Creating A Pharmaceutical Installation Qualification
PDHonline Course K111 (4 PDH)Creating a Pharmaceutical InstallationQualificationInstructor: William N. Weaver , P.E.2012PDH Online PDH Center5272 Meadow Estates DriveFairfax, VA 22030-6658Phone & Fax: 703-988-0088www.PDHonline.orgwww.PDHcenter.comAn Approved Continuing Education Provider
www.PDHcenter.comPDH Course K111www.PDHonline.orgCreating a Pharmaceutical Installation QualificationW.N. Weaver PECourse ContentINTRODUCTIONPharmaceutical Validation is a growing field for engineers. Not only is validation anFDA requirement, several states have determined that the process of validation fallsunder the heading of engineering and as such requires the supervision of a registeredprofessional engineer if performed by other than plant personnel.Validation of a pharmaceutical facility occurs in several stages. Depending on theoperational status of the facility we can choose one of three types of validation:Retrospective Validation:Concurrent Validation:Prospective Validation:Validation of an existing facility based on significantaccumulated production data.Validation of a facility while production is underway.Validation of a facility, which is in the final stages ofconstruction or just ready to start production. This is themost common type of validation and will be the oneconsidered in this course material.Validation is accomplished through the use of Protocols, which are designed to testcertain aspects of the Installation, Operation and Performance of the equipment orprocess. With the exception of the Installation Qualification, each protocol contains aseries of scientifically sound operational tests to evaluate the equipment or process.The validation process varies somewhat from company to company. This is generallyreflected in the content of protocols and occasionally in the number or type of protocols.The content of this course has been developed to include all items normally found in anInstallation Protocol. Deletion of some sections or additions specifically matching theneeds of the company is acceptable and the responsibility of the pharmaceuticalcompany.PROTOCOLSBefore we begin study of the Installation Protocol we need to understand therelationships between the various protocols.Design Qualification(DQ)An analysis of the design for compliance with the requiredprocess. If performed would be the first protocol in theseries.Installation QualificationAn analysis of the installation of a piece of equipment toPage 1 of 18
www.PDHcenter.comPDH Course K111www.PDHonline.org(IQ)ensure the installation meets the manufacturer’sinstructions and the process design.Operational Qualification(OQ)A series of tests designed to determine if the equipmentoperates in accordance with the manufacturer’s statements,the purchase specification and the process design.Performance Qualification(PQ)A series of tests designed to determine if a process stream(which could consist of one machine only) operates inaccordance with the process design.Creation of the protocols above is generally in the order shown. A DQ is not a commonprotocol as of this writing but is beginning to become popular. Each protocol builds onthe previous protocol. Before you verify proper operation of a piece of equipment (OQ) itis logical to confirm proper installation (IQ).The content of this course covers the mechanical aspects of the Installation Qualification.In the case of equipment with computer, PLC or DCS control these components arecovered in the Automation Installation Qualification, AIQ.A quick listing of protocols:DQIQAIQOQAOQPQPVCQDesign QualificationMechanical Installation QualificationAutomation Installation QualificationOperational QualificationAutomation Operational QualificationPerformance QualificationProcess ValidationCleaning QualificationGENERAL ITEMSAll protocol pages are numbered, have a “Header” which lists the company and location,identifies the type of protocol, the equipment for which the protocol is written, and thedocument number.Depending on the company the first page (Approval Page) may or may not be numberedand usually will not show the header. Numbering provides the FDA with assurance thatno pages with failing data were removed and ensures that all pages in the originaldocument are present.Sample Header for pages 2 and following.XYZ Pharmaceuticals610B Minuet LaneGrand Rapids, MIINSTALLATION QUALIFICATION forThe FA AUTOCLAVEPage 2 of 18Document #: AFIQPage X of Y
