EQUIPMENT QUALIFICATION AND VALIDATION - SOP

1.0
PURPOSE :
To provide a guideline for qualification and validation activities.
2.0 SCOPE:
Available to all aspects of manufacturing processes , equipments , control systems (including computer hardware and software ), utilities , facility , analytical methods and any significant changes to the above mentiones elements which may affect the quality of products directly or indirectly.
3.0 RESPONSIBILITY:
Production , Quality control , Stores , Engineering , R & d and safety staff and Quality Assurance.
4.0 ACCOUNTABILITY:
Maintenance Manager
5.0 DEFINITIONS:
Manufacturing process :
The transformation of starting materials into finished products through a single operation or a sequence of operations involving installations , personnel ,
documentation and environment.
Qualification :
Identification of equipment attributes related to the performance of particular function or functions and allocation of certain limits or restrictions to those attributes.
Equipment qualification :
The act of planning , carrying out and recording the results of tests on equipment to confirm its capabilities and to demonstrate that it will perform as intended is referred to as Equipment Qualification.
Design qualification (DQ) :
The document verification that the proposed design of the facilities , systems and equipment is suitable for intended purpose. The compliance of the design with GMP should be demonstrated and documented.
Installation Qualification (IQ) :
The document verification that the facilities , systems and equipment as installed or modified , comply with the approved design and manufacturer’s , recommendations. This provides documented verification that all key aspects of the installation are adhered to design intentions and that all equipment manufacturer recommendations have been suitably considered.
This covers equipment , system design and associated engineering aspects through to physical completion of the installation.
Operational Qualification (OQ) :
The documented verification that the facilities , systems and equipment as installed or modified , perform as intended throughout the anticipated operating ranges.
This provides documented verification that the facility , equipment , control systems and facility perform as intended throughout its operating ranges.
Performance Qualification (PQ) :
The documented verification that the facilities , systems and equipment, as connected together , can perform effectively and reproducibly based on the approved process method and product specification.
This stage is related to system performance in the production mode , using actual processing materials or data ( for computers ). Critical equipments undergo extensive validation studies to ensure consistent performance depending on validation protocol / validation report.
Validation :
The collection and evaluation of data, beginning at the process development stage and continuing through the production phase, which ensures that the facility , equipment, manufacturing process, control systems, utilities including personnel and materials are capable of achieving the intended results on a consistent and continuing basis and thus is capable of consistency producing a product that meets the established product specifications.
Prospective validation :
Establishing documented evidence that a process, procedure , system , equipment or mechanism used in the manufacture does what it purports to do based on a pre-planned validation protocol.
Validation of a process by this approach often leads to transfer of the manufacturing process from development function to production.
Prospective validation requires at least 3 consecutive batches with intensive testing to determine that each step is under control.
Scope :
Prospective validation is carried out during development stage to identify those individual steps and equipment settings or process timing, which can prove to be critical in the overall impact of product quality . All these steps , equipment setting and process timing are evaluated to finalize the setting parameter , which can form the basis of giving acceptable , reproducible results. This draft form of study can lead towards the finalization of Batch Manufacturing Record and Batch Packaging Record.
Concurrent validation :
Validations carried out during routine production of products intended for sale.
Scope :
Validation carried out during routine production intended for sale.
This validation comprises of determination and evaluation of process parameters applicable from scale up to final batch size of the product.
This should be performed on 3 process batches. The tests are finalized based on evaluation of the results of these batches. These batches should be monitored for stability and quality trends.
Matrix approach can be applied to process validation. The matrix approach means a plan to conduct process validation on different strength of same product manufactured by the same process and similar type of equipment. Example , validation on one strength (preferably smallest) as a representative amongst the multiple strength of same product.
This approach should be in accordance with cGMP and should demonstrate that the process is consistent for all the strength.
Retrospective validation :
Validation of a process for a product which has been marketed based upon accumulated manufacturing , testing and control batch data.
Scope :
Retrospective validation is historical trending of results of testing and IPQC evaluation on products manufactured by same process to demonstrate that :
• Critical quality attitudes and critical process parameters are still valid as they give consistency in results.
• IPQC and in process controls are appropriate for the given product.
Majority of the batches ( minimum 90%) should meet the processing steps, equipments, process timings, manufacturing environment and demonstrate consistency to specifications. All results , except ‘OOS’ results proven to be caused by analyst / operator error , should be included in the study. Minimum 20 batches should be included in the study. Any gaps in the chronological order of the batches used for the study should be documented and explained.
Revalidation :
Repeated validation of an approved process ( or a part thereof ) to ensure continued compliance with established requirement.
Scope :
Revalidation is done to evaluate the impact of changes in process, product, systems, computers (software), environment, intentionally or un – intentionally.

