Evaluation of a fungal collection as certified reference material producer and as a biological resource center

h tt p : / / w w w . b j m i c r o b i o l . c o m . b r /

Medical

Microbiology

Evaluation

of

a

fungal

collection

as

certified

reference

material

producer

and

as

a

biological

resource

center

Tatiana

Forti

_,

_Aline

_da

_S.S.

_Souto

_,

_Carlos

_Roberto

_S.

_do

_Nascimento

_,

Marilia

M.

Nishikawa

_,

_Marise

_T.W.

_Hubner

_,

_Fernanda

_P.

_Sabagh

_,

Rosane

Maria

Temporal

_,

_Janaína

_M.

_Rodrigues

_,

_Manuela

_da

_Silva

a_{Fiocruz-Fundac¸ãoOswaldoCruz,InstitutoNacionaldeControledeQualidadeemSaúde(INCQS),RiodeJaneiro,RJ,Brazil} b_{Fiocruz-Fundac¸ãoOswaldoCruz,InstitutoNacionaldeControledeQualidadeemSaúde(INCQS),PostgraduatePrograminHealth}

Surveillance,RiodeJaneiro,RJ,Brazil

c_{Fiocruz-Fundac¸ãoOswaldoCruz(Fiocruz),InstitutoOswaldoCruz(IOC),RiodeJaneiro,RJ,Brazil}

d_{InstitutoNacionaldeMetrologia,QualidadeeTecnologia(Inmetro),DivisãodeMetrologiaQuímica(DiQuim),RiodeJaneiro,RJ,Brazil} e_{Fiocruz-Fundac¸ãoOswaldoCruz(Fiocruz),Vice-PresidênciadePesquisaeLaboratóriosdeReferência(VPPLR),RiodeJaneiro,RJ,Brazil}

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received13March2015

Accepted23August2015

Availableonline2March2016

AssociateEditor:AndréRodrigues

Keywords:

Fungalcollection

Certifiedreferencematerial

BiologicalResourceCenter

ABNTNBRISO/IEC17025

NIT-DICLA-061

a

b

s

t

r

a

c

t

Consideringtheabsenceofstandardsforculturecollectionsandmorespecificallyfor

biolog-icalresourcecentersintheworld,inadditiontotheabsenceofcertifiedbiologicalmaterial

inBrazil,thisstudyaimedtoevaluateaFungalCollectionfromFiocruz,asaproducerof

certifiedreferencematerialandasBiologicalResourceCenter(BRC).Forthisevaluation,a

checklistbasedontherequirementsofABNTISOGUIA34:2012correlatedwiththeABNTNBR

ISO/IEC17025:2005,wasdesignedandapplied.Complementingtheimplementationofthe

checklist,aninternalauditwasperformed.AnevaluationofthisCollectionasaBRCwasalso

conductedfollowingtherequirementsoftheNIT-DICLA-061,theBrazilianinternalstandard

fromInmetro,basedonABNTNBRISO/IEC17025:2005,ABNTISOGUIA34:2012andOECD

BestPracticeGuidelinesforBRCs.ThiswasthefirsttimethattheNITDICLA-061wasapplied

inaculturecollectionduringaninternalaudit.Theassessmentsenabledtheproposalfor

theadequacyofthisCollectiontoassuretheimplementationofthemanagementsystem

fortheirfutureaccreditationbyInmetroasacertifiedreferencematerialproduceraswell

asitsfutureaccreditationasaBiologicalResourceCenteraccordingtotheNIT-DICLA-061.

©2016SociedadeBrasileiradeMicrobiologia.PublishedbyElsevierEditoraLtda.Thisis

anopenaccessarticleundertheCCBY-NC-NDlicense

(http://creativecommons.org/licenses/by-nc-nd/4.0/).

