Category: QA SOP

SOP Title: Handling of Product Complaints

 

1. Objective:

To lay down procedure for receiving, recording, investigating and taking corrective action against all customers as well as regulatory complaints regarding safety, efficacy, reliability or quality of the product.

2. Scope:

This procedure is applicable to all product complaints of products manufactured at site.

3. Responsibility:

QC Department: To review, analyse and prepare report of complaint sample along with retention sample as applicable. To assist or ensure investigation in the QC laboratory.

QA Department: to prepare and approve procedure and ensure that complaints are properly reviewed, investigated, communicated and necessary corrective action taken as per procedures.

Other Concerned Department: To follow the procedure and assist in the investigation whenever required.

4. Accountability:

QA Head/all HODs/Unit Head.

5. Procedure:

• Definitions:
• Complaint: A “Complaint” is defined as a written or an oral expression of dissatisfaction related to the identity, quality, durability, reliability, safety, effectiveness or performance of any product manufactured by this company. Complaints are classified in to 3 categories.
• Minor: Complaints which may not pose a significant hazard to health. e.g.

Complaints due to secondary material, shortage complaints, damage containers.

• Major: Complaints that could cause illness or mistreatment, but are not critical. e.g.
• Problem with the primary packing of the product.
• Extraneous contamination mix up etc.
• Missing or incorrect information (leaflets).
• Mislabelling (wrong or missing text of figures).
• Critical: Complaints related to defective/dangerous/potentially life threatening medicines that predictably or probably could result in to serious health risk or adverse events and in such case the product is required to be withdrawn from the market. e.g.
• Wrong product (Label and containers are different).
• Wrong active ingredient in a multi- component product.
• Mix-ups of some products.

 

• Confirmed Complaints:

5.1.7.1 When both complaint and reference sample show Out of Specification (OOS) results or  When only the complaint sample showed OOS results.

5.1.7.3 When only complaint sample shows OOS, it shall be confirmed that failing product might have undergone misuse or mishandling during transportation or storage after dispatch.

• Non-confirmed complaints:

When both complaint sample and reference sample comply with specifications.

• Procedure:

5.2.1	Receiving and Conformation
Note: The person who shall handle product complaint must have adequate qualification, training and experience.
A product complaint may be received directly from customer, Regulatory authority, Head office/ Marketing Office or any other sources; the originator has to provide their full details like letter reference (if any), name and address of the complainant.
Originator shall provide information about complaint like name of product, batch no., lot no., Mfg Date, Exp. Date, nature of complaint and total quantity of complaint sample to QA Department.
The person designated for handling the product complaint shall check and match the complaint sample and reference sample.
5.2.1.1	Confirm whether the complaint is minor, major or critical and based on this he/she shall take immediate action.
5.2.1.2	Complaint shall be maintain in the “Complaint log” as per format, having details like (Date of receipt, Product name,  Strength and Pack, Batch No., Mfg. Date, Exp. Date, Complaint No., Complaint received from/date, nature of complaint, Investigation report No., Closing date).
5.2.1.3	Once the complaint sample match with reference/control sample, both samples shall be subjected to laboratory analysis for relevant test parameters and the report is reviewed.
5.2.1.4	If the complaint is confirmed, immediate action e.g. Product Recall/Freeze, communication to Marketing Department/Regulatory Authority/Management etc. shall required and thorough investigation is recommended.
5.3	Investigation
5.3.1	Before investigation nature of non-conformance shall be analysed carried out.
5.3.2	The route cause for non conformance shall be investigated thoroughly with respective departments. Investigation includes two phases like Documentation and Laboratory Analysis Investigation.
5.3.3	A list for possible, likely possible and remote causes addressing root cause shall be made and investigation initiated.
5.3.4	Investigation shall be carried out in all Concerned Department as per nature of possible causes.
5.3.5	Investigation shall be completed within 7 days or as applicable and report shall be filled in the form.
5.4	Documentation investigation
5.4.1	Check the complaint files for previous complaints of the same nature for the same product.
5.4.2	Check the batch details like BMR, BPR, manufacturing logs and reports for non-conformance that can confirms or explains the quality problem.
5.4.3	Investigation shall covers all records related to reference sample storage conditions, log books, testing records, analyst performance records, RM/PM test reports.
5.5	Laboratory Analysis
5.5.1	In case of quality related complaint, send the complaints sample if available (or control sample to QC for analysis).
5.5.2	Depending on nature of complaint the Control Sample and Complaint Sample shall be analyzed for the relevant test parameters.
5.5.3	Analysis of sample shall be carried out as per the specification by which the product was initially released.
5.5.4	Test parameters to be performed for the complaint sample shall be specified. After completion of analysis, report of analysis shall be sent for review.
5.5.6	Review of QC testing procedures, specifications, personnel, logbooks and data based on the nature of complaint. Based on the QC analysis report it shall be ensured whether it is confirmed or non confirmed complaint.
5.5.7	If the QC analysis shows OOS results, it shall be handled through OOS SOP.
5.6	CAPA and Feedback to Customer
5.6.1	For all confirmed complaints, corrective actions must be implemented.
5.6.2	All the Corrective And Preventive Actions in detail and target date for the completion of the corrective action in the investigation report shall be mentioned.
5.6.3	Investigation report shall be reviewed and justified.
5.6.4	Complete investigation details along with the reply letter mentioning the Corrective And Preventive Actions taken to avoid future re-occurrence of the incidence (in case of domestic complaint) shall be forwarded to Marketing Department.
5.6.5	Complete investigation details along with the reply letter mentioning the Corrective And Preventive Actions taken to avoid future re-occurrence of the incidence (in case of domestic complaint) shall be forwarded to Regulatory Department.
5.6.6	As a part of investigation, the need for the batch to be Recalled depending on the nature of complaint.
5.6.7	Initial response shall be sent to Marketing Department within 7 days for Domestic Complaints and 10 days in case of Export Complaints.
5.6.8	Reply shall be sent to the customer, with copy of the same to QA Department.
5.6.9	Feedback from the customer/complainant on the reply is to be taken. Feedbacks (if any) received from the customer/complainant are to be forwarded to QA department for records.
5.7	Implementation, Follow up and Closeout
5.7.1	The action plan shall be executed and all tasks shall be completed and documented. The additional sheet shall be attached if required.
5.7.2	The appropriateness and effectiveness of the action taken shall be evaluated and verified.
5.7.3	The complaint shall be treated as closed out after receiving feedback from the customer. The time period for receiving feedback from the customer is: From Domestic Market within 3 weeks. From International Market within 4 weeks.
5.7.4	Review the customer complaint status and customer complaints every quarter to evaluate specific or recurring problems which require further attention.
5.8	Complaint Report Filing
5.8.1	Maintain all the records involving market complaints till one year after the date of expiry of the product or one year after the date of complaint received whichever is longer.
5.8.2	Additional sheets shall be attached if required.
5.8.3	Complaint log shall be maintained.

  

6. Abbreviation:

Abbreviation	Expansion
QA	Quality Assurance
QC	Quality Control
QAD	Quality Assurance Department
QAP	Quality Assurance Procedure
BMR	Batch Manufacturing Record
BPR	Batch Packing Record
No.	Number
CAPA	Corrective And Preventive Action
RM	Raw Material
PM	Packing Material

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

 

 

 

 

SOP Title: Validation and Qualification

1. Objective:

To lay down the procedure for Validation and Qualification for Manufacturing Process, Testing procedure or Method, Facility, Utility/System, Equipment/Instruments, Cleaning process etc as a part of Quality Assurance System to ensure Product Quality.

2. Scope:

This procedure is applicable to-

• Manufacturing process of product(s)
• Testing procedure/method of product(s)
• Facilities for product manufacturing and storage
• Utilities or system critical to product quality
• Critical equipment and instruments used for manufacturing and testing of product or materials
• Critical cleaning procedures

3. Responsibility:

Production Department: To assist in Validation and Qualification executed in the facility, review protocol and report.

Quality Control Department: To carry out testing, prepare test results as specified in the Validation or Qualification protocol, review protocol and report.

Engineering Department: To provide supportive services for execution of Validation and Qualification, review protocol and report.

Warehouse Departments: To assist in Validation and Qualification executed in the department, review protocol and report.

Quality Assurance Department: To prepare, review, approve, protocol and report, execute Validation or Qualification programme, ensure all aspects of product quality and GMP requirements are included in the Validation or Qualification Programme.

4. Accountability:

Head QA/All department heads

5. Procedure:

5.1 Definitions:

5.1.1  Calibration: The set of operations that establish, under specified conditions, the relationship between values indicated by an instrument or system for measuring (for example, weight, temperature and pH), recording, and controlling, or the values represented by a material measure, and the corresponding known values of a reference standard. Limits for acceptance of the results of measuring should be established.

5.1.2  Qualification: Action of proving and documenting that any premises, systems and equipment are properly installed, and/or work correctly and lead to the expected results. Qualification is often a part (the initial stage) of validation, but the individual qualification steps alone do not constitute process validation.

5.1.3  Validation: Documented series of actions that prove that any equipment, process, procedure, material, activity or system performs its intended functions adequately and consistently, and lead to the expected results of uniform batches that meet the required specifications and quality attributes.

5.1.4  Revalidation or requalification: The repeat of the initial validation or qualification to provide assurance that changes in the equipment, process and/or in the process environment, whether intentional or unintentional, do not adversely affect process characteristics and product quality.

5.1.5  Validation Master Plan (VMP):  A policy document that establishes an overall Validation plan for the company and defines the approach for establishing performance adequacy. It includes the validation work program and details of time-scales for the validation work to be performed, and the responsibilities relating to the plan.

5.1.6  Validation or qualification protocol: A written plan stating how validation will be conducted, including Test parameters, Product characteristics, Production equipment and decision points on what constitutes acceptable results.

5.1.7  Validation or qualification report: A document in which the records, results and evaluation of a completed validation or qualification programme are assembled and summarized. It may also contain proposals for the improvement of processes and/or equipment.

