ISPE-GEP

A Good 'V Practice

Guide --.Good

Engineering Practice

I

I I

ISPE Good Prot;lice Guide: GoOcf Engineering Pr3.tice

Tabla of Contents 1 Introduction ....................................................... .... ............................. ....... .................... 7

1.1 Overview ................................................................... ................. ................ ................ ................ .............. 7 1.2 Purpose ...................................... ..................... .......................... ................ ................ ............................... 8 1.3 Scope and B~nefit Ol:l;OOtives........ ................ ................ ................ . .............................. 8 1.4 Koy Concepts .................................................. .......................................................................................... 8 1.5 Struccure of the Guide ........... ...................................................................................................................... 9

2 Breadth and Coverage of GEP .......................................................................................... 11

3 Good Engineering Practice ................... ................. ......................................................... 13 3.1 CO

Pagee 1$PE Good PfO

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ISPE Goc:::4 PractiCe GuidEr. Good Engineering Practit~

1 Introduction This ISPE Good Practice Golde alms to provSdo a deflnit.k>n and explanation of the tenn "Good Engineering Practice" (GEP). It doscnOes the fundamental elements of GEP as they shoufd exist in pharmaceutical and related industries. it should be noted thet the conc~epCs are fundamental and applicable in many indust~.

1.1 Overview

In tM oonteXt of pharmaoeutieal engineering and GxP guidance. GEP is frequently referred to in documents as a prerequiS-ite to compliance activity and may be loosely defined. GEP ia often used to describe an engiM&~Ing man&gemef'lt system that is expec:t6d in a regulated company, but which Is not mandated by GxP rcgu!atk>ns. For example, effecliva project progress monitoring and controt is not a regulatory issue, but is neoessary for the efficient operation of a company. and Is part of GEP.

This Guide oonsiders the entire range of phsrm:aceuticel engineering activity and klentifies key allributM of GEP within it. including how GEP recates to, and interfaces wilh GxP. The scope of GEP covers the compfe!e life cycle of engin&efing from concept to retirom(lnt. GE.P provides a tout~dalion t&QtJitcd across the pharmaooutical industry upon wf'lieh othet atoas, such as GxP, build.

Figure 1.1: Postttonlng of GEP in retatlon to GxP

The aspects of GEP discussed in this GuKfe are intended to deS

Po ISPE Good ProeUco Guide: Good Eng;noeolng p,_

Figure 1.2: How this GPG fe:t~tet: to other ISPE Technk:al Documents

Tho - running of a buolness, demand$ woo1clng pr11dlces wl1ich will d-()9UnUm vob> for a g'-> oc:cpe of """"- lhl$ ge oeteded and adapted.

1.2 Purpose

Thl:s document was devaloptd lhrough the oof!abofaOon of representatiw professionals from various seetore and geographie regions of ttle photm.9oeutieal industry whh the iltentiOn of CSetermlnlng 1 common understanding of the concept and principles ol GEP.

This CIOrument identillos praclloes ""'ich exemplify,_ GEP ccncepcs may t>e appllad In 111e pllatrnaceullc: fndllllry.

1.3 Scope and 84!nefl t Objectives Tho &eope of this Guide is limited to the hoallhcare lnduslty but oonslders all aspec11 of e~ineerlng. The motives for asp!rlng to pOOice .. good ong1neering" are wider than tho Med to comply with GxP JegulaiOry expectations and onoompass prooludivity and buslooss related driveR.

Tlte odop1;on ol GEP slu>uld -to a -.ce of ex~ and -.oily in - 10 - Benefil is ,_ li

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tSP'E Good Practioc Gtlidc; Good Engineering Practice

common praclioes

opetalion and maintenance

Project Engineering: The aQivities associated with implementing new Qf significantly changed equipment or facltltfes; lypically associated with &.!location cf capital funding and additional resouttes.

Common Ptactics: Thos& ptactices with fetevance to t::oth project engineering and normal operation and maintenance

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oporatlon and Maintenance: The sctivibes required to sustain equipment and facilities in a satisfactocy cooomon and use them for production purposes.

Common to these three key concepts are th& further key concepts of "risk management." eost management.~ and organization and oontrol:~

Risk management the systematic application of quatity man&9&ment polf

JSPE Good Practioe Gufde: Good ~!ng Ptacclot

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2 Breadth and Coverage of GEP Agure 2.1 illustrates the breadth and coverage ot Good Engir')Q:Q11ng Pmcuoos In the diSciplines of Project Engiooertng (blue), Operations and Maintenanco (green), and practioes Ulat are common between tho t\vo (toal). Cote Concepts which permeate all aspects or Good Engineering Practices also are indicated.

Figure 2.1: Breadth and Coverage of Good Engineering Practices

1SPE Gtt

ISPE Good Prbelloe Gulcll: Good Engileemg P-

A tegut.ated oompany shOuld have an Mtablished system for obtaining an lnltlal C0$1 estimate for a ~ scope of wort in otdef to ev-aluat& its viabll:ty. Througtlout lhe ccusa of the actMty the Kltmale shOuld be updated and expenditut& ttacked to predict final coat o.nd ai\&UI'e contmulng viabifiry.

Sub-Practice 2: Planni ng

The appropriate leetlnieal and angklMrtng (Separtmel\ls should wotk wtth 1he riooncial and oontract department W develop models doterminiog contract stratogy, factotlng In nee present value, moneta.y cost. Return on lnvestmenl (ROt), ond cost of aa:e!eraliool. The rolnllonshlp between schedule and cool should be understood and opUmiZed lor -ROt.

Sub-Pracctca 3: Ratum en lnvestmont

The relatb"'shlp between the 006ts ol an IICI.Ni1y and the ROI should be understood li'ld used to provide a ratlonalo for procoodlng during eac:h stage or dovetopmont.

SubPractice 4: Front End Lcwsdlng

CommiUing more cM:ources in the planning and design stage of a project moy Improve design coordinetion and detln!Uon. and. therefore, help mln1mlza the risk of oost and schedule overYun. lt may, however, seem to slow down progroos during the early s1ag9$ cia PfO)ect.

SuW,.actiGe 5: PaybaCk Polley

ROIIIloufd be st.C>ject to rules delotmtnlng occepiBble payback periods ""'"l"ll'blo W>lh a regufaied ~y's lnvennont and long tam busa-tess attotegies.

Sub-Practic 6: Cost of Ownorshlp

Tho full cost of ownership. including operating costs. dooommissioning and dlaposal costs should be oonstdered in inveslrnent decisions.

Sub-Praclk:e 7: Cost Control

Cort otlima1ea ShOtJid be &nalozed at delign -oval. Conltds shOUd be es-10 ensure thalal proposed c:llangosiO an -oved design or. osseaaed fer 0051 and sche

!SPE Good Ptac:!!ce Golde: Good Eng;~Mering Prt~C:IiOO

Sub-Practice 3: Monitor

Control mechanisms within a r~ulated compa.ny shOukJ monitor the pe-rformance and progress of assigned activities.

3.2 Project Engineering 3.2.1 Project Infrastructure

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The n!gulated company should organize its project engineering activities aooording to defil1ed proced~es and processes.

Sub-Practice 1: Defined Organiution

For QaCh pro}ect. reg~Jiated companies should have defined project groups with clear decision making responsibilities and fiMncial authority. Key stakeholders should be identffied, and should have ownership, aocoontablity, and responsibility for a project and its outcome.

Sub-Practice 2: Defined Procedures

Regulated compan!as shOutd have defined procedUrGs. to cover the anticipated range of projects. including appropriate governance procedtlfes, either on a general basis or for an individual projecl. These procedures should Include the project group strvcture. reporlin9 structure, and inclu

t ISPE GoOO Pruc:tJco GuiQe. Good En;,..~ Practice

3. 2. 2 Project Organization ..

The managom-" o1 projectS whhin a regulalod company ehOleve cottand Q!Jal;jy offodlvolm_.,m.

SUb-Practice 1: Project ldentiflc:at1on

Regulated compeniea shouid havG systems fOt recurring reviclw of current and tulure requirements against CUrTent cspabaltles and available technologies. This Information shoutd bo used to iden1ify lho need and justification for Change.

Sub.Practice 2: Profect Definition

Rsg!Aated ~nioa should haw !Md\anlsms tor the review ol pn>POSfld ch311Q0S ond a mew o!>iily to ylold wtue.

Sub-Practice 1: ROI and Risk Analysis

Regulated companies should assess lhe ROl and consldor any pocentlal risks and beoorrts to determining the vklblflty and manner of oxooullon of the project Th9 need for timety execution and the ri~s os&ockttod with felure thoukl be dMtly underetOOd by stakehok:ler..

SutH'ractlee 2: SuppUer Selection

Ragulat9d oompankts tthoutd ensure that appc()l)tlate methods am O&tablish&d to &asess and select svpp!iora based on defiJled project aocoptonce criterla1 Including:

ISPE Good PraetJc~> Guide: Page 17 Good Engineering PratiCO

quality

costs

experience

technical support

scope of wort(

$Chedule

Sub+PracUce 3: Cost Contr~

Regulated companies shoiAd be cspab!& or estimatittg the anliclpal9d costs of projects, reviewing and controlling them during ptojoo:t imptem&ntation on an ongoing basts.

For an example of protect management guidance refer to Attachment E.

Sub-Prac-tice 4: Value Engineering

Regulated companies should have systems for reviewing proposed solutions against the def.ned project requirements to ensure that adequate quality is delivered at optimum cost. The total life cyde oo-st of any proposed solution should b& oonsfdered In this review.

3.2.4 Planning and Monitoring 1:'/:'!&.:.

._18 ISPE Good PtdCtie$ Guidi: Good Engineering Practice

Sub-Practice 3: Projeet q~Hty Planning

Regulated companies should ensure project qua~ty plans cwe available and appropriate f

ISPE Good Prect)cE Guide: GoOd El'l(lineerllg Procllce

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Sub.Practlc:o 1: User Requirements

RegU'Iated companies should have estabtished methods for developing and reviewing a rcnnal User Requirements Specification (URS). capturing both the fundamental aspects and scope of tho users' roQUfroments. Users shoukl be involved as muc::h as possible in this process. As a minimum, users should be requlced to review and epprove these requirements. Requimments should be objectively stated such that they can be verified during testing ;:md ccmrnissioning. Alignment with objectives of any company strategy or ma-ster plan should be confirmed.

Requireme.nts should be focused oo prodt.'Ct and process requ:ir~nts and as far as poss!tl!e ~ave engineering aspects open for subsequent definition.

URSs vary immensely In their seop& and comple>lity: examples and approaches for equipment may be ~en at the JETT Web site hosl10d by ISPE (se

final st.aga: detail droV~!'QS specifications and purchase orcters

fSPE. Good Practice Guide Good Engitltee:ting Practice

specific local documentation d&liverables tor compliance with regulaUoi'I1irflum cost. :~: j~. >:;, _ ,,., '.' ~ :~ : : ' -;: ......... : --' :.f,_ .~ .. ; :;_ . ~~- --~ ._; ..... ..,. .. .,:_,-;.

Sub-Practice 1: OGslgn Quality Control

Usets: shOUld agree with desigoefS a system for quality 0011trol o1 drawings, speclflcatioos. and cak:uJations. typically defined In a project quality ptan.

