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.
- 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.
- Department Head & QA Head shall be accountable for implementation of this SOP.
- Abbreviations and Definitions
|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|
|Change Control||:||Formal review, evaluation and approval of changes to processes, procedures, specifications, analytical methods, vendors, machines, facilities and utilities|
|Critical||:||“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, strength, quality, purity, or potency of a product as they may relate to the safety or effectiveness of the product|
|Major||:||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, purity, or potency of the product as they may relate to the safety or effectiveness of the product.|
|Minor||:||“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 potency of the product as they may relate to the safety or effectiveness of the product.|
|Level-1||:||“Level -1 signifies level of approval required to approve a change” Initiator department and the quality assurance department only e.g. SOPs related to single department like operating procedure of equipment’s, cleaning procedure of equipments, etc.|
|Level-2||:||“Level -2 signifies level of approval required to approve a change” 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||:||“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 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.|
- 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 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.
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).
- 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
- Master copy – Quality Assurance
- Controlled copies- Quality Assurance, Production, Quality Control, Stores, Engineering, & Human Resources.
MFR of Dextromethorphan, Bromhexine, Chlorpheniramine Maleate & Guaifenesin Tablets (drugsformulations.com)
Reason for Revision
|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)|
|Changes in Interlinked documents, if any (attach extra sheet if required):
|Approved By (Initiator Department Head/Designee) (Sign. and Date):|
|Type||Document Name or Number(s)|
|License||DCGI or Local FDA license|
|BMR||Domestic/ ROW/ or any other|
|Specification(s)||Domestic/ ROW/ or any other|
|STP(s)||Domestic/ ROW/ or any other|
|SOP(s)||Plant/ All formulations|
|Artwork(s)||Domestic/ ROW/ or any other|
|Stability||Domestic/ ROW/ or any other|
|Safety, occupational health and environment aspect||NA|
|Machine change part||NA|
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:
|Comments from QC:
|Comments from Engg.:
|Comments from Others (if required):
|Comments from RA.:
|Final Comments from QA.:
|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
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:
|Change Control Closure|
Proposed Changes and Data Requirements
|Sr. No.||Nature of Proposed Change Involved||Data Requirements
|1.||Significant change in method of manufacture||Equivalent batch analysis data on 3 batches|
|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|
|Expert comment for changes|
|2.||Change of specification :|
|a. Tightening||Updated Specification|
|b. Loosening||Updated Specification|
|Batch data on 3 batches|
|Expert report justifying the change|
|Dissolution data, if applicable|
|c. Addition of a new test||Updated Specification|
|New test methods with validation|
|d. Update of specification||Stability results to agree with specification proposed|
|3.||Change in Control Methods||New analytical method|
|Analytical validation for new method|
|Comparison of results by old and new methods|
|Justification / Expert Report|
|Training of analyst on new method|
|4.||Change of equipment type||Statement that there is no change in method of manufacture|
|Batch analysis data on 2 batches (internal)|
|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
|Comparative impurity data|
|QA approval of new site|
|Additionally for internal-approval samples, full term stability data, justification|
|6.||Addition of Alternative
|Site Master File|
|Batch analysis data on 3 batches manufacturing at both previous and new site|
|A GMP certificate from regulatory authority or government licensing body for the new site|
|QA approval of new site|
|7.||Formula changes : Change in excipient /coolant /flavour /colour/ active salt
|Qualitative ID tests and specifications for new excipient /coolant /flavour /colour/active salt
Batch analysis data on 3 batches
Stability data on 3 batches at 40°C/75% RH at 6 months and ongoing at 25°C /60% RH
Dissolution data where applicable
Bio-equivalence study or Clinical Expert Report
Qualitative ID tests including colouring matters
Stability data for the whole shelf-life
|8.||Change of excipient supplier||Data to show equivalence with existing supplier. Meet old 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
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.|
|10.||Update of excipient specification (Compendial)||New Specification|
|11.||Change in imprints, embossing or other marking on drug products||New finished product specification for countries that have registered marking previously
Justification of change
For addition of a breakline, gravimetric validation of tablet, comparative friability and comparative dispersion time.
Notification on package literature as appropriate
|12.||Change of dimensions of drug product||New finished product spec for countries that have registered dimensions of drug product, previously|
|13.||Addition of ‘in-house test’||New specs and test method and validation of test method|
|14.||Change in name of product||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
When the name is generic name, proof is required that proposed name is in accordance with pharmacopoeia.
|15.||Change in batch size||Comparative batch analysis data on 2 batches (except where specified in the dossier) and process validation|
|16.||Change in batch release site and
|Copy of contract stating who is responsible
GMP audit of new site by Pharmaceutical CompanyPharmaceutical Pvt. Ltd.
|17||Change in batch release site with||Copy of contract stating who is responsible
GMP audit of the site by Pharmaceutical CompanyPharmaceuticals Pvt Ltd.
|no change of responsibility|
|18||Change in manufacturer / importer responsible for batch release||Proof that the proposed manufacturer/ importer responsible for batch release is the holder of the appropriate authorization (copy of authorization)
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|
|20||Change in shelf life||Real time stability studies at recommended storage temperature and conditions|
|21||Change in storage conditions||Real time data on 3 production batches stored at the proposed storage conditions, in authorized packaging material|
|22||Storage address of finished product||Proof that the proposed site is appropriately authorized (copy of authorization)|
|23||Change of primary packaging material||Stability data on 3 batches at 40°C/ 75% RH for 6 months + ongoing study at 25 °C/ 60% RH|
|Product / packaging interactions study|
|Specification of new packaging|
|Comparative stability with previous packaging|
|24||Change in primary packaging source||Packaging material specifications and analysis to show equivalence|
|Vendor Approval from QA and purchase
|25||Change in the quantitative
composition of primary packaging
|Product/packaging interaction study|
|Comparative stability data on the new packaging vs. the old and stability data|
|Specification of new packaging (if changed)|
|26||Change in test procedure of primary packaging||New packaging specification including validation data
|27||Change in non-primary packaging||Updated packaging description and specification|
|28||Change in pack/ size/ container, shape etc.||Updated packaging description and specification|
Change Control Logbook
|Date of Change Control login||Change Control No.||Initiator Dept.||Change Control
|Category||Change Control approved on||Review of Implementation||Comments after review of implementation||Status after review||Compiled by (Sign/Date)|
List of Personnel Responsible For Approval of Change Control
|S. No.||Department||Head of Department||1st designee||2nd designee|