equipment qualification toolkit

Ins t i tu te o f Val idat ion Technology38

Equipment Qualification

ToolkitDavid M. Stephon

Adolor Corporation

S P E C I A L S E C T I O N

E Q U I P M E N T Q U A L I F I C A T I O N T O O L K I T

S P E C I A L S E C T I O N

E Q U I P M E N T Q U A L I F I C A T I O N T O O L K I T

Equipment and Inst rumentat ion Qual i f icat ion 39

In recent years, the pharma-ceutical industry has comeunder an increasing amountof scrutiny by the Food and DrugAdministration (FDA) for a vari-ety of regulatory compliance is-sues. Daily headlines in thehealthcare industry trade presshave repetitively discussed com-pliance issues with regularity.The pharmaceutical industrys re-sponse to these challenges hasbeen to take a positive approachin order to provide education, in-formation, and communicationon these issues, rather than coun-terattacks towards the regulatoryagencies, including the FDA, that have cited these de-ficiencies. This educational approach probably can beattributed to lessons learned within the industry re-garding regulatory compliance.

The manufacture of pharmaceutical products, bio-logics and medical devices are regulated by Good Man-ufacturing Practice (GMP) regulations. GMP ensuresthat consumer products are both safe and effective,and includes many requirements for the drug or med-ical device manufacturer to follow, including testing ofraw materials, manufacturing controls, documenta-tion requirements, handling of deviations, laboratorycontrols, and personnel training.

Another aspect of GMP regulations is the require-ment to use equipment that has been demonstrated tobe suitable for its intended function. The suitabilityof the equipment used to manufacture, package, label,and test drugs and medical devices has a direct effect

on the quality of the product. Compliancewith FDA requirements related toequipment suitability or qualificationcan result in greater control and assur-ance that products are both safe and ef-fective.

For years, equipment qualificationand validation were areas that were ad-dressed, if at all, only after equipmentwas designed, purchased, and installed.Manufacturers viewed the generation,execution, and detail of this documenta-tion as an afterthought. In recent years,FDA and other regulatory agencies havefocused on compliance data and docu-mentation. This, in turn, resulted in amovement in the pharmaceutical indus-

try to start conducting self-assessments and internalaudits in order to evaluate firsthand the firms compli-ance status on an ongoing basis. The results of theseself assessments allowed pharmaceutical manufactur-ers to develop proficient skills in the areas of qualifi-cation and validation. This increased knowledge inthe rationale behind compliance emerged as a conduitfor the integration of validation and equipment quali-fication requirements into the total project process.This integration of the compliance and business re-quirements has served to provide manufacturing, pro-cessing, and laboratory equipment better suited for itsintended use.

Throughout the regulated pharmaceutical industry,it has been recognized that equipment qualification isa prerequisite to any validation activity. While theterms qualification and validation have been usedinterchangeably to have the same meaning, it is read-

Throughout the regulated

pharmaceutical industry, it has

been recognizedthat equipmentqualification is a prerequisite

to any validationactivity.

Equipment Qualification Toolkit

David M. StephonAdolor Corporation

E Q U I P M E N T Q U A L I F I C A T I O N T O O L K I TE Q U I P M E N T Q U A L I F I C A T I O N T O O L K I T


Audit: Systematic and independent examination todetermine whether quality activities and related resultscomply with planned arrangements, and whether thesearrangements are implemented effectively, and aresuitable to achieve objectives.

Calibration: The set of operations that establish,under specified conditions, the relationship betweenvalues indicated by a measuring instrument or mea-suring system, and the corresponding known values ofthe measurand.

Corrective Action: Short-term action taken toeliminate the causes of an existing nonconformity, de-fect, or other undesirable situation in order to preventrecurrence.

Defect: Non-fulfillment of an intended usage require-ment or reasonable expectation, including one con-cerned with safety.

Design Review: Documented, comprehensive, andsystematic examination of a design to evaluate its cap-ability to fulfill the requirements for quality, identifyproblems, and propose the development of solutions.

Equipment Design Qualification: The initial phaseof qualification in which specifications and require-ments are developed and established.

Equipment Installation Qualification: Document-ed verification that determines whether all necessaryequipment components were delivered and correctly

David M. Stephon

ily recognized under current compliance trends thatthe term validation refers to activities that are con-sistent with the FDAs definition of establishing,through documented evidence which provides a highdegree of assurance that a specific process will consis-tently produce a product meeting its predeterminedspecifications and quality attributes. This definitionof validation has been appropriately applied to otheractivities, such as analytical control methods, process,cleaning, and software systems.

Qualification is the action of proving that any equip-ment works correctly and leads to expected results. Theterm validation is sometimes broadened to incorpo-rate the concept of qualification. The term qualifica-tion is also applied to other GMP-related activities,such as utility qualification, water, and Heating Vent-ilation and Air Conditioning (HVAC) systems, as wellas facility and employee qualification. When the con-cept of validation is extended to equipment used formanufacturing, packaging, labeling, or control testing,validation means qualifying (or verifying) that theequipment consistently functions within a specifiedrange of operations.

Equipment used in the pharmaceutical, biological,

or medical device industries, whether it be for manu-facturing, processing, labeling, packaging, or labora-tory control testing, is required to be qualified for use.The same principles and definition of validation, asstated above, apply to equipment qualification. Onlynow we are demonstrating the suitability of a compo-nent or validation, in the same way, for example, as weuse qualified or trained personnel as a prerequisite toperform any validation or other GMP-related activity.Properly installing equipment and verifying its perfor-mance for its intended use is a pre-validation activityin demonstrating that a manufacturing process, pack-aging operation, or quality control test method per-forms reliably and consistently. Equipment qualifica-tion incorporates extensive testing, verification, anddocumentation to establish that equipment meets min-imum requirements and functions as desired. Quali-fication is required to not only provide assurance of thecurrent state of control, but must also substantiate theexistence of procedures and practice that maintain theequipment in continuous working order.

Terminology



David M. Stephon

connected, and installed in an environment suitable forrequired operation based on the manufacturers re-quirements (e.g., voltage, frequency, temperature, humid-ity, space, etc.)

Equipment Operational Qualification: Docu-mented verification which determines that equipmentperforms as expected throughout its entire operatingrange.

Equipment Performance Qualification: Docu-mented verification that determines that the equip-ment performs as expected during routine use, underboth routine and unusual conditions.

Equipment Qualification: The practice of estab-lishing that equipment operates as it was designed forits intended use in a reproducible manner.

Factory Acceptance Testing (FAT): Pre-deliveryequipment testing designed to establish confidencethat the equipment and ancillary systems will meet func-tional requirements, and is capable of consistent oper-ation. FAT is performed at the supplier site, and the re-sults are used to release the equipment for shipment.

Good Manufacturing Practice (GMP): Regula-tions that must be followed for the manufacture, pro-cessing, packing, or holding of a drug product. GMPpractice include Title 21 Code of Federal Regulations(CFR), Parts 210-211, and European Community (EC)Directive 91/356/EEC for products destined for the U.S.or EC, respectively.

Grade: Category or rank given to entities havingthe same functional use, but different requirements forquality.