Sub.Practice 2: Design Review Stages

ThA design should be reviewed at preo

tSPE Good P"'Ciioo Guide: Good Engineering PrtcUct

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abil\y 10 be maintained (e.g .. ae

_._ping and~

""'""''Jon ond """""""' ol melhod-

pundllioting ond ~flnitlon ol completion

handovor for commissioning

manogement of subcontractors

contractor training

Subol'racllco 2: Quality Standards

ISPE Good Prat.1ic0 Guld&' Good Engineering Praclloo

Regula&ed compotlles should en!Ure adequate means of defining and achieVIng quality standard$.

Qua1ity .,..,_mont oystems should Include:

- ond IIPil"'V"' of samples

moano of dewotk. lnlBf stage inspectionstprojeCC hOkl points

consltucllon qualily teals

documentation standard$ and delivefY of oonstruction rocords

Sub-Practice 3: Construction Execution ,.

Otf..ai.t& and lite pradioe$ thcxll

ISPE Good Practice Guide: GoOd ~lng "'"";oe

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Sub.Practlcc 2: Constructior; ~ermitting

R~uirement& fOf vatious petmUs required to construct, occupy, and approve desJg.ns should be determined and responsibililia>s dearly assign&d to obtain the appropriate permits.

Sub.PracUce 3: Construction Records

Th6 specific k>cal regulatory requiremantslor formal racords should be deftned, and resjX)(lslbility for creating, updating. and filin.g lha records requlfed be deafly assigned.

For an example of a document certifying electrical comp6etion refer to AttaChment K.

3.2.9 Commissioning and Qualification "::: .. :J"""''' ~" .; . ...-. --.; _-_- . ' .7 ' '- 0 .,,- : .'.' .--.-7;..-,.~, '': N-0~ < :;;~-'- .- :; ' '--:~ 0 ~--,,,~ .-_,_ .... .:. ' + ' - .i. ' : :-;,.-;:.-: .: , the' ,.egvtated OOinPsto5':~gl,lld hi:IV~ a. system to en:s.ure .satisfat!_6rt c;ommissioli.ing--afld .qualifiea.t!onlverlflqatlon f:fQr pro}ects.; f()( an exa~ Of ta.Cmw. oonlmissk>ri.ing-guidat.Oe rerer to Auachment'L:::-'" :": N . ; _;~: ., ' ;.~.

f:~-....~.:.- ,_. .. ,::;::,., .. -;,. . . . ;.. ;_ . . - ';.. .. ' ... :, . . . ;- ... Sub~Practice 1: System Definition

Regulated comparOOs should have established melttods fOf defining systems and sub systems to be used in commissioning and qualification. These should be k:lgical sub-divisions and wherever pOS$!ble ctlv'do systoms Into GxP and non-GxP to redoce the G.xP qualfficatlon effort.

For an example of strategies for defining $y&:tem boundaries effectfvely refer to Attachment N ..

Sub..Practic& 2: Sys.tom RJsk Assessment

Regulated companies shook:! have established methods fOf risk assessment or systems and determlo!ng the level of risk to product quality and patient safely.

Sub~Practice 3: Commi!~sfoning

Regulated -companies shoukl have systems to ensure tt\et effeotive oommiasioning is performed and appropriatety doc\lmented. particulariy where it relales to high risk systems. Comr'ni9sioning should be teferooced to user requiremeols and testing ehoukl verify that the requirements have. be&n met. The commissioning team sttoutd have$ means of procuring: oonsumables, managing maintonanoo and ca!ibral!on roquirei'I'IGnts. and maintaining operational logs during the startup to handover petlod. :

For examples of commmioning plans refer to Attachments 0 and P.

SubPra

ISPE Goo

ISPe Good Proalco G\Jiclo: Gt>Od Engln~ Pfactloa

3.3.2 DocurrNntalion Pnteoces .

Tho regula*' QOmpolly_sho~~~tsystom.lr !he genera\filrl, reviow. opproval, Nltleval, and.-llrciJ)}Ilng 01. ,wntlon otandards . prc~u.~. !1(ld rteO0 gontrated and main~inSd in a manner to onsurO lhatlnformaiiOfi OOhfaiotd thMein it ' aecuroie, Cliiai-, unambiguoua, ond Current: '

:.. . .-. ... . \. ;,,

Sub.Prctlce 1: Stora.ge

The eyaloms sllould -., rapOI ....,.. to ooples and data to appropria10 slaW The syoaomo

ISPE Good P-cplonatlons are requited as SOng as an entry is clear aoo un8mblguous.

Enltlo ohould not be alenld. oblitara!ed. 0< ~ansalbo dala from one form to anolhe< (e.g , pl1nlod !ab

'5P Good Pnlebco Guide: Good t;ngln-Practice

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Rogu!ated companies Shoufd h~ye potlcfes for duplicate records, and protection of stOfed original documents.

Projed turnover proceduJes shoukl indicate wflich records and docu.mants vhll be tumed ovet to the operating unit at the completion of th& project

SubPractiCG 6: Oostructlon of Documents

Proeedutes for destruction of documents. should be established t-o eflsuro destruction. where required, at the expiry of the f8tention period of documents.

Sub.PractiCElectronic rocords of GEP documents are pefTlltssib!e aBd not sub;ect to any -specific regulation. R&eords should be controlled in a manner to ensure that they are seouro; a means of reacbng them and of ensoring that ttleir integrity ls maintained. Electronic records should have Lhe same ktvel of control and acoeptability as the equivalent paper cooords.

3.3.3 Chango Management

5:C~~#~~~.Qe.Y.:~!lt is criti~j k, ~~EP. ~~ shoold be d~flned f~t. ch;allg~ ru.anagement vAlich ;are ~c~erj tq f ... ~{t~ .. ~~-~~~~; ~n

ISPE Good Practice Guide: Good Englneertng Practice

There sholAd be a fom\SI Pr.99MS to communicate the change to the stakeholders e.g . Uset$, the quality depc~rtment, protect cost control, and senior management

Sub-Practice 4: Operational Impact

ThA chang& management system for existing assets ahoukl be consider potential impact upon operation and on malntonanoe.

Where the scope or scaJe of a Ghange is signfficant. managillQ the work performed tl\!ough lhc project eng.!neerlng process should be considered.

Sub-Practice 5: Change Plan

The proposed method of implementiog a change request should be defined. The level of detail contained In this plan shouk:l be appropriate to the assessed impact of the cflange.

Sub-PracticG 6: Testing

The W!vel of testing and documentation app(ied to changes shookl be commensurate with the associated risk.

SutrPractf.ce 7: Records and Change Completion

Ally dlanoes tmplemented shou$d be recorded via updates ro appropriate records (e.g., design speclficatM:Jo, drawings. or maintenance procedures), either as suppiOOlcntal data or revisions to oxls.t!ng rGooc'ds.. A concls.& Change hjstory that includes the unique change klentlfler should be lnoorpcwated ln revised records.

The SyStem shoukl provide confirmation that work has been oompleted in a timety manner. So called 'l iving Oocum~nts, ' which need to document current status should be maintained in a similar manner.

Sub-Practice 8: AnJlys.ls

Regulated oompanies $hOUid estabfish systems to monitor changes, e.g,, by type or Jc>cation, to identify trends and identity potential underlying issues (e.g . a poorly defined design) whictl may require en alternative approach in order to eliminate the root causa.

Sub.PracUce 9: Audits

Regulated eompant&s should have audit pJocesses. using prearranged extetnaJ or intemaJ auditors, to ensuta that chsnge control procedures are btNng followed. The review period should be commensurate with the associated risk.

f or further Information see Section 3.4.5 o1 this Guide.

3. 3.4 Innovation and Conllnuous Improvement t~~i""'*;~:.. .... :~:_:f '! ~f":"'!'.::::-..:: "*:!''0:~'-1, 0 '":''"' =1' ,.,, .. "; ~ ~ "': \'.;', ~ YO-."~'"l':::~c:"" -: =':'.' ' "'..;;" , ''-":'' '::" /f.'Ce;i:z':~/_";;;c'-;7'::"7;-:c- ~; 7~ r~~~a~~~rry~y;~o~IC;t~r~l~,-~;:&q~~~~iCh-.~~~~~-~~~~-tO.h~1::a:~i~e ,t? .. lV,.~~~f~I~.;':':- ::-.~~~~,!~~'1Yi~~~~~~~~t8~~~~~~~~-~"*~C~:~~~\: -. ~.-:: .::---:~~~--:'; -.;:'.-/:,, . .. Sub-Practice 1: Benchmarlclng

Regulated compc~nies should be aware of their performance compared vlith s!milar entetprises and 'best In Class.' Benchmari

~/ JSPE GoOd Prectfoo Guidet Good Englneeritlg Pracli0

Pag~ 29

calibration and malntel\8flce

bullding costs and times

equipment utllzation

rnanpov~er and staffing levels

This data shoukf be usad to detarmlne areas for Improvement and define best practices. Best practices should be u$ed to improve performance.

Sub-Practice 2: Continuous Improvement

Regul3ted companies should have a system for avaluating returns and complaints. Evalvation of Qoo.vn time and time taken for maintananoe and operatlona1 tasks should be included

Regulated companies should- have processes to improve products and processes OOf'ltinuousty.

For an example of a project management oomp!&l.lon document that seeks to drive continuous improvement refer Co Attacllmenl Q .

Sub-Practice 3: Train ing and Development

Regulated comcanies shoukf recogn~e the need for, enootm'lga, and raclt:1ate staff tra!nlng and development using cost effective mett'IOd$. VMue rather than cost should bo thO main consideration. This may indude fin&neialsupport or incentives, tOgatM r wfth mk!ase from day to day activity subject to review and approval. The membership of profooslonallnslltutlons and active particfpation in their activitil8s should be encouraged.

Sub-Practice 4: Professional Pathways

Regulated companies should define care0r groVIth paths allowing professional development and encourage successioo planning and personal development to the benefit of the company.

Sub.Ptactloo 5: S taff Retention

Regulated companies ehould appreciate the value of retaining staff and the expertise apptopriate to tl'\efr busines-s, and review staff eapabiiiUe$ against requirements to ensuto best fit. adjusting the structure where neees;Saf)'. Benchmark.ing to ensure renul'nQI'atJon and tenns are aligned wltn local and industry norms should be performed.

Sub.Practice 6: Position Requirements

Regulated companies should be aware of profes-sionaJ qualificatiOns required for tndMdual positions. These shlxlkl be avai able as part of job descrlplioos/role profiles.

