Qualification ,Purpose :
Qualification , The purpose of this SOP (Standard Operating Procedure) is to provide guidelines for carrying out the qualification at the site.
Qualification , Scope :
This SOP is applicable for qualification of all equipment, instrument, facility and utility at the site of General Block and Sterile Block of XX Pharmaceutical Ltd.
Definitions / Abbreviation:
[][]Qualification: The action of proving and documenting that equipment or utility are properly installed, work correctly, and actually produce the expected results.
[][]User Requirement Specification (URS): Documented requirement of the equipment, utility for its intended purpose. Functional design and specification according to cGMP and regulatory requirements.
[][]Design Qualification (DQ): Documented verification that the proposed design of the equipment, utility is suitable for the intended purpose.
[][]Installation Qualification (IQ): Documented verification that the equipment, utility as installed or modified, comply with the approved design, manufacturer’s recommendations and user requirement. FAT& SAT to be added.
[][]Performance Qualification (PQ): Documented verification that the equipment, utility is performing effectively and reproducibly, based on approved method and specifications.
[][]Factory Acceptance Test (FAT): Documented verification of the equipment at vendor’s site against approved design.
[][]Site Acceptable Test (SAT): Documented verification of the equipment at user site against approved design.
[][]HVAC: Heating, Ventilation & Air Conditioning
[][]LAF: Laminar Air Flow
Responsibilities:
[][]The roles and responsibility is as follows:
User department
[][]To prepare the URS of equipments, instruments, facility, utility.
[][]To prepare DQ (if required).
[][]To prepare PQ protocols
Validation Team
[][]He I She shall be responsible to carry out this procedure as defined
Engineering Department
[][]To prepare IQ, OQ protocols whenever required.
[][]To provide technical assistance to the user department for preparation of require documents.
[][]To prepare protocols for facility and utility in co- ordination with user department
Quality Assurance
[][]To review protocols and to provide technical inputs
[][]To review reports for its completeness and correctness all data and report.
Head of Engineering
[][]He I She shall Be Responsible for Effective Implementation of this Procedure.
Head of Plant
[][]He I She shall Be Responsible for Effective Implementation of this procedure.
Head of Quality Assurance
[][]He/ She shall be responsible for effective implementation of this procedure.
[][]To approve protocols, reports and master plan.
[][]Approval of the SOP.
External agency
To provide technical assistance for preparation of documents and execution of activities whenever required
Procedure:
Methodology
[][]Facilities, Utilities and Equipment’s used for manufacturing, processing, packaging, labeling, storing, testing and controlling of drug products shall be qualified prior to use.
[][] It shall be performed for new equipment /instruments/utility/facility, after major breakdown in equipment/utility, after modification in equipment/instrument/utility and facility.
[][]Re-qualification shall be performed at define frequency.
Introduction of a new equipment/ facility/ utility:
[][]After receiving the new Equipment Engineering shall make entry in respective format and Concern
[][]department shall update the Equipment Master List as per respective of SOP.
[][]Equipment no. shall be assigned as per the SOP for Equipment and Instrument Numbering System.
[][]For new equipment following activities shall be done to demonstrate conformance to design documents, characteristics, and capabilities specified in required documents.
[][]User requirement specification (URS)
[][]Design qualification(DQ)
[][]Factory Acceptance Tests (FAT)
[][]Site Acceptance Test (SAT)
[][]Installation Qualification(IQ)
[][]Operation qualification(OQ)
[][]Performance Qualification(PQ)
User Requirement Specification:
[][]The URS is made to verify that the owner/user requirement, which includes establishment of critical operating or operational parameters or specifications before the final design agreed, has been met.
[][]User shall prepare the URS considering all operational, safety and GMP requirements.
[][]The user requirement shall be submitted to manufacturer/supplier, based on which manufacturer/supplier will prepare design.
DQ:
[][]The DQ is made to verify that the owner/user requirement, which include establishment of critical operating or operational parameters or specifications before the final design is agreed, has been met.
[][]Based on URS, manufacturer/supplier shall prepare design it documents and submit to user for approval.
[][]On the basis of approved design it documents, manufacturer /supplier shall start manufacturing/fabricating the equipment/utility.
Factory Acceptance Test:
[][]The FAT is prepared to verify that the main items or system meets design specification and conforms to agreed performance intent.