Inspection: Activity, such as measuring, examin-ing, testing, or gauging one or more characteristics ofan entity, and comparing the results with specified re-quirements in order to establish whether conformity isachieved for each characteristic.

Preventative Action: Long-term action taken toeliminate the cause(s) of a potential nonconformity,defect, or other undesirable situation in order to pre-vent recurrence.

Preventative Maintenance: A maintenance systemdesigned to detect and prevent problems before theyoccur.

Qualification Protocol: A written procedure thatstates how qualification testing will be conducted, in-cluding test parameters and acceptance criteria.

Quality: The total characteristics of an entity thatbear on its ability to satisfy stated and implied needs.

Safety: State in which the risk of harm or damageis limited to an acceptable level.

Standard Operating Procedure (SOP): A docu-ment that describes how to perform an operation ortask. SOPs contain step-by-step instructions of how anoperation or task is carried out in order to completethe operation or task reliably and consistently.

Supplier: Organization that provides a product orservice to the customer. Also referred to as a vendor.

Validation: Established documented evidencewhich provides a high degree of assurance that a spe-cific process will consistently produce a product meet-ing its predetermined specifications and quality attrib-utes.

Verification: The process of evaluating the productsof a given phase to ensure correctness and consistencywith respect to products and standards provided as in-put to that phase.


The regulatory compliance ex-pectation for equipment qual-ification has its origins in theGood Manufacturing Practice (GMP)regulations under several sections ofthe Current Good ManufacturingPractice (cGMP) for the Manufac-ture, Processing, Packing or Holdingof Drugs. Most notably under sub-parts D for Equipment, but also underSection 21 Code of Federal Regula-tions (CFR) 211.160(b)(4) under Sub-part I, Laboratory Controls. While theword qualification is not specifi-cally mentioned in 21 CFR 211, theinterpretation of these regulations through the years byboth industry and regulatory agencies, such as the Foodand Drug Administration (FDA), has allowed termslike Installation Qualification (IQ), Operational Qual-ification (OQ) and Performance Qualification (PQ) toevolve. Consequently, other terms were added to thisgrowing list of terms and nomenclature, most notablyacronyms, such as Factory Acceptance Criteria(FAT), Site Acceptance Criteria (SAT) and DesignQualification (DQ).

As with any compliance topic, regulatory agencyinterpretation of current expectations also plays arole in the development of knowledge for the phar-maceutical industry, which is geared to be proactivein minimizing compliance issues. For example, atypical FDA inspectional observation FD-483 reads:

Failure to assure automatic, mechanical, elec-tronic, or other equipment used in the manufacture,processing, packing and holding of a drug product,performs or functions satisfactorily. Specifically, yourfirm failed to perform Installation Qualification, Op-

erational Qualification or Perfor-mance Qualification studies on anyequipment used in the manufactureof your drug products (FDAWarning Letter [WL-5-8], Nov 18,1997).

This FDA-483 refers to a specific21 CFR 211 GMP requirement; inthis case 21 CFR 211.68(a) underSubpart D, Equipment. Here, theFDA investigator has provided aprime example of the Agencys cur-rent expectation for a manufacturer tohave IQ, OQ and PQ for manufactur-

ing equipment. While the two terms are related, and often used inter-

changeably, it is readily recognized by todays perfor-mance standards, that the terms validation and qual-ification have different meanings. The term valida-tion has the distinct advantage of being around muchlonger in the pharmaceutical industry than qualifica-tion. Historically, validation was defined in the now in-famous May, 1987 FDA Guideline General Principlesof Process Validation.1 This document defines valida-tion as it is still applied to as establishing documentedevidence which provides a high degree of assurance thata specific process will consistently produce a productmeeting its pre-determined specifications and qualityattributes. Qualification is often referred to as a condi-tion or state of control that must be met in order to as-sure the validity and reliability of test results. There-fore, it is best to refer to qualification as a precursor tovalidation in the broadest of terminology. Thus, pro-cesses and systems are validated using qualified per-sonnel and qualified equipment.

Manufacturing and processing equipment is likely

Regulatory InterpretationDavid M. Stephon

Adolor Corporation


FDA field investigators

are trained to askquestions on the

suitability of equipment used to manufacture

and test pharmaceuticals.


David M. Stephon

to have a vital and critical impact on the quality of theproduct, and even small differences between equip-ment operational capability can potentially have a largeeffect upon a process. Often, the nature of such an ef-fect will not be noticed until well into the process,where it could conceivably be difficult to detect. Pro-per qualification of manufacturing equipment estab-lishes the reliability of the operation, and the output ofthe equipment. Analytical equipment, on the otherhand, while being very important to establishing thequality of the product, has a defined and measurableoutput that can be readily evaluated.

The regulatory expectation for equipment qualifica-tion is further exemplified in the Current Good Man-ufacturing Practice for Finished Pharmaceuticals un-der Subpart D, Equipment. Under 21 CFR 211.65(a) itstates:

Equipment shall be constructed so that surfacesthat contact products shall not be reactive, additiveor absorptive so as to affect the safety or qualityprofiles of drug products.

The intent of this section is to promote the use of in-ert materials during equipment fabrication that is in-tended for pharmaceutical manufacturing. To accom-plish this, product contact surfaces for equipment areusually fabricated from high grades of stainless steel,such as 316L and 304. In addition, equipment fabrica-tors would want to incorporate certain tests at their site,for example, that would allow determination of surfacefinish, and quantitation of residual iron contaminants onthe surface, in addition to other process quality controltests. These test results are later challenged under thepharmaceutical manufacturers FAT at the equipmentfabricator, prior to shipping the equipment to the manu-facturing site.

In addition to the current cGMP requirements forFinished Drug Products, the May 1996 Current GoodManufacturing Practices; Proposed Amendment of Cer-tain Requirements for Finished Pharmaceuticals, alsostate the requirement for equipment qualification:

A written plan describing the process to be val-idated, including production equipment, and howvalidation will be conducted, including objective testparameters, product and/or process characteristics,predetermined specifications, and factors which will

determine acceptable results.The manufacturers determination of equipment

suitability shall include testing to verify that the equip-ment is capable of operating satisfactorily within op-erating limits required by the process.

If your company has experienced an FDA inspection,the FDA field investigator probably asked questionsabout your companys equipment procedures. FDAfield investigators are trained to ask questions on thesuitability of equipment used to manufacture and testpharmaceuticals. For example, the FDA ComplianceProgram/Pre-Approval Inspections Compliance PolicyGuide (CPG) 7346.832 states:2

The field investigator will be responsible for de-termining the adequacy of the facility, personnel andequipment qualification information as part of thecGMP inspection of the particular facility.

These GMP regulations and regulatory interpreta-tions form the basis for FDA expectations that manu-facturing, packaging, and labeling equipment be quali-fied and demonstrated suitable for their intended use. Inaddition, laboratory equipment must also be demon-strated as being suitably qualified for use. In responseto this, laboratory, as well as manufacturing equipmentvendors in the last ten to fifteen years, have respondedto FDA and other regulatory agencies for industry re-quirements and regulatory expectations for equipmentqualification, by providing qualification services and/orexecutable qualification protocols as part of theirequipment sales and installation package.