3.3.5 Calibration ; . ...... ;;c' :, :."-".''X' -.~;.;.e-::-~~~: . ~,., ~ .. ~:~ >'=' .. ~ . ;~ ... ~ . :. :"fO.'.: .-: .. v::-v.--,.- ., ;.:~;," .:_,.-,: ' ; .~

~Th~:~gu~t~d ,cor:t.P~~.Y.~~Id h.~ve a.system ~ ensure'Jt'lat all in.sfQJ~ts are man~ge

Pa~30

Sub-Practice 1: Instrument Selection and Assessment

ISPE Good Pt:JCUOO GviCI Good Engineering Praetioo

All instruments shoukJ have a e!eafly defined function in particular whe1her the data output ts used to support product qua:!ity. Each instrument shou!d be asse&sAd by IM appropriate staff before being put into service, to detennine their potential to affect produC1. qua!!ty and productlvlty (tlsk). and the risk of instrument uncertainty increasing with time (nood for caJlbratlon). This data should be used to determine:

the selection of the type of instrument used for the awueaUon

the initial frequency of calibration and periodic review agaJnst pcrlormance

the tnsttument category, e.g., prtXIuct. process. EHS, or non-critical

the cal:lbfation range a.nd accuracy required

Sub.PracUc& 2: lnttrument Schedul& and Recordt

An accurate record should be maintained- of instruments entered into the calibration program. The process f&q\.drements. calibration activity, and any adjustment required ror an Instrument should be recorded.

Sub-Practice 3: Calibration Rocord Rovlow

Reootds shook! be securoly stored, retained for a defined period and evai~~eted periocJlcally to cmswe thal lhe approl)fiale instrumentation is in use and is routinely calibrated at the a.pprCJPfiate frequency.

Sub.Practic:e 4: Cost Control

Data from Lhe calibratlon management system sh-ould be periodically reviewed to determlne the oost of calibraUon acoordtng to instrument category.

Sub-Practice 5: Pertormanc:e revH!w

Data from calilratiOn actlvflj~ shookl be Mviewed to aS$8$$ trends and drift. These should be used to determine the fre.que-ncy of catlbrallon instrument typ& raqulred to maintain the desired aCQ.Iracy at an aooeptable tevel of risk.

3.3.6 Asset Management

. ~ ma~g~ryu~~i'inc.l~~~th~ ..aQui.~~ni for do~~rnenting . m.ar.aging. ~d .traddng the .rife .. ~~; of assetS. . - . . '. '

Sub-Practice 1: Ass~n Register

Asset registers may exist fOf a number of purposes:

regulatory requirements

financial aeoounling (e.g., auditing depre-clallon or general ledge-r enttles)

r11e and record keeplng organization at~d Identification tagging

security and ownership verification

maintenance

calibralion

lSP Good Prac(ioe Guide: Good ~ring Pr.>etico

Page 31

soft aSSG-ts vetsus tlard ass::ts

Financial etsset reg;st&rs are requJred rOt accounting purposes., dapreci.ation, and security. Asset regis.tet and asset 1egister tags are useful iden!HicatiOO tools to facilitate thi$.

Equipment and tag numbering systems may exist for oUler purposes. e.g . identifying proce$$ elements for calibration or maintenance. The numbering system $hovld indicete function as well as locatiOn.

Prior to equipment and faeilitie$ being used, they shOoukl be assossGd and lnventOf'ied on an asset register reoordlng usage arld value. This data can b& used to make informed forward planning assessments and ROI decisions. This register coukllink with other components (e.g .. maintenance and breakdown cost, calibration, procklctivity dGtil, preventative maintenance. or spBJes) so that ROI reporting can be performed fOf major equipment and systems.

Sub.Practice 2: Strategy and Planning

Major systems should have maintenance and StJppori strategies as well as plans and procedl!fes for future enhancements and upgr&OOs. Evaluation tools such as Reliability Centered M,aintenanoe (RCM), Failure Mode end ElfectAnalysis (FMEA). and Root Cause Analysis (RCA) sllould be OOflSidere

ISPE Good Prxuc. Guf

tSPE Good P~ Guide. Good Etlglnoo!lng Pr..,t;co

Sub..PraetJee 3: Record Availability

E.nglnooring f9COI'ds Shedd be readily aval&ble to support statr and roullnely Inspected for accuracy, completeness.

3.4.2 Englnooring Manuals and Records

A roguloted oompany shook! ha"" a dolned molhod of crea1ing and malntolnl!lg englnoering manuals and records relll\l11g 1o ra.iilies. equipment. and product$.

Sub-PractJce 1: Assessment and Revtew

Rego .,.., com;>a11ies sho as~. c!N~Wlg. modifyW!g. mointaining. and~ O

ISPE Good PraOlioe Gt.tide: Good Engineering Praefioo

Sub+Praetlco 3: Prioritization

Rouline maintenance activit.ie$ -should be priorilized and SCheduled according to producUpatlent Impact, regulatory non-compliance, or producliVity oonsequenoos Resources should be matched to the manpower and equipment maintananoe requi(ements.

Sub-Practice 4: Malntonanco Sc:hedu$e and Records

A record should be mainlained of ru1 equi,pment antef9ct inlo th9 maintenance program detafing the activity a.nd any work peffonned.

Pmveotatlve maintenance shoutd include scheduling tas.ks based on both running hours and lime.

Sub-Practice 5: Procedures

Preventative maintenatlce shoutd be pertormcd against approved procedure and recorded ed~\late!y by noting activities porformed. Feedback should be obta.ined from the personnel performing the tasks lo de1ermitle 100 continuing benefit and relevance and a-ny potential adj\Js!ments needed.

For an example of a PM compt.e!Xln document that seeks to driv& continuous Improvement refer to Attachment 0 .

RecordS should be stored and retained for a predefined period and trends monitored.. Data review and Change Manag&ment shookl be used to revise maintenan.ce pfooedt.Jree and intervals. This infonnation Should also ba used to detennine the continuing su~ilily end service 6fe of the equipment.

SubPrt~ctice 6: Reliability Based Maintenance

Reliability based maintenance ls an exampka of using risk based measures io foQ.JS and adap! GEP effort where most needed, according to mea-sored reliability performance.

subPrac:tlce 7: Utilization Monitoring

A GEP tool facilitating optlm12atlon of asset usage Is the use of on.-i, e perfOf'mance monitoring of equipment activity and downtime.

Sub-Practk:e 8: Design Con$lderatlons tor Uaintanotnce ~

The need to maintain equipment and minimize disruption lo oprefabOns should be considered as a factor in system and facility design, e.g . du1y and standby pumps; allowing one pump to be maintaiood while the process runs using the alternative pump.

Allowing adequate space for wit"drawal and disassembly of fixed equipment.

System utinties shou'd be designed to alkYN isolation &;nd segregauon. there,by mitigating ot minimizing the a

ISPE Good Ptf'le11oe Gvie~&;(i()o(t Engitleoflng Procb

Sub-Practice 10: Spares

Pa.go 35

GEP pt9YQ(I~IIve mantenanoe $1lould consider spates holding reqt~irements. determ~ed against a risk assesstnenl conslderl>lg tho'

Cl'tUceli1y of acuvtly

Meoo Time Between Failures (MTBF)

Prodicled Mean Time To RepiOO&menl (MTTR)

Fe< ""'port aclNille6lleyllnd the rogutoold OO

E E Good Pmctite Guids: !~.~~Good EfiO~ne&ring Proctloo Pag&37 '

3:4.5 Internal Audit

f,~;~qCl.Pn.ented. proceSS"shOiJ.td ~ ~sta~!is.hed . to ensure that ~EP Is adequa~~ and effective in a'!l areas. ~;~ ,, . .

Sub-Ptae-tice 1: Audit Plan

Regulated companies should have establistlecl plans to cover the routine audit of intemal engineering functions (incl\lding Pfoje

Pago 38 lSPE Good PrC!dice Guide: Good Ertgineering Praclice

Sub-Practice 2: Disposal

Regulated companies should have established methods of deteonln!og envlroomentaVcommercla!lsoclal risks associated with lhe va.rious means of disposal in order to select the optimum.

Sub-Practice 3: Associated Activities

Regulated companies should have established ~Y~ethods to ensure that

associated records are arcl'lived and retained, as required

quallt!catklntverl'ficatlon reootdS are t::los~d

malntenanc:;e and calibration routines/oootracts are adapted In a timely and cost effective manner

spares inveniOry requirements are modified and existing stock disposed of, as required

required petmlts and licenses are obtajn.ed

Sub.Practlce 4: Environmental Risks

Regulated companies should have eslablished methods to et~sure that po!ential environmenta-l contamination is identified Md addressed appropriately and in accordance with ell relevant regulatory requirements.

3.4.8 Facility and Equ;pment lnhen"tance and Recycling

The regulaJed company should have a .system for due diligence asses.s.ment and mana.:gement of pofen~al acquisllicns to ensur& that they are. cost effective.

Sub.Practice 1: Inheritance

Regulated companies should review any potential asset relocation or acquisition to determine associated nsks aoo evaluate the benefit C~gainst alternative options.

Where regulated oompanies do not have adequate akils intemaliy, suilab!y qualified consullanls shoukl be identi6ed to ensure that all ato.as of rts:k are oon-sldamd.

....

Sub-Practice 2: RCK:ycllng

Regulated companies ehould evaluate the continuing requirement for any piece of equipment. Where utiliZation i& low. allemative$ for its use. or disposal should be ooosidered.

Equipment efficiency should be revt6W'Eid against current technologies, and a detecmination made of LM potenlia! beoeflt of replaci,..g, modifying, refurbishing, ()( recycll"g tht!: equipm&nl

!SPE Good P(ae!loe Gvlde! Good Engineering Pracli

4 Appendix 1 - Explanation of Example Enginaaring Management Process Figure 4.1 is an oxamplo of a managellleflt process for the $pe

P~c40 .Awendix l

~ : u e G. 0 & E ~ 0> ~ c

~ ll 0> c 'C & & .E 01 c w

i ~ = w ~ ..

e , !1' ....

ISPE Good Practioe Guido: Good Eogln""""s Pf\>Ctloe

,.

ISP GOOd Praetfee GuiCIIY. Good Engineering Pro.ctke

5 AppendiX 2 - Glossary and Acronyms

Pll!IO 41 Appendlx2

For further infonnalion on the$e definitions, please see the ISPE Onltne Glossary at www.ISPE.org/gklssary.

5.1 Glossary

Change Control (fDA Glossary) (1) (API Baseline Gulde)(2)

(1) The processes, authorities for, and prooeduree to be used for all changes thot aro made to UU) computGtized system and/or the systems data. Change controf is a vital aubset of the Quality Assurance (QA) program within an establishment and shoukl be clearly descrlllod in lho ostal>Hshmont's SOPs. (2) A lonna! system by which qualiHed representatives of appropfiat-e disciplines review proposed or adual changes which might affect validated s.tatus. The intent ts to determhlA lhe need for action wflioh woukl ensure th.at th& system Is maintained in a validated alate.

Critical Qu ality AM bute (COA) (PQLI)

A physical, chemical. bio.logical or microbiological property or

Pagt 42 Appendbc 2

Maintenance (QA)

lSPE GOOd Prnctice Guide: Good Engineering Practice

Aclivilie'5 such il$ adjusting, cleaning, modifying. O\lerhauling equipment 10 as"Sure performance in accordance with requirements. Maintanenoe to 1;1 softv..e.re system includes ootreding sortware errors, aOapting software to a new environment. or making enhaoc&ments to softw;;re.

Project Plan (NIST)

A managem&nt document describing the approach taken for a pr*ot. The plan typically descri>es wOtk to be done. resources requ-Ired. methods 10 be uaed, the configuration management and quality ~suranoe procedures to be followed, the schedules to be met. th& prOjeCt organization, etc. Project In this context Is a genaric te1m. Some prcjec1s may also need Integration plan$, ~wily plans, te.st plans .. quality assurance plans, etc.