5.1.8  Validation Committee: Representatives of different departments selected and assigned job responsibility to execute validation and qualification on the basis of adequate qualification, experience and training

5.1.9  QA Associate: The QA person who is trained for performing task as per this SOP.

5.2  Procedure

5.2.1	A need assessment of validation and qualification for the facility, utilities/systems, process/procedure, material/products, equipment/instruments, supplier/vendor etc shall be carried out, through discussion related to various aspects of product quality, customer satisfaction, regulatory requirements and continuous improvement of quality management system and described in the Validation Master Plan.
5.2.2	Validation and qualification shall be performed: — for new facility, equipment, utilities/systems, processes and   procedures — at periodic intervals — when major changes have been made
5.2.3.	Validation Master Plan
5.2.3.1	A validation master plan (VMP) for manufacturing site shall be prepared in consultation with the Head Production, Head Quality Control, Head Engineering and Head Warehouse and approved by the Head QA Department.
5.2.3.2	The validation master plan shall reflect the key elements of the validation programme. It shall be concise and clear and contain at least the following: — a validation policy — The responsibilities of the members of the Validation Committee. — summary of facilities, utilities/systems, equipment and processes validated and to be validated — documentation format (e.g. protocol and report format) — planning and scheduling for validation and qualification — change control — references to existing documents.
5.2.3.3	Validation master plan shall be reviewed and updated as per frequency mentioned in SOP.
5.2.4	The Head QA shall constitute a Validation Committee by selecting representatives from Production, Quality Control, Quality Assurance and Engineering Departments as appropriate. This committee will be responsible for the performance of all the validation and qualification activities given in the VMP.
5.2.5	Every validation or qualification exercise shall be carried out only on the basis of a written and authorized protocol that sets out the details of the tests to be carried out, and shall be completed by the accumulation of documentary evidence and review of data against agreed acceptance criteria.
5.2.6	Validation  and Qualification Protocols
5.2.6.1	Validation/qualification protocols and report (blank) shall be prepared, numbered, approved and maintained as master document as mentioned SOP.
5.2.6.2	As a minimum the protocols shall include the following basic information: — the objectives of the study — scope — responsibilities — description of procedure/SOPs to be followed — equipment to be used — standards and criteria for the relevant products and processes — the type of validation or qualification — the processes and/or parameters — sampling, testing and monitoring requirements — predetermined acceptance criteria
5.2.6.3	The master protocol and report shall be copied and issued for execution of validation or qualification as CONTROLLED COPY after approval as mentioned in SOP.
5.2.7	Validation  and Qualification Report
5.2.7.1	A written report shall be prepared, reviewed and approved after completion of each validation or qualification.
5.2.7.2	Reports should reflect the protocols followed and include at least the following information: — reference to the protocol —objective — scope — responsibilities — description of procedure/SOPs followed — details of material, equipment, programmes and cycles used — procedures and test methods. —deviation and investigation report (if occurred) —recommendation and conclusion —calibration certificates of test equipment/measuring devices where appropriate
5.2.8	Revalidation
5.2.8.1	Processes and procedures shall be revalidated to ensure that they remain capable of achieving the intended results over a period of time
5.2.8.2	Revalidation shall be performed by two ways 1. Periodic revalidation 2. Revalidation after changes
5.2.8.3	Periodic revalidation shall be performed at a frequency mentioned in the Validation Master Plan on the basis of previous history of any process/procedure and risk associated with the system over time.
5.2.8.4	Revalidation after change shall be performed, if following changes found : — changes in starting materials (including physical properties, such as density viscosity or particle size distribution that may affect the process or product) — change of starting material manufacturer — transfer of processes to a different site (including change of facilities and installations which influence the process) — changes of primary packaging material (e.g. substituting plastic for glass) — changes in the manufacturing process (e.g. mixing times or drying temperatures) — changes in the equipment (e.g. addition of automatic detection systems, installation of new equipment, major revisions to machinery or apparatus and breakdowns) — production area and support system changes (e.g. rearrangement of areas, or a new water treatment method) — appearance of negative quality trends — appearance of new findings based on current knowledge, e.g. new technology — support system changes.
5.2.8.5	Revalidation after change shall be performed as a part of change control system and change control shall be filed as per SOP.
5.2.8.6	Criteria for revalidation after change shall be mentioned in the validation master plan.
5.2.9	Requalification
5.2.9.1	Requalification shall be performed by two basic ways 1. Periodic requalification- performed at a frequency mentioned in the Validation Master Plan 2. Requalification after changes- changes to utilities/systems, equipment, transfer to another site, maintenance work, major parts etc.
5.2.9.2	Changes of equipment which involve the replacement of equipment on a “like-for-like” basis would not normally require a requalification and revalidation. For example, installation of a new centrifugal pump to replace an older model would not necessarily require requalification or revalidation.
5.2.9.3	Requalification after change shall be performed as part of the change control procedure as per SOP.
5.2.10	Archival of Validation and Qualification Protocols and Reports
5.2.10.1	All the validation and qualification protocols and reports shall be archived in QA Department in a safe and secure manner readily available whenever required.
5.2.10.2	Such documents/reports shall be retained for a period as mentioned in SOP.
5.2.11	Calibration
5.2.11.1	Calibration of equipment/instrument shall be performed: 1. For new equipment/instrument during initial qualification stage 2. For the instruments used for calibration of other instruments 3. At a frequency mentioned in the Validation Master Plan or SOP for individual equipment/instrument.
5.2.11.2	Standards used in the calibration shall be traceable to national, regional or international standards and certificates be attached in the report.
5.2.11.3	A calibration schedule shall be prepared for all instruments or measuring devices and followed meticulously in the routine operation.
5.2.11.4	Calibration of each equipment/instrument shall be performed as per approved procedure.
5.2.11.5	Certificates of calibration or reports shall be archived in QA Department after approval.

6. Abbreviation:

Abbreviation	Expansion
QA	Quality Assurance
QAP	Quality Assurance Procedure
GMP	Good Manufacturing Practice
QC	Quality Control
VMP	Validation Master Plan
SOP	Standard Operating Procedure
DQ	Design Qualification
IQ	Installation Qualification
OQ	Operational Qualification
PQ	Performance Qualification
URS	User Requirement Specification

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

SOP Title: Incident Reporting and Investigation

1. Objective

To lay down the procedure for Incident Reporting related to the Product Quality in the Site.

2. Scope:

This procedure is applicable to any incident, evidence notified in the Manufacturing Area, QC Laboratory, Warehouse and Storage Area, Critical Utilities and other Product/Material related activities in the Site.

3. Responsibility:

Officer/Executive Concerned Department: To report the incident to Supervisor/HOD of department, fill Incident Report Form and follow the procedure.

QA Officer/Executive: To verify incident, issue incident report form, documentation of incident and follow the procedure.

Head Concerned Department: To review and report the incident to QA Department, analyse, investigate, review the CAPA and implementation.

Head QA: To review, analyse incident report, investigate, recommend and implement CAPA

4. Accountability:

      Head QA/Concerned Department

5. Procedure:

5.1 Definitions:

Incident: A discrepancy in implementation of GMP or failure of systems in day-to-day operation. Any event that can affect product quality directly or indirectly or not but that is against GMP

Critical Incident: An incident that is likely to affect the quality, safety and efficacy of the product.

Major Incident:  An incident that may result in the production of a drug product not meeting the standards.

Minor Incident: An incident that may not significantly affect the quality of product and/or system.

Note: Incidents vary in nature and severity, hence proper identification and elimination of root cause needs to be done by adequate procedure.

5.2 Procedure:

5.2.1	General Approach to file Incident Report
	In following circumstances incident shall be filed but not limited to: General incidents: -Missing entries -Transcription error – Any document error -Calculation error and typo error -Deviation of standard procedure -Wrong document issuance -Any abnormal activities in premise or department -Any hazard related to safety -Wrong procedure prepared for any operation/activity – Wrong intimation and issuance of stereo
5.2.1.1	Production Department Incidents: -Spillage of materials -Minor black particles found in the RM during sifting -Sudden increase/decrease in temperature and RH -Breakdown of equipment during processing -Observation of metal particle/parts in granules/tablets -Water dropping from ceiling -Escape of material through FBD bag during drying -Tablets found compressed with wrong punch size -One material is added in the product in place of another (mix up)/cross contamination -Mislabelling during packaging -Empty pocket of strips/blisters found during terminal inspection -Document error -Missing of log book entries -Power failure -Wrong parameter setting in equipment
5.2.1.2	Quality Control Laboratory Incidents: -Spillage of chemical/solution -Breakdown of laboratory instrument during testing/operation -Wrong dilution -Mislabelling to the solution, reagent etc. -Contamination found during microbial testing -Growth found in negative control sample or no growth found in positive control sample -Wrong standard selection -Wrong HPLC column selection -Wrong instrument parameter setting -Wrong standard and sample weighing -Document error -% RSD failure for standard and sample -Sampling error -Missing of log book entries -Power failure
5.2.1.3	Warehouse Department Incidents: -Spillage of RW materials -Sudden Increase/decrease of Temperature or RH -Insect found inside the storage area -Breakdown of RLAF during sampling or dispensing -Missing of log book entries -Under test RM drums found kept in approved racks -Document error -Wrong material dispensing -Wrong weighing
5.2.1.4	Engineering Department Incidents: -Equipment breakdown -Wrong parameter setting in equipment or instrument -Missing calibration and preventive maintenance of any equipment/instrument as per planned schedule -Power failure equipment/instrument as per planned schedule -Power failure -Leakage in water generation and distribution system -HVAC breakdown -Choking of HVAC filters during operation -Sudden increase or decrease of pressure difference, temperature and relative humidity -Wrong filter replacement after cleaning

 