The revalidation process is intended to ensure that validated systems continue to perform in accordance with the parameters defined during the original validation.
All systems subject to validation should be re validated with in a pre-specified period of time. The revalidation frequency will be determined upon completion of the initial validation of a system.

Revalidation are of two types :
1. Revalidation after the changes to evaluate impact on product quality.
Revalidation after change is done in the following circumstances :
• Major changes in processing steps e.g. change in formulation , input materials, batch size.
• Major change in equipment , design, construction and its material of fabrication.
• Major change in area and support system . e.g.AHU , water system e.t.c
• Major changes in Quality Control Analytical Methods.
• Major changes in Computer – Software and Hardware.
2. Periodic revalidation at scheduled intervals.
Periodic Revalidation is done to evaluate consistency in operations, equipment wear and tear , processing steps , IPQC standards and the overall product quality.
Periodic Revalidation is done for unit process such as mixing , drying, compression, coating , homogeneity etc.. for systems, computers(software), utilities e.g. compressed air and steam.

Note : The extent of revalidation will depend on the nature and significance of the changes.
Validation protocol :

A document describing the activities to be performed in a validation , including the acceptance criteria for the approval of a manufacturing process or a part thereof for routine use.
Validation report :
A document in which the records , results and evaluation of a completed validation programme are assembled . it may also contain proposal for the improvement of process and / or equipment.