References1. FDA. General Principles of Process Validation. May. (1987).2. FDA. Compliance Program/Pre-Approval Inspections CPG

7346.832.


There are three (3) primary levels ofqualification which apply to equip-ment qualification. These include In-stallation Qualification (IQ), Opera-tional Qualification (OQ), and Per-formance Qualification (PQ). Theseequipment qualification steps arecommonly referred to as their re-spective acronyms IQ, OQ, and PQ.There are other qualification stepsthat are also used, for example, De-sign Qualification (DQ) and Maintenance Qualifica-tion (MQ). These latter qualification definitions, DQand MQ, while used in industry, really are backwardsand forward extensions, respectively, of the commonthree (3) qualification category types. There is also acategory collectively referred to as legacy qualifica-tion, used to qualify existing equipment that was pre-viously in your facility prior to your firms equipmentqualification initiative.

Typically, the first step in developing a procurementmethodology for the acquisition of equipment andqualification, especially custom equipment, is the de-velopment of user requirements. The user requirementsallow creation of a Request For Proposal (RFP) to pro-spective equipment vendors. As part of the selectionprocess, an assessment of the equipment vendor maybe performed. Assessments of the vendor by the phar-maceutical manufacturer usually include teams of en-gineers, manufacturing, and quality staff. Such assess-ments often allow the pharmaceutical manufacturer todetermine if the equipment fabricator has a suitablequality system in place, has experience in providingequipment to the pharmaceutical industry, and under-

stands documentation requirements.In sequence, the equipment is se-lected, specified, and designed as ap-propriate for the intended application,then the equipment is bid, purchased,and fabricated, followed by deliveryand installation.

It is important to understand com-pliance requirements when sourcingequipment. Equipment specificationand design can vary greatly between

cGMP and non-cGMP equipment. Equipment used inpharmaceutical manufacturing must meet all GMP re-quirements as specified under 21 CFR 211, currentGood Manufacturing Practice (cGMP) for FinishedPharmaceuticals. The specific section is listed underSubPart D, Equipment, under Section 21 Code of Fed-eral Regulations (CFR) 211.63, 211.65, and 211.67.These regulations detail equipment requirements. Thepharmaceutical industry has interpreted these regula-tions so that performance standards can be defined forequipment fabrication methods, materials of construc-tion, surface finishes, and controls. However, docu-mentation requirements often cause confusion betweenthe pharmaceutical manufacturer and the equipmentfabricator.

While equipment fabricators will supply a generalset of documents, such as fabrication drawings, mater-ial lists, parts lists, and Standard Operating Procedures(SOPs), normally more detailed procedures are re-quired by the pharmaceutical manufacturers engineer-ing department. This includes more detailed documen-tation, such as instrumentation loop drawings, softwarecoding, logic diagrams, calculations, and welding cer-

Equipment Qualification:

Getting StartedDavid M. Stephon

Adolor Corporation


It is important to understand

compliance requirements

when sourcingequipment.


David M. Stephon

tifications. In some cases, the equipment is shipped andinstalled at the pharmaceutical manufacturer withoutrequesting the required documentation upfront. Thiscan interfere with the proper execution of the equip-ment qualification by the pharmaceutical manufacturerafter delivery and installation. This is where a well-de-signed RFP or equivalent document can often help.Rather than request the equipment vendor to provide therequired documentation after the placement of an order,or after delivery of the equipment, exact documentationrequirements are determined prior to placing the orderand incorporated into the specifications. While this istime consuming, equipment requirements become partof the bid package and specifications, and can later beused during the equipment qualification execution.

The equipment should only be bid to equipmentvendors who have met the minimum standards for fab-rication quality and compliance uniformity. This is of-ten determined by conducting a vendor assessment thatcan involve an inspection of the vendors facilities, andreview of their internal procedures, production cap-abilities, previous work, and financial stability. In somecases, a quality questionnaire completed by the pro-spective vendor can also provide assistance in the eval-uation process. Purchase orders should include pro-visions for pre-shipment factory testing and training.Factory testing of the equipment and staff training onthe equipment is a valuable prequalification exercisethat should be used. Indeed, the design and executionof the Factory Acceptance Test (FAT) by the equipmentvendor, and review and critique by pharmaceuticalmanufacturer, serves as the precursor to the actual per-formance of the equipment qualification.

The most opportune time to identify problems, cor-rect problems, incorporate changes or upgrades, andconduct testing is prior to the equipment leaving thefactory, rather than have these problems later arise dur-ing the formal equipment qualification by the pharma-ceutical manufacturer. This also serves as a good op-portunity to train personnel who will later be re-sponsible for the operation, cleaning, and maintenanceof the equipment. Typically during the FAT period,maintenance personnel can use this time to understandfrom the equipment vendors expert staff how to main-tain and troubleshoot the equipment. Users can workon the equipment for a short time to understand its ca-pabilities, as well as recommended modifications,some of which may be considered for implementation

prior to shipment. Overall, the integration of the qual-ification needs to be incorporated into the FAT processand orientation exercises.

When the equipment is finally delivered and in-stalled, this regulatory compliance integrated thinkingmust be continued. The installation exercise should beconducive to working with the equipment for its in-tended use. Another general consideration is the devel-opment of a master plan. Project execution plans areoften one of the first documents generated for a project.Each section of a master plan should include scope, de-velopment, design, execution methodology, required re-sources, safety, construction, and environmental con-siderations. The mechanism for communicating the over-all methodology, resources, and time for qualification isreferred to as the Master Plan. The Master Plan is ahigh-level document that highlights the requirementsfor equipment qualification, lists equipment that willrequire qualification, and specifies the format to beused for all documentation. While Master Plans aretypically used for facility qualifications, they incorpo-rate the details necessary to plan for equipment qualifi-cation, and should be used for manufacturing, as wellas laboratory equipment. Maintaining the qualified sta-tus of the equipment should be outlined in the mastervalidation plan. Continued qualification includes man-aging and evaluating changes to the equipment, peri-odic checks (e.g., performance verification), calibra-tion, and performing preventative maintenance, and forcause maintenance, as required. All for cause (non-scheduled) maintenance operations should be docu-mented using a change control system in order to sub-stantiate that the equipment is still performing withinrequirements and specifications as outlined in the Func-tional Requirements Specifications (FRS).

Maintenance Triggers for Qualified Equipment

Replacement of key com-ponents in the system

Loss of product quality

Upgrades to equipment Change in location Change in personnel


Design Qualification (DQ) isused as a start-up activity be-fore the equipment is pur-chased and installed. DQ defines thefunctional and operational specifica-tions of the equipment, and providesguidance in the selection of the equip-ment vendor. DQ ensures that equip-ment will have all the necessary func-tions and performance criteria thatwill allow the equipment to be suc-cessfully implemented for the requiredapplication. DQ is mainly used for thedesign and fabrication of equipmentthat will be specially designed for thecustomer. DQ ensures that the equip-ment will have all the necessary func-tions and performance criteria that will enable theequipment to be successfully qualified for its intendedapplication. The proper implementation of DQ requiresthat planning for location and required utilities be con-sidered before the equipment is delivered to the site. Inaddition, the specifications, as well as the equipmentsimpact on the overall performance of the sites utilities,such as water, gases, electrical, steam, Heating Ventila-tion and Air Conditioning (HVAC), exhaust, plumbing,and cooling water are evaluated. Miscalculations in theDQ can potentially have a significant impact later on.For example, determining the incorrect specificationsduring the DQ phase that will later be used during theOperational Qualification (OQ) of the equipment, cancause substantial delays and consume time and re-sources. Furthermore, the equipment vendor evaluation,

which is often concurrently con-ducted during the DQ phase, allowsthe equipments capability to be deter-mined. DQ should be performed whennew equipment is being purchased, orwhen existing equipment is beingused for a new application.