5.2.2	Reporting of Incident
5.2.2.1	Any incident taking place in the Site shall be reported and further proceeded as per “Flow Chart for Incident Reporting”.
5.2.2.2	Report to Senior Personnel/Supervisor or Section Head immediately when incident occur. The supervisor shall perform initial investigation to find out cause of incident.
5.2.2.3	Incident shall be reported in the “Incident Report Form” as per format and shall be notified to QA Department.
5.2.2.4	The Incident Report Form shall be reviewed and send to QA Department for further action.
5.2.2.5	The “Incident Report Log” shall be maintained as per format (having the details like Incident Report No., Department, Date, Description of Incident, Type of Incident Minor/Major/Critical, Closing Date, Closing Remark and Sign of QA.)
5.2.2.6	Incident Report number shall be allotted to each incident as mentioned below: IDRQAYYNNN where, IDR denotes Incident Report QA denotes Quality Assurance Department YY denotes last two digit of the current year and NNN denotes three digit serial number as (001, 002, 003….). For example Incident Report Number for first incident of year 2024 shall be assigned as IDRQAD24001.
5.2.2.7	Incident investigation shall be done as soon as possible after the incident.
5.2.3	Immediate Action to be taken:
5.2.3.1	If the incident was very recent, secure the scene of the incident to ensure and preserve any evidence that may contribute to the investigation.
5.2.3.2	Identify the potential sources of information, such as the injured person, witnesses and any physical evidence.
5.2.3.3	If the incident occurs in product/material/related activities /equipment /operation stop the same and segregate the material/product with proper identification.
5.2.3.4	Gather the facts about the incident.
5.2.4	Evaluation and Analysis of Incident:
5.2.4.1	Evaluation and analyses of the incident shall be done depending on the nature and severity; it shall be classified as minor, major or critical.
5.2.4.2	Review the following necessary information during evaluation and analysis of incident: ·     Any similar incident history related to equipment, operation, area and activities. ·     A review of similar causes in the past. ·     Any potential quality impacts on the product. ·     Any impact on regulatory commitment. ·     Impact of incident to any other batches.
5.2.5	Investigation of Root Cause
5.2.5.1	QA Department shall investigate the root cause of the incident along with Concern Department.
5.2.5.2	During root cause investigation always use words like what, when, where, why, who, how and which for detail investigation and to find out the root cause.
5.2.5.3	The maximum time for investigation and closeout of incident shall be 30 working days from the date of incident filing.
5.2.5.4	If the investigation is extended then justification shall be documented for the same.
5.2.5.5	When the incident happened. Date and time may be crucial.
5.2.5.6	If an employee was involved, or a piece of equipment damaged, be specific about piece of equipment and the extent of damage or injury.
5.2.5.7	Specific details may be critical for investigation like department, product, activity, area etc.
5.2.5.8	What work element was deficient and most directly caused the incident. If there was a specific condition (i.e. lifting, twisting, spills, poor maintenance, falling objects, defective equipment, lack of procedure, poor lighting, human error, lack of training etc.)
5.2.5.9	If the incident is Minor then necessary Remedial Action shall be taken immediately and it shall be authorized by Head QA Department.
5.2.5.10	Summary of the root cause investigation shall be entered on the incident form. A separate sheet may be attached for investigation with reference if required.
5.2.6	Some Examples of these Root Cause Elements are as follows:
	Materials Machine/Equipment -Defective Raw Material(s) or lack of procedure for Vendor Selection/Approval – Incorrect selection of tool or equipment – Poor equipment maintenance or design – Defective equipment or tool Mother Nature (Environment) Man – Out of order workplace – Area poorly maintained – Lack of man power – Lack of training
	– Other environmental conditions (noise, inadequate light etc) -Safety precautions no followed properly – Mental stress/work pressure Methods – No or poor procedures – Practice does not match with written procedures – Poor communication
5.2.7	Generally following Checkpoints may be considered during incident investigation but not limited to:
5.2.7.1	Production Department: -Check correct Manufacturing Procedure followed as per BMR/BPR -Check correct RM/PM taken -Check Validity of RM/PM -Check training record of manufacturing personnel -Check cross contamination -Check calculation error -Check cleaning and washing of equipment -Check Qualification/Calibration of equipment -Check environmental condition Temperature and Humidity -Interview with personnel with respect to incident, check whether procedure was followed
5.2.7.2	Quality Control Laboratory: -Check correct STP/SPC followed -Check correct standard taken -Check correct chemical taken -Check Validity of Chemical/Reagent -Check correct dilution made -Check correct glassware used -Check training of analyst -Check calibration status of instruments   -Interview with analyst with respect to incident and check whether procedure was followed   -Check calculation error -Check document error -Check correct weighing -Check degradation of standard/reagent -Check environmental condition -Check correct SOP was followed
5.2.7.3	Warehouse Department: -Check correct RM/PM dispensed -Check calibration status of equipment/ instruments -Check proper storage of RM -Check cleaning of dispensing booth -Check environmental condition temperature and humidity -Check weighing error -Check calculation error Interview with Warehouse person with respect to incident -Check document error -Check cross contamination -Check labelling status RM/PM -Check correct SOP followed -Check cleaning of dispensing accessories -Check training records
5.2.7.4	Engineering Department:   -Check procedure for Calibration and Preventive Maintenance was followed -Interview with the personnel with respect to incident -Check log books of respective equipment -Check whether system is operating within the set operating range -Check whether correct parameters are set for operation -Check training records of respective personnel -Check incident history if previously occurred -Check correct material/tools/accessories were used -Check whether equipment or component is working properly -Check whether correct assembly or disassembly done
5.2.8	Corrective and Preventive Action (CAPA)
5.2.8.1	Based on the Root Cause Analysis, all tasks required to correct the problem and prevent reoccurrence shall be identified and included in an action plan.
5.2.8.2	Corrective Actions to be taken for the particular incident shall be discussed with related department and mentioned in the “Incident Report Form”.
5.2.8.3	The need for maintenance of machine, retraining, development/ modification of procedure shall be evaluated.
5.2.8.4	Preventive Actions to prevent occurrence of similar potential incident with respect to other equipment/product/activity shall also be mentioned in the “Incident Report Form” if applicable.
5.2.9	Review of CAPA
5.2.9.1	Based on nature of incident, Incident Report Form shall be circulated to other departments for impact assessment and review of action plan.
5.2.9.2	The CAPA shall be reviewed by QA, Production, QC, Engineering and Warehouse Department as applicable. Finally the report shall be reviewed by QA Department.
5.2.10	Implementation of CAPA, Follow up and Close out
5.2.10.1	The Concerned Department Head shall be responsible to ensure execution of all tasks and implementation of action plan recommended in Incident Report Form.
5.2.10.2	The actions that were taken shall be documented.
5.2.10.3	The appropriateness and effectiveness of the action taken shall be evaluated and verified by QA Department.
5.2.10.4	Finally the Incident Report shall be reviewed for completeness, implementation of CAPA shall be verified and Incident Report shall be closed out.
5.2.10.5	A photocopy of the incident report form shall be attached to the batch document (if required) and original shall be retained with QA Department.

 

6. Abbreviation:

Abbreviation	Expansion
GMP	Good Manufacturing Practices
RH	Relative Humidity
RM	Raw Material
PM	Packing Material
RSD	Relative Standard Deviation
CAPA	Corrective and Preventive Action
HOD	Head of Department

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

SOP Title: Good Documentation Practice

1. Objective:

To provide comprehensive training in accordance with the requirements of Good Documentation Practice, a pre-requisite to the process of product release in the market place. This document is to ensure that all actions are documented correctly and in a standardised approach.

2. Scope:

This document describes the requirements for Good Documentation Practice as required by regulatory  rules and guidelines. The approach is applicable to all type of documents.

3. Responsibility:

QA Department: To prepare and approve the SOP. To follow the Procedure for Good Documentation Practices as per this SOP.

Other Departments: To review and follow the Procedure for Good Documentation Practices as per  this SOP.

4. Accountability:

Head – Quality Assurance

5. Procedure:

• Good Documentation Practice: is an important part of Good Manufacturing Practice which specifies the standard of document completion should meet the minimum requirements based on regulatory guidelines, requirements and expectations. It is the responsibility of all employees to  follow Good Documentation Practice.
• Procedure:

