

including marketing, RA and Quality and Compliance, etc. e.g. Change Controls
Level-3 : which include change in specifications / STPs / GTPs / Artworks / License
related issues / BMR / process change / Vendor change, etc These type of
changes may require company’s R.A. department to ask for approval of
regulatory agency(ies) that have impact on regulatory dossiers submissions.

Procedure

Any change shall be proposed through a form ‘CHANGE CONTROL FORM’ (Refer Annexure-1).

Any personnel can propose a change through “CHANGE CONTROL FORM”. Personnel shall fill the
details like Initiator department, date, Initiator (Name & Designation), proposed changes along with proper

justification (Justification shall include the existing system and proposed system) and shall assess the
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 need of training. Head of initiator department shall assess the type of change and changes required in the
interlinked documents and finally countersign on the proposal.

Head of concerned department shall categorize the change as “Critical / Major / Minor as per the definition
of the changes. Once the ‘Change Control’ form has been signed by the initiator’s department head /

designee, the same shall be forwarded to QA department.

Note:  If documents are required from other departments, initiator department shall collect the data and
submit along with the filled “Change Control Form” to QA. Refer Annexure-II for indicative data required for

any type of proposed change.

QA personnel shall evaluate the basic requirements of the change control and assess whether change

control requires comments / approval from Level 1 or Level 2 or Level 3 (refer abbreviations and definitions
for explanations of Level 1 or Level 2 or Level 3).

After assessment QA personnel allocates a unique number to the change control and log the same number
in the “Record of Change Control” (Annexure-III). After logging the change control QA personnel shall
circulate the change control for approval to different department Heads or designee.

Note: Comments on the change control can be asked from out-stationed departments through email/fax by
sending the complete details of change control by any means of communication.

QA personnel shall allocate a nine-digit number to the change control form and sign with date. The number
shall be in CCFXXX/YY format, where

CCF:Change Control Form

XXX:Serial number of change control i.e. 001, 002, 003, etc.

/ :‘Slash’

YY:Indicate last two digits of the calendar year e.g. 16 for 2016 e.g. the third Change Control for the year
2016 shall have a number of CCF003/16.

A new series of Change Control number shall start at the beginning of new calendar year.

All the Department Heads or Designee shall evaluate the change control at their respective ends and give
their comments (acceptable or not acceptable) on the change control form and submit back to QA

department for further action plan.

The comments shall be written by concerned / relevant department head or his designee, in his absence
only (Refer Annexure-IV for format of list of personnel responsible for approval of change control, this list

shall be updated twice in a year on half yearly basis and shall be maintained by QA personnel). 
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 After receiving comments from all relevant departments Head QA or Designee shall approve or reject the

change controls based on the sound scientific assessment.

Note: If a Change Control is pending for approval for more than 30 working days from the date of login, it is

the discretion of Head QA or designee to approve or reject the change control.

After approval of change control from Head QA / designee, QA personnel shall send the change intimation

to all concerned department heads / designee for planning the implementation of the change control
through electronic means of communications.

After approval of change control, QA Personnel shall evaluate the implementation of the change control and

shall close the change control only after all documents or any activity mentioned in the change control is
closed.

Note:  QA personnel shall take the re-evaluation of the change controls after every three months or need
based.

Different types of data requirements for different types of changes are enlisted in Annexure-II, but not
necessarily the requirements shall be limited to this list only. If appropriate, QA head or designee may

requisition any other type of data to review the proposed change(s).

Approval from different departments shall be sought by Quality Assurance department depending upon the

criticality of the change control (Please refer Annexure-IV for details).

Incase approval from any specific regulatory agency is required, Regulatory Affairs department shall co-
ordinate with concerned regulatory authorities and shall give the comments / approval as per their

comments.

Forms and Records (Annexures)

Change Control Form – Annexure-I

Proposed Changes and Data Requirements-Annexure-II

Change Control Logbook – Annexure-III

List of personnel responsible for approval of change control-Annexure-IV

Distribution

Master copy –           Quality Assurance

Controlled copies- Quality Assurance, Production, Quality Control, Stores, Engineering, & Human
Resources.