DQ serves as the precursor to defin-ing the equipment Installation Qual-ification (IQ) and OQ protocols. Typ-ically, when purchasing new equip-ment, the Quality Assurance (QA) de-partment will be involved in the se-lection of a suitable equipment fabri-cator. The equipment is first selected,specified, and designed as appropri-ate for the intended use. Next, the

equipment is identified from a suitable vendor, pur-chased and (if required) fabricated. Finally, the equip-ment is delivered and installed. However, current GoodManufacturing Practice (cGMP) requirements requirethat certain regulatory requirements be satisfied duringthis process. Under the cGMP for Finished Pharma-ceuticals, 21 Code of Federal Regulations (CFR) 211.62,211.65 and 211.67 state the general requirements forequipment design qualification. Industry has inter-preted these regulations, from an engineering stand-point, as the requirement to have fabrication methods,materials certification, and specifications for surfacefinishes and controls. The level of detail that one com-pany may require when purchasing equipment mayvary greatly in some cases. Reputable equipment fabri-cators will normally supply a general set of documen-


Design QualificationDavid M. Stephon

Adolor Corporation


change control, in terms

of revision control of functional

specifications,is advantageous

during the execution of

the DQ phase.


David M. Stephon

tation, such as fabrication drawings, material lists, partslist, and equipment operational procedures. In addition,the equipment vendor should supply, or have available,more detailed documentation, including loop diagrams,software coding procedures, ladder logic diagrams, cal-culations, construction logs, and welding certifications.

Factory Acceptance Testing (FAT) is performed tohave assurance that the equipment and components ar-rive at the drug manufacturers site, and meet all spec-ifications for construction and operation. Typically, thedrug manufacturers QA, engineering, and manufac-turing representatives inspect, test, and document theequipment before it leaves the vendors facility, insur-ing that the equipment will meet qualification criteria.Vendor factory release testing is conducted to demon-strate equipment suitability and performance before itis shipped to the manufacturer.

DQ is required to be completed prior to the equip-ment delivery and execution of Site Acceptance Testing(SAT) and IQ. Even at this early stage, change control,in terms of revision control of functional specifications,is advantageous during the execution of the DQ phase.When installing multiple equipment types, often a Val-idation Master Plan (VMP) or qualification plan is help-ful in identifying start and end activities, precursorevents, project team members, resource requirements,and associated costs. A Request for Proposal (RFP) isrequired to be developed from the User RequirementSpecifications (URS), and submitted to prospectiveequipment vendors that have the operating and designprinciples of the equipment class that is being consid-ered for purchase. Typically, a technical assessment con-ducted by the engineering and manufacturing depart-ment, and a vendor assessment are conducted duringthis part of the DQ phase. Ideally, an audit team withprocess engineers, quality professionals, and manufac-turing personnel are assembled to conduct a quality, aswell as a technical assessment of the equipment vendor.As part of the DQ phase, the vendor should be qualifiedfor use. The returned and completed RFP from the ven-dor becomes a useful performance audit standard inwhich to evaluate the vendors capabilities. In addition,a pre-audit quality questionnaire, if designed and usedproperly, can often pay dividends during the actual ven-dor audit by confirming commitments and verifyingclaims made on the returned quality questionnaire.

The RFP should also include a request for a list ofreferences from customers that have acquired similar

equipment. These references should be checked froma qualified member of the project team. When onethan more vendor is being evaluated, a comparabilitymatrix can be developed using weighted scores forevaluation and listing critical attributes, specificationsand requirements that the firm is requiring the equip-ment to be capable of performing. This is especiallycritical when purchasing customized equipment. Insome cases, the equipment may be used for differentapplications with associated different functional andperformance requirements. Under these circumstances,it is recommended that a description be developed forthe most critical applications, and to specify the func-tional and performance specifications that will meetthe criteria for all applications.

Your firms QA department will also want to per-form an assessment of the potential equipment ven-dor(s) to ensure that all equipment that will be pur-chased will be able to undergo successful qualifica-tion after the equipment is purchased and delivered.The QA departments responsibility is to verify theproduct lifecycle of the equipment vendor, and thevendors ability to support the equipment and pur-chase. Sometimes, a vendor quality questionnaire ishelpful in collecting this information, which can alsobe supplemented by an onsite physical audit.

A sample equipment vendor quality questionnaireis included on the following pages.

Design Qualification Protocol Elements

Description Selection of the Specific

Equipment Application Description of the In-

tended Operating Envi-ronment

Definition of URS Preliminary Selection

of Functional and Per-formance Specifications

Preliminary Selection

and Assessment ofSuitable Vendors

Demonstration of theVendors Ability to meetFAT Requirements

Final Selection of theVendor

Documenting the FinalEquipment Functionaland Operational Spec-ifications


David M. Stephon

Distributor/Broker InformationPrimary ContactFull Street AddressTelephone NumberFax NumberWeb Site/E-Mail Address

Fabrication SitePrimary Contact Full Street Address Telephone NumberFax Number Web Site/E-Mail AddressEquipment 1.

2. 3.

General Information

1. Please state your firms Corporate Headquarters information, including name of primary site contact, full street address, telephone number, fax number, and web site/e-mail address.

2. Will your firm permit an on-site visit? If no, please explain. Yes No ____________________

3. In what year was the company established?4. Attach an organizational chart showing

reporting structure of company.5. Total number of employees.6. Number of employees within the quality unit?7. How many shifts operate at the fabrication site?8. What percent of staff is temporary/contractual?9. Do you provide new employee training (e.g.,

covers skills, GMP/International Organization for Standardization (ISO)/Quality concepts? If no, explain. Yes No ____________________

10. Is there current employee training (e.g., covers skills, GMP/ISO/Quality concepts)? If no, explain. Yes No ____________________

Equipment Vendor Quality Questionnaire Sample (Full Assessment)


David M. Stephon

11. Are written training records maintained for all employees? If no, explain. Yes No ____________________

12. Does the quality unit have sign-off on SOPs? If no, then who does? Yes No ____________________

13. Which departments review and approve master production documents?

14. Is there an SOP system for making changes to engineering drawings, Process and Instrument-ation Diagrams (P&ID) and other control documents? If no, please describe system used. Yes No

15. Will you agree to provide notification of significantchanges made to the equipment fabrication/software development process being used? Yes No

16. If yes to #14, please list contact person and contact information.

17. Which department approves equipment specifications?

18. Is a confidentiality agreement required to audit your facility? If yes, attach a copy of agreement. Yes No

19. Is your firm ISO 9000 certified? If yes, please provide a copy of the most recent registrar accreditation. Yes No

20. If your firm is ISO 9000 certified, will you furnish an index of the quality manual? If yes, please attach. Yes No

21. Do you understand and experience Good Manufacturing Practice (GMP)? Yes No

22. If your firm is not ISO9000 certified or does not practice GMP, what other regulatory or quality program is being utilized?