[][]User shall prepare FAT protocol according to URS/DQ, manufacturer specification and purchase order User shall ensure that the equipment/system is manufactured as per designed specification at manufacturer’s site.
[][]User also check the basic performance of the equipment/ system delivered at plant meets the design specification.
[][]User shall take photocopy of the approved FAT protocol and execute at the manufacturer’s site with QA and Engineering representative.
[][]All the test shall be performed and reported by the supplier. All tests performed during FAT must be performed in accordance with reviewed and and approved protocol and procedure.
Site Acceptance Test:
[][]The SAT is to establish documented evidence that the receipt of the item at site confirms with the standards laid down in the protocol, FAT, purchase order and manufacturer’s specification.
[][]User shall prepare SAT protocol according to the manufacturer specification, purchase order and FAT report.
[][]User shall take photocopy of the approved SAT protocol and will check the entire test mentioned in protocol with the QA & Engineering representative at the site when item I equipment I system reaches to the factory premises and reported by the production and engineer.
Installation Qualification:
[][]Installation Qualification of Equipment/utility shall be carried out is to ensure that the equipment I utility is installed according to design documents, purchase. Specifications, FAT and SAT report and planned modification.
[][]The parts of the systems, which are disassembled prior to shipping, shall be noted and be verified again after re-assembly at the final site during IQ.
[][]Equipment/utility shall be inspected either visually or by measurement for its critical parts. Wherever applicable other instruments shall be used for this purpose.
[][]All the relevant tests mentioned in protocol shall be checked after proper installation of equipment. Calibration of instrument attached with equipment and other related shall carried out before starting OQ.
[][]After completion of IQ the equipment shall be released OQ.
Operation Qualification:
[][]The Operational Qualification is carried out to verify that an Equipment/system or subsystem performs as intended throughout all anticipated operating ranges.
[][]Operation qualification activities shall start only after completion of successful IQ.
[][]QA and User representative shall use photocopy of approved protocol, which is used earlier during IQ.
[][]User department shall verify proper operation by performing the critical operating parameters that have significant impact on the equipment ability to operate and meet specifications satisfactory.
[][]User department shall prepared final conclusion after the test functions are checked and observed within specification.
[][]After completion of OQ the equipment shall be released either for PQ or for routine use as the case may be.
Performance Qualification:
[][]The performance qualification is carried out to provide documented evidence that an integrated system or processing operation is capable of performing consistently (during multiple cycles or extended periods) to give an outcome that meets predetermined specifications.
[][]PQ activities shall start only after completion of successful OQ.
[][]PQ of equipment depends upon equipment intended use and its operation.
[][]Data shall be generated to establish that the equipment meets the requirement as expected of it.
[][]A final report shall be prepared, summarizing the results obtained, commenting on any deviation observed and final conclusion shall be given after the PQ.
[][]PQ can be performed on commercial batches for new equipment. The batches shall be released only after the qualification of the equipment is completed or can be performed on placebo /dummy / trials wherever applicable.
[][]PQ shall be performed for consecutive three batches/trials with load.
[][]After completion of execution, all raw data and reports shall be compiled and a final conclusion shall be drawn.
[][]After final approval of conclusion/report by plant head and quality head the respective equipment, instrument, facility and utility shall be allowed for routine use.
Note: Operation and PQ shall be carried only if desired utility is available and environmental conditions (wherever applicable) are achieved in the area.
Qualification for introduction of a new Instrument:
[][]For new Instrument following activities shall be done to demonstrate conformance to design documents, characteristics, and capabilities specified in requirements documents.
=>Installation Qualification (IQ)
=>Operation qualification (OQ)
=>Performance Qualification (PQ)
[][]IQ : for new Instrument shall be carried out as per procedure mention above.
[][]OQ : OQ for new Instrument shall be carried out as per procedure mention above.
[][]PQ : OQ for new Instrument shall be carried out as per procedure mention above.
Protocol Preparation for FAT, SAT, IQ, OQ and PQ:
[][]The protocol for Qualification (FAT/SAT/ IQ / OQ / PQ) shall address and include, but not necessarily be limited, to the following topics.
[][]FAT: Approval, purpose, procedure, verification criteria, Manufacturer’s Machine Identification Code / Identification No., Final report approval.
[][]SAT: Approval, purpose, procedure, Documentation, Verification criteria, Final report approval.