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MFR of Dextromethorphan, Bromhexine, Chlorpheniramine Maleate &
Guaifenesin  Tablets (drugsformulations.com)
History

Date Revision Number Reason for Revision

– 00 New SOP

Annexure-I

Initiator Department:                                                                                         Date:

Initiator (Name and Designation):

Proposed Change(s) (attach extra sheet if required):  

Justification for Change: (attach extra sheet if required):

Category:                      Critical                           Major                            Minor                                 (Tick

the appropriate)                                                                  

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Changes in Interlinked documents, if any (attach extra sheet if required): 

Approved By (Initiator Department Head/Designee) (Sign. and Date):

Remarks
Document Name or
Document Type
Yes/No/NA Number(s)

DCGI or Local FDA

License
license

Domestic/ ROW/ or any

BMR
other

Domestic/ ROW/ or any

Specification(s)
other

Domestic/ ROW/ or any

STP(s)
other

GTP(s) NA

Facility NA

SOP(s) Plant/ All formulations

Process validation(s) NA

Analytical Method

NA
Validation(s)

Domestic/ ROW/ or any

Artwork(s)
other

Domestic/ ROW/ or any

Stability
other

Equipment Qualification NA 
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 Calibration NA

Safety, occupational health

NA
and environment aspect

Machine change part NA

Any other

Put “NA” where not applicable

*Level of Change Control for approval:     Level 1              Level 2                Level 3          

 (Tick the appropriate)

*Level-1:- Initiator department and the quality assurance department only e.g. SOPs related to single

department like operating procedure of equipments, cleaning procedure of equipments etc.

Level-2:- Initiator department and all other interlinked departments within the plant e.g. Change in SOPs
which are being followed at different departments at plant level.

Level-3:- Initiator department and all other relevant departments (within plant or outside the plant) including

marketing, R&D, RA and Quality and Compliance etc. e.g. Change Controls which include change in

specifications/ STPs/GTPs/ Artworks/License related issues/ BMR/ process change/ Vendor change etc
These type of changes may require company’s R.A. department to ask for approval of regulatory agency

(ies) that have impact on regulatory dossiers submissions.

CC Number Number Allotted By Signature with login date

     

Comments from QA:

Comments from Production:

(Sign /Date) 

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Comments from QC:                                      

                                                                                           

 (Sign /Date)

Comments from Engg.:

(Sign /Date)

Comments from Others (if required):

(Sign /Date)

Comments from RA.:

                                  

(Sign /Date)

Final Comments from QA.:

                               

QA Personnel

(Sign /Date)

DISPOSITION BY QA DEPARTMENT

Category:Critical                           Major                            Minor

(Tick the appropriate)      

The proposed change(s) is / are accepted / rejected and shall be / shall not be implemented

Remarks:  
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Re-evaluation of change control required / not required

                                                                                                Head QA/ Designee                                         

                                                                                                     (Sign/Date)

Re-evaluation done on:                                      by:                                                 Designation:

Documents review and status of implementation: 

Remarks:

Change Control Closure

Name   Designation  

Sign./Date   Department  

                                                         Annexure-II

                                      Proposed Changes and Data Requirements

Data Requirements
Nature of Proposed Change
Sr. No.
Involved  

1. Significant change in method of Equivalent batch analysis data on 3 batches

manufacture
Stability data on 3 batches at 40°C/ 75 % RH for at least 6

months and ongoing long term stability data at 25°C / 60%

RH

Data on any tested impurities

Manufacturing validation for internal use

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 Expert comment for changes

Change of specification :

a. Tightening Updated Specification

Updated Specification

Batch data on 3 batches

b.  Loosening
2. Expert report justifying the change

Dissolution data, if applicable

Updated Specification
c. Addition of a new test
New test methods with validation

d. Update of specification Stability results to agree with specification proposed

New analytical method

Analytical validation for new method

3. Change in Control Methods Comparison of results by old and new methods

Justification / Expert Report

Training of analyst on new method

Statement that there is no change in method of

manufacture

Batch analysis data on 2 batches (internal)

4. Change of equipment type
Stability protocol (internal)

Equipment Qualification data and comparison with existing

equipment.

5. Change of manufacturing site Batch analysis data on 3 batches separately and

presented as Certificate of Analysis from the new site.