www.PDHcenter.comPDH Course K111www.PDHonline.orgAll protocols also have two signature lines on the bottom of most pages, shown below.Depending on the format used the “Executed By” and Reviewed By” lines may appearafter each test function or data recording activity as opposed to the end of each page.Executed By: Date:Reviewed By: Date:THE CONTENT OF AN INSTALLATION QUALIFICATION (IQ)The intent of the IQ is generally stated as being the verification of the installation. This issomewhat of a simplification. The following are the basic contents of the IQ. Eachsection will be reviewed in detail as we move along.1. APPROVAL PAGE2. TABLE OF CONTENTS3. SIGNATURE PAGE4. GENERAL5. PURPOSE / SCOPE OF PROTOCOL6. SYSTEM DESCRIPTION7. RESPONSIBILITIES8. EXECUTION PROCEDURES9. DOCUMENTATION10. TEST EQUIPMENT11. VISUAL INSPECTION12. EQUIPMENT COMPONENTS13. INSTRUMENTATION14. UTILITY VERIFICATION15. SUMMARY REPORT16. APPROVAL PAGE1.APPROVAL PAGESApproval for a specific document is a matter of choice by the company, as long as thoseindividuals providing approval have the authority and knowledge necessary to achievingthe goal of maintaining quality, efficacy and purity.There are two approvals for each protocol: initial approval and execution approval.Approvers vary from facility to facility but as a general rule are the following individuals:Quality Assurance ManagerProduction ManagerEngineering ManagerPage 3 of 18
www.PDHcenter.comPDH Course K111www.PDHonline.orgRegulatory Affairs ManagerValidation ManagerFrequently facilities are not large enough to have all of these positions; that is not aproblem as long as those in “responsible charge” of the facility are approving theprotocol.Likewise some facility managers do not have time to read and approve each protocol, inthese cases the manager may designate someone to use his authority for review andapproval. If this is a temporary assignment and not part of the normal facilityorganizational structure then a letter of authorization from the manager should be placedin the validation files for the equipment or process represented by the protocol.1A.INITIAL APPROVALThis approval page is generally the cover page of the document and approvals represent areview and acceptance of the content of the protocol; it signifies that the appropriateindividuals have reviewed the protocol and have determined that it indeed providesadequate details about the equipment and installation. There will also be a signature linefor the individual preparing the protocol. See Attachment A for a sample of thisdocument.First Rule: No protocol may be executed without all required approvals.Second Rule: Field execution of the protocol is done on a COPY of the approvedprotocol. Generally stamped COPY on each page.1B.EXECUTION APPROVALThis approval page is generally the last page in the protocol and represents a review ofthe executed document for consistency and completeness. It is essentially a verificationthat all of the testing was done per the requirements of the protocol and their signaturesare an acceptance of that execution. The original signers or newly designated individualsfrom the same departments as the original approvals are required. See Attachment B for asample for this document.2.TABLE OF CONTENTSGenerally self-explanatory and there are no differences in its usage in a validationprotocol.Protocol content and arrangement are not specified by the FDA or any other regulatorybody. The intent of validation is proof of consistency in production and control of theoperations to the extent necessary to maintain product quality, purity and efficacy.Therefore to this end there are as many acceptable protocol arrangements as there arepharmaceutical companies.Page 4 of 18
www.PDHcenter.comPDH Course K111www.PDHonline.orgThe order of appearance of items within the protocol mimic the contents listing of thecontents of this course. They are generally covered in this order: General Information,Procedures, Tests, and Approval.3.SIGNATURE PAGEThis is simply what it says, a page showing the signature and position of each personapproving, executing or reviewing the protocol. All persons who will or have written inthe executed protocol, including Approval pages, must complete this signature page.Identification of individuals is provided in three formatsPrinted or typedSignatureInitialsXYZ Pharmaceuticals610B Minuet LaneGrand Rapids, MIDocument #:AFIQINSTALLATION QUALIFICATION forThe FA AUTOCLAVEPage X of YNameCharlie WeaverSIGNATURE PAGETitleCompanyValidation Engr. XYZ PharmaSignatureInitialsCOMMENTS:Use this section to explain that Mr. Smith, QA Manager, hasdelegated signature authority for this document to Mrs. Jones. This statement isin addition to the file letter mentioned above.Reviewed By:Date:There is no “Executed By” line since we’re getting signatures. However someone shouldreview this page to ensure that all necessary signatures and initials are present. The firstthree columns may be typed in but the last two must be a valid signature and initial.4.GENERALIf present this section details how the overall validation effort will be accomplished, howthis protocol fits into the Master Validation Plan and what the schedule for completion ofthe total validation effort will be. Unless the company requires this section it is generallynot used.Page 5 of 18