∗ _{Correspondingauthor.}

E-mail:manueladasilva@fiocruz.br(M.daSilva).

http://dx.doi.org/10.1016/j.bjm.2016.01.021

1517-8382/©2016SociedadeBrasileiradeMicrobiologia.PublishedbyElsevierEditoraLtda.ThisisanopenaccessarticleundertheCC

Introduction

AccordingtotheInternationalVocabularyofMetrology(VIM),

reference material (RM) is the material that is sufficiently

homogeneousandstablewithreferencetospecified

proper-ties,whichhavebeenestablishedtobefitforitsintendeduse

inmeasurementorinexaminationofnominalproperties.The

VIMdefines certifiedreferencematerial(CRM)asreference

materialaccompaniedbydocumentationissuedbyan

author-itativebody,whichprovidesoneormorespecifiedproperty

valueswithassociateduncertaintiesand traceability,using

validprocedures.1

Forvalidationmethods,interlaboratorialcomparisonsand

qualitycontrol,referencematerialscanbeused.Invalidation

methods,theaccuracyinparameterestimationmustbe

per-formed with certified reference materials, when available.

Certifiedreferencematerialsshouldbeusedtoprovidevalues

toothermaterialsandforcalibrationinordertoassure

trace-ability.However,ifnocertifiedreferencematerialisavailable,

referencematerialsmustbeusedforassigningvaluestoother

materialsandforcalibration.2

Theuse of reference materialsupports the laboratories

tocomplywiththerequirementsofISO17025:2005(General

Requirements for the Competence ofTesting and

Calibra-tionLaboratories),regardingvalidationmethodsand useof

internalandexternalqualitycontrol.3_{Ideally,thereference}

materialmustbeproducedinaccordancewithamanagement

systemthathasbeenauditedandacknowledgedbyathird

party.2

Itisessentialthatthereferencematerialproducers

demon-stratetheir technical and scientific competenceas a basic

requirementtoensurethequalityofthematerialproduced.

The competence of reference material producers will be

demonstrated based on specific guides. The ISO 30 Series

Guidesgivesdirectionson bestpracticesinthe production

and characterization of reference materials. According to

internationalguidelines,accreditationofreferencematerial

producersisbasedontherequirementsofABNTISOGuide

34:2012–GeneralRequirementsfortheCompetenceof

Ref-erenceMaterialProducers4 _{alongwiththe requirements of}

ABNTNBRISO/IEC17025:2005.5

BiologicalResourceCenters (BRCs)include

microbiologi-calcollections from variousfields, whoseroutineactivities

include the acquisition, characterization, authentication,

preservationanddistributionofbiologicalmaterialwiththe

higheststandardofquality.Theseactivitiesgenerate

informa-tionofscientificandtechnologicalinterestonthedeposited

materialinthecollection,whicharestoredinadatabase.The

definitionofBiologicalResourceCenters(BRCs)asakey

com-ponentinthescientificandtechnologicalinfrastructureoflife

sciencesandbiotechnologywaspresentedforthefirsttimein

2001bytheOrganizationforEconomicCooperationand

Devel-opment(OECD)inthepublicationBiologicalResourceCenters:

UnderpinningtheFutureofLifeSciencesandBiotechnology.6_Later,

OECDpublishedin2007theBestPracticeGuidelinesfor

Biologi-calResourceCenters.7_{Thisdocumentencouragescollectionsto}

meetthehigh-qualityoperationalstandardsrequiredtoday,

providingthebasicrulesandpracticalguidanceforculture

collectionscandidatestobecomebiologicalresourcecenters.8

Therefore,collectionsthatfollowtheseGuidelinesareable

toachievebestpracticesinacquisition,maintenanceand

pro-visionofbiologicalmaterialstoassurebiologicalmaterialwith

highstandardofqualityandauthenticity,generatingareliable

databaseindifferentlaboratoriesandcontributingtothe

pro-tectionofthehealthofstaff,thepublicandtheenvironment.7

As a response to the OECD initiative on BRC, in 2008

thedemonstrationprojectfortheGlobalBiologicalResource

CentersNetwork(GBRCN)wasinitiated.Theproject

recom-mended thatallstakeholders shouldimplementpoliciesto

ensurethatthebiologicalmaterialsuppliedworldwideisof

highquality.ThedesignofGBRCNwasestablishedtoimprove

accesstohigh-qualitybiologicalresources,associated

infor-mationandservices.9

Brazil, which hasbeen implementing the Brazilian BRC

Network(Br-BRCN),hasbeen followingtheseGuidelines,as

wellasmanyothercountriesthatarealsopartofGBRCN.Since

thereisnointernationalstandardforculturecollections

nei-therforBRCs,somecountrieshaveestablishedinternalrules

mainlybasedonISO9001thatspecifiesrequirements fora

qualitymanagementsystem,suchasFrance.8,10

Consideringthisscenarioandduetotheconcernofthe

BrazilianGovernmentregardingqualityassurancewithin

cul-ture collections,the GeneralCoordinationforAccreditation

(Cgcre) ofthe National Institute of Metrology, Quality and

Technology(Inmetro),whichistheofficialaccreditationbody

inBrazil,createdtheTechnicalCommitteefortheStudyofan

AccreditationModelfortheActivitiesofBiologicalResource

Centers (TC-BRC). These Technical Committee, constituted

byexpertsfrom various culturecollectionsand from other

relevantareasfromBrazilianInstitutionsthatcomposethe

Br-BRCN,wasresponsiblefordiscussingandproposingamodel

ofaccreditationforBRCs.11

Thus,theTC-BRCelaboratedandapprovedthefirstedition

ofthedocumentontheaccreditationprogramrequirements

forBRCs,theNIT-DICLA-61(Requirementsforthe

accredita-tionoftestinglaboratoriesandreferencematerialproducers

fromBRC),whichisadocumentoftheDivisionof

Accredita-tionLaboratory-DICLA/Inmetroandthatwaspublishedinthe

endof2012.12

TheNIT-DICLA-061isbasedontheaccreditationbyCgcre

ofBRCtestingactivities,usingtheABNTNBRISO/IEC17025

(General Requirements forthe Competence ofTesting and

CalibrationLaboratories)ascriteriaorofBRCasareference

materialproducerusingthe ABNTISOGuide 34:2012

(Gen-eralRequirementsfortheCompetenceofReferenceMaterial

Producers)incombinationwithABNTNBRISO/IEC17025as

criteria, and bothpossibilities complementedbythe

appli-cablerequirementsoftheOECDBestPracticeGuidelinesfor

BRCs.10,11

OswaldoCruzFoundation(Fiocruz),whichwasoneofthe

institutions whose representatives participated in the

TC-BRC,isaBrazilianfederalorganizationfromtheMinistryof

Health.Fiocruzcoordinatesawell-structurednetworkof

epi-demiologicalcontrolandpublichealth,hostsdifferentculture

collectionsholdingstrainsofarchaea,bacteria,fungiand

pro-tozoa, representingpart ofthe Brazilianmicrobialdiversity

andexpressingavarietyofinfectiousagentsrelatedto

In 2007 Fiocruz started a project, funded by the

Min-istryofScience,TechnologyandInnovation(MCTI),thathad

theobjectiveofpreparingitsvariousinstitutionalmicrobial

collections to be part of the future Fiocruz Health-BRC,13

including the Fungal Collection that constitutes the

Col-lectionofReferenceMicroorganismsonHealthSurveillance

(Fiocruz-CMRVS),registeredontheWorldFederationfor

Cul-ture Collections (WFCC) under the World Data Center for

Microorganisms(WDCM)numberWDCM575.

Withinthiscontext,in2010astudycomprisingthe

evalu-ationofthe FungalCollectionbasedonthestandardABNT

NBRISO/IEC17025:2005and theOECD BestPractice

Guide-linesforBRCswasconductedtochecktheconformitytothese

documentsinordertoguaranteetheimplementationofthe

requirements,aimingatreliability,traceabilityandqualityof

microbialstrainsprovidedandtheadequacyoftheCollection

totheFiocruzHealthBRCProject.14

Theresultofthisstudywastheaccreditationofviability,

purityandauthenticationtestsperformedbytheFungal

Col-lection,in2012,byCgcreinaccordancewiththerequirements

ofABNTNBRISO/IEC17025:2005,makingitthefirstBrazilian

Collectiontohaveaccreditedtests.Thisstepwasessentialto

theconductionofthepresentstudy.