5.2.1	Principles of Good Documentation Practice:
5.2.1.1	A document bearing original signatures should never be destroyed.
5.2.1.2	Never falsify information.
5.2.1.3	Never use a White-out and cover-over-tapes.
5.2.1.4	Never obliterate information or record.
5.2.1.5	Never over-write a record.
5.2.1.6	Never use pencil – all information should be completed in permanent Blue ink.
5.2.1.7	No spaces, lines or fields are to be left blank.
5.2.1.8	Never use symbols e.g. ditto marks or arrows to indicate repetitive and consecutive.
5.2.2	Different Types of Documents and Records:
Documentation and records used throughout the manufacturing process, as well as supporting processes (e.g. Quality Control or Quality Assurance), must meet the basic requirements of GDP. These include (but are not limited to): ·         Batch Record Forms ( BMR and BPR) ·         Bills of Materials (BOMs) ·         Specifications ·         Policies ·         Protocols ·         Standard Operating Procedures (SOPs) ·         Work Instructions (WIs) ·         Test Methods ·         Checklists ·         Forms/Log sheets ·         Training Assessments ·         Electronic and hardcopy Quality records (e.g. Non-conformance, Corrective  and Preventative Actions, Internal Inspection, Change Control, Training Records etc.) ·         Certificate of Analysis (CoA) or Certificate of Compliance (CoC) ·         Technical transfer reports ·         Validation documentation
5.2.3	Common Documentation Errors:
·         Missing signature and dates at the time of activity performed. ·         The write-over. ·         Non-uniform date and signature entry. ·         Writing a note that activity was performed on one day and signed for on other day. ·         Blank spaces. ·      Illegible writing. ·      Too many corrections.
5.2.4	General Requirements for Good Documentation Practices: General Elements GDP Requirements Clearly written documentation All documents must be accurate and written in a manner that prevents errors and ensures consistency. If documents are to be used together, e.g.  SOP and a format then each should reference the other. Ensure there is traceability between two or more documents/records using formal document numbers or record identification. Using indelible ink All records must be filled out in indelible blue ink ball point pen for long term legibility. Do not use pencil or ink that can be erased. Legible handwritten entries A document is unusable if it cannot be read, so care must be taken to ensure that handwriting is legible. All entries must be made at the time the tasks are performed and should be legibly signed and dated. The same is true of electronic documents and records – language should be clear and unambiguous. Reviewing and Approving Documents and records should be reviewed by someone who did not perform the task to ensure that the information is correct and accurate. A signature and date by the reviewer/approver confirms that a review has taken place. Unsigned documents or records are incomplete and should not be used to perform any task or considered as evidence of a completed task. Staff Signatures Handwritten signatures must be unique to the individual and listed within the site signature specimen signature list to ensure that the signature is traceable to a member of staff (or contractor). Staffs are not permitted to sign for another member of staff unless delegated. Signatures must never be forged. GMP records are accurate and any changes or amendments are made in a complaint manner ·     Deliberately amending or destroying GMP records to hide or falsify data is fraud. ·     Do not discard a GMP record just because you might have made a mistake, it is still required for traceability. ·     It is not acceptable to discard GMP records for any reason unless the retention period expiry is reached. ·     Loose unofficial papers, notes and uncontrolled documents that can easily be lost or changed without appropriate approval do not meet GDP requirements. ·     Do not use notebooks/legal pads with easily removed pages, scrap paper or post-it-notes to record GMP information.
5.2.5	The Following Requirements Outline the Ways in which Handwritten Entries may be Amended.
5.2.5.1	Making legible correction: If a correction needs to be made, the original record must still be legible:
5.2.5.1.1	Make a single line through the error – never use correction fluid, multiple cross-outs or marker pen to obscure the original record.
5.2.5.1.2	Record the correction close by – numbering corrections is acceptable when space is limited. If the record becomes too congested with corrections, an attachment may be used, however the original record must indicate the number of pages attached and the attachment reference the record it is related to.
5.2.5.1.3	Put a star mark as (*) and give a brief comment why the change is required (as appropriate).
5.2.5.1.4	Initial (sign) the change so that it is clear that the correction is deliberate.
5.2.5.1.5	Record the date of the correction next to the initials so that there is a record of when the change was made.
5.2.5.1.6	During entering the data on any GMP record incorrect entries are not applicable, if more than three incorrect entries on the same page should be replaced with additional page which is issued by QA and incorrect page should be retained with the same document. e.g.: The A.R. No. for the finished product is FP/PK/24/001 while entering in to the logbook it was written as FP/PK/24/010,rectify the mistake follow the above mentioned procedure
	Date A.R. No. 01/01/24   *    FP/PK24/010   Sign/date FP/PK/24/001   At the bottom of the same page *(Remark): Wrong entry done 01/01/24       FP/PK24/010              This is very poor example for correction
5.2.5.2	Handling  of Delay in Recording Data: If an entry was omitted and must be made at a time later than the activity was performed then:
5.2.5.2.1	Clearly indicate the date the activity was performed and the date the activity is recorded on the documentation.
5.2.5.2.2	Document an explanation to substantiate the entry and the reason for the delay in recording.
5.2.5.2.3	Sign and Date the change. Important: Back dating of entries is not permitted. e.g.: As shown below:
	Standards UV absorbance  Std 1 1.055 Std 2 0.944 Std 3 0.986 1.  Data collected 12/12/24 but not recorded due to fire evacuation. Data retrieved from instrument on 13/12/24. 2.  Done by : Sign/Date                                                                                    Checked by: Sign/Date
5.2.5.3	Completing all Fields on a GMP Record:
5.2.5.3.1	If any field or space such as multiple blank spaces, rows, columns within the document which are given for the intention of data entry/record but remains unused due to excess or not applicability then must be marked out with a single line across the whole field or space as shown below.   Data: A b c ————etc m n o————-etc. x y z————-   N/A Sign/Date     Date Result                                        N/A Sign/Date
Note: ·         A GMP record is incomplete when fields or spaces for entries have not been filled. ·         Do not discard a page of a record just because the fields are not applicable because the page could be mistaken as missing. ·         Do not use ditto marks to indicate the field is the same as above.
5.2.5.4	Checking Corrections:
5.2.5.4.1	Review the change and ensure that it has been made in a complaint manner – clear, legible, accurate, original entry is still visible etc.
5.2.5.4.2	Review the change with respect to the content of the rest of the document.
5.2.5.4.3	Sign and Date of correction.
5.2.5.5	Recording Numbers:
5.2.5.5.1	Decimal Numbers:
The company GDP procedure should stipulate any specific requirements for recording data. In general, if a decimal value is a fraction of 1 then a zero must be placed before the decimal point. e.g.:  Record 0.98 rather than .98 The number of decimal places to be recorded should be outlined in a procedure. e.g.: When a specification limit is 2.55 – 2.85 and the result is 2.7, then record the result as 2.70 and not 2.7
5.2.5.5.2	Date Format:
Date must be unambiguous and follow the standard format DD/MM/YY               e.g.: 01/01/24 Dates are to be recorded at the time of activity. Pre-dating or back dating should not occur and is considered as falsification.
5.2.5.5.3	Time Format:
Time must be unambiguous and follow the standard format HH:MM                      e.g.: 15:46 The 24 hour format is to be used.
5.2.5.6	Handling attachments GDP Requirement Attachments to forms     Attach one record to another (for example if a report is to be attached to a form): ·      Staple the attachment to the record. ·      Cross-reference the record and the form with each other, e.g. the Dealing with Attachments and Printouts : The following requirements must be met when attaching records and printouts to GMP document:
	Handling attachments GDP Requirement   The record reference the report number and the report reference the record number. Attachments to Workbooks/Logbooks   ·      Secure the attachment to the appropriate page of the Workbook/Logbook . ·      Do not obscure any data on either the workbook page or attachment. ·      Ensure sufficient identification on the attachment to ensure traceability in the event it becomes separated (cross-referencing). ·      Indicate on the original document that there is an attachment. ·      Sign and date both the workbook and attachment. Thermal Printouts ·      All printouts made on thermal paper must be copied before attaching to a report or filing. Indicate ‘Copy of Original ’or ‘True Copy,’ on the copy and initial and date. ·      Do not tape over information on thermal paper as the tape will cause the data to rapidly fade. After making a copy, secure the original and the copy with the report.
5.2.5.7	Using Scanned Documents: Scanned documents, converted to pdf files, are very useful for companies or department operating across different locations. Following table indicate how to treat scanned documentation and other compliance requirements associated with electronic media. Scanning Document GDP Requirements Obtaining Approval  Signatures Obtaining approval signatures from staff located at different sites/locations/time-zones can be completed using scanning rather than hardcopy: 1.      Print the document to be approved 2.      Sign and date the hardcopy and then scan the hardcopy with the signature. 3.      The pdf file of the scan is emailed to the appropriate signatories, who each print out the pdf file, sign and date their signature field, and then re-scan the document and email back to the preparer. 4.      The preparer receives a pdf file from each signatory indicating their approval. 5.     Attach the signatory page from each approver to the original, hardcopy with the preparer’s hardcopy signature.   Scanning Document GDP Requirements   6.      Indicate on the front page the number of attached signature pages. 7.      File all the pdf files in the same storage folder as per the company policy for electronic versions. Access to pdf and MS Word Versions   Generally, pdf versions of documentation can be accessed by staff because they are not able to be changed (without specific software). However, MS-Word files (or equivalent software) can be changed and so should have limited access for most staff (unless other security functions are enabled).
5.2.5.8	Communication Styles Used in GDP The following table contains suggestions for communication styles useful for GDP. Actions How they help Using words that everyone can understand (reduce Jargon or Abbreviations)   Unfamiliar words reduce the reader’s understanding of what is written. It can also interrupt their flow of learning if they need to search for the meaning of a word. Therefore, jargon or abbreviations should be avoided if possible, unless well known to the audience. Definitions of jargon or abbreviations should always be included in the document for reference. This is most effectively done by included the definitions in a table format, at the start or end of the document.   Actions How they help Using words with unambiguous meaning The English language is full of descriptive words which can have different meanings depending on the context, the understanding of the reader and even cultural differences. For this reason, words should be chosen very carefully. Using whitespace Ensure that the contents of the document are not squeezed into a smaller area just to limit page numbers. Documents with small margins and no spaces between paragraphs and headings can be difficult to look at, hard and slower to read. Space the contents out so that the type/font is easy to read for all users (consider the overall audience age, or potential colour blindness or dyslexia). Providing enough detail to make sense of  it in the future When creating a document, consider the context in which the document may be used in the future and whether the reader has enough background information. However, too much non-critical information can also detract from the document and make it too wordy. Using pictorial or graphical aids (including tables) Many people remember information best when there is a strong visual prompt, such as a diagram. When the document has to be wordy, consider using tables to structure the information so it is less overwhelming to the reader. Previous  experience and expectations The level of detail, written style and type of document should all be ruled by the documents target audience. Consistent wording to avoid confusion Referring to something by two different names, even if only slightly different, can be confusing. Consistent styles templates Consistency with styles will give any document a greater sense of professionalism.
5.2.5.9	Record Control: In an emergency, if no official means to record an observation is available, then:
5.2.5.9.1	Initial, date and provide a comment on the paper record of the observation and attach to the official hardcopy record as soon as possible.
5.2.5.9.2	Transcribe and attach the data to the official record and annotate ‘Transcribed, see attached original’. The transcription must be signed and dated by the Preparer and filed/stored together with the original record.
5.2.5.9.3	The data must be checked for accuracy by a second staff member.
5.2.5.9.4	Investigate why an official record was not available at the time. Implement corrective  actions so that the same situation may not arise again, e.g. create a form for the record, amend the procedure, change the process so that the record is captured electronically etc.
5.2.5.10	Original Records:
5.2.5.10.1	The initial or first record made is the original; for example, the first recorded value entry, computer readable media, non-durable printouts, photographs. If the original record is in electronic format, e.g. an HPLC chromatogram, this can be printed as the original record. This must be then reviewed for completeness and correctness, then signed and dated to signify a true accurate record.
5.2.5.10.2	Unless with good reason, the initial record and the reproduced record should both be retained, even if the original is not durable
5.2.5.10.3	Electronic data and information must be retained and archived on a controlled location; use of a back-up copy is required. The back-up copy must be stored in a secure and controlled location away from the original.
5.2.5.10.4	It is a requirement that the means to retrieve and re-create electronic data is available throughout the shelf-life of the product plus one year.
5.2.5.11	Original Documents:
5.2.5.11.1	Original documents must be controlled against a register or log. Each document must have a unique identifier, in the format required for the document type.
5.2.5.11.2	For any document e.g. a Standard Operating Procedure, only one version can be current at any one time. This is the only document that can be available and in-use.  Previous versions are to be removed and are to be retained in accordance with current procedure.
5.2.5.11.3	Externally generated documents e.g. pharmacopoeias, manufacturer’s manuals etc. are to be similarly controlled.
5.2.5.12	Photocopying of  Documents:
5.2.5.12.1	All original controlled documents must be marked as ‘MASTER COPY’. Photocopy of master documents may either be marked as ‘CONTROLLED COPY’ indicated by the stamp in blue ink.
5.2.5.12.2	Controlled documents must be issued against a control register; where a controlled document is revised, the previous controlled document returned to Quality Assurance for destruction, according to current procedure and a controlled copy of the new document is issued.
5.2.5.12.3	Where second generation copies are required e.g. formats, these can be taken by photocopying at the time required by the holder of the original copy; these documents are effectively ‘free-issue’. It is the responsibility of the area supervisor to ensure only the correct version number of the document is used.

 

6. Abbreviation:

Abbreviation	Expansion
GMP	Good Manufacturing Practice
GDP	Good Documentation Practice
A.R. No	Analytical Report Number
BMR	Batch Manufacturing Record
BPR	Batch Packing Record
N/A	Not Applicable
*	Remark (Reason)
HH:MM	Hour Minute
HPLC	High Performance Liquid Chromatography
e.g.	Exempli gratia
pdf	Portable Document Format
MS	Micro Soft
etc	etcetera

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

SOP Title: Environmental Health and Safety Procedure

1. Objective:

To lay down procedure for environmental, health and safety at the site

2. Scope:

This procedure is applicable to following aspects of environmental health and safety:

• Safe work practice
• Sign and Tags
• Personal Protective Equipment
• Medical Examination
• First Aids Procedures
• Emergency Equipment and Facility
• Waste Management
• Documentation of Training

3. Responsibility:

HODs	:	Shall be responsible for identifying the needs and ensuring compliance of procedure in their departments.
HOD Admin	:	Shall be responsible for arrangement of safety requirements including equipment and medical examination as per procedure
HOD QA	:	Shall be responsible for developing procedure, counter checking the requirements, compliance reports, and records thereof.

4. Accountability:

Head QA department

5. Procedure:

5.1  Definitions:

QA Associate: Executive or officer of QA Department or any personnel trained to perform duties as per this SOP.

QC Associate: Executive or officer of QC Department or any personnel trained to perform duties as per this SOP.

Production Associate: Executive or officer of Production Department or any personnel Trained to perform duties as per this SOP

Hazardous waste: Means any waste which by reason of any of its physical, chemical, reactive, toxic, flammable, explosive or corrosive characteristics causes danger or is likely to cause danger to health or environment, whether alone or when in contact with other wastes or substances.

Scraps: Include rejected packing materials, labels, container, used poly bags, paper, used gloves, clothes, masks, cupboard, plastics, glass etc.