www.PDHcenter.com5.PDH Course K111www.PDHonline.orgPURPOSE / SCOPE OF PROTOCOLTwo common names for essentially the same information.Here we are detailing the reasons for the protocol; everyone already knows from the titleand some companies have deleted this paragraph. We are intending to prove that theequipment has been properly installed and at the conclusion of this IQ will be ready fortesting under the OQ. A sample paragraph follows.“This protocol provides testing and documentation to indicate proper installation inagreement with the manufacturer’s recommendations and the intent of the design.Adequate documentation exists to ensure continued proper operation to ensure quality,efficacy and purity of the product.”Within this series of paragraphs we describe the “boundary limits” for the protocol. As anexample suppose you have a bottle washer in line with a depyrogenation oven (destroysbacterial body parts) which is in line with a bottle filling machine and capper. See SketchBoundarylimits1. below.Sketch 1: Filling eyorWe only want this protocol to refer to the Bottle Washer so we verbally describe theboundary limits of the protocol. In complicated situations you may want to refer to aspecific drawing (P&ID or Equipment Arrangement) which has been marked to show theboundary and is kept on file with the validation protocols. Generally you would notattach the drawing to the protocol. Following is a sample paragraph.“This protocol will examine the Bottle Washer, Number ABC (equipment number) andrelated utilities. Utility connections will be verified but will be tested under a separateprotocol. This Installation Qualification will verify the mechanical equipment andcomponents; verification of the control system will be found in a separate document titled“AIQ for The Bottle Washer, Number ABC”.Additional restrictive comments may be added as necessary to limit the scope of work tothis particular piece of equipment. Generally the scope should include any part of theequipment line that was supplied with the bottle washer. For instance the output conveyorfrom the bottle washer would most likely have come with the washer and thus should bepart of the system.Page 6 of 18
www.PDHcenter.comPDH Course K111www.PDHonline.orgAs a general rule ALL components of a process stream must be included in the protocolsso even if the output conveyor came from another source if it logically fits into theprotocol for the washer that is where it should be.6.SYSTEM DESCRIPTIONAlthough this may contain some of the information from the Scope of Work section itgoes into much more detail. As a guide this section contains paragraphs covering thefollowing:Equipment Location: Generally the name and address of the facility along with thelocation of the equipment within the facility.“Bottle Washer ABC is located on the premises of XYZPharmaceuticals located at 610B Minuet Lane, Cedar Rapids,Michigan in Building 101 on the second floor of production unitNumber 2.”Equipment Function: A descriptive paragraph giving the basic purpose and capacity ofthe equipment.“Bottle Washer ABC is manually fed and discharges by anautomated conveyor system into the Depyrogenation Oven, DEF.The unit is manufactured by the My Washer Company ofDearborn, IL and is a model 1410.The unit is a vertical bottoms up washer utilizing hot Water ForInjection for washing and heated sterile air for drying. The unit iscapable of washing bottles in the size range from 10 milliliters to 1liter at rates varying from 180 per minute to 40 per minuterespectively. Bottles are inverted from the feed table, washed,dried and re-inverted to feed the Depyrogentation Oven DEF.”Utility Requirements: Here we want a brief description of what utilities are required forproper operation.“Bottle Washer ABC requires electrical power at 240 volts, hotWater for Injection at 140 ºF, sterile air at 60 ºF, connection to aprocess sewer and installation in a Class 1000 classifiedenvironment.”7.RESPONSIBILITIESHere the major players in the validation activity are detailed along with what they areresponsible for in the validation effort. Generally you will not list individuals, however,all applicable departments are listed. Not all of the “departments” listed will be part of thefacility since a large percentage of validation is provided by outside companies.Page 7 of 18