[][]IQ/OQ/PQ: Purpose, Scope, Responsibility, Intended Use, Location, Reference, History, Attachments, Study for qualification, Responsibilities, Signature log, Training record.
[][]IQ : Equipment/Instrument Detail, Procedure, IQ table, Conclusion.
[][]OQ : SOP training, Procedure, OQ table, Observed deviation, Conclusion.
[][]PQ: Procedure, Acceptance criteria, Observed deviation, Final Conclusion Report approval sheet.
[][]Specimen of Header and Footer for above protocol is as per given below.
At the Header Section
1st Column: Company Logo
2nd Column: Company Name, Address Details
3rd Column: Doc. Title, Document No., & Location
Specimen of Footer on all Page
CONFIDENTIAL TECHNICAL DOCUMENT
[][]Numbering and Issuance system for Qualification protocol shall be as per SOP for Document numbering system.
Area Qualification:
[][]Area Qualification is carried out to provide the documentary evidences that particular area is constructed and qualified as per predefined specification.
[][]Below mentioned activities shall be performed during execution of Area Qualification, but not limited to.
[][]Construction and finishing of wall, floor, doors, view panels and ceiling.
[][]Dimension measurement wherever applicable.
[][]All the required utilities and other facilities supplied.
[][]Lighting lux of every room in all four corners and center of the room.
[][]Temperature Mapping for Classified area.
[][]Environmental condition monitoring for classified area.
[][]Water drains ability of drains.
[][]Cleaning and Sanitization Procedure.
[][]User department shall prepare the qualification protocol and organize the qualification study in co- ordination with Quality Assurance and Engineering department.
[][]Protocol/Report shall be finally reviewed by Multidisciplinary authorized personnel along with QA personnel and approved by Quality Head.
[][]Specimen of Header and Footer for above protocol is as mentioned above.
[][]Numbering and Issuance system for Qualification protocol shall be as per SOP for Document numbering system.
Qualification of HVAC system:
[][]HVAC qualification shall be carried out to supply the required air quality to the various section of individual department to provide product protection from air borne contamination, to maintain the temperature and humidity, to provide differential room pressure or air flow movement to provide product protection from cross – contamination.
[][]All HVAC system like AHU’s shall be qualified as per procedure described above as per approved protocols.
[][]Engineering department shall prepare the qualification protocol and organize the qualification study in co-ordination with Quality Assurance.
[][]Engineering person shall record the observations as per designed protocol and prepare a report.
[][]Below mentioned test shall be performed during qualification of AHU, but not limited to.
DOP or PAO Test
Air velocity & Air changes Test
Non viable particle count
Filter efficiency & integrity.
Particle count Test.
Microbial Count.
Air Flow Direction & Air Flow Pattern
Recovery Study
Protocol/Report shall be finally reviewed by QA and approved by Head of QA.
Specimen of Header and Footer for above protocol is as mentioned above.
[][]Numbering and Issuance system for Qualification protocol shall be as per SOP for Document
numbering system.
Qualification of LAF:
[][]Qualification of LAF shall be carried out to provide the air with high-pressure compare to surrounding area and to prevent microbial and particulate matters contamination during dispensing/sampling of Raw material, prevent dusting during dispensing/Sampling.
[][]All LAF shall be qualified as per procedures described as per approved protocol.
[][]User department shall prepared the qualification protocol and organize the qualification study in co-ordination with QA & Engineering department.
[][]Numbering and Issuance system for Qualification protocol shall be as per SOP for Document numbering system.
[][]Installation Qualification: IQ of LAF shall be carried out to check LAF size as per requirement, to check pre-filter, motor blower, Magnehelic gauge and final HEPA filter as per specification.
[][]Operational Qualification: OQ of LAF shall be carried out to run the LAF and to check the operational parameter functioning.
[][]Performance Qualification: PQ of LAF shall be carried out to check LAF air velocity, Air flow pattern, air cleanliness by non viable particle count and HEPA filter efficiency & integrity, etc.
[][]User department shall record the observations as per designed protocol and prepared a report.
[][]Protocol/Report shall be finally reviewed by QA and approved by Head of QA.
Qualification of Water System:
[][]Water system qualification shall be carried out to generate Potable water & purified water of desired quality.
[][]Engineering department shall prepared the qualification protocol and organize the qualification study in co-ordination with QA.
[][]Qualification protocol shall carried following details but not limited to, IQ: Equipment/instrument details, procedure, Acceptance criteria, Pre-
qualification, Installation check, summary & conclusion.