5.2  Procedure:

5.2.1	The need of safety system for health and environment shall be assessed, determined and documented by the key personnel/safety team in the premise.
5.2.2.	Safe Work Practice
5.2.2.1	All equipment and machinery shall be provided with SOPs for operation, cleaning, maintenance & safety.
5.2.2.2	All areas shall be provided with appropriate fire extinguishers at strategic points.
5.2.2.3	All areas like production, warehouse, storage, quality control etc shall be well lit and provided with adequate HVAC/Ventilation system depending on the nature of process.
5.2.2.4	QC laboratory shall be provided with lab specific SOPs for fuming room, eye shower, wet shower, hazardous chemical storage and handling, safe disposal of chemicals etc and all personnel shall be trained on these.
5.2.2.5	MSDS supplied by the chemical/equipment supplier shall be referred and instructions are followed properly where required.
5.2.2.6	Sign and Tags DANGER- signs shall be used only where immediate hazards exist. CAUTION- signs shall be used to warn of potential hazards or unsafe practices. SAFETY INSTRUCTION- signs shall be used where there is a need for general information and suggestions relative to safety measures.
5.2.2.7	The Engineering department regularly monitors all mechanical breakdowns and electrical safety in the premise as per SOP.
5.2.3.	Personal Protective Equipment (PPE)
5.2.3.1	Proper gowning, personal protective equipment’s system shall be followed by the personnel during working in the site as specified for area/activity.
5.2.3.2	Following types of personnel protective equipment shall be available and used by the personnel while handling with the chemical substance or hazardous substance or during any maintenance work in the premise, as applicable: Clothing as mentioned in the SOPs of respective departments Gloves Safety shoes Safety glasses Respirators- used where hazardous dust or fumes are generated Ear plugs Gum boot Head coverings used to prevent any chemical and physical hazards
5.2.4	Medical Examination
5.2.4.1	All personnel working in the premise shall be monitored for their medical examination initially and periodically as per SOP
5.2.5	First Aid Procedures
5.2.5.1	All areas shall be provided with first aid facility. First aid kit shall be located at right places in all departments; all the staff members must be familiar and trained with the use of first aid kit. Following types of first aid actions may be taken while taking incident with hazardous substance: Inhalation: Remove to fresh air. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical attention. Ingestion: Never give anything by mouth to an unconscious person. Rinse mouth with water.  Get medical attention immediately. Skin Contact: Immediately flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Wash off with soap and plenty of water. Get medical attention immediately. Wash clothing and shoes before reuse. Eye Contact: Immediately flush eyes with plenty of water for at least 15 minutes, lifting lower and upper eyelids occasionally. Get medical attention immediately.
5.2.6	Emergency Equipment and Facility
5.2.6.1	In case of any accident occurred within the premise like serious injury, damage to property, fire or toxic release, emergency services shall be arranged by the organisational emergency squad as deputed/nominated time to time.
5.2.6.2	Each working area e.g. manufacturing, warehouse, laboratory shall have emergency exit doors with proper labelling/signs for safety.
5.2.6.3	Fire fighting equipment: ·         Water pipe 2’’ around the factory connected ETP pollute and overhead water tank ·         Portable fire extinguisher of ABC type. ·         Fire bucket stands with water and sand. Emergency medical service: Emergency medical service shall be promptly arranged by the squad as nominated/deputed by the Unit Head on timely basis as per Annexure.
5.2.7	Waste Management
5.2.7.1	Any kind of waste shall not be accumulated/dumped or thrown in to environment. Proper laid down procedure shall be followed for handling the waste materials.
5.2.7.2	Hazardous waste or scraps generated during processing/operation, handling or storage in production area shall be handled as per SOP.
5.2.7.3	Waste Disposal Procedure: Label Waste- Hazardous waste label shall be affixed on all waste containers Store Waste – Hazardous waste shall be stored in closed containers and must be under the control of the person generating & disposing it. Dispose of Waste- Disposal of regularly generated chemical waste and scrap shall be done within two months as per SOP of Waste management.
5.2.7.4	Special precautions such as wearing proper gowning, masks, gloves and other protective equipment shall be taken during collection, transfer, storage and disposal of hazardous waste.
5.2.8	Documentation of Training
5.2.8.1	Training shall be provided to all personnel specific to the hazards involved and safety procedure for substance, work area, safety equipment, health and hygiene and emergency procedures prior to assigning job responsibility and records shall be maintained.
5.2.8.2	Special safety training regarding evacuation, communication, use of fire fighting equipment, use of protective equipment,   first aids, etc shall be given to the personnel working in the site.
5.2.8.3	A periodical audit after every six months including provisions to check health and safety regulation compliance and training updates shall be conducted and records shall be maintained as per Annexure.
5.2.8.4	The employees shall be responsible to follow Health & Safety procedure

  

6. Abbreviation:

Abbreviation:	Expansion
SOP	Standard Operating Procedure
PD	Production Department
WH	Warehouse Department
QC	Quality Control Department
QAP	Quality Assurance Procedure
QA	Quality Assurance Department
MSDS	Material Safety Data Sheet
HVAC	Heating Ventilation and air conditioning
EGD	Engineering Department
HR	Human Resource

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

SOP Title: Routine Monitoring of Facilities and Utilities

1. Objective

To lay down procedure for routine monitoring of facilities and utilities.

2. Scope:

This procedure is applicable to manufacturing facility, warehousing and storage area, QC laboratory, packaging area critical and utilities.

3. Responsibility:

Officer/executive respective/QA department – To check and verify the facility & utility as per procedure and report to concern department head and QA head if any non conformance is observed.

Head QA/Head of department – To evaluate and analyse the problem, investigation of root cause, ensure CAPA and implementation.

4. Accountability:

Head QA/ Head concerned department

5. Procedure:

5.1 Definitions:

Contamination: The undesired introduction of impurities of a chemical or microbiological nature, or of foreign matter, into or on to a starting material or intermediate during production, sampling, packaging or repackaging, storage or transport.

Cross contamination: Contamination of a starting material, intermediate or finished product with another starting material or product during production.

Mix up: A mistake that result from taking one thing to be another or a wrong action leading to bad judgement or ignorance.

QA Associate: Officer/executive QA Department trained to perform duty as per this SOP.

Production Associate: Officer/executive Production Department trained to perform duty as per this SOP.

Warehouse Associate: Officer/executive Warehouse Department trained to perform duty as per this SOP.

QC Associate: Officer/executive QC Department trained to perform duty as per this SOP.

Engineering Associate: Officer/executive Engineering Department trained to perform duty as per this SOP.

5.2  Procedure:

5.2.1	Buildings
5.2.1.1	Ensure separate entry/exit is followed for materials and personnel to prevent cross contamination and/or mix-ups.
5.2.1.2	Ensure that the washroom and toilet facilities are separate, maintained at clean and hygienic condition and provided with necessary items like soap, hand dryer etc.
5.2.1.3	Ensure that appropriate changing/gowning facilities are provided and followed at the entrance of production area
5.2.1.4	Ensure adequate room/area designed for specific operations are used properly
5.2.1.5	Ensure segregated areas for waste materials are used
5.2.1.6	Ensure lighting, temperature, humidity and ventilation are appropriate for the operations carried out and do not adversely affect product manufacturing, storage or equipment functioning.
5.2.2	Structure & Finish
5.2.2.1	Ensure that preventive measures have been taken to prevent entry or harbouring of insects, birds, and rodents.
5.2.3	Warehouse/Storage Areas
5.2.3.1	Ensure that warehouse/storage areas are maintained in a good state of repair, and have appropriate cleaning procedures.
5.2.3.2	Check outside doors and receiving docks must minimize exposure to outside environment. Storage racks and materials can be cleaned. Windows are sealed or closed.
5.2.3.3	Ensure that storage areas have adequate space for material storage with segregation where needed.
5.2.3.4	Ensure only approved materials are dispensed for batch manufacturing.
5.2.3.5	Ensure that materials are stored off the floor.
5.2.3.6	Check whether materials are spaced to allow cleaning and inspection.
5.2.3.7	Labels for different products, strength, dosage forms, etc stored separately with suitable identification.
5.2.3.8	Rejected components, materials, and containers quarantined and clearly marked to prevent their use.
5.2.4	Production Areas
5.2.4.1	Access to the manufacturing area is controlled; no unauthorized person should enter the manufacturing area. Ensure that entry change room(s) manufacturing and packaging area is clean and provide protection from ingress of outside contaminations.
5.2.4.2	Ensure that the path or flow of materials from receipt to finished product should be one way. If some materials do cross paths, procedures must be in place to minimize potential mix-up.
5.2.4.3	Ensure that the personnel movement within or between departments/areas cannot contribute to contamination from the external environment or internal product dust from one area to another.
5.2.4.4	Check whether air locks separate the outside environment from the manufacturing areas.
5.2.4.5	Check whether floors/walls are smooth, non-porous, easy to clean surfaces in a good state of repair, resistant to cleaning materials.
5.2.4.6	Check whether wall/floor/ceiling junctures are smooth or coved for cleaning. Floors sloped to drain and drains are trapped.
5.2.4.7	Check whether ceilings are smooth, cleanable with no holes or crevices. Utilities (electric, water, gas) are sealed at point of entry/exit. If utility service lines are exposed, the surfaces of the pipes, ducts are cleanable.
5.2.4.8	Ensure that all equipment are provided with SOPs for operation, cleaning and maintenance.
5.2.4.9	Check whether cleaning procedure is in place and followed properly.  Cleaning procedure should include cleaning schedules, methods and appropriate cleaning agents.
5.2.4.10	Where disinfectants are used to sanitize surfaces such as walls, floors, and ceilings and are rotated according to a written procedure.
5.2.4.11	Check whether records of machine usage, cleaning and maintenance are maintained.
5.2.4.12	Check whether control of air pressure, dust, humidity and temperature adequate for the manufacture, processing, storage or testing of drug products.
5.2.4.13	Check whether air filters are routinely cleaned and replaced as per existing procedure.
5.2.4.14	Ensure drains are designed to prevent standing water inside the facility.
5.2.4.15	Check whether the procedure for preventing infestation by rodents, birds, insect and vermin’s are followed.
5.2.4.16	Check whether sewage, trash and refuse are disposed in a safe and sanitary manner.
5.2.4.17	Check whether design and operating precautions are taken to ensure that lubricants and coolant do not come in contact with the contact part to the drug components.
5.2.4.18	Ensure that each piece of equipment is clearly marked ‘to be cleaned’ or ‘cleaned’; under maintenance etc.
5.2.4.19	Ensure whether equipment is promptly cleaned after use.
5.2.4.20	Ensure that each equipment have preventive maintenance status describing due date and servicing date, equipment ID, model, make, authentic signatory etc.
5.2.4.21	Ensure whether washing facility for equipment and accessories are maintained in sanitary conditions and do not allow any source of contamination and cross contamination.
5.2.5	Packing Area
5.2.5.1	Ensure that packing operations are carried out in separate and segregated manner.
5.2.5.2	Ensure that access to primary packing area is controlled
5.2.5.3	Ensure that materials are handled and transferred in safe and secure manner in order to avoid cross contamination and mix up in packing area.
5.2.5.4	Check whether gowning procedure is followed properly during entering the primary packing area.
5.2.5.5	Check whether packing operations in primary packing cubicles are carried out in an environment (temperature and humidity) as per product requirement and monitored continuously.
5.2.5.6	Ensure that log books of machine usage and cleaning are filled correctly and maintained up to date.
5.2.5.7	Ensure that packing cubicle is maintained in clean and sanitary condition to prevent risks of contamination, cross contamination and mix ups.
5.2.5.8	Ensure that each piece of equipment is clearly marked ‘to be cleaned’ or ‘cleaned’; under maintenance etc.
5.2.5.9	Ensure whether equipment is promptly cleaned after use.
5.2.5.10	Ensure that each equipment has preventive maintenance status describing due date and servicing date, equipment ID, model, make, authentic signatory etc.
5.2.5.11	Ensure washing area for equipment and change parts are designed and maintained to facilitate adequate cleaning as per approved procedure.
5.2.5.12	Ensure that coding operations are performed separately in segregated manner and control measures are being taken.
5.2.5.13	Ensure that products and materials are kept in the clean pallets in segregated manner.
5.2.6	Quality Control Laboratory
5.2.6.1	Ensure that interior surface (walls, floor, and ceilings) are smooth and free from cracks, and permit easy cleaning and disinfection.
5.2.6.2	Ensure that safety installation such as shower; eye washer, fire extinguisher etc are working properly in the laboratory.
5.2.6.3	Ensure that drainage system facilitate proper maintenance and prevent water logging in the laboratory.
5.2.6.4	Ensure that preventive measures have been taken to prevent entry of insects and rodents in laboratories.
5.2.6.5	Ensure that all personnel wear laboratory coats or other protective clothing including gloves and face masks and eye protection wherever required.
5.2.6.6	Ensure that all laboratory equipment/instruments are identified and labeled with unique ID.
5.2.6.7	Ensure that all laboratory instruments are calibrated as per schedule and properly labeled.
5.2.6.8	Ensure that all equipment/instruments are provided with SOPs for operation, cleaning, maintenance and calibration and records are maintained
5.2.6.9	Ensure that SOPs for handling and storage of test samples, retained samples, reference standards/cultures, reagents are followed properly and records are maintained.
5.2.6.10	Ensure that all reagents and solutions in the laboratory are properly identified with a label.
5.2.6.11	Ensure that stock solutions, standard solutions, volumetric solutions are prepared as per SOP and records are maintained.
5.2.6.12	Ensure that hazardous or poisonous materials are stored and handled as specified in the SOP.
5.2.6.13	Ensure that all the personnel working in the departments are trained in their respective job responsibilities and safety system in laboratory and records are maintained thereof.
5.2.6.14	Ensure that STPs and SPCs of all raw materials, semi-finished and finished products are available and followed.
5.2.6.15	Ensure that SOP for preparation of working standards is available and followed meticulously.
5.2.6.16	Ensure that SOP for preparation and sub culturing microbial cultures are available and followed.
5.2.6.17	Ensure that laboratory is provided with latest and updated compendia, supplement or addendum.
5.2.6.18	Ensure that all the records generated are archived in separate area in secure and safe manner.
5.2.7	HVAC System
5.2.7.1	Ensure that HVAC service floor is away from the production, warehouse/storage and QC area and do not lead to these areas directly.
5.2.7.2	Ensure AHUs, dehumidifiers, duct lines, filters, dampers, exhaust fans etc are placed at strategic points to facilitate easy operation, maintenance and cleaning activities.
5.2.7.3	Ensure each AHU/dehumidifier has drawing to indicate its supply system and component arrangements.
5.2.7.4	Ensure that critical equipment of HVAC system are identified with a unique ID number.
5.2.7.5	Ensure that all the supply lines/ducts are marked with signs to indicate nature and direction of supply.
5.2.7.6	Ensure that routine cleaning of filters are carried out as per procedure and records are maintained.
5.2.7.7	Check whether filter cleaning area is maintained under negative pressure and adequate preventive measures are being taken to prevent dust.
5.2.7.8	Ensure that facilities provided for filter cleaning like cleaning machine, water supply, compressed air supply, drains and drying section are in proper working condition.
5.2.7.9	Ensure that cleaned and un-cleaned filters are handled and replaced in safe manner and procedure has been established.
5.2.7.10	Calibration procedure for measuring devices like pressure gauges, timers, thermometers etc are followed and records are maintained.
5.2.7.11	Ensure that a scheduled preventive maintenance programme is followed for critical equipment and records are maintained.
5.2.7.12	Ensure that SOP for operation, cleaning and maintenance for all critical equipment are available at the location and followed meticulously.
5.2.7.13	Check whether break down records of production equipment are maintained.
5.2.7.14	Ensure that approved spares/parts where necessary are kept to maintain continuous operation of the system.
5.2.8	Water System
5.2.8.1	Ensure that the current schematic drawing of the water system is in place.
5.2.8.2	Ensure that PW generation area is maintained in clean and sanitary condition.
5.2.8.3	Ensure that SOPs for operation, cleaning, sanitization, regeneration and maintenance are available for all equipment involved in the purification steps at the location.
5.2.8.4	Ensure there is no any leakage in the PW generation and distribution loop line.
5.2.8.5	Ensure that all the equipment are properly labelled with name, ID number, maintenance and calibration status etc.
5.2.8.6	Ensure that sanitization of PW tank and distribution system is routinely carried out as per current procedure and records are maintained.
5.2.8.7	Ensure that softener is regenerated periodically as per current procedure and records are maintained.
5.2.8.8	Ensure that chlorination and de-chlorination procedure is followed and records are maintained.
5.2.8.9	Ensure that chemicals for chlorination, de-chlorination and other treatments are analysed and approved by QC department prior to use. Check approved label.
5.2.8.10	Ensure that all measuring devices i.e. pressure gauges, timer, conductivity meter, pH meter, ampere meter, voltmeter, flow meter etc are calibrated and records are maintained.
5.2.8.11	Ensure that sampling procedure for chemical and microbiological analysis of water are followed meticulously and records are maintained.
5.2.8.12	Ensure planned preventive maintenance programme is available to the engineering department and records are maintained.
5.2.8.13	Ensure that RO membranes are cleaned/replaced periodically and records are maintained.
5.2.8.14	Ensure mixed bed is regenerated periodically as per procedure and records are maintained.
5.2.8.15	Ensure tanks are cleaned and sanitized appropriately as per established procedure and records are maintained.
5.2.8.16	Ensure that each sampling points are identified and labelled properly and preventive measure are being taken during sampling.
5.2.8.17	Ensure that necessary approved spare parts are available in the engineering department where applicable.
5.2.8.18	Ensure that operating ranges and alarm system for critical parameters have been established and appropriate troubleshooting action plan is in place.
5.2.8.19	Ensure that vent filter is routinely subjected to integrity testing and integrity test records are maintained.
5.2.8.20	Ensure that documentation related to deviation, change control, OOT, investigation, incident in the water system are maintained.
5.2.9	Compressed air system
5.2.9.1	Ensure that current schematic drawing of compressed system is in place describing details of components functions.
5.2.9.2	Ensure that compressed air equipment are maintained in cleaned condition and properly labelled with name and ID number.
5.2.9.3	Ensure that SOPs for operation, cleaning, calibration and maintenance of all equipment are at the location.
5.2.9.4	Ensure that sampling points of compressed air system are clearly identified and labelled.
5.2.9.5	Ensure that current sampling procedure for compressed air system and records are maintained.
5.2.9.6	Ensure that planed preventive maintenance programme is followed for CAS and records are maintained.