PROCEDURE : Qualification is an integral part of Process Validation.
Qualification protocols are prepared for those systems , utility, facility, equipments and area defined as critical for the process . They are prepared following a structure defined in the following sections.
The qualification protocol should provide an index indicating the phase of the program ( DQ,IQ,OQ,PQ )included and documented in it. The scope is to facilitate the location of the information pertaining to Design , installation , Operational and Performance Qualification.
The following sections are to be included in the validation protocols :
Protocol title : This section should provide the title for the protocol and the phase it covers ( DQ,IQ,OQ,PQ ).
Protocol approval section :
The following information should be recorded as part of the approval process of every protocol :
 Code number
 Location
 Supplier
 Protocol Number
 Purpose
 Protocol compiled by : Signatures of User Department , Quality Control , Engineering , and Safety with date.
 Protocol Approved by : Signatures of Quality Assurance with date.
 Protocol Authorised by : Signature of Unit Head with date.
Protocol approval section to be completed prior to the execution of the protocol.
Protocol final approval section which is to be completed upon satisfactory execution of the protocol shall provide space for signature and dates of representatives of the following :]
User Department
Quality Control
Engineering
Safety
Quality Assurance
Unit Head
Completion of the final approval section indicates concurrence with the results and approval of the data by those responsible.
Design Qualification (DQ) :
The following sections are to be included :
• Purpose
• Project requirement
• Critical variables to be met : All critical variables with respect to equipment , area or system under qualification to be mentioned.
• Documents to be attached : Relevant Documents like proposal,purchase order , Approved diagram e.t.c..to be attached.
• Any changes made against the formally agreed design parameters.
• Review (Inclusive of follow up action , if any)
• Recommendation
• Design Qualification signing off : Signatures of user Department , QC , Safety , Engineering,QA and Unit Head.
Installation qualification (IQ) :
The following sections are to be included :
• Purpose
• Critical variables to be met : All critical variables with respect to equipment , area or system under qualification to be mentioned.
• Documents to be attached : Relevant Documents like installation certificate , Training schedules , Layouts etc..to be attached.
• Any changes made against the formally agreed design parameters.
• Review (Inclusive of follow up action , if any)
• Recommendation
• Installation Qualification signing off : Signatures of user Department , QC , Safety , Engineering,QA and Unit Head.
Operational Qualification(OQ) :
The following sections are to be included :
• Purpose
• Critical variables to be met : All critical variables with respect to equipment , area or system under qualification to be mentioned.
• Documents to be attached : Relevant Documents like SOPO’s,MOC Certificate, calibrations reports , training reports e.t.c to be attached.
• Any changes made against the formally agreed design parameters.
• Review (Inclusive of follow up action , if any)
• Recommendation
• Operational Qualification signing off : Signatures of user Department , QC , Safety , Engineering,QA and Unit Head.
Performance Qualification (PQ) :
Note : Performance Qualification for this facility will be executed as a part of process validation whenever possible.
The Performance Qualification protocol for process eqipmentcan only be executed after the installation and Operational parameters of the process defined.
The following sections are to be included :
• Purpose
• Critical variables to be met : All critical variables with respect to equipment , area or system under qualification to be mentioned.
• Documents to be attached : Relevant Documents like validation reports , performance reports e.t.c to be attached.
• Any changes made against the formally agreed design parameters.
• Review (Inclusive of follow up action , if any)
• Recommendation
• Performance Qualification signing off : Signatures of user Department , QC , Safety , Engineering,QA and Unit Head.
Note : The Qualification protocol and report should be prepared by validation team members, approved by Quality Assurance and authorised by Unit Head. Once all the protocol steps have been completed , all the documentation is to be organized . The data and information obtained must be reviewed and its acceptability against the specified acceptance criteria must be determined. A report detailing the acceptability and any deviations in test procedures , methods , or results must be identified and explained. A final conclusion must be prepared and included as a part of the report.
Computer Hardware and Software (DQ/IQ/OQ/PQ) qualification :
Computer hardware and software used as apart of the equipment and systems to control equipment or system must be validated. Design , Installation and Operational qualification of hardware and software should be executed prior to performance qualification of the associated equipment or system.
For reasons of expediency , computer validation can be executed as part of the systems or equipment validation.
The following is suggested content for a computer software / hardware validation.
Computer control system :
Detailed description of control system :
 Control panels
 Power supplies
 Temperature sensors , where ever applicable
 Humidity sensors , where ever applicable
 Smoke detectors, where ever applicable
 Exixting Front-end PC
CPU :
Location
Manufacturer
Model
Processor ( Mother board )
RAM capacity
Disk type
Hard Disk Drive and capacity
Floppy Disk Drive
Ports
Monitor : Manufacturer
Model
Type
Size
Software :
Operating system version
Application program version
Password control
B. Computer Hardware :
Computer system configuration : ( for each Local Control Unit list )
i. Unit ID :
• Type (PLC,PC etc)
Manufacturer
Model number
Serial number
• CPU board
Model number
Serial number
• Communication processors
ii. Peripheral equiupment
• Printers
• Screens
• Others
iii. Floppy Disk Drive (FDD)
iv. Computer Operating Environment :
• Temperature
• Humidity
• Electromagnetic field
v. Calibration :
List of all calibrated instruments for the computer control system (s) and file a copy of the calibration record with the validation documents , where ever applicable to be provided.
vi. Electrical :
Verification that the control system and / or control wiring has been installed as per manufacturer’s supplied drawings.Verification that all wiring has been done in accordance with specifications.Execute a point-to-point verification to confirm correct identification of wires and / or air control lines in the control panel and / or computer are properly grounded.
C Software:
i. verification that the following phases of software life cycle have taken place
• Requirements
• Design phase
• Installation and check out phase
• Operation and Maintenance phase
• Performance phase
ii. Verification that the manufacturer has provided the logic flow diagrams for the control system installed in the unit . Actual logic programmed into the control system will be verified vs the vendor supplied documentation as part of the Operational Qualification protocol for the equipment.
iii. Verification that the equipment / system manufacturer has provided the following :
• Logic Flow Diagram
• Sequence of Control description
• Ladder diagram
• Operating manual
• Software description
• Software vendor
• Version
• Where does memory reside ? (i.e. RAM, Tape , Disk etc)
iv. Security protection :
Hardware
Software
UPS

v. Verification whether the controller operates as a stand – alone device or as a part of a distributed system.
If the controller operates as part of a distributed system, verify that the program is written to prevent un authorised access between the systems.
vi. Verification that the software prevents unintentional access.
vii. Verify backup procedures
viii. Verification of restart software procedures after a system failure
ix. Verification of software change control procedures.

D. Controlled Devices :
Verification that the controlled devices for the system as per approved drawings.(Specification reference (s) including authorised change orders )