www.PDHcenter.comPDH Course K111www.PDHonline.orgContractors:Prepare and execute validation protocols under thedirection of the Validation Department of XYZPharmaceuticals.Validation Department:Supervise preparation of protocols, approveprotocols for execution and review executedprotocols for approval.Engineering Department:Ensure all equipment is properly installedand operational for protocol execution. Providetechnical support to validation engineers asrequired. Approve protocols for execution andapprove executed protocols.Regulatory Affairs Department:Provide training in plant SOP’s as required foroperating personnel and validation engineers.Approve protocols for execution and approveexecuted documents.Quality Assurance Department:Provide testing of samples as required duringprotocol execution through the QC labs. Approveprotocols for execution and approve executeddocuments.Production DepartmentProvide trained operating personnel, necessarysupplies and process materials as needed for thevalidation effort. Approve protocols for executionand approve executed documents.Depending on the structure of the company and the departments available this list cangrow but would most likely not shrink. Additions and deletions for specific protocolsoccur. It is not unusual to see Maintenance included with equipment such as Pure SteamGenerators and Water For Injection systems. The IT department is usually added if thesystem is controlled by computers, DCS or PLC’s.Maintenance Department:Ensure all equipment has been serviced and that allcritical instruments have been calibrated. SupportContractor’s validation engineers.IT Department:Ensure all computer control systems are functionaland that backup software is available. SupportContractor validation engineers as needed.Third Rule: Protocol approval must include those responsible for systems operation.Page 8 of 18
www.PDHcenter.com8.PDH Course K111www.PDHonline.orgEXECUTION PROCEDURESThis section details how the protocol is to be executed. There are some peculiarities witheach company but the following are generally accepted guidelines. A short paragraphcovering each item is the accepted format.A.Training of the validation engineer in SOP’s for specific equipment although notalways required is generally a sound plan. The FDA inspectors tend to think it isbest if the person doing the execution understands the purpose of the equipmentand in protocols requiring equipment operations this makes sense.“Prior to commencing protocol preparation the validation engineers will betrained by appropriate plant personnel in the following SOP’s: “ValidationDocument Preparation, VD-111”, “Validation Protocol Execution, VD-112”,“Operation of Bottle Washers, BW-140”, “Gowning Procedure for ClassifiedAreas, GP-150”.B.Recording of data in the protocol is always in ink, always in a copy of theapproved protocols and always by the person(s) doing the execution. Somecompanies will require only blue ink (from the days when copiers couldn’t copyblue) and some will require black ink. Ink smears, wrinkles and stains are anindication to the FDA that the execution occurred in the field and not at the desk.“All execution data is to be recorded in black ink using a standard ball point pen.Pencil, felt tip pens and similar markers are prohibited.”C.Correction of data entry errors always seems like a big deal and something to beavoided. However, an executed protocol without some data entry error is suspect.In this paragraph detail how data entries are to be corrected.Protocol Instructions (each “test” within a protocol will have an instruction setgenerally on the page where the data is to be recorded, the following is an excerptfrom such an instruction set)Record the Serial Number of the equipment SN 78349WNW / 1/20/04The actual number should be SN 87349Corrected data is entered as follows:WNW 1/20/04Record the Serial Number of the equipment SN 78349 SN 87349 WNW 1/20/04Normal Paragraph“Data entry errors are to be corrected by striking through the incorrect data with asingle line and recording the correct information along with your initials and thePage 9 of 18