RaquinJment (ISO)

Need ot ekpectaUon !halls stat&d, generally implied or obligatory.

Reqlremenls Traceability Matrix (IEEE)

A matrix that reoords the relationship between two or more prOducts: e.g., a malJix.lhat recots the relationship between the requirements and the OO$ign of a given softwar& ocmponant.

~isk Analysis (ICH Q9)

Estimation of the risk ~ssociated with th.& kle.1~116ed hazards. It is the qualilative or quantitative process of Jlnki.tlg the tikermood of ocoorrerlQe end severity of harms. In so!M risk manage~nt tools, the ability to detect the harm (detectablllty) also factors in the estimation of the risk..

Risk Assossment (ICH 09)

A SY$tematic process of organizing infonnatlon to support a risk decision to be made within a r!sk manage~Y~ent procass. ft oonsists of the identification of hazards and th& ar\8.1ySis and evaluation of risks associated with exposure to those hazards.

Risk Monagomont (ICH 09)

Systematic apptication of quality management polircies. procedures, and practices to the tasks of as.sessing, controlling, communicating and reviewing risk.

Risk Review (ICH 09)

Review or monftOflng of outputrresulls of the risk management process eoMidering (if appropriate) ne'\v knowledge and experience about the risk.

Qualrty P~n (1$0)

Document specifying which prooedures and associated ~souroes shal! be app4ied by whom and when to a specific project, product, process or contract.

Spplier (GAM!" 5)

An organi:z:ation or individual intetnal or &Xtem.al to the user associated wllh the supply andfot support of products or servioes al any phase throughout a systems life cycte.

tSPE Good PtaeiJCe GuiQe: Good Engineering Procti~

Use (GAMP. 5)

Page 43 Appendlx 2

The pharmace\ltical customer or user organization contracting e_ supplier to provide a product In the context of this document it is, therefore, n~ intand&d to eppty orey to individuals wflo use the system, and is synonymous with customer.

use Requii'Cmcnt Specification (URS) (GAMP' 4) (1) (Biopllann Baselin .. Guido) (2) (C&Q ol W&S Systems GPG) (3)

(1)A requirement specification that describM what the equipment or systG:n'IIS supposed to do. thus containing at least a set of aiteria or conditions that flaY& to be met (2) Generalty the tlrst In a series of specification documents. It provides a high level description of the user's expectation of the project scope, with emphasis on product parameters and process performa:nce parameters. (3) A description of the requirements of the f~itity in terms of product to b& manufactured, required throughpu1 and oondii;Qns in which the product &hould be made.

Vel Out

Ft~lture Mode and Effect Analysis

Any regulatory mandated requirement for Good Practice GMP (Good Manufacturing Practice)

Good Laboratory Practice

Highly P.oloctd R;sk

International Conference on Harmonisation

Jssued for Construction (Drawing aod Specification issue)

Mean Time Bel\veen Failures

Predicted Mean n me To Reptac&ment

Process and lnstrumentatfon Oiagfam

Preventaiive Maintenance - pertormed on equipment and components to mitigate failure and failUre consequeOC$

OMS

RCM

ROt

SOP

Oually Manag"!"""' Sylllam Root cause Analysis

Reliability Centered Ma,ntenanoe

Re.tum on Investment

Standard Opemtlng Pl'ooo

ISPE Gcod "'*"let o..odt: Good Eng!ntetlng P~loe

6 AppendiX 3 - References

Poos Appcndbc 3

1. Ouality Ri$k M~emant - 09, lntematlonal Conference on Harmonlsadon o Technical Requirement& tor RegisiMtlon of Phannace

S

Introduction to the Attachments The altaehmonts to the ISPE Good Practice Guide: Gcoc! Ellgineerlng Practia> O.ci"de o grOp of docu"""'ts oontributecl by Oed. OCher than 10 provlc!o anonymily lor the dono< organizat.lons. Tholr development prooodoothe producllon of thio ~ide and may not be fully aligned. Tho 0011lent of lho auechroonts is not endorsed by !SPE.

Attachment A Principles of Good Engineering Practices

Ths document oullineo o>ql"ded pniCiice In engineering areas '*'*""alto GMP. a:~ow~ng o more approptlalo -CJt ccnoot. It demonstrates a rlskbooad approach, scetlng tho conoot apPropriate ro too regulalory (and potlent) risk. Attachment B Project Quality Planning This doc:oolenl or(glnoiM lnlm Ill& same ..,. CJt ~ ,. Altaci'IMnl A. n providos a common method for Of9llll!zallon and control of the (!Cai!y aspecu of a projoct. In oclditJOrl. ~ provides o fo

ISPE GOOd Prttellce Guide! Good ~!neef1ng PrecUce

Attachment H ProjGj;t Change Control 1m~ originates from the same set of g

Pagot 50 ISPE Good PrtOIIC6 Guk:l.: Good~!~-

Attachment R Audit Template

This documenl has been- flt>m o docUmont uoed to evalua!e projecO and 8f1gineering orgenizationl against pre-c:setemined crteria. II provides a list o1 por;nt.s to consider. Attachment S Supplier Quality Questionnaire This doc:unont IS an exawpiO cia ques5on.-e for o penial auo cia euj)lllel's Quolily t.lanagemonl Sysl8m&. Such aud:'l$ can reduce or eliminate the nre&d for fOllOw up or provide the focui for an on-site review.

Pago 52 Attachment A

"Company A" Guidance Do.~:ument

SI..Jbject prinCiples of Good Engineering Practices Issue Oafe: dd/mmmlyyyy Supersedes: None

Purpose

tSPE Gnod Practice Guldec Good Engi~ Pradioo

Guldaooe No. Version No. n yy,yyyy diJ/mmm/yyyy DRAFT Page 1 of6

The purposa olthls document is to descsibe Good Engineering Practices (GEPs) as defined In Worldwide Quality Standard >O

ISPE Goocl Pracllc. G3.4 GEP Documents - Documents fnelucf!ng, but not limited to. those described in w orldwide Ouahty Standard xx,xxx wh!cn are not dosignatec;t as GMP documents. These include drawings., speclftceUons, submittals, etc. which oro Included in the life-cycle o1 a project up co Equ~nt Qualification.

3.5 Pro}cct Control!> Documents - OoclJMtntt. pertaining to project actrv!Iies not twJIAng a GMP impact but necess.aty 10 --!he project's business objective (a g., eatimatjng. schodule man_..,nt).

3.8 Mafor Pro)oc1 - A

Pa9U 54 Atcac.hmenlA

ISPE Good Praed and controltld booll:, form, ~~. or electronic

template at the time each action is taM-n or observation is made.

4.3.1 .3 Co~llance olol:>eerve

!SPE GoOd Practice Guldet Good Engineering PracUet

"Company A" Guidance Doc'!ment

Subject: Principles of Good EnglnQoring Prac:tio&s Issue Date: dd/mmmlyyyy Supomodes: None

Guidetlce No. yy,yyyy DRAfT

4 .3.1.6 A oopy i$ required lOt' unstable media (e.g., thermal paper) in addi1i0n to Lhe original1eoocd.

Pa.ge ss Attaehm&nl A

VGtSion NO. n ddlrrunmlyyyy Page 4 of 6

4.3 .1.7 Recotds containing phoocopted information must reference the original source. (Note: Source of the photocopy may be annotated manually).

4.3.1.8 All pages and printouls from in$ttuments or d&la acquisition sy&tems shouk:l have a unique trao&able Identifier end page numbar.

4 .3 .1.9 Pages should be numbered: '"pg. x of y" method is preferred. When documents are in sections. each section may begin a new numbering seq\lence.

4.3.1.10 Blank spaces may be filled inwi lh ~NA/ SIMh, dash, Otother reoognlz.able symbol. It is not Moessary to Initial or date blanks.

4 .3.1.11 Records are to be signed a.nd dated by the person performing the function. It is not necessary to sign, initial or date each entry. Checklist or data sheet must be signed aJld dated upon oompletion.

4.3.1.12 The concept or"ir it isn't documented, it isn't done .. appties, because evidence of proper execution t:s necessary. It is permlsslb!9 to transa!OO documentation aftQr lh9 fact, pro\Aded ll\al !t Is signed by the p9tSon who perfOt'med the function. (It must be dated on the day signed and aMotated to indicate the date performed. Original data sheets should be maintained.)

4.3 .1.13 Data superseded by a subsaql)eflt test or inspection (e .g ., after a 1epair or correction) may be deiE:t&d. ThE: final record shou!4 be an nota tOO lo indicate if (1 repair or COrrection h&S been made.

4 .3 .1.14 All pt.ans, forms. speclflcatlons, and drawings used to conslruct. purChase. Install. or commission facilities, equipment, and systems must be approved according to a Pro;ect Execution Plan or PfOject procedures. Pre-approval of SAT. FAT documents is prererred.

4.3.1.15 Control of pr&-executed forms is not reQuired. Control or oompleted forms should be defined by Lhe Prdjed Execution Plen ot ptojact pt009dutes.

4.3.2 Revl&w and Approval of Documents

4.3.2.1 Approvets must have the education, training, or experience or any oombination thereof to review and/or approve the record.

4.3.2.2 OE:!egatiOn of autttority to a desig.ne& must be Indicated in projE:ct procE:dutes oc dooument~d in a memo to file as defined in the Project Execution Plan or ptojec:l ptocodures.

4.3.2,3 Revio'IY and approval of a major document (specification. ceport, drawing, etc.) tequires fllll signature and date. Initials may be used for review and appJoval of calculations, data sheets. and checkll$ts.

4 .3.2 .4 Si9nature and initials of reviewers must be clear1y identifiable and documented according 10 project ptocedures {e.g . a signature log).

._ ...

AlfnohmentA

"Company A" Guidance Doc~ment

Subject: Principles of Good Engineering Praetioes Issue Date: dd/mmmfyyyy

Supersede~ None

ISPE Good Practice Guido: Good EnglneerW'lg ?tactioe

Guidance No. Version No. n yy,yyyy ddlmmm/yyyy DRAFT Pa,ge 5of6

4.3.2.5 Copies of app~oved documents (e.g., drawings) may contain printed revieY..1 or testlinspectlon concklston require notification or Project Managar and may be subject to project chahQE.t management procedures.

4.3. 4 D/sastor Rocovery

There should be a system in place to handle the reconstrudion of records. All measures should be taken to recover the original doQ.Jmenl. For a record that is lost or destro)'Gd and oot recoverable a copy of the original record is acceptable as the omd:al oopy, which shouk! be approvEid by Management.

4.3.5 RGtr/Qva/ and Retention of DocJ.Jm&nts ,,

4.3.5.1 Projects wBI establish prooedures for retention and retrieval of recotd:S as requlrOO to carry out the project. Documents superseded by subsequent revisions should be clear1y marked.

4.3.5.2 Protect turnover procedures will dictate whiCh reOOfs and documents will be tumed over to the site at the completion of the project

4.3.5.3 Sll(IS and Global Engineering Services will esWblish internal methods of document storage, as dictated by company policies and procedures and in a manner that allows them to bl1 located and mtritwed within a reasonable time period. as required.