Therefore, the objective ofthis work was to assess the

FungalCollectionaccordingtothecriteriaofABNTISOGUIA

34:2012correlatedwiththeABNTNBRISO/IEC17025:2005as

wellastoevaluateit asaBiologicalResourceCenter(BRC)

according to the requirements of the Brazilian norm

NIT-DICLA-061.

Materials

and

methods

Theevaluation ofthe FungalCollection was performed by

applyingachecklistdesignedtofacilitatetheimplementation

ofABNTISOGUIA34:2012(Generalrequirementsforthe

com-petenceofreferencematerialproducers).Thedecisiontouse

thischecklistwastoavoidthatanyrequirementisoverlooked

atthetimeofevaluation,consideringthatthisnormisnot

partofthescopeofthemanagementsystemoftheNational

InstituteforQualityControlinHealth(INCQS/Fiocruz),oneof

theFiocruzInstitutesandwheretheCollectionislocated,

nei-therisitpartoftheINCQSroutineaudits.Anexampleofthe

structureofthechecklistispresented(Table1).

In addition tothe checklist,an internal auditwas

con-ductedinordertoevaluatethenecessarydocumentsandto

followtheproductionofreferencematerials.Alldataand

evi-dencescollectedduringtheinternalauditwererecordedinthe

AnnexesofSOPNo.65.1120.043(InternalAudit).Theinternal

auditwasanessentialcomplementtothechecklistinorderto

formalizetheprocesswithintheINCQSManagementSystem.

Whereasthechecklistapplicationandtheinternalaudit

wereconductedatdifferenttimes,andsincebothprocedures

werepartofasamplingprocess,theresultsmightbedifferent

forthesamerequirement.

For each result, the checklist presented the following

options to answer: meet the requirements, does not meet

therequirements,partlymeettherequirementsanddoesnot

apply.Foreach requirementcomplied,theevidencesfound

duringtheapplicationofthechecklistwheneverapplicable

werelisted.Insomecasesbesidestheevidences,additional

informationwasinsertedinthelastcolumnofthechecklist.

Thechecklistwasappliedduringinterviewswiththe

Col-lection staff conducted by auditors. Besides the checklist

interviews,thecriticalanalysisofclauses4–Requirements

oftheManagementSystemand5–ProductionandTechnical

RequirementsofABNTISOGUIA34:2012wasalsoconducted.

The evidences were recorded on the checklist itself. The

internalauditwas basedonthe ABNTNBRISO 19011:2012

(Guidelinesforauditingqualityand/orenvironmental

man-agementsystem).TheauditusedthecriteriafromtheABNT

ISOGUIA34:2012andABNTNBRISO/IEC17025:2005.

TheauditoftheCollectionstartedinthelastweekof

Jan-uary2013andwasfinalizedatthebeginningofFebruary2013.

DuringtheaudittheproductionofCryptococcusgattiiINCQS

40324(CFP78MC3)asapilotbatchwasfollowed.The

produc-tionofC.neoformansINCQS40323(CFP78MC2D),alsoaspilot

batch,wasfollowedbytheanalysisofrecordsrelatedtothis

production.

TheNIT-DICLA-061wasappliedintheFungalCollection,

aftertheinternalaudit,byassessingalltherequirementsthat

Table1–ExampleofthestructureofthechecklistappliedintheFungalCollection(Fiocruz-CMRVS).

ItemABNTISOGUIDE34 Correspondentitem ABNTISO/IEC

17025:2005

Definition Requirements Meet,doesnotmeet,partly meettherequirementsand

doesnotapply Describetheevidencesof

complience 4 4 Organizationand management requirements – – 4.1 4.2 Managementsystem requirements – –

4.1.1 4.2.1 General Thereferencematerialproducer shallestablish,implementand maintainadocumented managementsystemappropriate tothescopeofitsactivities, includingthetype,rangeand volumeofthereferencematerial productionitundertakes.

wereansweredbyindicatingmeettherequirements,doesnot

meet the requirements,partly meet the requirements and

doesnotapplyinaspecificreport.Thisreportwasdivided

intotheNIT-DICLA-061items:

• 10–ApplicationofABNTNBRISO/IEC17025standardfor

theaccreditationoftestinglaboratoriesfromBRC;

• 11–AdditionalrequirementstoABNTNBRISO/IEC17025

standardfortheaccreditationoftestinglaboratoriesfrom

BRC;

• 12–ApplicationofABNTISOGUIA34incombinationwith

ABNTNBRISO/IEC17025standardfortheaccreditationof

referencematerialproducersfromBRC;

• 13–AdditionalrequirementstoABNTISOGUIA34in

com-binationwith ABNTNBR ISO/IEC17025 standard forthe

accreditationofreferencematerialproducersfromBRC.