 

6. Abbreviation:

Abbreviation	Expansion
SOP	Standard Operating Procedure
QAD	Quality Assurance Department
HVAC	Heating Ventilation and air conditioning
AHU	Air Handling System
ID	Identification
PW	Purified Water
OOT	Out of Trend
CAS	Compressed Air System

                 

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

SOP Title: Training

1. Objective:

To lay down procedure to ensures that personnel engaged in the manufacturing, processing, packaging, Quality Control and storage of drug products have the proper education and/or training to perform their responsible function. In addition, the theory and practice of GMP must be addressed.

2. Scope:

It covers all employees involved in the effective implementation and maintenance of quality system.

3. Responsibility:

Plant Head : Identifying and approving training needs of HODs.

HODs         : Identifying training needs of personnel reporting to him and down below. On Job training of personnel in his department.

Concerned Department: To identify, initiate, evaluation and document the training.

4. Accountability:

Head – Quality Assurance

5. Procedure:

• Definition:

Training: Training is defined as a process of teaching or learning a skill through interaction.

On-the-Job Training: is a form of training taking place in a normal working situation in their respective areas of operation according to the training need identification of individual departments.

Training Need Identification: is the procedure before going to operation of any job in individual department trainee/trainer shall identify the procedure/SOP in which he/she needs training.

• Procedure:

5.2.1	Requirements:
5.2.1.1		It is necessary that all the employees at the Plant shall have an appropriate combination of Education, Training and Experience to enable them to perform their assigned functions.
5.2.1.2		Therefore a training programme covering the following aspects shall be designed for all the  employees.
5.2.1.3		Training shall cover the specific operation that the employee performs and the relevant aspects of GMP & hygiene.
5.2.1.4		In house qualified individuals and external faculty shall conduct training.
5.2.1.5		Individual employee shall maintain training record given in the course of employment.
	Training of New Recruits:
5.2.2	Induction Programme:
5.2.2.1	Every new employee shall be given Induction Training with a view to facilitate entry into the organization and to acquaint with the systems and procedures as applicable. During the induction training, all new employees shall be formally inducted to the company.
5.2.2.2	Training need of new recruit shall be determined and the trainer shall be responsible for training the employees at this stage.
5.2.2.3	During induction training, the employees shall receive general information in the following department as appropriate. Administration Department, Quality Assurance, Quality Control, Production, Warehouse, Engineering and Purchase and Accounts.
5.2.2.4	The Induction Training shall be carried out in accordance with the format specified in SOP.
5.2.3	SOP/On-the-Job Training:
5.2.3.1	SOP/On-the-job training shall be given to the employees in their respective areas of operation according to the training need identification of individual departments as per “Training Need Identification” format.
5.2.3.2	During on-the-job training period, employees shall be trained for usage of equipment, unit operations, safety norms to be followed, Quality Assurance Procedures and Standard Operating Procedures, Validation and Calibration procedures, Preventive Maintenance as applicable. Adequate time shall be allotted to complete SOP training and on the job training.
5.2.3.3	Training Log shall be maintained for each training as per “Training Log Sheet”.
5.2.4	Evaluation:
5.2.4.1	Evaluation shall be done by preparing a questionnaire based on the topics covered during the training. The Evaluation sheet shall be filled by the trainee by writing answers of the questions asked.
The details of evaluation shall be recorded in ‘Training Evaluation Sheet’. 1.      Trainee shall have to secure minimum 80% marks to qualify. 2.      Maximum marks will be 100%. 3.      If any employee obtain less than 80% marks, he/she shall be considered as disqualified for that topic and retraining shall be given. 4.      Evaluation questionnaire shall be generally objective type e.g. multiple choice questions, true and false or fill in the blanks etc. 5.      If by- mistake wrong answer selected can be cross cut with single line with sign and date and select or write correct answer.
5.2.4.2	After completion of induction training and SOP training, new employee shall be directed to Concerned Department for assessment and certification as per “Training Certificate” form.
5.2.4.3	Calculation for % marks obtained:  No. of correct Answers Percentage (%) Of Mark Secured = ————————————- x 100 No. of Questions   =  ________________ x 100                                                          =  _________ %
	Training in the Course Of Employment:
5.2.5	Training by in House and External Faculty: In-house training or training from outside faculties including symposia and seminars shall be organised as per need.
5.2.5.1	An “Annual Training Plan” shall be drawn as per SOP and  it shall be imparted on a periodical basis throughout the year covering GMP aspects.
5.2.6	In Addition to the Training Imparted Based on the Annual Plan, Training shall be given in the Following Events:
5.2.6.1	Introduction of new standard operating procedure.
5.2.6.2	Change in SOP content, observation of audit, laboratory testing error, manufacturing error, document error and packing error etc.
5.2.6.3	The trainer shall intimate the concerned persons for attending the training programme.
5.2.6.4	The SOP which has been revised to do some minor changes and will not have impact on procedure content or meaning like grammatical correction, typo error, footer change or formatting in that case no need to fill evaluation sheet. Information shall be given to concern regarding changes.
5.2.6.5	The details of training shall be updated in the individual “Training Need Identification”. The Training Evaluation Sheet shall be maintained in individual training file. Evaluation sheet is not required for the trainer for that particular topic.
5.2.6.6	As and when required, the personnel shall be sent for attending training programme conducted by external training institutions, manufacturers for machinery and equipment etc.
5.2.6.7	Separate training record shall be maintained as “Outside Training Record” for external training.
5.2.7	Re-training of employees :
5.2.7.1	If an employee has been absent from the company or is returning to a specific task after a period of greater than six months, the need for re-training must be evaluated in association with the employee. This evaluation shall be documented and the decision recorded as per “Retraining Assessment” format. Where applicable questionnaire relevant to the employees job description may be used as part of the evaluation process.
5.2.8	Training for contract employee:
5.2.8.1	Training shall be conducted for workmen, housekeeping personnel and contract workmen of Specific working areas.
5.2.8.2	Wherever required SOP shall be converted to vernacular language or training shall be imparted in vernacular language for better understanding of procedures to contract workers.
5.2.8.3	Evaluation sheets are not required for contract workers.
5.2.8.4	Contract workers shall work under supervision of trained staff.
5.2.8.5	Training Attendance Log shall be filled for contract workers.
5.2.9	Trainer Certification:
5.2.9.1	Trainer shall be assessed for skills like subject matter expert, subject understanding, presentation skill, training skills, communication skills, interaction skill, voice clarity etc.
5.2.9.2	Training topic shall be prepared and a trial presentation shall be held in front of Department Head and QA Head for training skill assessment.
5.2.9.3	If training skills found appropriate the trainer shall be certified as per “Trainer Certificate” form.
5.2.9.4	If training skills found not appropriate then give suggestion for training skills improvement and call back for re-trial.
5.2.9.5	After successful completion of training assessment training shall be conducted.