23. Has your firm addressed requirements of 21 CFRPart 11, Electronic Records; Electronic Signatures. If yes, describe your program. If no, indicate yourfirms understanding of the regulation. Yes No

24. Do you employ an SOP or other type of documen-tation system to describe activities? If no, explain. Yes No ____________________

25. Will your firm furnish an SOP index of procedures? If yes, please attach index. Yes No

26. Will your firm provide a certificate of materials? If yes, will a Certificate of Acceptance (COA) be based on your testing, an outside laboratory, or both (please identify). Yes No



David M. Stephon

27. Does your firm have an instrument calibration program (e.g., pressure gauge, calipers, profilometer)? Yes No

28. Are there calibration records for each instrument requiring calibration? If no, explain Yes No ____________________

29. Is there a list of approved suppliers for raw materials you purchase (e.g., 316L and 304 steel? If no, describe how suppliers are selected at thetime of purchase. Yes No

30. Is there a First In First Out (FIFO) system for stock rotation? If no, describe system in use. Yes No

31. Are there separate labeled areas for untested, released, and rejected materials? If no, describe the method assuring separation of materials. Yes No

32. Is there a written sampling plan for incoming raw materials? Yes No

33. Are any of the raw materials accepted only on the |basis of the manufacturers COA without any additional testing? If yes, please explain why identification testing is not performed. If no, how frequently are these materials tested? Yes No ____________________

Equipment (Software)1. Does your firm have written software design,

development, and test procedures? Yes No2. How does formal review of system specifications

and integration test plans occur?3. What process is used to develop software code

by your firm (e.g., Software DevelopmentLife Cycle [SDLC])?

4. What type of software testing is conducted by your firm (e.g., structural, functional)?

5. Are third-party tools incorporated into the Yes Nosoftware product? If yes, please explain Explain:

6. Are there formal procedures for deviation, exception, or problem reports? Yes No

7. Is the software code maintained in escrow? Yes No8. Does formal separation of duties between de-

velopment, testing, and release exist in your firm? Yes No9. Please describe your firms patch/bug-fix process.



David M. Stephon

10. Is your firm aware of any FDA warning letters orFD483s issued in relation to the use of any of your software products? Yes No

11. Is software designed to allow restricted accessto systems limited to authorized individuals as set by the system administrator? Yes No

12. Is software designed to permit access only after inputting a user name and password? Yes No

13. Is software designed to allow the system to require frequent changes of each username and password? Yes No

14. Is software designed to allow for an audit Yes Notrail of changes to entered data? Please explain:

15. Is software designed to allow archiving of changes to data information by time/date stamps? Yes No

16. Is software designed to allow for system validation by the user that demonstrates compliance with 21 CFR 11; Electronic Records; Electronic Signatures? Yes No

Equipment (Hardware)1. What quality standard(s) does your firm follow to

ensure that quality products are produced (e.g., American Society of Mechanical Engineers(ASME), current Good Manufacturing Practice (cGMP), American Society for Testing and Materials (ASTM), etc.)?

2. Is there a process flow diagram for the fabricationof the equipment piece(s) being purchased?P&ID, diagrams, blueprints? If yes, please attach to questionnaire. Yes No

3. Are subcontractors used for any part, or all, of equipment fabrication, raw material, or product Yes Notesting? If yes, please explain. Please explain:

4. Please explain your firms program for ware-housing, inspection, and release of equipment components and other materials.

5. Please explain how user requirements and functional specifications are incorporated into your design process.



David M. Stephon

6. During equipment fabrication, how are non-conforming events handled (deviations, bad welds, etc.)

7. Please describe in general what testing is performed on the equipment fabricated (riboflavin, surface finish, etc.)

8. Is more than one grade of steel used in the fabrication facility (e.g., carbon steel, 304, 316L, etc.)? If yes, explain how these materials are segregated to minimize contamination. Yes No


Name and Title of person who completed this questionnaire (Signature Required):

Date this questionnaire was completed:


Based on the outcome from theDQ and initial equipmentevaluation, such as testing ofthe equipment at the vendor site (e.g.,FAT), and/or SAT conducted uponinitial receipt of the equipment, a for-mal Installation Qualification (IQ)protocol can be developed. When theequipment and the vendor certifica-tions are received, IQ can proceed.Based on the Design Qualification(DQ) report or executed Factory Ac-ceptance Test (FAT), or red-linedFAT protocol, with required changes, design of the IQprotocol can proceed.

It is important to consider location, utility, and spacerequirements for the new equipment before it arriveson site. A comprehensive understanding of the require-ments for the new equipment must be obtained fromthe vendor well in advance. Issues, such as humidityand temperature requirements for proper operation, and

utility needs, such as volt/amp speci-fications and compressed gas(es) re-quirements need to be planned for.Care is also required to ensure allsafety concerns, such as electricalgrounding, are within specified lim-its, and that correct cables are usedfor power connections. This is re-ferred to as the pre-installation phaseof equipment qualification.

When the equipment actually ar-rives, the shipment should be inspect-ed for agreement with the Purchase

Order (PO) specifications. A visual inspection of theequipment should also be conducted to identify the ex-istence of any physical damage.

The IQ phase ensures that equipment has been prop-erly installed. The IQ must meet the equipment manu-facturers specified guidelines and requirements. Areas,such as supporting electrical utilities, electrical codes,and environmental condition requirements, are requiredto be evaluated during the IQ phase of qualification.Typical information required during the IQ includesverification of equipment identification, required docu-mentation, such as as-built drawings and purchase or-ders, equipment utility requirements, major componentspecifications, list of component materials, lubricants,and equipment safety features. Equipment identificationwould normally include attributes, such as name ofmanufacturer, purchase order number, serial number,model number, internally assigned equipment or assetnumber, and the location where the equipment will beinstalled. Documentation that should be available dur-ing the IQ phase includes the equipment manufacturers


Installation QualificationDavid M. Stephon

Adolor Corporation


The IQ protocol should

provide completeinstructions for

performing the IQ

requirements

Factory Acceptance Testing Out-line Sample

In order to ensure that the equipment is manufacturedand performing to specifications and expectations,company representatives will perform the following:

Audit equipment fabrication site Verify existence of vendor requirements Witness, verify, and document equipment operation Execute equipment safety inspection Execute equipment FAT protocol Establish required modifications to FAT Approve equipment for shipment delivery


David M. Stephon

and maintenance manual, equipment drawings, such asP&ID. In addition, SOPs that address the equipmentset-up, operation, calibration, maintenance, and clean-ing should also be available during the IQ phase, andverified as accurate. Equipment utility requirements areused during the IQ phase to compare the manufacturersspecified volts, amps, and for example, compressed airrequirements to the as found conditions at the time ofthe qualification.