4.3.6 DeslfuctiOn of Documents

Siles and GES will deteiTI'Iine destruction methods in compnanoe with ~Company A. policies and proooduros.

lSI' Good """'""' o.lclo: Good Engin~ Prac:tlot

"Company A" Guidance OOCUI':'ent

4.3. 7 Eloctlonlc R-

Guklanc:e No. yy.yyyy ORAFT

EIQC:tronlc red regulttlont hiM> -. COIJlllied- and !hal ape>roprlatt docu,..,......,. pract;ces have been used.

Rem-of Anschmont A examplo document om/ned 11om ISPE GEP Good Prac&ta Guide.

AtWehmont8

" Company A" Good Englnee_r_ing Practice

Subject Project Quality Planning Issue Date: ckJ/mmmtyyyy SUpersedes: Verston n-1

1 Purpose

lSPE Good Practlce Gu!c:le: Good Engitttt:ring Practice

Practice No. Version n GEPn

Page 1 of7

The purpose of this doetJment ls to pro'VId& guidance for the preparation of Project Quality Plans as required by Work:twide Quality Standard xx,xxx - """tanagemont of GMP Projeets."

Quality planning is necessary to enstJre that projects meet all stal&d reqult&m&nt&. applicable standards, oodes, end r6QuftJiions unci stakeholder expectations. The purpose of the Qua!ity Plan Is to assist In developing and executing an effe

fSPE Good Prt ctiOt g methods and standard& that at& applied tl\roughout tho projocj Wfe cycle to deliver OPP

Attacllmeni B

ISPE GOOd Pra

JSPE Good Practice Guide: Good EI'QjnOOiillQ Pra

JSPE Good Practice Guide: Good Englneer.ng Pr&aiOI

"Company A" Good Engineer!ng Practice

Subject: Pro,oct Quolity Plo nning Procllce No. Version n Issue Date: ddlmmnv'yyyy GPn Supel'$0dos: Veralon n-1 Page5of7

7.6 Specific Acl/v/1/011 ond Dellvorables

7.6.1 Thil eeetlon oontains the output of the projecc q.r,alty progmm, usualty

ISPE Good PriOCtiOO Ot;de: Good Engl~ Ptoc!loo

"Company A" Good Engineerll)g Practice Subject: Pro,ect Oualrly Plan~ Pr;;tetice No. Ve

ISPE Good Practk& Guido: Gooel Engfneerlng Prncllce

"Company A" Good Engineering Practice

Subject: Project O

fSPE Good Practice Guide: Good Cl'lgfi'ICCiing Pr;;~Ctk'.e

Attachment 81: Partial_ Quality Responsibilities Matrix

Deliverable Projoot Englr>Ooring Project Manager Project Assurance

Manager Team

Project Quality Plan R A p Design Quality Plan A R Cor>$1ruelk>n Q""'1ty Plan A R GMP Design Revie-,y R A R

System GMP Assessment$ A A Commissioning PJan p R Validation Ptan A A

Oocut"n&nt Control Procedure A p

Design Change PrOC(:dure A p Field Change Procedure A p

Koy: P Prepare R a Review/Consult A= Approve

Validation

R

p

p

A p

Page &7 Attachmant B

Quality UnH

A

A

A

R

A

These are suggested responsibility assignment$ only. Responsa:M!ily for these tasks should be. fonnalty deklgated within ttte Project Execution Pfan, Project Qualily Ptan, or other formal pro;e~ document.

ISPE Good PfeC11oe Guklt.:. Good &1QiMd111g f'>aolice

Attachment 82: Quality Planning Points to Consider

Proeoss Points to CoMJdcr

QuaUty Mana91f1Mnl . P"''>OIIoo. re>lew ar>d opplan . ,_ and """"""" ol ptOjoct procedures

. au!Ms of qUasse8$ment an

ISPE Good Placlio& Guielo: Good engineering Pracnco

Page 69 Alt3Chmtnl 8

Attachment 82: Quality Planning Points to Consider (continued) ..

Proce$$ Points to Consider Construction materials and equipment reoolpt an" Inspection

h_ydrostatic te.stlng wa!d inspection prleumatic testing piping flushing/cleaning

. passivation pipe slope verification dud'Wor1

Attachment 83: Typl~l Project Quality Model

REQUIRED QAINPUTS,

REQUIRED QA_! AS!(

- '

I

. .._ .........

- Vddfll Dran $fa~rd

Opern~ng PtOQidur.t

- E:roc:vt.ed Q

Protocol"""""ll\llfY .......

As.Suiilt GMP 0t&Win9f

-.-

.;.,;..

~.,

';

P~72 A."tiCtvnenl c

1 Purposo and Scope of Document

Site Improvement Project

ISPE Coocl Pt.eta OUdt;, Good 8.,. 1861f11Q Pfaclice

Thm c!ocu"'""';, written to p>lllde e brief~ of the project- to -lhe design cot\$01tant 10 develop a deSlgn ..-..glhe-nfs tlqiOdations. It is not Jntanded to roviso lhla document.

The Bduels ~"' otorng6"' eilher +2 to+8'C. I to 11YC 20 lo 40'C anc160 10-80'C; lhe ~ pnMdes laclllies 10 ,_ each d these requiremen!S, end has a valldoled moniloMg oystem oontirming that the conditions Ate being maintained.

The project scope wil include revising the morMt hold..-p be validated to -31YC.

lSPE GooCI Prt1C1JOQ Guido Good ErQineerlng P!'i~Cttce

PlOt 73 Alhldlmoi'Jf!l C

Eldot>ng Fnoozer Room 20: - nol "'*l crll"* produel. ody raw molerio!s end will be dG lhe tuppottfng ldotlos. lndudlng HVAC ond ~f

ISPE Good PmCIIOG GuldG' Good ErcJ!nsof'lng PracUca

P19t 73 Altl1dlllWlfll C

Elcflllng FrMZer RCQfll 20: does not hold oilal procjuct. odf raw ..,toriols ord will be deoljjned as duly standby coclng syslem, will> common oon!J'Ois (Jli the IUpponlng Ulilot.,s. lncttdlg HVAC ord ligtlllng

hge74 -. ... c

4.5 MecMnlcol Yord

LSP Good Practice G!Jcle: GOOd Engine6rlng Practb

A -~lOr""'" 8-SO

ISPE Good PtftC:Cioo Guide: Good Enginoe1lng P1actce

4.13 UPSSyor.m

PfQe 75 Atlaehmonl c

Two UPS systems are lO be provided fot a 2Cktl!nute baekup time. Each UPS will be l)lOvided wilh oo exlem81 marr>blnanc:e bypass. The UPS ou1put 6strlboardl. gutt6tS. etc.

Allporb ollhe power

t Atlaehmenl C

ISPE Good Ptactioo Gulel9 Good Engineeri1g Precdce

Tho OldtDng romo~ annuncia!Dr vri1l be upgr8dod. The Fore Alann Cn-will poo.ldo 011 eqo.ipme

.

.-,:. .

.

.: -'-

.. --:- -~ .

...

II\ ' ,r.

P0190 78 Attachment 0

ISPE Good Practice Guide: Good Eng~rlng Pracuce

"Company A" Engineering Services Project Control Guidelines Project Risk Analysis and Management

1 Purposo

Projects, by their nature, are unique events witfl inherent risks. Risks, vAlM:h it not Identified an

ISPE God Practice Guide: Good Engl~ ProctiO&

Page79 Attachmtnt o

The risk register shal be prepa.ret1 from data coUected at either a Formal risk wOfkshop or from risk questionoa!tes completed by Proj ect stakehOic(ef$ as Attachment 03. The project shall r&tain a file of completed questionnaires.

The risk register -$hou!d be preoedOd by an Introduction which. summarizes the main risks to the project and IJ'te source of the data.

The risk register will fom1 one of tile key pto;eet indiCators and should be mainlatned, updated atld summarized In the regular monthly project l'eport.

AI proj&c:ts exceeding us sn million must

Prepare a Risk Management Plan setting out review process, risk ownets and manage-.rs and proposals for risk mitigation. Cost of mitigating risks should be inoor(Xlfaled into lhe Project Estlmat& of Contingency as approptiate. Refer to procedure PCG-00, Cost ManagQo.oont and Reporting (see Attachment E of this Guide).

Carty oot a formal risk workshop at a oonvenient ~me during the design process to identify potential pro;ect risks.

Carry out a formal quantitative risk assessment on the project budget and project schedukt.

Repeat this worbhop/l;lssessmenl et mii&Sionas tdant!fl&d in the Risk Manaoement F'tan to ensure lhl31t evolving risks are identified ood managed.

An external party shoukl be used > facilitate the risk workshop and carry out the risk modelrng ot the estimate and schedule to provide an independent unbiased view and challenge the 1eam on assumptioM and Issues.

Risk modeting Qf the es.timat-e and schedule should be based on a Monte C.ar1o simulation using a minimum of 1000 iterations to detetmlne confldenoe ~vets of achieving project costs or schedule.

ihe format for reporting the cost risk analysis should be simiar to that .shown in AttaChment 04.

The format for reporting the schedule risk analysis should be similar !o that shown In Anachment 05.

5 Responsibilities

PrOduction, delivery end updating of the risk register and risk analysiS sllatl at all times remain the responsibility of the "Company A" Project Engineer.

6 Specific Related Procodures

Alt Project Managers Pro;ect Controls Procedures.

7 Attachment$

Attachment 0 1: Risk An.atysis Matrix

Attachment 02: Risk Register Pro Fonna

Attachment 03: Ri~ ldentificaUon and Interview Record F'onn

AH9Chment 04: Cost Risk Analysis Format

AUachm@nt 05: Schedute Risk AnaJysis Format

Page ao Attlllc:hment D

Altllchment 01: Risk Analysis Mall1x

Tnk ProjKI Valuo 150 High 3. Coot Impact High (3), Med"m (2). LOw (1) to be ogreed for each projed- typNcal obov US SSOOk High: below

US S100k Low 4. Sc:heduie impact High (3~ Medoum (2), Low ( t) to be agreed lor eoch projOd - l)llical avor 12 weeks High;

befow .. week$ LOW

iSPE Good Practke Guide: Good Engineering ?ra.ctie.

Attachment 03: Risk lde!1tlfication and Interview Record Form

Risk Interview Record Project T~ije: lntecviewee: Date:

u-am Rlsl< Consequen006 Likelihood%

1

2

3

4

5

Compleled By

Attachment 04: Cost Risk Analysis Format

lime l~cl +14 Wk.s Mosl Likely

Date

Page 81 At.t&ettment 0

Cost Impact US$ Most Ukely

Paga B2 Altadvn ... o

Attachment 05: Schedule Risk Analysis Format Entire Plan : Finish Date

01N'ICI6 ,..;!)ed)8 D;otribdon (S1llll of ir

...

:i:' ..... :-;-..

~ _T.. .~

. r---

M ' ,

. ::

ISPE Good Practice Guide: Gm Engineering Practi

ISPE Good Pracllco Gukte: Good ~ing Pftdlo

Plgt 85 AttactwnotteE

18 Estl'.mete of Com.mibnent5 to Compr.t. - The boel ostimale of COI'Iwililli6tt8 owr nd above those already lncured lo dolo il1olore required lo bmg 11'01 proled to ~edon.