A GMP certificate from regulatory authority or government

licensing body for the new site

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 Comparative impurity data

QA approval of new site

Additionally for internal-approval samples, full term stability

data, justification

Site Master File

Batch analysis data on 3 batches manufacturing at both

Addition of Alternative
previous and new site
6.
manufacturing site A GMP certificate from regulatory authority or government

licensing body for the new site

QA approval of new site

Qualitative ID tests and specifications for new excipient

/coolant /flavour /colour/active salt

Batch analysis data on 3 batches

Formula changes : Change in

excipient /coolant /flavour /colour/ Stability data on 3 batches at 40°C/75% RH at 6 months

active salt and ongoing at 25°C /60% RH
7.
  Dissolution data where applicable

  Bio-equivalence study or Clinical Expert Report

Qualitative ID tests including colouring matters

Stability data for the whole shelf-life

Data to show equivalence with existing supplier. Meet old

8. Change of excipient supplier supplier specification

New vendor approval from QA and purchase

9. Change of excipiengrade Stability data on 3 batches at 6 months and ongoing to

support shelf life

Batch analysis data on at least one full scale

New in-process spec for tablet weight if affected

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 Expert statement to show that efficacy / safety of the

product is not affected

ICH stability guidelines (40°C/75% RH) should meet

internal market need.

Update of excipient specification

    10. New Specification
(Compendial)

New finished product specification for countries that have

registered marking previously

Justification of change
Change in imprints, embossing or
11.
other marking on drug products For addition of a breakline, gravimetric validation of tablet,

comparative friability and comparative dispersion time.

Notification on package literature as appropriate

Change of dimensions of drug New finished product spec for countries that have
12.
product registered dimensions of drug product, previously

13. Addition of ‘in-house test’ New specs and test method and validation of test method

When it is an brand name, declaration in writing is required

that after approval, the package leaflet and labeling will be

adapted at the same time

14. Change in name of product

When the name is generic name, proof is required that

proposed name is in accordance with pharmacopoeia.

Comparative batch analysis data on 2 batches (except

15. Change in batch size
where specified in the dossier) and process validation

Copy of contract stating who is responsible

Change in batch release site and

16. GMP audit of new site by Pharmaceutical

Responsibility
CompanyPharmaceutical Pvt. Ltd.

17 Change in batch release site with Copy of contract stating who is responsible
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 GMP audit of the site by Pharmaceutical

CompanyPharmaceuticals Pvt Ltd.

no change of responsibility

Proof that the proposed manufacturer/ importer

responsible for batch release is the holder of the

Change in manufacturer / importer appropriate authorization (copy of authorization)

18
responsible for batch release
Declaration in writing that after approval the appropriate

product information will be adapted by a stated date.

19 Change in manufacturing overage Stability data on multiple batches

Real time stability studies at recommended storage

20 Change in shelf life
temperature and conditions

Real time data on 3 production batches stored at the

21 Change in storage conditions proposed storage conditions, in authorized packaging

material

Proof that the proposed site is appropriately authorized

22 Storage address of finished product
(copy of authorization)

Stability data on 3 batches at 40°C/ 75% RH for 6 months

+ ongoing study at 25 °C/ 60% RH

Change of primary packaging

23 Product / packaging interactions study
material
Specification of new packaging

Comparative stability with previous packaging

Packaging material specifications and analysis to show

equivalence

24 Change in primary packaging source Vendor Approval from QA and purchase

25 Change in the quantitative Product/packaging interaction study

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 composition of primary packaging Comparative stability data on the new packaging vs. the

old and stability data

Specification of new packaging (if changed)

New packaging specification including validation data

Change in test procedure of primary
26
packaging  

27 Change in non-primary packaging Updated packaging description and specification

Change in pack/ size/ container,

28 Updated packaging description and specification
shape etc.

                                                             Annexure-III

                                                Change Control Logbook

Change
Date of Change Review of
Change Control Comments Status Compiled
Change Initiator Control Implementation
Control Category after review of after by
Control Dept. related approved
No. implementation review (Sign/Dat
login to on On By

                                                             Annexure-IV

                          List of Personnel Responsible For Approval of Change Control

S. No. Department Head of Department 1st designee 2nd designee

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Mr. Shiv Kumar is the Author and founder of pharmaceutical guidance, he is a pharmaceutical Professional from India having more than 14 years of
rich experience in pharmaceutical field.

During his career, he work in quality assurance department with multinational company’s i.e Zydus Cadila Ltd, Unichem Laboratories Ltd, Indoco
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TGA, EU –GMP, WHO –Geneva, ISO 9001-2008 and many ROW Regularities Audit i.e.Uganda,Kenya, Tanzania, Zimbabwe. He is currently leading
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