The IQ protocol should provide complete instruc-tions for performing the IQ requirements for equipment.In addition, SOPs for operation, calibration, cleaning,maintenance of the equipment, as well as associatedlogbooks, should be established. The equipment manu-facturers operation and installation manual is typicallya good source of information for drafting these SOPs.

Execution of the IQ protocol is performed mini-mally by two (2) trained operators. As in a batch pro-duction record, each step in the qualification protocol isrequired to be initialed or signed, and dated as the stepsare executed. Each operator should have the education,training, and experience that supports their participa-tion in the protocol execution. Evidence of the trainingshould be referenced or appended to the protocol. Thisis also important when third-party operations are usedin the execution of the qualification protocol. Verifi-cation that a protocol step has been successfully com-pleted can be accomplished by visual inspection, or bya measuring device. The method of determinationshould be denoted accordingly in the protocol.

During the execution of the IQ protocol, it is im-portant to ensure that all instruments and componentsof the equipment are properly calibrated. A section inthe protocol should denote calibration of critical andnon-critical instruments and gauges. The IQ protocolshould reference the calibration procedure used, cali-bration date, and whether or not the calibration wassuccessful.

In the event that a non-conforming event is en-countered during the execution of the IQ or any quali-fication protocol, it is important that a report be gener-ated that explains the occurrence, references the proto-col step number, describes the non-conforming event,provides an investigation, actions taken, and states thecorrected and conforming test result. It is important thatthe investigation into the non-conforming event be ini-tiated prior to retesting of the test parameter.

In some cases, it may be preferably to combine the

IQ and Operational Qualification (OQ) together intowhat is commonly referred to as Installation/Oper-ational Qualification (IOQ) protocol. When using thisform of protocol, it is important to ensure and docu-ment that the IQ portion of the IOQ protocol has beensuccessfully completed before the OQ section is initi-ated. In fact, the first executable step in the OQ proto-col, regardless if it is combined with the IQ, is the ver-ification that the IQ was successfully completed.

A installation qualification protocol sample form islocated on the following page.


David M. Stephon

Installation Qualification Protocol SampleEquipment Identification:

Purchase Order Number __________________________ Identification Number __________________________ Model Number __________________________ Serial Number __________________________

System Utilities Required (Y/N) Specifications Completed (Y/N)Compressed Gas, Water, Nitrogen SupplyElectricalLightingSteamVentilation RequirementsHVAC RequirementsSoftware Requirements Acceptance Criteria __________________________ Test Results __________________________ Non-Conforming Test Results _________________________ List of SOPs __________________________ Spare Parts List __________________________ Review and Approvals __________________________

Key Information for Installation Qualification Protocol Design1. Scope of protocol2. Pre-execution acceptance/approval of protocol3. Description of equipment, including manufacturer names, serial number, model, capacity, and function4. Equipment asset/tag number, location 5. Verification of purchase order6. Equipment drawings, including an accurate P&ID. The process engineer should be able to identify the crit-

ical parts of the process necessary for proper operation of the system7. An accurate P&ID tag list, sorted functionally and/or numerically8. Manufacturers specifications, installation and operation manual, and any recommendations from the

manufacturer regarding installation (e.g., critical environmental and utility requirements)9. A list of critical components components without which the equipment would not operate properly.

This list should also include special long-lead components that could jeopardize start-up and/or pro-duction schedules if they were to fail.

10. A complete list of specifications on critical components. A list of limits that the components will en-sure, and are designed and engineered to, should be available. If no, specification is available for acomponent. Suitable judgement should be used in determining a reasonable evaluation criteria.

11. A list of engineering design data on critical parts. In most cases, this information is available on thespecification sheets, or is part of the equipment data. If the part is custom-engineered and affectssafety or critical operation, a review of the engineering calculations is advantageous.

12. A listing of product contact areas. The product contact, solution contact, air contact areas, as well as all ofthe materials in contact with any one of these areas, should be identified, and the components listed by lotnumber.


Operational Qualification (OQ)evaluation should establishthat the equipment can oper-ate within specified tolerances andlimits as established by the equipmentmanufacturer. OQ requirements in-volve demonstrating that all equip-ment and equipment characteristicsmeet design standards under operat-ing conditions. OQ usually includesverification of equipment parameters,such as speed, RPM, power con-sumption, and cycle duration. In addi-tion, OQ involves testing and verify-ing that all sensors, switches, controldevices, logic circuits, gauges, systemdiagrams, and safety controllers arecalibrated and operating correctly.The OQ challenges the mechanicalranges of the equipment as intendedby the equipment manufacturer. In-formation required in the OQ includesverification of calibration of the instruments and devicesthat will be used to control the equipment, such asswitches and push buttons, and equipment operation,such as motor rotation direction, RPM, flow rates, etc.Verification that all critical instruments on the equip-ment have been logged into the calibration system,Standard Operating Procedures (SOPs) are in place forthe instrumentation, and all instrumentation is in cali-bration at the time of qualification testing are typical re-quirements during the OQ phase.

Operational qualifications typically require thatthe following general information be generated in

the functional requirements:

a. Display specifications if Cath-ode Ray Tubes (CRTs) are used,or if discrete instrumentation isused, a description of their pur-pose, and detail of how the in-strumentation relates to the pro-cess should be provided.

b. Security specifications allpharmaceutical processing equip-ment requires evidence of secu-rity systems, passive or active.

c. A fundamental sequence ofoperations Exactly how isthis equipment or process sup-posed to function and interfacewith the real world? What arethe inputs and outputs? Howdoes it operate? How is itcleaned? How is the equipmentset up for use?

In addition, when designing the OQ protocol, ad-ditional information should be acquired, such as:

Does the equipment have several modes of op-eration? If so, described each mode in detail.

Does the system use any diagnostics or interlocks? Does the system have alarms? Are there any other specifications unique to this

equipment? If so, these should be listed.

Operational equipment qualifications should be


Operational QualificationDavid M. Stephon

Adolor Corporation


the equipment

qualification report should state that the

test results conform with the original acceptance

criteria and thatthe equipment

has been successfully qualified.


David M. Stephon

conducted in two (2) stages: component operationalqualifications (of which calibration can be considereda part), and system OQs (including whether the entiresystem operates as an integrated whole). During theOQ, input and output are evaluated and checked forproper operation. For other devices that are not cali-brated or able to be calibrated (such as CRTs, soft-ware, Programmable Logic Controllers [PLCs], etc.),special tests must be designed from the developedfunctional specifications, such that the range of inter-locks, alarms, displays, and functional operations aretested adequately to assure consistent operations.

The use of the Piping and Instrumentation Diagram(P&ID) is instrumental in verifying system opera-tions. If possible, tests for each component of theequipment having Input/Output (I/O) requirementsfor critical parameters should be conducted that verifythat it operates according to the designated function ofthe P&ID diagram. If loop diagrams are provided,these can provide an accurate way to categorize check-lists. References to P&ID loops and/or loop diagramscan effectively be used in the individual designed equip-ment OQ tests.