www.PDHcenter.comPDH Course K111www.PDHonline.orgdate. Under no circumstances is data to be “scribbled” through or totallyobliterated, no “white out” is allowed.”Fourth Rule: Data entry is corrected in such a manner that the erroneous data islegible. Always initial and data corrections. Corrections to data entrymay be made by the protocol reviewer or other authorized person.D.Frequently you will find (or create) spaces for COMMENTS and other data entrywhere nothing is written during execution. These blank spaces are unacceptable tomost companies and the FDA. The concern is that after execution someone maywrite in additional information for whatever reason. That is an unacceptablepossibility and so there needs to be instruction to eliminate these possibilities.“Blank data entry spaces and blank COMMENT lines are to be lined through withdiagonal lines as needed to cover the blank spaces which will be initialed anddated by the person reviewing the document.”COMMENTS: None WNW 1/25/04In this case there were no Comments and all lines were marked through to preventadditions at a later date.E.On occasion you will need to add a page; the page may be a copy of a protocolpage to record additional data or a data sheet from a recording instrument. Againthe protocol must provide instruction to the executioner.“Additional pages and or data sheets incorporated into the body of the protocolduring execution shall be numbered the same as the proceeding page with theaddition of an “alpha” character.”If you’re doing the execution and need to add a copy of page 36 it
Installation Qualification An analysis of the installation of a piece of equipment to . www.PDHcenter.com PDH Course K111 www.PDHonline.org Page 2 of 18 (IQ) ensure the installation meets the manufacturer’s instructions and the process design. Operational Qualification A series of tests designed to determine if the equipment .
5.D Qualification of water supplies 5.D.1 Introduction 5.D.2 Risk analysis 5.D.3 Design qualification 5.D.4 Installation qualification 5.D.5 Operational qualification (OQ) 5.D.6 Transfer to the user 5.D.7 Process validation/performance qualification (PQ) 5.D.8 Qualification report 5.E Operation of water supplies
An equipment qualification is handled in different phases of the equipment lifecycle, start-ing with design qualification, installation qualification, and then operational qualification and performance qualification. Every step in the equipment qualification formally comprises a plan, the execution and a report.
exempting qualification. B Structure of the qualification The structure of the qualification and syllabus subjects is shown on the following diagram. C Progression through the qualification Subjects within each learning pillar of the qualification are designed to be sequential, from operational to strategic level, encouraging
Operational qualification Operational qualification (OQ) 13. Operational qualification (OQ) should follow Installation qualification. 3.10 OQ normally follows IQ but depending on the complexity of the equipment it maybe performed as a combined Installation/Operation Qualification (IOQ). OQ could include but is not be limited to the following:
Installation Qualification Plan Sample Revision Number: 1.0 Page 12 of 16 Revision Date: 8/7/2012 8.6 Installation Qualification Summary Report The Installation Qualification Summary Report for Sample will be updated to describe the testing associated with the Prerequisite Software and Hardware section, including
INSTALLATION QUALI INSTALLATION QUALIFICATION FICATION (1) INSTALLATION INSTALLATION QUALIFICATION QUALIFICATION (1) 1 rue du Petit Clamart - B.P. 50 78142 VELIZY CEDEX - FRANCE Tél. 01.46.29.99.60 - Fax. 01.46.30.87.30 ETUDES & DEVELOPPEMENT VALIDATION C 1/4 NSCA 161/16 LC reference : 37K53E Page Rev. Page Customer reference : 45382135/392 IQ .
covers the three stages of qualification needed to release a temperature-controlled storage area for routine use: installation qualification (IQ), operational qualification (OQ) and performance qualification (PQ). Related topics are covered in the following Technical Supplements: Temperature mapping of storage areas.
American Gear Manufacturers Association AGMA is a voluntary association of companies, consultants and academicians with a direct interest in the design, manufacture, and application of gears and flexible couplings. AGMA was founded in 1916 by nine companies in response to the market demand for standardized gear products; it remains a member- and market-driven organization to this day. AGMA .