3.9 Estimated Underruni(Ovorrun) - Calculated on in

PagoM Ataactwnenl e

ISPE Good Pmaloo Guido Good Englnoonng Praollot

4.7 -ell-g;.en by any--ollhe ptojod 1o8m. including .... Ptqoc:l ~- $ha] !l!!t be reoov- .. a chango lo oommiOnenl u.d lonnallud In wrI" the C..,~al Projecl Slatus Report (Reference C) on a quanatly oo,.. Md fOtWatd to "Colrlj)MY A fHIQineerirlg manag

ISPE Good l>rae.tiot

Pago 90 Attachmonc F

Site Development Plan Sample

ISPE GOOd Prac:tle4t O!JcN: Good Enginee1lno PNictk:t

1.1 Introduction

Tho Client Campus Expat~sion projec;t constitutes the second phase in the deVOk:lpment or the Mester Plo..n for tho campus. The first phase. oonsGting of 1 research M d development building woa. oomploted in 1998.

TN expansion project is imended to p

ISPE Good Ptactloe Gt~ide: Good Eng'inMring Pr.-.euc.

Provkta mote functional artd consistent tech liiOtkstalions.

Resolve atrium noise issues.

Provk:le addtttonal storage spaos for lab areas.

1.3 Mothodology

Page91 A.ttachmont F

The project initial y began in July of 2000 as a concept design study to determine lhe overaD pcoject scope, pre!im.Tnary buikling occupants and program, concept design fOf all buildings. and anticipated conslrudion costs. At this time the project scope included lhe foi!O'Ning elements:

Building N - research and development buikfi:ng

Building A- cenltal utility planl expansKlo

administrative btlitdlng

employee service$ and conferencing

structured parkif'l:g

associated site infrastructure. landscaping and utllltiM

Initial efforts focused on development of a preliminary program which attempted to define the probable oocupants fOf each building and their general space requirements. leading to definition of the overall scope for the administrative building, ~mployae s.at'Vioos and buikling N.

At thO tlmo ttl at tho program was OOing dGveloped, design studios weus also under way with the architect These Investigations focused on the overall organization of the build log noor plans and revle'lv of lessons teamed from the past Suikfing T project After a number of iterations, a successful ooncept was devetoped that combined program requirements, m&-ster plan oonforrnanoe, les$008 teamed, and makltained the strong atchileetura.l character of the campus.

TM scopo of the design was agroed and th~ oonoopt OOslgn phase was completed at the end of November 2000 and documents were Issued for pricing. The conoepl design, preliminary program, and cost estimate were presented for approval to the Cltent Board of Directors on 9 february 2001. After a one month review period, the pro;e~~;t was approved for design and constn.Jction In "-'\arch 2001. The cftent authorized the deslgn teem to pnx:eed with deveklpment of the project shortly thereatter.

1.4 Project r .. m

The ptoject team setocted by Cfient to implement the expans.ion of the Emeryvi!lo campus consists primarily of the same learn members that participated in th.e original project. This was done primarily to take advantage of the past experience and knowledge of the previous leam members. Team members that have participated to date in the development or thA projACt inClude the following:

owne.t

d(ls~n architect

executive architect, programming, and lab planning

s!Juclural onginaering

Afi3Chment f

MEPdesig ll

civil

landscape design

code eonsulling

atrium oode consulting

environmental consutting

geotEM:h.tttca:l COR$UJianl

process consultant

preconstruction setVioes, estimating

welding testing and inspection

A directory of contact information end key project participants foltows.

1.!5 Project Schedule

ISPE Good Pmctico Guide: Good Englneerlng Pt3cttnal information rogarding tho anticipated activities to $upport the proposed oonstruction start dates.

1.6 Outstanding Issues

The foUovtli)Q fs a summarv of unresolved design issues that will r&qulre further investl9atfon and/or development during the early stages of the Des>gn Development phaso.

I&$Ue Responsibility Atrium and off.oa coofigu~tiOn on f loors N-5

ISPE Good P~ice Guide: Good Engino~ Pr&ctioe

2 Archlt&etural Doscription

2.1 Building Description

PJge93 Attachment F

Building N is the second phase in the ctevetopment of the Master Plan for the Client campus . Buildlng N abuUi the north wall of Building T, separated by a seismic joint. When. oomplet6d, Buildings Nand Tare intended to funeuon as a single building. Tl'!e oveorall tluik:ling Cl'laraCler and mattW!als are intended to generally match Building T.

2.2 Ares Summary

Concept Phase Area Summary

Floor level Program Area (!';SF) Overall Area (GSF) Basement 29.000 58,000 Level 1 17,000 57,000 Level 2 27,500 45.000 Level 3 28.000 55,000 Level 4 32,500 50,000 Level S 31,000 50.000 Level 6 16,000 36,000 Level l (Penthouse) 0 6.000 TotaJArea 181,000 357,000

Overall S..ilding Efficiency (GSFINSF) 50.7%

Area Summary

Floor Level Program Asea (NSF) OVerall Area (GSF) Basemen.L 29,000 58,000 L&Vel 1 17,000 57,000 Level2 27,500 45,000 Level 3 28,000 55,000 Level4 32.500 50.000 LevelS 31,000 50,000 level6 16,000 36,000 LOvol7 (Penlhouse) 0 6,000 Totai Asea 181,000 357,000

Overan Svllding Efficiency (GSF/NSF) 50.7%

A~t;:hmenl F

2.3 Code Summary

ISPE Good Praelioo Guida: Good Englneedng Pr3c

tSPE Good Practice Guid&: Good Et>Qtneenng Pro

&.. Dlste:noe from labs to offloes.

1. Offlc:e to lab v.~ndows not beneficial.

2.~ ArchltocturaJ Matorlalssmd Systomc Narrative

2.6.1 Extofiot

FJ!rlor Walb

~E Good Prtlctietl Guider. Good EngineeMg Pfec:lloe

~ wo1o ot the 1rst and secood lloor mnaill o1 precast conaete panels wftl> Integral COlO~ ~te. CMtln tonns ~nod will> rw!lfl """" oodor - Panets typc:a!ly.....,

ISPE Good Predioe Guide: Good EngirteeMg Praotloe

fi()Q{ E@ljshm: Office Atoas: catp&t. glue down

Stajr Cpnstructjoo

Staii'Nays c:on$ist of...

Ceil jog f !ol&hft&

PU'blic Areas

Specja!ties

Toile! panlllons

2.5.4 ConveyJ'ng Sy$/ems

Passa~er ElovatO

Pogt QS Attachment F

ISPE Good Procclco Q\Adt: GOOd Etlgineering Prectlce

..... Rooms (1/lloor): ~cal gf81n eel< base ea-. tal cai>O\Qto, and mel.-. 0.11< coon- . Kilchen"'-lillQ Areas (1/lloor): -leal grain oak base ond tall cabinets WI!I11Uiinle$$ $!eel oounteriOI)S and becks plash.

W!ndow Treatment

LabOratory Areas: Manually opeteled solar oontrol &hades (Mecho Sl'ladft) In

ISPE GoOO Pn:u::lice Guld~: Good Engineering Practice

ACI N 15 ~tails and Detailing.~ Concreto Relnforoemen~

ACI N15R ~Manual of Engineering and Placing Drawings for Reinforced Concrete Structures"

C~SI ~Manual of Standard Practice' and "Placing Relnf.otck'lg Bars"

AISC 'Sp9Cifications k>r the Design, Fabfication, and Erection of Structural Steel for Buildings.," 1997.

AISI "Specifications tor the Design of CO!d-Fotmed Steel Structura.l Members"

AWS 'Structural Welding Code'

SOl .. Design Manual for Composite Decks, Form OeGks, and Roof Decks"

AISC '"Soismio Provisions for Struct\lral Steel Bulldlngs,''1997

3.4 Structural Computer Softwat'fl

Gravity l oads Seismic Loads

3.5 Oeslgn Loads

1. Floor Dead loads

RAM Steel 2000 Releose ETABS Release 7.22 MATHCAD Spread Shoot Program

Typical Structure Weight tN" composite steel dock, 5' NW conaete an

5. Wind Loads

.._.

Basic Wh1 Speed W..., L08d Pressuto- P~l'nll'f F"""o

Elemenis and Components OvforIP Piles (A!J72 0< A992 GR 50)

4. Ugl>lgogo Steel (Fy)

Root Deck

5. Foun(-10 GeoOedVlical Roport No )

3. 7 Sel$171/c Approach and Loods

a. The Selamk: Syst@f'l"' will ...

Utilize Coooopl of Vision 2000 Document. as lunhor refined by 1999BiuebookAppendlx I

Use Enhanced Ol>jecllve 1 as a petfonnanoe tramawo11< for the seismic System Slluclurol Design C

ISPE Good Praellct GJdt: Good Engineering Prncllco

Code Roqufrod EQ Ltwl Cheek

Ccmply "''h Clly ol Eme

Pag102 _ ....

4.3 Pilot Plan:tiGJauwah/Reagent Prep Report

5 VIvarium Description

5.1 General Oe$criptJon

5.2 Mat~s and S)""tems Nrrative

5.3 Vlvonum Equipment

6 MEP Basis of O&sign

6.1 Piping Systems

6.2 M-ISystems

6.~ COnttol Syslem

6.4 Eloctrical Systems

6.5 lnformEtolion Technology

7 Appendix

7.1 Soil AnaJys;s

7.2 Office Study

1.3 Prkfng Study

1 Building Organiz-ation Study

7.5 Louons- Leamed Discussions

7.5. t Mt>efingAiinutes

7.5.2 Cliont COmmonts

8 Adc:llUonallnformation - Rofor to SGpa.rate Documtnts

& 1 Program Summaty

8.3 Pilot Plant Study

8.4 Construction Cos-t E.stlmato

ISPE Good Proc:tloo G"""': GoodE-ring P...:lice

Project Execution Plan - Table of Contents

3 Bus!neu Goals

5 Project Scope

6 Monagott1onl Plan

7 E11$1inoerlng Managcmnt Plan

8 Ptojoc:t Exocutlon Ris~ Management

9 Organk8tlon Pion

10 Scurdng and Procurement Ma-Pian

II Value Men~ Plan

12 Team Performance Plan

13 Conatrucdon Lglatlca Management Plan

14 EH&S - R0111JIOIOry Manege'"'"'! Plan

15 Quat!ty Mon&gem&nt Pion

16 Scl\edul& Management Plan

17 Cost Management Plan

18 Cornmunlcetlons Management Plan

20 Commlstiol1ing Plan

21 Validation Plan

22 Consuuc:alon Ptan

23 Tutnover pq.,

24 Closoout Pton

IS?E Good Pt:K.tiot Guide;. Good Engineering Practice

Artac:h

ISPE Good Pracrlce Otkle: Good EngineeJing PraC'Iioe

Page 101 Anachment H

3.8 t~Comp.any A" Engineering F!~pr9$Gt1talive- Engineer worlting for ~company A~ Engineering Services. This pefSOO Is also known as the Project Engineer.