Determining which equipment functions are to beevaluated during OQ is an important step. Consid-eration should be provided as to the function of thesystem as a whole, followed by which specific equip-ment attributes control those functions. For example,when designing the OQ protocol for a blender ormixer, the system, as a whole, is intended to blendbatches of product. However, the specific elements ofthe equipment that facilitate this operation could con-sist of a vessel, a mixing arm, and an automated valveat the bottom of the vessel. The fundamental equip-ment functions that facilitate blending might includethe motor on the stirrer, stirring direction, speed, andthe actuator that controls the bottom vessel valve. Thesebasic functional attributes of the blender should betested under the OQ protocol.

Some equipment manufacturers provide diagnosticprograms and systems. PLCs normally have force in-structions to manually force I/O on and off. Otherequipment manufacturers may provide maintenanceitems that allow diagnostic exercises to be executed onvarious substructures of the equipment. Another areato consider in designing the OQ is the interlock andalarm listings that are the most comprehensive and or-ganized functional descriptions of the equipment.

Tests should be developed that evaluate this function-ality. Used properly, these diagnostic, interlock, andalarm tests are invaluable in making the OQ phase ofequipment qualification more efficient.

Finally, after execution of the OQ protocol, as inthe case with the equipment Installation Qualification(IQ) or PQ, a qualification summary report should begenerated and reviewed by the same responsible per-sonnel that reviewed and approved the pre-executedprotocol and executed protocol. The final approvalshould be performed by the QA department. Whilesometimes executed qualification protocols are usedas documented evidence that qualification was success-ful, generating a separate equipment qualification re-port is recommended in that it allows a separate writ-ten assessment of the qualification exercise. The qual-ification report should contain a copy of the approvedexecuted protocol, including any primary data andprintouts, discussion of test results, discussion of anynon-conforming events, and actions taken to preventrecurrence. Finally, the equipment qualification reportshould state that the test results conform with the orig-inal acceptance criteria, and that the equipment hasbeen successfully qualified.

The maintenance of the qualified state for equip-ment is another important consideration. Under somecircumstances, the qualification for processing or lab-oratory equipment may be needed to be repeated on aperiodic basis. This schedule may be determined bythe vendor, for example, in the case of some labora-tory equipment, which is often referred to as a perfor-mance verification. In other cases, abbreviated or fullqualification of the equipment may be required if it isdetermined that the equipment undergoes significantchange. Under these cases, an approved change con-trol or change notice form is used to determine anddocument the level of change, and evaluation of theimpact on the equipments operation and functionalcapabilities. It is important that a written operatingprocedure for change control management be em-ployed to evaluate and document all proposed changesto determine the impact on the equipment after theequipment has been deemed to be operating in a stateof control after the qualification process has been suc-cessfully completed.

An equipment change control sample form is locatedon the following page.


David M. Stephon

Equipment/System Description: ______________________________Description of Change: ____________________________________Requalification Test Requirements:

Not Required Full Qualification Required Abbreviated Qualification Required

Qualification Plan to be used: ____________________________________

Results of Test Requirements: ____________________________________ Attached

Qualification Documents Impacted: Installation Qualification Operational Qualification Performance Qualification Calibration Preventative Maintenance

Approved By: ___________________________Quality Assurance

Equipment Change Control Form Sample


After it has been establishedthat equipment is properly in-stalled and functioningwithin specified operating parame-ters, the PQ is performed. The pur-pose of the PQ is to demonstrate thatthe equipment can operate reliablyunder routine, minimum, and maxi-mum operating conditions. The PQevaluates the equipments perfor-mance under actual use conditions. Itis advantageous during the PQ phaseof this test phase qualification tohave knowledgeable and trained per-sonnel that are familiar with theequipment, involved in creating andapproving the PQ equipment proto-col.

PQ typically involves:

Evaluating equipment operation under normal(nominal) processing conditions.

Evaluating equipment operation at several bound-ary conditions that would be normally be en-countered under routine use. For example, capa-bility that the equipment can operate within aproven acceptable range, intended use of range,worst-case conditions, or edge of failure.

Evaluation of equipment operation under less-than-optimal conditions to verify boundary criteria

Retesting within selected boundary criteria toverify that the proper boundary criteria are accept-able to use during routine use.

Testing of alarm and interlocksetpoints resulting from the op-erational boundary testing. Theequipment should be demon-strated to protect itself (withinreason) from abnormal operat-ing conditions, and alarm, mod-ify, or discontinue the operationaccordingly.

A good example of the design ofa PQ protocol is to consider the PQrequirements for a moist heat steril-izer or autoclave. The PQ for an auto-clave should include minimum andmaximum loads of the componentsto be sterilized that will represent ac-tual intended use conditions. Theminimum and maximum load shouldrepresent worst-case conditions for

positions of the components in the sterilizer. The com-ponents should be placed in locations in the autoclavethat have the potential to not receive the same heat pen-etration as other more optimal locations. ResistanceTemperature Detector (RTD) and spore strip readingswill allow these worst-case conditions to be evaluated.The PQ protocol should challenge the temperature andexposure time that is required to sterilize the compo-nents to the required sterility assurance level.

The use of PQ to laboratory instrumentation, such asan High Performance Liquid Chromatography (HPLC),also presents a good example of this qualificationphases application. After completion of the IQ and


Performance QualificationDavid M. Stephon

Adolor Corporation


The PQ protocol should

challenge the temperature

and exposure timethat is required to sterilize the

components to the required

sterility assurance level.


David M. Stephon

OQ phase, PQ can be considered a combination ofboth routine method specific system suitability re-quirements and also planned, routine examination ofinstrument performance, such as calibration checks,and where appropriate, recalibration. In addition toconcentration standards, method specific system suit-ability criteria allows monitoring of the critical com-ponents of the equipment. System suitability criteriacan include the detectors baseline noise, precision ofquantity of analyte injected, peak resolution, peaktailing, and column efficiency. PQ usually consists ofa combination of such method specific concentrationstandards and system suitability criteria applied foreach analytical run, together with a regular, plannedset of non-method specific calibration checks carriedout at appropriate intervals.

Legacy Equipment QualificationThe concept of Legacy Equipment Qualification (LEQ) isused under those circumstances where manufacturing,packaging, labeling, and quality control testing equip-ment was already in place prior to implementation of theequipment qualification initiative. LEQ addresses the re-quirements of the three (3) qualification phases, IQ, OQ,and PQ, in a retrospective manner. Under LEQ, a his-torical review of the equipments service repair historyand frequency, calibration, and maintenance records isconducted to confirm that the equipment operates his-torically in a consistent and reliable manner. To confirmthe reliability of existing equipment, it must also bedemonstrated that the equipment can operate satisfac-torily within required limits and ranges. It is also impor-tant to indicate the period of time that the equipmentshistory of operation was evaluated, as supported bydocumentation, such as equipment use, preventativemaintenance, and service logbooks. Instances of any forcause maintenance performed on the equipment shouldbe documented, and the impact on the equipments op-erational status evaluated. An LEQ summary report isthen prepared. A schedule of completion for all existingequipment required to undergo LEQ should be main-tained in the Validation Master Plan (VMP).