 

6. Abbreviation:

Abbreviation	Expansion
SOP	Standard Operating Procedure
QA	Quality Assurance
GMP	current Good Manufacturing Practice
HOD	Head of the Department
e.g.	Exempli gratia
etc	etcetera

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

SOP Title: Resource Management Process

1. Objective:

To lay down the procedure for identification, evaluation, procurement/recruitment and implementation of resources to implement and improve the processes of the quality system

2. Scope:

This procedure is applicable to all resources  i.e. Personnel, Equipment, Instrument, Tools, Spares, Consumables, or other items that influence quality or quality related operations in the plant.

3. Responsibility:

Senior Management: Responsible to appoint department Heads and approval of other resources.

Head of Departments: Responsible to appoint new manpower and to procure new machines and other resources.

4. Accountability:

Plant Head/Department Head

5. Procedure:

• Definition:

Concerned Department: To identify, initiate the need of resources, review and document the PO as per this SOP.

 

• Procedure:

5.2.1	The need of resources shall be determine or identify and communicate to the Management adequate and appropriate resources (Human, Materials, Facilities, and Equipment) to implement and maintain the Pharmaceutical Quality System and continually improve its effectiveness.
5.2.2	Ensure the requirement of resources are appropriately evaluated, identified, communicated to management, procured and applied to a specific product, process, or site.
5.2.3	A need assessment shall be conducted by the discussion with the Management/Resource Approval Authority to determine resource needed. Besides identifying specific resource for any task.
5.2.4	The Needs Assessment should Consider the following Questions:
·       What quantity of resource is required? ·       When will the resource be needed? ·       What capability does the resource need to have? Are there any limitations? ·       What is the cost of procuring the resource?
5.2.5	To approve the resources as per requirements of different departments.
5.2.6	Once the Preliminary Approval is obtained from Management, the procurement process shall be initiated as per Annexure.
5.2.7	Requisition/Indent for supplies, services and financial commitment shall be prepared through competitive and non competitive process (as appropriate) by discussion with Purchase and Account Department as applicable and sent to the Management/Resource Management Authority for Approval.
5.2.8	After Requisition/Indent Approval, request for quotation shall be sent to different Agencies/Suppliers/Manufacturer.
5.2.9	Quotations for customized Products/Equipment/Instruments/Services shall be reviewed before an order made to the Supplier/Manufacturer.
5.2.10	Review of quotation orders for Products/Services shall consist of verification of the user requirements specification, including requirements stated by the customer, are adequately defined and documented and have been fully understood. If the quotation order requires clarification, then it will not be accepted until the missing information is obtained from the Supplier/ Manufacturer.
5.2.11	Consideration shall be given whether our capability and capacity are adequate to satisfy the product need.
5.2.12	If required, a Site Inspection and Evaluation Programme shall be conducted to review the Product/Service/Equipment Design and Specification as per URS.
5.2.13	After complete Evaluation and Analysis order shall be accepted from adequate Supplier/Manufacturer and decision shall be made in order to place Purchase Order (PO).
5.2.14	Records of contract/order review shall be documented. A copy of the quotation, signed by authorized representatives of all participating functions, in addition to a copy of the PO order shall be filed.
5.2.15	Purchase Order shall be generated and sent to the Supplier/Manufacturer.
5.2.16	A suitable procurement plan shall be made by considering specification, method of delivery at site, time, mode of payment, financial approval and legal requirements.
5.2.17	The procurement plan, product specification, supplier and contract details and specific responsibilities shall be communicated to all personnel involved in the procurement process.
5.2.18	The procurement of resources shall be verified, documented and subjected to further Qualification as applicable.
5.2.19	Requirement of Equipment, Instruments and other Items: The resource requirements for Equipment and Instruments shall be identified on the following basis:
5.2.19.1	Quality Requirements:
·         Up-gradation or improved version of existing equipment for particular operation. ·         Requirement for current GMP or quality audit compliance. ·         Requirement due to wear and tear of existing equipment/instrument, spare, component etc. ·         Requirement of consumable for routine operation and activities.
5.2.19.2	Quantity Requirements:
·         Additional quantity requirement shall be decided based on more output required, increase in production, smooth functioning of plant and maintain desire quality of product. ·         For critical equipment/instruments the User Requirement Specification (URS) and Design Qualification details shall be prepared through defined and an approved procedure before procurement wherever applicable.
5.2.19.3	Requirement of Personnel/Human Resource: The requirement of Human Resources shall be identified as follow:
5.2.19.3.1	To identify and appoint key personnel in the factory like Unit Head, QA Head, QC Head, Engineering Head, HR Head, Production Head etc.
5.2.19.3.2	To identify the need of man power and communicate the request to Management for approval. After approval the request for recruitment shall be sent to the Human Resource Department.
5.2.19.3.3	The recruitment for manpower may be required for New Expansion, Replacement (due to Resignation) or any additional purposes. By following sources manpower pooling can be achieved: ·         Through manpower consultants/Employment agencies. ·         Through advertisement in news paper. ·         Through website posting. ·         Employee referral. ·         Walk in applicants.

 

6. Abbreviation:

Abbreviation	Expansion
HR	Human Resource
URS	User Requirement Specifications
GMP	Good Manufacturing Practice
etc	etcetera

*Note – Ready to use SOP available in “DOWNLOAD” Section.

SOP Title: Handling of Deviations

1. Objective:

To lay down the procedure for handling of deviations in the premise

2. Scope:

This procedure is applicable to all deviations observed during any stage of receipt, handling, storage, processing, testing, manufacturing and packing operations of the product (s) or material (s) including planned activities like training, audits or self inspection etc

3. Responsibility:

It is responsibility of every personnel working in the respective department to report deviation to QA department and follow the procedure.

Department heads- To ensure deviation is raised, reviewed, evaluated, investigated, CAPA taken and recommendations are implemented and documented

Quality Assurance Head – To review, evaluate, analyse impact and authorize deviation, ensure investigation, CAPA taken, implementation and approval of deviation

4. Accountability:

Head Quality Assurance department

5. Procedure:

5.1 Definitions:

Deviation: A departure from standard practices or specifications resulting in non-conforming material /or processes, with potential to impact on product quality, safety, efficacy or data integrity. The deviation is an event occurring within the quality system, usually detected by the staff of the area in which the event occurred, which may result in non compliance with the quality system or the product requirement/contract giver.

There are two types of deviation:

Planned deviation: A planned deviation occurs, for example, when an unexpected event prevents an SOP from being followed exactly as written.  Such deviations must be authorized before they are implemented and are expected to be short term solutions to a problem with immediate impact.

Unplanned deviation: An unplanned deviation is a deviation that is discovered after the procedure /process has been carried out.

To assess the risk & severity involved, the deviations are categories as followings:

Critical: A deviation that has a significant impact on the quality and/or safety of the final product

Major: A deviation that is likely to have an impact on quality of the product, but does not make any   significant impact in the final quality of the product

Minor: A deviation that may not have an impact on the identity, quality, purity, strength, stability, safety and efficacy or physical characteristic of the product

Root cause: Root cause is that basic reason for an undesirable condition or problem, which if eliminated or corrected would have prevented it from existing or occurring.

Corrective action: It is action taken to eliminate the causes of an existing deviation, defect or other undesirable situation in order to prevent recurrence.

Preventive action: It is action taken to eliminate the causes of a potential deviation, defect or other undesirable situation in order to prevent occurrence and improve quality trends.

Immediate or remedial action: An action taken with immediate effect to minimize the harm to the product quality or customer before investigation.

QA Associate: Officer/executive or any personnel of QA department trained to perform duty as per this SOP

Concerned Department: Department in which the deviation has been noticed and raised as per the scope of this SOP

Concerned Department Associate: Officer/executive or any personnel of concerned department trained to perform duty as per this SOP

Designee: The person who is having adequate training, experience and qualification and assigned or delegated by the department head to perform the responsibility of deviation handling as per scope of this SOP