The assessment was based on the analysis of

non-conformitiesidentifiedduringtheinternalauditandbased

ontheresultsofthechecklistapplication.Theresultofthe

NIT-DICLA-061applicationwasalsoexamined.

TheproposalfortheadjustmentsoftheFungalCollection

wasdesignedconsideringtheresultsoftheseassessments.

Results

ResultsfromtheinternalauditonABNTISOGUIA

34:2012

The audit identified nineteen non-conformities regarding

non-compliance withthe requirements ofABNT ISO GUIA

34:2012.

Fig.1showsthe19non-conformitiesidentifiedduringthe

auditbytypeofrequirementsofABNTISOGUIA34:2012.

Quality policy n=1 (5%) Management system n=3 (17%) Organization and management n=1 (5%) Documents and information control n=2 (11%) Records n=1 (5%) Measuring eqipment n=1 (5%) Data evaluation n=1 (5%) Characterization n=1 (5%) Assignment of property values and their

uncertainties n=1 (5%) Certificates and documentation for user n=1 (5%) Production planning n=5 (27%) Accommodation and environmental conditions n=1 (5%)

Fig.1–Numberofnon-conformitiesbytypeof

requirementsofABNTISOGUIA34:2012fromtheFungal Collection. Met n=95 (45%) Partly met n=44 (21%)

Did not meet n=45 (22%)

Not applicable n=25 (12%)

Fig.2–Resultsfromtheapplicationofthechecklistfor ABNTISOGUIA34:2012requirementsintheFungal Collection.

ResultsregardingtheapplicationofthechecklistofABNT

ISOGUIA34:2012requirements

Theapplicationofthechecklistallowedtheidentificationof

45 (22%)items that didnotmeet therequirements from a

totalof209items.Ontheotherhand,95(45%)itemsmetthe

requirements,44(21%)itemspartlymettherequirementsand

25(12%)itemsdidnotapplytotheFungalCollection(Fig.2).

ApplicationofNIT-DICLA-061

TheresultfromtheNIT-DICLA-061application,regardingitem

10 – Application of ABNT NBRISO/IEC 17025 standard for

accreditation oftesting laboratoriesfrom BRC was15(48%)

items that met the requirements from a total of

31item-srequirements, in addition to 7 (23%) that partly met the

requirements,8(26%)itemsthat didnotmeetthe

require-ments and just 1 (3%) that did not apply to the Fungal

Collection(Fig.3).

Foritem11–AdditionalrequirementstoABNTNBRISO/IEC

17025 standard forthe accreditationof testinglaboratories

45

35

25

Item 10 Item 11 Item 12 Item 13

15 5 0 40 30 20 10

Met Partly met Not applicable Did not meet Total

Fig.3–AnalysisoftheFungalCollectioncompliance towardtherequirementsofitems10,11,12and13from NIT-DICLA-061.

fromBRCtherewereatotalof10requirements,fromwhich4

(40%)itemsmettherequirements,2(20%)partlymet,3(30%)

didnotmeettherequirementsand1(10%)didnotapplyto

theFungalCollection(Fig.3).

Foritem12 –ApplicationofABNTISOGUIA34in

com-bination with ABNT NBR ISO/IEC 17025 standard for the

accreditationofreferencematerialproducersfromBRCthere

wereatotalof44requirements,fromwhich30(68%)itemsmet

therequirements,6(14%)itemspartlymettherequirements

and8(18%)itemsdidnotmeet.Therewasnorequirement

thatdidnotapplytotheFungalCollection(Fig.3).