3.9 Scope Change- A dlange in the agreed pro;ect scope that may affect factors such as quality, oost or time for completiOn of projoots:.

3.9.1 Major Scope Change - A major scope change requires approval of aB patties Ylho approved the original Request for Concurrence.

3.10 Design Change - A change to !he agreed upon Approved Oe$ign that may affect factors such as quaity. cost or time tor completion of pr*cts. A dQS:Ign changa Is oot nonnal

ISPE Good Prnc:cloe Guide;: GoO4.5 Tho source or any addnlooal.rundlng shall bel creody ldenlifiod (Development, Contingency or Mdhloool RFC) 4.6 The Change Form shall be approved aooordlng to the PrQieCt Procedure-s. which shall make du& ref&fanoe to

financial oulhoriUIIJon ldnil:s and speany A" Engineering Enginoor is responsible '"' ensurlng lhol Changes ore closed ond lhallhe Project Olange log Is updald

5 Rosponslblll1lot

5.1 The eompany A Engineering Enginf:Htf is rosponslbfe for tho development and appflcellon of apptoptlato Change Control Procedures

5.3 The "Company A" Engineering Engineer Is rosponsille 1'0< ensuring !hat Changes ctosed and tllallhe Projacl Chonge tog is updated.

6 AtUichmonta

Altadvnent H1: Typical Projec;l Change Control Flow Chocl

All""""'"' H2: Typical Project Change Form Attoohmeol H3: Typlcol Project Chango Lorg Summal)l

7 Referencft

PC~B. Cos! Monagamont and Reporting (see Auachmont E ol this Glide)

ISPE Goocl Preelice GuiO.. Good Englntt!lng PrJCtlco

Page10SI AtlacllmoniH

Attachment H1 : l'yplcai .Project Change Control Flow Chert

Business Unit Project Project Project Finance Representative Engineer Manager Representative

Part 1 c: Oooaibe ohange,ldetltify reason lOt

~ dlange, and prepare justification. --- --------i~------- ------- -------- -

.. Part 2

~ Assess proposed change, inctudi'lg "'

;...,..~on sylem$. safety. drawings.

~ docu11"1Dr1ts, etc. Prepare buctget and schedule assessments. ---

--------ir------- f------- ---------10 Part3 .. Sivn change projed 1om> Oltd lolward ~ cr IO Projt Manage< and Project Fl'\lnce .. ROI) NOT v c: :0 APPROVED c: ~ u. ., c: Identity souroe of funding

" ii Proceed with if-- Ref Cap~al lnveslmem ~ > Change P- and Prooedureo 0 (Sdon3300) !5.

... ~ Upcla:o Projocl Change Leg

- -----------

1--- -:}--- ------- - --------Part 5

.. Compfete ~ Project Chango 0 : Fonn - Closeout Section. Verify oil .2 changes have (.) been pteperly

documented.

ISPE Good Practice GuicM: Good Engjneeno Praodc:o

Attach ment H2: Typical ProJct Change Form Part 1 Details Projoct Name: Projoct Number: Change Initiated B y: Chang Numbl)r: Oaptutmont Description of Ch ange:

Chod< If Additional Pages AttaChed: o Type ol Change: s._o DHign 0 F"oeld 0 Rteson for Change: 1. lloalnKo Neod 0 5. Re~ Comptl&nce 0 2. Ptoeoss Chaoge 0 6. Ride Managemenl Compliance 0 3. Etror/Omlsslon 0 7. SecurHy Com plio nco 0 4. Sofety Corrc>llance 0 8. Other" ("Dscrlbtt) 0 oesctibe:

JustlfleaUon for Change:

Cl>ed< WAdditiooaiPogeoAttachod; 0 Part 2 - A$sessment of Change Design Baals Assessment: Does the proposed change affect OJ alter:

Sofoly (Process and/0< Contlruction)? YesO NoD If )'05. elqllmil ~vcl'langs ts be ecktMMCI Dl~cl lmpllcl Of GMP Sys1om? Yes 0 No 0 'If ytt. eliPt.in how d1enge I& to tie adO'ee!IOd Approved Drawings (P&ID, Loop Ologrnmo, etc.)? Yes 0 No 0 ' If y&ll. txCJI~It\ I~J cll

lSPE Good Pracliee Guidt : GOOCI En_o1neerlng Practice

Attachment H2: Typlca!.Project Change Form (continued) Part 3- Req uest for Change Based on th& infotmat!on provided above, it Is requested lhet this change be approved.

Pugo 111 Altacllrnen! H

Bttsiness Unit R_epresente.tive Date "Company A" Engineering Representative Date

Part 4-Approval and Funding Approval:

Change is Approved a Change is Not Apptoved a

Project MaMg&r Date Project Finance Representative OatG AddiUonal funding for thl:s chango will come from:

Design Oevelooment a Contingency: a Supplemental RFC: a

Date: Change Request Number: Revision: MortthiDayJ'f

Attachment H3: Typical Project Change Log Summary Change

Order Initiated Numb Briof DK

PaSiJe11 4 Atiachment I

t$PE GOOd Prectiee Guielt: Good Englneeting P.radice

Sys.t_em User Requirements Specification Sample

Cold Storage Areas

XXX Project

Document Number: n Effective Data.: mmwyyyy

System Us.Gr Roqulromonts Spoeification

Cold Storage Areas

Project: Completed By: Location Sl.lpefSedes: None

Review and Approval

Rolo Nama OGpartment

Project Manager Operations

Quaiily Assurance

Revision History

Version Cha_nges

0 New doc:vment

1 Introduction

1.1 Purposo and Scop of this Document

The scope of this project applies to the Cold Storaga.Amas (2 . B"C).

Document Number.

Rev: O

Dale: ddlmmmlyyyy

Page; 1 of xx

Signature Date

Complied by Date

This System User Requirements Specification (URS) sorves as a foundation bringing togethe.t multl-di$C!pline system requitaments into s single doC'A.Iment to support system design, construction. commtssion!ng, qualltlca(k)n, va!!dation ~nd ongoing operation/ m~intenance for the Cold Rooms.

The cold room systems have been assoosOO as Direct Impact systems, refer to the fmpacC A&sessment section of the Project Valklation Plan. document # .

A $ys.lem US-ef Requirement is a colldition that must be satisfied In order for a system to moot Its fotandGd putpOSt) ftom the pel'$peecfve& of all stakeholdefs. User Reqlrirements Specifications focus on what Is tequlted wi thout befng presctiptive M to how the reQI,rirements are met.

The cGMP requirements of the Sys-tems URS are captured in speclf'ted s~Ciions of the URS document All otfler miscellaneoU$ reqvirements (e.g .. businoss drivers, safety, etc.} are sogregated from the cGMP requirements.

ISPE GOOG Pt.;c:Uoe Gutde: Page 115 At13chmont l Good EngineeMg Practice

The cGMP requirements of lhe Systems URS shall be illCI)tpOrated into the design and ve.tlfied durltlg ~esign qualif~ation, instaJJation. coOimtssioning, and q\lalificetion actiVities. This document shall be maintained as a living document during the course of the project and is controlled under change management as new requirements are reatized and existing ones enhanced or 1emoved.

Following project completion. update and maintenance of this document wUI bo a sito operations responsibility, managed through the site change control pJocedure.

1.2 Project Descrlptlon Overview

The projeCC scope is the installation of new cokt sto.-age rooms to hOld flniShed product with a storage temperature tequirement of 2 to ate.

Th.is URS will provide the rationale fOC' Lhe cold storage system validation &eceptance criteria.

AJI goods are received on pallets at the goods reoeipt area in eccordanoe with appropriata procedures.

The goods are stored In the propor rafrigomted or freezor storage areas in aocoo:Sance v.ith appropriate procedures.

1.3 General Requiroments

1.4

2

The cold storage system must be developed in complianoe with aH relevant FQderaJ, Sta!e and local codes and regulations as well ss adhere to th& OOftlparnes Corporate E.nglne&rtng Oeslgn Standards and Specifications.

Definitions and Abbrovlatlons

cGMP Curront Good Manufacturing Practice

OQ Design QualilicatiOn IQ Installation Ouallflcatlon IV Installation Verification

OQ Operation Qualific:ation PQ Pelfotmanoo Queltttcatlon RV Reoeipt Verification

URS User Requirements Specification

$)'$tt:m Requirements

The sys1ems user requirements are deftned in distinc:t sections in the table belOw. Regulatoty requi(ements specific to the specific system are also referenoed in the system tabtes.

AttochrnMI I

ISPE Good Practlee Guide: Good Engineeong Prac1ioe

User Requirement SP9l'ifications for Cold Rooms

sys1am $1'loukt bB dasigned to operate with external design conditions ot -2.8 to Rq.Jirement 36. 7'C (27 to 98

ISPE Good Practi"...e Guide: Good Engineering Practice

User Requirement Spe~lfications for Cold Rooms (oontinued) Sub-

Item Parameter/Subject Matter Item Requirement ! 3.5b Diagnostics shall cover cocnmunlcations,

prooessor pefformanoe. engineering date stotagc and hardware faults.

' 3.6 Oiagoostics sh~JII oover communications, processor performa.nce, engiOGering data -stOI&gQ and hardware faults.

3.7 The automation design shaU ensi.Jre thai all elements of the oontrof system shall recover from power fe~ih.s:re to a notmal operating state.

3.6 An appro'Wed method of software back up and restore shall be prCNided.

Monitoring/A1atms 3.9 The monitoring probes utiU~d for GMP record purposes must be separate rrom the control sensors.

3.10 A minimum of tv1o probes must be used to monitor each refrigeration system..

3.11 Alarms muse be configured so that th9y are easity distingu~ha.b!e bas&::~ on theit J)fesent condil!on - i.e., ul\ad

Attachment I

tsPE Good PttJCtfee GutdtL: Good Engineering PIOCIIoe

Usor Requirement Specifications for Cold Rooms (continued)

--

Source of nom Paramete.rlSubjeot Matter 11om Requirement Requirement

Soourlty 3.17 A u&&r must be logged in and hove the ptoper Operaticm.al secu1lty pMtnegQS to in order to l&tiue commands. or change set po.lntJtvatues. (Nolo: llle system Is not rgquhcl to comply with CFR 21 Part 11).

3.18 The system must haYe an automotk log ctr Operational featute wllh a cooflgurat>le time out.

3.19 When oo ....,. is logged ln. the Olra wil ()peB!lonal dlploy lot easy replacemont "' lioclilola """" Oimet~slons Cold Rooms .6a Cdd Rom 1121: olorage IINIPP

!SPE Good Practice Guide: Good engineering Pmclice

User Requirement Spec:~ficatlons for Cold Rooms (continued)

ltom Parameter/Subject M&tter

Fire Ptotedlon

Equipment Protection

Level of 0x)'9en

Particulates - Viabte and Non-1/lallie Emergecy Systems

3 Attachments:

Sub Item

5.3

5.4a

5.4b

6.1a

6.t b

6.~

Requirement

Provision sy$t&m in$100 cokl room requ-ired. The system materials of oonstrvction and design requirements must meet Faelory Mutual (FM) requirements. Tho fire protectk>.n oxtcmal to and within the untt must meet FM requirements.