5.2  Procedure:

5.2.1	Numbering of Deviation Report
5.2.1.1	Each deviation noticed shall be number as mentioned below: DRQAYYNNN where DR denotes deviation report, followed by QA denotes Quality Assurance department, followed by YY represents last two digit of the current year and last three digits NNN represents serial number as (001, 002, 003….). For example the deviation report number for first deviation of year 2024 shall be assigned as DRQA24001.
5.2.2	Reporting of Deviation
5.2.2.1	Any deviation from instructions or procedures should be avoided as far as possible. If deviations occur, they shall be done in accordance with this procedure. The authorization of the deviation shall be approved in writing by a designated person, with the involvement of the QC department, when appropriate.
5.2.2.3	The department head/designee shall initiate the deviation report in the prescribed format ‘Deviation Report’.
5.2.2.4	Initial investigation shall be made for the deviation and mentioned in the report along with reason.
5.2.2.5	Type of deviation i.e. planned and unplanned and period for which deviation is requested to be permitted (in case of planned deviation) shall be mentioned in the report.
5.2.2.6	Each deviation shall be logged in the current version of the ‘Deviation Log’ as per format.
5.2.2.7	All deviation reports shall be authorized by QA head/designee prior to implementation.
5.2.3	Evaluation and Analysis
5.2.3.1	Deviation shall be evaluated and assessed for its potential impact on   product quality, validation or regulatory commitment and on the basis of evaluation the deviation shall be categorized as minor, major or critical.
5.2.3.2	Immediate remedial action shall be taken when the quality, efficacy or safety of the product may be compromised by the deviation.
5.2.3.3	In case of contract manufacturing product, deviation shall be sent to the contract giver for impact assessment and approval.
5.2.3.4	Following aspects should be considered during evaluation of deviation but not limited to: — Scope of the validation- batch affected — Trend related to similar products, materials, equipment, testing procedures, previous complaints, previous deviations, APR and returned goods where appropriate. — A review of similar causes — Potential quality impacts — Regulatory commitment impact — Other batches potentially affected — Market actions
5.2.3.5	Deviation shall be authorized or allowed for further processing /activities if it does not adversely affect the product quality and system/operating procedures.
5.2.3.6	All planned deviation shall be authorised for limited batches/or with a valid period of time as appropriate.  Any extension of the authorized time period should be mentioned on the deviation form.
5.2.3.7	After depth of deviation is analysed, it has to determine whether   investigation is necessary.
5.2.3.8	If the deviation requires a permanent change in documents /system consequent to the deviation shall be handled through SOP ‘Change Control Management’.
5.2.3.9	If a deviation leads to a non-conforming product, it shall be handled according to SOP ‘Control of Non-Conforming Product’.
5.2.3.10	If deviation leads testing results out of specification limit then it shall be handled according to SOP, ‘Out of Specification’.
5.2.4	Root Cause Investigation
5.2.4.1	Thorough investigation of the deviation shall be performed to find out the root cause of the deviation. The root cause shall be investigated considering ‘5 M approach’ i. e. man, material, machine, method and mother nature (environment).
NOTE: Primary root cause is essential for determining appropriate corrective action and/ or preventive action. These root cause may help in suggesting whether inappropriate training, operation, equipment, procedure or environment have lead to failure or deviation.
5.2.4.2	All investigations shall be completed within 30 days of initiation of the deviation unless otherwise authorized by QA.
5.2.4.3	Summary of the root cause investigation shall be entered on the deviation form. A separate sheet may be attached for investigation with reference if required.
5.2.5	Development of action plan (Corrective and Preventive Action)
5.2.5.1	Based on the result of the root cause analysis, all tasks required to correct the problem and prevent reoccurrence shall be identified and included in an action plan.
5.2.5.2	Corrective actions to be taken for the particular deviation shall be discussed with related department and mentioned in the deviation form.
5.2.5.3	The requirement for revalidation, retraining, stability testing etc. shall be evaluated and if required, clearly mentioned in action plan.
5.2.5.4	Similarly preventive actions to prevent occurrence of potential problem shall also be mentioned in the said form.
5.2.5.5	Responsibilities assigned and due date for implementation shall be mentioned in action plan.
5.2.5.6	If required, a separate CAPA may be initiated as per SOP to eliminate the existing and potential root cause after approval by QA head.
5.2.6	Review of action Plan (CAPA)
5.2.6.1	The CAPA shall be reviewed by all other department i. e. production, QC, QA, engineering, warehouse and admin/HR etc (as applicable).
5.2.6.2	Finally the report shall be reviewed by head QA department.
5.2.7	Implementation of CAPA and Follow up
5.2.7.1	It shall be ensured that the action plan is executed and all tasks are completed as mentioned in the deviation form within the specified time frame.
5.2.7.2	The actions that were taken shall be documented.
5.2.7.3	The appropriateness and effectiveness of the action taken shall be evaluated and verified after implementation.
5.2.8	Final review and Close-out
5.2.8.1	Final review of the completed deviation report shall be done and comment shall be made with closeout date.
5.2.9	General
5.2.9.1	Flow for deviation handling shall be maintained as procedure mentioned above.
5.2.9.2	A photocopy of the deviation report shall be attached to the batch documents (if required) and original shall be retained with QA department.
5.2.9.3	All deviations and their related investigations shall be reviewed as a part of the batch record review before the batch is released.
5.2.9.4	If similar type of minor deviations occurs frequently, these should be trended. Based on this trend, a permanent change can be proposed and implemented.
5.2.9.5	In case of critical deviation, it shall be notified to higher management for review and decision shall be made accordingly to avoid any harm to the user.
5.2.9.6	Any deviation in product for exports shall be communicated to the export department/ customer.

 

6. Abbreviation:

Abbreviation	Expansion
SOP	Standard Operating Procedure
DR	Deviation Report
QA	Quality Assurance Department
CAPA	Corrective And Preventive Action
APR	Annual Product Review
e.g.	Exempli gratia
i.e.	id est (that is)

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

SOP Title: Change Control Management

1. Objective:

To document and evaluate approval system for initiation and/or implementation of technical changes in procedures, Raw Materials, Packing Materials, manufacturing process, Analytical Testing Methods, equipments, utilities and operating environment etc.

2. Scope:

This SOP covers the following:

1. Change/s in Quality System and its documentation.
2. Manufacturing Process or Testing Method and its Equipment and/or Instrument.
3. Approved Facility/Utilities, Specifications (Raw, Packing, In-process, Finished

Product/Finished Product shelf life).

4. Modifications in Water System / HVAC System or Compressed Air System.
5. Storage Conditions, Formulations, Vendors of Raw and Packing Materials, Packaging Material, Packaging Configuration/ Style / Text Matter and Artworks etc.
6. Responsibility:

Concerned Department: To identify and assess need of change required & initiate through Change Control procedure.

QA Department: To review and approve the change; to verify the implementation and ensure compliance of the procedure.

Other Departments: To analyse the impact of the change in their respective departments and review the change as applicable.

 

4. Accountability:

Head Quality Assurance and Head Concerned Department

5. Procedure:

• Definition:

         Change: Change includes any Addition to, Deletion of or Modification to a System, Process, Materials, Product, Procedure and Equipment or Instrument. Changes can be categorized as follows:

1. Minor change:

A change that may not have an impact on the identity, quality, purity, strength, stability, safety

and efficacy or physical characteristic of the product.

2. Major change:

A change that is likely to have an impact on quality of the product, but does not make any

significant change in the final quality of the product.

3. Critical change:

A change that has a significant impact on the quality and/or safety of the final product

• Procedure

5.2.1	A proposal for any change i.e. addition/deletion/modification shall be initiated in change control format.
5.2.2	The Change Control Log for all changes taking place within the facility shall be maintained in format.  (having the details like: Change Control No., Date, Initiating Department, Document No., Description of change, Type of change i.e. Minor/Major/Critical, Change Control Approved/Rejected, Closing date, Closing Remark and Sign of  QA).
5.2.3	All supporting and reference documents shall be attached to the change control form before sending for QA approval. e.g.: Draft SOP, Proposed layout design, Draft STP, Specification, Guideline, Regulatory document etc as applicable.
5.2.4	Change control form and supporting document shall be reviewed for its appropriateness before sending to QA Department.
5.2.5	If changes are more and cannot accommodate in space provided in Change Control Form then separate annexure shall be prepared by making column for proposed change, existing procedure and justification for change with Prepared By, Checked By, Sign and Date.
5.2.6	After review of Concerned Department Head, initiator shall submit the change control form to QA Department for approval.
5.2.7	A Change Control number shall be allotted to each change  as mentioned below: CCQAYYNNN Where, CC denotes Change Control, QA denotes Department Code for Quality Assurance Department, YY denotes last two digits of the current year and NNN denotes three digits serial number (e.g. 001,002,003…..). For Example:-first change notified for year 2024 shall be numbered as CCQA24001.
5.2.8	Review of proposed changes and supporting documents shall be done before approval.
5.2.9	If needed, additional supporting documents may be required with respect to proposed changes.
5.2.10	The Change Control form shall be circulated to Concerned Department for impact assessment and comments. Impact of proposed changes on other department shall also be assessed.
5.2.11	After receiving comments from all Concerned Department QA shall review the comments to assess any other impact of the change.
5.2.12	After complete assessment, change shall be approved or rejected.
5.2.13	The review of a proposed change shall involve activities such as conducting experiments, analysis, review of master documents, stability data etc if required.
5.2.14	In case of a change pertaining to the product manufactured for specific customer on contract basis, approval of the change shall be taken from the customer prior to the implementation by sending notification of the proposed change with justification and proposed change data generated to support evaluation of the change. Upon receipt of acceptability from the customer, the change shall be implemented.
5.2.15	The change shall be implemented with immediate effect based on the information, review and recommendation.
5.2.16	After implementation of the proposed change necessary data shall be collected and forwarded to Head QA.
5.2.17	The verification shall be carried out to ascertain whether the changes and the consequent changes have been implemented satisfactorily.
5.2.18	All the documents undergoing changes due to implementation of change control shall be revised and controlled as per SOP.
5.2.19	The change control shall be closed within 30 days from the date of initiation. However, based on the nature of the change, extent of the work involved or any experiments / validations studies to be carried out; extension to closing time can be approved for completion and it shall be written as in the Change Control forms.
5.2.20	Trending of changes shall be done once in a year during product quality review. If frequent changes observed on a particular subject, then Corrective and Preventive Action shall be followed to reduce the number of changes.
5.2.21	Recommended supporting studies for changes
	Sr. No. Type of change Recommendations 01 Change in procedures Training to concerned persons, change in relevant documents and/or Validation wherever required. 02 Change in manufacturing formula Validation of 3 consecutive batches with Stability Studies or as per the requirement. 03 Change in BMR Training to the concerned. 04 Change in manufacturing process Validation of 3 consecutive batches with Stability Studies or as per the requirement.
	05 Change in specifications Stability studies on the changed specifications, test Method Validation. 06 Change in Test Methods Method validation study. 07 Change in SOP Training to the concerned, change in relevant documents. 08 Change in expiry Stability studies, change in relevant documents, intimation to Concerned Department. 09 Change/modification in manufacturing equipment Validation of 3 consecutive batches, equipment, Re-qualification. 10 Change in storage conditions Stability Studies in changed conditions change in relevant documents. 11 Change in RM source or supplier Stability studies of the lots comprising the changed RM. 12 Change in packing material other than primary PM Change in relevant documents, intimation to concerned dept., transport trials if required. 13 Change in pack style Change in relevant documents, intimation to Concerned Department. 14 Change in printed text Change in relevant documents, intimation to Concerned Department. 15 Change in Primary PM Validation of 3 consecutive batches, Accelerated / Long Term Stability Studies. 16 Change in manufacturing lot size Validation of 3 consecutive batches accelerated / long term Stability Studies. 17 Change in control procedures i.e. computers, configuration of software etc. Complete validation of the New Software. 18 Change in Room Specification Area Re-qualification / Validation. 19 Transfer of Instrument/Equipment Instrument Re-qualification.
5.2.22	List of Major  and Critical Changes
	Sr. No. Major Changes Critical Changes 01 Source of Excipients Manufacturing Process 02 Storage Conditions Manufacturing Formula 03 Specifications Manufacturing Batch Size 04 Secondary Packaging Materials Manufacturing Location 05 Packaging Style Source of Active Raw Materials 06 Printed Text Bill of Material 07 Modification in existing Equipment Primary Packaging Materials 08 Testing Methods Addition of New Equipment 09 Standard Operating Procedures Change in Equipment 10 Formats Structural Change in the Premises 11 Protocols ———- The list is not exhaustive and can be extended based on practical changes occurring.

 

6. Abbreviation:

 

Abbreviation	Expansion
SOP	Standard Operating Procedure
QA	Quality Assurance
RM	Raw Material
PM	Packing Material
BMR	Batch manufacturing Record
STP	Standard Test Procedure

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.