It is recommended that a pro-spective equipment protocol bewritten and approved for theequipment IQ, OQ, and PQ. In somecases, combining the IQ and OQ toform an Installation-OperationalQualification (IOQ) protocol is ac-ceptable, provided the completion ofthe IQ is verified and documentedprior to execution of the OQ. Thequalification protocols are controldocuments, just like SOPs and batchrecords, and require final approval be-fore and after execution by the qualityunit.

A format is required for stating theequipment qualification requirements,method of verification, and the system for collecting anddocumenting the information that will be acquired dur-ing the execution of the qualification protocol.

The design of the qualification protocol usuallyinvolves the following elements:

Scope: Defines the intended purpose and majorfunctions of the equipment.

Equipment Definition: Provides a detailed de-scription of the equipments hardware/software,utilities, and other components that define theequipment and its functions.

Responsibility: Defines the individuals responsiblefor the preparation and drafting of the qualificationprotocol, and the individuals expected to executethe testing. As required, define the responsibility ofthe equipment vendor in the qualification process.

Qualification Procedures: Liststhe SOPs that define how thequalification will be carried out.

Expected Results/AcceptanceCriteria: This should list the ex-pected results of each test, withblank fields available to recordthe actual test results. The proto-col should also have prospectivefields for documenting any non-conforming events that may beencountered during the executionof the protocol, and remedial/cor-rective action taken.

Forms, Attachments, Appen-dixes: Any forms, attachments, orappendixes should be listed andattached to the qualification pro-tocol.

Primary Data: Primary data generated duringthe execution of the qualification protocol shouldbe attached or referenced.

Approvals: Appropriate review and approvalsignatures are required for both pre-executionand post-execution.

Change Control/Requalification Criteria: Inaccordance with a lifecycle approach, the VMPthat directs equipment qualification requirementsshould include the criteria for requalification ofthe equipment when deemed necessary, based onchanges. Depending on the extent of the change, ab-breviated or full requalification may be required.

Ongoing Monitoring: This area should be ad-dressed by ensuring SOPs are in place to address

Qualification Protocol and Report Design

David M. StephonAdolor Corporation


The final qualification report should

summarize the test results andcompare these results against the approved acceptance

criteria used.


David M. Stephon

[a] equipment security controls to safeguard dataintegrity [b] data archival and retrieval require-ments to ensure that data can be reinstalled, asrequired (for equipment capability of storingelectronic records) [c] system operation (includ-ing equipment operators manuals or a brief list-ing of operations and parameters) [d] training (toensure that only qualified operators use the equip-ment).

Maintenance and Calibration: Maintenance andcalibration schedules should be defined using theequipment vendors operation manual and/or qual-ification template as a guide.

A final equipment qualification report should bewritten, as opposed to using the approved executedqualification protocol as evidence that the equipmentwas successfully qualified. The final qualification re-port should summarize the test results and comparethese results against the approved acceptance criteriaused.

The author of the qualification report should in-clude a statement that the equipment was successfullyqualified. If any non-conforming events were en-countered during the execution of the qualification,these should be discussed with an explanation of howthey impacted the qualification exercises, investiga-tions, retest results, along with any corrective and pre-ventative action taken. Ideally, a qualification reportshould be written after each phase of the qualificationis completed. However, where the OQ is performeddirectly after the IQ, or where these two phases arecombined, a single qualification report would be con-sidered sufficient. In other cases, a final qualificationreport can be written after the IQ, OQ, and PQ havebeen completed.

Furthermore, it is important to ensure that the sameindividuals from the same functional departments thatreviewed and approved the qualification protocolspre-execution, are the same individuals that reviewand approve the executed qualification protocols andfinal qualification reports. Exceptions should be doc-umented with appropriate rationale, e.g., training ofthe replacement personnel, as required. The qualifica-tion protocols and reports should be designed to havethe QA function always be the last approval signature.It is important not to have another department approveand date the qualification protocol and report after the

quality unit has approved it. This could imply thatquality has a subordinate role to another functionaldepartment, which is contrary to the basic premise ofcGMP.

About the AuthorDavid M. Stephon has more than 17 years experiencein the pharmaceutical industry with in-depth experi-ence in regulatory compliance and quality assurancetopics. His experience includes working in qualityassurance, compliance, chemistry, manufacturing andcontrol operations for Sterling Drug and Sanofi Re-search, NanoSystems, and Elan Pharmaceuticals.David is an Editorial Advisory Board member for theJournal of GXP Compliance, In 2002, David receivedan Industry Recognition Award from the Institute ofValidation Technology. Currently, he holds the posi-tion of Senior Director, Quality Assurance, at AdolorCorporation. He can be reached by phone at 484-595-1091, by fax at 484-595-1573, or e-mail [email protected].

Equipment Qualification Report Contents

Equipment Qualification Report Approval: Uponcompletion of the equipment qualification report,which includes documentation that the test protocolswere successfully followed, executed, and completed,an executive summary should be drafted, and thequalification report circulated for approval by the coreproject team. Final approval by QA is required.

Executive Summary: The executive summary willclearly state that the equipment has been qualified.The summary should include historical information onprevious equipment model/type qualifications, as ap-propriate. This executive summary should also includea list of each of the major tested functions of the com-ponents. The executive summary should also note:

Completed and Approved Equipment Qualifica-tion Test Plan: A copy of the VMP or equipmentqualification master plan should be included.

Completed and Approved Equipment In-stallation Qualification Protocol and AttachedTest Data (Appendix): This should be appendedto the equipment qualification report.

Completed and Approved Equipment Opera-tional Qualification Protocol and Attached TestData (Appendix): This should be appended to theequipment qualification report.

Completed and Approved Equipment Per-formance Qualification Protocol and AttachedTest Data (Appendix): This should be appendedto the equipment qualification report.


ASME: American Society for Mechanical Engi-neers

ASTM: American Society for Testing and MaterialsCFR: Code of Federal RegulationscGMP: Current Good Manufacturing PracticeCOA: Certificate of AcceptanceCPG: Compliance Policy GuideCRT: Cathode Ray TubeDQ: Design QualificationEC: European CommunityFAT: Factory Acceptance TestFDA: Food and Drug AdministrationFIFO: First In First OutFRS: Functional Requirements SpecificationGMP: Good Manufacturing PracticeHPLC: High Performance Liquid Chromatogra-

phyHVAC: Heating Ventilation and Air ConditioningIQ: Installation Qualification

IOQ: Installation/Operational QualificationISO: International Organization for Standard-

izationI/O: Input/OutputLEQ: Legacy Equipment QualificationMQ: Maintenance Qualification OQ: Operational QualificationPLC: Programmable Logic Controller PO: Purchase OrderPQ: Performance Qualification P&ID: Process and Instrumentation DiagramQA: Quality AssuranceRFP: Request For Proposal RTD: Resistance Temperature DetectorSAT: Site Acceptance TestSDLC: Software Development Life CycleSOP: Standard Operating Procedure URS: User Requirement SpecificationVMP: Validation Master Plan

Article Acronym Listing

David M. Stephon

Originally published in the February, 2003 issue of the Journal of Validation Technology

equipment qualification toolkit

Documents

i f i c

t i o n t o o

s e c t i o n e q u

e n t q u

t s p e c

laboratory equipment

compliance data

integration of validation