[][]OQ: Training, Procedure, Acceptance criteria, operating inputs, summary & conclusion.
[][]PQ: Study plan, sampling Frequency, user point, summary & report.
[][]PQ of water system shall be carried out in a two phase.
[][]In phase 1, water quality parameter trend shall be evaluated on monthly basis.
[][]In phase 2, water quality parameter trend shall be evaluated after one year to evaluate impact of seasonal changes on quality of water.
[][]Engineering department shall record the observations as per designed protocol and prepared a report.
[][]Protocol/Report shall be finally reviewed by QA and approved Head of QA.
[][]Numbering and Issuance system for Qualification protocol shall be as per SOP for Document numbering system.
Re-qualification strategy:
[][]Equipment futility shall be re-qualified either in following conditions:
[][]Major Break Down.
[][]After modification in equipment, utility, facility which may have an impact on product quality only.
[][]Design change of spares that have impact on the performance of equipment and quality of product.
[][]In case of during Location change of equipment. (In case of balances only recalibration shall be done).
[][]As per scheduled re-qualification of critical and non equipment/utility.
[][]OQ & PQ shall be performed during requalification.
[][]PQ shall be performed with one batch during requalification.
Re-qualification criteria for critical equipment:
[][]Operational and performance qualification shall be done as per approved protocol for re-qualification of critical equipment.
[][]All critical equipments shall be re-qualified after every three years ± 1 month.
[][]During re-qualification of critical equipment/utility, only 00 and PO shall be performed. PO shall be conducted with one batch only.
[][]Re-qualification criteria for non critical equipment.
[][]Re-qualification of non critical equipment shall be conducted whether there is significant change that has influence on quality of product.
[][]For re-qualification of non-critical equipment, history of maintenance and utilization of the equipment shall be reviewed and documented as per format of Re qualification of non-critical Equipments (Attachment 1).
[][]All non – critical equipments shall be re-qualified after every three years ± 6 months.
Re-qualification criteria for Instrument in following conditions:
[][]When the instrument is shifted from one laboratory (Change in premises) to another laboratory, re qualification (10, 00 and PO) is required.
[][]When the instrument is upgraded or after having a major repairing, qualification (OO/PO) is required.
[][]When the instrument is shifted within the laboratory premises (one room to another room), re qualification is not required, in house calibration is required.
Re-qualification criteria for HVAC System:
[][]Re qualification of HVAC(AHU) shall be carried out in below mention criteria, but not limited to Change in a location of the equipment/system.
[][]Major change in equipment, Change of spare/ parts that have a direct bearing on the Performance of the equipment.
[][]Schedule Re-Qualification.
[][]Frequency of Re-qualification of AHU shall be One Year.± One month. Below mentioned test shall be carried out at defined frequency.
Parameter/Frequency
=>Air Velocity /Initially and Once in year
=>Air Changes /Initially and Once in year
=>Filter Integrity Test /Initially and Once in year
=>Particle Count /Initially and Once in year
=>Microbial Count /Initially and Once in year
=>Air Flow Direction /Initially and Once in year
=>Air Flow Pattern /Initially and Once in year
=>Recovery Study /Initially and Once in year
Re-qualification criteria for LAF:
[][]Re qualification of LAF shall be carried out in below mention criteria, but not limited to.
[][]Change in a location of the equipment/system.
[][]Major change in equipment, Change of spare/ parts that have a direct bearing on the Performance of the equipment.
[][]Critical gauges shall be replaced or corrected if the gauge is found out of calibration during calibration of the gauges.
[][]Schedule Re qualification.
[][]Frequency of Re-Qualification of LAF shall One Year.± One month.
Re-qualification criteria for utilities:
[][]Re-qualification shall be carried out to ensure that change I modification in utilities remain under
[][]Control and within the parameters defined and certified.
[][]Re qualification of utilities shall be carried out in below mention criteria, but not limited to.
[][]Change in location
[][]Any modification that has a potential to impact the product quality.
[][]Scheduled re-qualification after every 3 years.
Re-Qualification of Compressed Air:
[][]Re qualification of Compressed Air shall be carried out in below mention criteria, but not limited to,
[][]In case of any modification which has impact on product quality.
[][]Scheduled re-qualification after everyone year.
Annexure:
Annexure-I: Requalification of non-critical Equipment’s