The refrigerated siOfa119 ama &hou!d have protectiVe boltards on ei'th&r skte of the truck acce-ss doorway.

Bollards must afso be st either side of the control cabinets.

The refrigerated storage area should have a door height lndk atoc.

RflmaJhder of Attachment I exampie document omlt:ted from ISPE GEP Good Procticft Guide.

Page 119 Attachlll$rll l

Source of Rcqulromont

Corporate

Operational

Operational

NIA

NIA

Safety

Safety

J

Extra~! From a Set of Design Review Challenges

ISPE Good Pf'ac.tioe Guide: Good &>Qineenro Proctlolingos lO the relevant mernbel$ of the prol4ct ._..,.

WheJe1Mfe are c:ompony 'standant cplosion venting, solvent storage. ale.?

Ooos the llfOI)OSed iayoul allow fo< - lor '"*O

ISPE Good Practice Guidt: Good Englneertng Praclice

Challenge .. Response Resolution

Is pM

Attaenn'IOM J

ChaiiOflge ..

Are there any winck>ws - are they specllted to be ap~ by lhe insQrooce authority? Haw specific hazards been Ktentified, and fire protection measures defined - food prepara.tion areas, computer rooms, reoord rGtontion areas, 9'1S cylinders or tanks?

How does the design minimize the risk of ingress of ins.ectJrodentslother pests?

1.3 Building Challenge$ - Production Area

Challenge

Has account b99n taken o4 the following li$ks: Earthquake, Hooding, structural movement both major and local. local extremes of condllions -rain, wind, heat? How doe$ tf'le cfeSign provide good insulation rrom tho extetnal environment, using noncombustible oons.truclloo tslemants? Does the design consider pGI'$0nno11mtJterial flows and departmental interactions?

Is ther& a requirement for security in the buUding -if so how Is it managed?

What access oontrm pro\1slon Is thato for services rooms? Is it adequate? Does the design incorporate local custom and practice ror ~orage of outer co

1SPE Good Practice Guide Good Etlgineetlng Practi::e

Challenge

Have $pecific hazatds been Identified. and fire protection measures defined - solvent stores, oomputer rooms., reoord retention a~as. gas cylinder-a or tanks? How does the design minimize the risk of Ingress of 11\$001$?

Are emergency egress doors sealed with alarms on them?

How does tho design separate production areas from non-production areas?

Is there a maintenance 8CCess philosophy to facilitate maintenance access vlilh the minimum need to enter a manufacturing area? Ate them facilities to show visitors around the facility, minimizing the need to access produclion areas. and change - e.g., separate viewing oooidors?

Are separate areas ot means or segregation provided for: Roce,ipt, identification, sampling, quarantine of lncomlrtg materials, quatantine before release of API, intermediates, or finished product labOfattXY areas

1.4 Area Chalfenges - NonManuflK:turing Area r---

Challenge

1-S the cleaning methOd defined? What Internal finishes are specified - are they easity cleaned and resistant to the cleaning agents wtUch will be used? How is th

Aflaehmont J

C~Konge

How wlll!llo Slandard 1o< the -be clOfMd, and monkOted?

Hm! preess ftows been establishod lor lhe -.g. ond arell;ey """"-I.e.~ unlduectiooar? How c:an i be shown Ulellhe layout Is 1M ..,._m?

H .. adoq1.181e storage spaeo Md raclflg oquipm&nl required? How ore utllltios alstribt.lted In the facility. Md what would be the impact cf ~ak3ge? Is lhls en optimum aolution, altov.ing for 9Xpai1!8Jon? Wllal llghtlng 1ovo1s ore pocitiod for 1M fociiOty, nom>ol and """"!JE!I"'r are IIley adoquole? How d th

lSPE Good PracOOe Guidtt: GOOd fngineerlng Practice

1.5 Area ChaJienge-s - Manufactu!ing Area

Chellenge

IS the cleaning method d&ftned? What lntem.al finishes ate specitiOO - are they easity cleaned and resistant to (he cJeaofflg agents which will be used? Ai& the finishes cturabi!ity/repair a.bility

Al1aChmnt J

Challenge

How has it bean established that there is adequate spac~ to Install. ctean. molntain. and ope-rate the process and utalty equipment? What Is the maximum si~ repli!ceable part for the utility equlpment. and the manufacturing equipment? How will it be taken out? (Ho\\' Is the oqulptnent going to be taken ln. are doors and OQ(Iidors big onoogh?) Has adequate st013ge $pace and racking been defined for: Samples, test equipment, batch r0001ds, qualillcatiOn documentation, facility. utility. and equipment spate parts. raw materials. labels. packaging oompooents and finished goods? Has there been a foonal assessment for e~se of Maintenance eod a eroS$ contamination risk assessment oonsklt:tl'ing the

lsPE Good PractiCe Guide: Good f _ngineering Practice

Challenge .. Response Resol:ution

What 3000$$ control provisk>n is there for services May be G~Cetronlc control. rooms. production and storage areas? Is It suited keys, etc. Some adequate? segregation with controlled

aocess is required by the regulations for: Labels, Including reject labels. Reject materials.

How are areas labeled. ~nd status of them shovm, e.g . clean, or in used batch 2003/03? How is th$ packaging area laid out in order to A separate d&eardlng area 1s mlninlze risk from decarding. and separate pdmary pteferrE>d. wl1h primary from seooodary packaging? packaging In a dedicated

room. having aiflow of the appropriate cl.aS$1ficatlon on the product.

How are packaging lines separated? Spatially is a minJmum requirement, with a physical barrier to the floor of at least 3 leet (1 meter) tall being preferred?

How Is cross contamtnallon being prevented'? Airflow directions, airtoc!

ISPE Good PraOiioe Guide: Good Engineering Practice

~ompletlon and Inspection Certificate

Particulars of the Electrical Installation

Dopartmont: Date:

Name of Installation Circuit Ref. Plant ID No (If appUcal>le)

Type of Installation New Alt&ratlon Adciilion to Existing Installation

(ind;cate as appropriate)

Type of Ear!Wng TN.C TN-S TN-C-S TT IT

(indicate as appropriate)

Characteristics of supply at Ot"'gln of ltle Installation: N "nal voft89 V F om1 e roquoncy H z um er o N b f ph ....

AscMalned Determined by Enqwry by caJcu!ation Measured

ProspGCtiva Shon Circuit Current kA Earth Faull Loop lmpdance (Ze) ohms Mwumum Demand-------------- A

Ovetcurrant Protective Device Type 6S rating A Maln Switch or Circuit Br&aJter Type BS rating A No of poles __ _ (H an Residual Current Device (RCD) Is fitted. rated rasldual operating curren''-- - - --- rnA )

1/We being the persons responsible for the OeslgniConstructionllnstallation of the e~etJicel installatiOn. CERTIFY that the s.aJd work for which 1/We have been responsible is to the best o f our know!edge and OOIJef in accordance with th& Statutory R~ulations tor Eleclfical tnstallations.

The extent of the llablfity of the signatory Is limited to the work described above as ttle sutlject of this certificate.

For tho Design of t ho lnstalladpn Name (block letters): _____ _________ _____________ _ For and on behalf oi: ____________________ -,:-----------Signatura: ------------------- Date:--------For tho CAAftrUGtlpn of tht lneta!lation Name (block letters): ____________________________ _ Forand on behalf of: ____________________________ _ Signature: _______ _ ___________ ___ Date: ________ _

For the IMpactjon and Test of the !ostal!atjoo Name (block letters): __________ __________________ _ FO< and onbohall o f: _________________ ___________ _

Slgnature: - --- ------------------ Date:---------

I RECOMMEND that this installation be furthor Inspected and tested after an inteiVal of not mora than __ yea~> (5)

tSPf Good Preca!oe Guid~ Good Engln001 lng Practice

Schedule of Items lnspJicted

11dc items in.,eeted. Delete ftcms that a"' not applicable.

connection and Identification or conduetors

routing of c~es

aalectlon of conductors In oocordanca with design

plagll delllcles lalxtllong of-ion. circuit. rut ... OWilehes. terminals

Po ''' Anacl'lrnonl K

connection of titlgl.a pde device In phase oooductor only c:otreet connection of socket outlets and lamp 1\okferg

PfOSOMOI Of flnt barti9fS

adequocy of ...,....lo swichilear and equlpmenl

.,._..,.of danger and othef'"""'"'V-diagrams. 1.-.trudlons, and simiatlnloonatn

cllolce and ming of p

Circuit Design Details Q-cu~ Ref.

Plant tO No. (W aP!llicable)

Otigln of Circuits Ooa1!1'\8tlon ot Circuits

lnsldatlon Method Calllo 1)'114 Route Length (me!.,.) Doslgn Voltage Design Current

Grouping Foc:lor Amb!ont T&mp. Factor

RoQt.ln!d CUrrent Qwrying CopaQty Clrcufe ~ CSA Tob

lSPE Good Pructico Gui

Attochmtnt L


SUilj9cl: Focillty Corrm;ssio3.2 F~Uity -A:s it perta!rls to this GEP, a facility Is a defined structure or building where manuf.actuting Of Sl4lPQrt oper&11ons ere cattied out. This does nee lndude any installed or assodat8d mec::t'lanical or electrical ~

4.1 Sites and project !earns may use the IOJnpLatM In the attachments fOJ the aQI)fOC)f'lete facility to be commlssloi'Mtd. ModillcatJons lo the miT4Jialo can be mode as roqulrad to sun tho projoct n

ISPE G

Attachment l

Attachment L 1

(Enter buildinghoom/areallocalion hare) Description Specified

(f')fit,.,.,.$ ooJy - '*' ~-till eniet $()~} Otawing No./SChedule or 1234WLIOan bearing hinge on LHS of

doorlooklng from room 131 Door Hafldle Hinge Lock Handle Vision Panel Double Glazed Rush Finish

lighting Intensity e" 3CO tux@ 1 ~ter above floor levol Switch Operation Sfng}G togglb switch by on ltle LHS of

door 34lums fights on and off;

Windows Ooubi

ISPE Good Practice Guide: Good Ef'lgillOOtlng Procliee

Attachment L2

(Enter b ildlnglroomlarea/toc;,llon hen>} AI A clfl t I V r. lion FLOORS "'

ea r ec ura en 1ca -

Hom Description Complies (

Pago 14"2 Attachment L

A ttachm ent L2 (oontinu

ISPE GOOd Ptactioe Guk:fe: Good Engftetring Practice

Attachment L2 (continue!!) (Enter buifdinglroomlareallocation hero) Area Architectural Verification GENERAL

-

Item Oe&c:riptlon Complies (

ISPE 0000 Pr-OUdo: Good Engmcring PI'ICIIce

Approval Page

Good Engineering Pracllco app

P.;t 1.C8 AttachmtnC M


SUIJjoc:t: Projoct GMP Assessment Oato: Cldfmm,.YYYy Supersodes veraiOn n-1

1 Purpose

ISPE Good PracllQo a.lcle: GoodfrQineering Prada

Practice No. V..l$lon n GEPn

Pag

ISPE GOlled oocordirlg to projec1 procedures.

$.2 Pro~ MIJII ger

The Project MaMger represents the project owner