i Verification that all control devices have been installed and tagged.
Information to be verified includes :
 Manufacturer
 Model
 Serial number
 Location
 Location Tag number
 Description
 Function
 Calibration date ( if required)
 Maintenance or ID number
Verification of Tag numbers against “as built” drawings.
ii. Verification that all wiring has been done in accordance with specifications. Execution of point-to-point verification between the control panel and the devices on the equipment to confirm correct identification of wires and / or air control lines.
iii.Evaluation : Evaluate the controlled functions for their potential effect on the quality, strength, purity and safety of the final product.
Additional considerations are in order if the computer is to be used as a stand alone or part of a network. All control functions must be verified in the full process range.
Process validation should take into account the fundamentals of the process and resulting products. Following are the guidelines for Process Validation.
Process validation are to be performed in the following situations :
 For new products
 For new equipment
 For establishing parameters and ranges for each step of manufacture which can influence the product quality.
 For accumulating documentary evidence relating to a process , equipment or facility.
 Hold time study of lubricated drug blend , compressed tablet, coated tablet, filled capsules, blinder and coating suspension should be done for all new formulations and after major change in the formula and storage condition.
Pre – requisite of Process validation:
• Approved process validation Protocol / Report for the unit process.
• Validated analytical methods.
• Approved sampling plan.
Establish master validation plan , validation protocols and validation reports for the unit process.
Nominate a team comprising of User Department , stores , QA , QC and Engineering members.
Initiate plan for performance of studies based on production schedule.
Carry out the validation as per the respective MVP/MVR
Summarise the findings and observations of the validation studies with conclusion of process capability.
Statistics can be made to interpret data obtained and provide meaningful information during validation exercise.
Process validation program(plan and number of batches to be monitored) for individual site should be a part of Master Validation plan and should be available at each site.
Note : The batches manufactured for South Africa ,Germany, Australia,Newzealand , U.K and U.S.A. should not be dispatched unless and until the analysis of validation sample is completed and conclusions and recommendations are drawn.
Cleaning validation should be done to ensure that the procedure being followed for cleaning of equipment and accessories is effective and remove all residues of previous batch / product upto a pre-determined acceptance level thereby avoiding the risk of cross contamination.
Cleaning validation are to be performed in the following situation :
 For new equipment
 Change in cleaning procedure or
 Change in cleaning aid e.g. cleaning agent.
Pre – requisite of cleaning validation :
• Approved Cleaning Validation Protocols / Report.
• Validation analytical method for estimation of previous product in the rinse.
• Validated analytical method for estimation of previous product in the swabs
• Validated analytical method for estimation of cleaning agent in the rinse.
• Approved sampling plan.
Establish Master Validation protocols and reports for the cleaning process.
There are two methods are employed for sampling during cleaning validation . They are rinse method and swab method.
Nominate a team comprising of User Department , stores , QA , QC and Engineering members.
Initiate plan for validation based on production schedule.
Summarize the findings and observations of the validation studies with conclusion.
Cleaning procedures for products and processes , which are very similar, do not need to be individually validated . A representative of similar range can be selected to justify a validation programme , which addresses the critical issues relating to selected products and processes ( matrix).
Cleaning validation can be performed on ‘Worst Case’ products. To decide upon a ‘Worst Case’ product/s for each formulation with in the facility , solvent used for cleaning, cleaning agent used , characteristic like Solubility , Therapeutic potency , strength of the drug , equipment chain , batch size and maximum daily dose of the next product should be taken into consideration.
A single validation study under consideration of the ‘Worst Case’ can be carried out which takes into account the relevant criteria . cleaning validation can be evaluated on the highest strength for multi-strength products. This term can also be referred as “bracketing”.

This validation should also cover sanitation and microbiology as well as removal of external agents like detergents using sampling techniques capable of detecting and measuring to very low levels when ever applicable.

Cleaning validation program(plan number of batches to be monitored) for individual site should be a part of Validation master Plan and should be available at each site.

All the data collected during the validation should be analyzed to determine the cleaning parameters to ensure reproducibility of steps or to alter the existing procedures.

Holding time for cleaned equipment should be determined on the basis of a validation.

In case of any failure during the validation , critical parameters to be checked and process to be reviewed for the deficiency and validated again.

If needed , possibility for the process modification to be checked . for cleaning validation cleaning agent may be changed.

Validation of Analytical methods should be performed in accordance with procedure given in Quality Control procedures and is applicable for any changes in finished dosage from manufacture and analytical procedure.
8.0
ENCLOSURE :NIL
9.0
ANNEXURES : Nil

ABBREVIATIONS:
CGMP : Current Good Manufacturing Practices
DQ : Design Qualification
IQ : Installation Qualification
OQ : Operational Qualification
PQ : Performance Qualification
QA : Quality Assurance
QC : Quality Control
R & D : Research & Development
P & ID’s : Piping and Instrumentation Diagram
HVAC : Heating , Ventilation Air Conditioning
MOC : Material of Contact
AHU : Air Handling Unit
MVP : Master Validation Protocol
MVR : Master Validation report
IPQC : In process Quality Control
SOP : Standard Operating Procedure
UPS : Uninterruptible power supply
RAM : Random Access memory
UK : United Kingdom
CPU : Central Processing Unit
PC : Personal Computer
PLC : Programmable Logic Control
ID : Identification + identifier
U.S.A : United States of America.