Foritem13–AdditionalrequirementstoABNTISOGUIA34

incombinationwithABNTNBRISO/IEC17025standardforthe

accreditationofreferencematerialsproducersfromBRCthere

wereatotalof17requirements.Fromthese,6(35%)itemsmet

therequirements,5(30%)itemspartlymettherequirements

and6(35%)itemsdidnotmeettherequirements.Againin

thiscasetherewasnorequirementthatdidnotapplytothe

FungalCollection(Fig.3).

Discussion

ConcerningtheinternalauditonABNTISOGUIA34:2012,the

numberofnon-conformitiesrelatedtoProductionand

Tech-nicalRequirements(clause5) washigher thanthe number

relatedtoRequirementsoftheManagementSystem(clause4).

Probablythisresultisduetothemanagementsystem

imple-mentedintheFungalCollection,aswellasthefactthatthe

testsforpurity,viabilityandauthenticationperformedbythe

Collection are accredited according tothe requirements of

ABNTNBRISO/IEC17025.

During the process of producing CRM (clause 5) it was

observedthatmostofthenon-conformitieswererelatedto

thelackofproceduresconcerningCRMproduction.Inrelation

toclause4,mostofthenon-complianceswererelatedto

ade-quacy/developmentofprocedures/recordsaswellasaspects

referringtoorganizationanddefinitionofqualitypolicy.

Regardingthenon-conformitiesbytypeofrequirements

of ABNT ISO GUIA 34:2012, the largest number of

non-complianceswererelatedtoProductionPlanning(item5.4),5

(27%)outof19non-conformities(Fig.1).Despitethefactthat

theproductionplanningwasavailable,itwasnotpresentin

theManagementSystemand didnotmeetcertain

require-ments,therefore it needed amendments. The requirement

regardingManagement System (item 4.1.3) had three

non-conformities and that was due to the absence of some

standardoperatingprocedures(SOPs).

The items that did not meet the requirements reflects

theneedforthe adequacyofthe INCQSManagement

Sys-tem tothe organization and directionrequirements ofthe

ABNTISOGUIA34:2012,asalsoobservedduringthe

execu-tionoftheinternalaudit.Itemsthatwerenotapplicablewere

related to some requirements on metrological traceability,

validationmethoddevelopedbythelaboratoryandaspecific

requirement,withvarioussub-items,onnon-certified

refer-encematerial.

ByanalyzingFig.2itisclearthattheFungalCollectionmet

orpartlymet mostofthe requirementsofABNTISO GUIA

34:2012.Fromtheitemsthatdidnotmeettherequirements,

mostofthem referredtotheadequacy/preparationof

doc-umentsrelatedtothe production,besidesasubcontracting

issue. Within the INCQS Management System the

subcon-tractingisnotdescribed,howeverfortheCRMproductionthe

characterizationandtransportwillhavetobesubcontracted,

thereforerequiringproperdocumentation.

In relationto the applicationofthe NIT-DICLA 061, the

non-complianceconcerningitem10(ApplicationofABNTNBR

ISO/IEC17025standardforaccreditationoftestinglaboratories

fromBRC)(Fig.3)referredmostlytoissuesrelatedtointernal

auditandtocriticalanalysis,aswellastobiosecurity,

inci-dentresponseplananddefinitionoflevelforvisitoraccessin

accordancewiththeBestPracticeGuidelinesonBiosecurity

forBRCsfromtheOECDBestPracticeGuidelinesforBRCs.

The requirements partly met by the Collection referred

toadjustments neededinthe ManagementSystem mainly

relatedtoairmonitoring,quarantineandinformationonthe

validityoftheculturemedia,aswellasotheraspects

concern-ing controlsystemforvisitors,informationonaccesslevel,

definitionofabiosecurityagent,andtheneedofastrict

con-trolofthechainofcustody,whicharealsoinaccordancewith

theBestPracticeGuidelinesonBiosecurityforBRCsfromthe

OECDBestPracticeGuidelinesforBRCs.

Biosecurityisanewtopic inBrazil,whichhasbeen

dis-cussedbytheFederalGovernmentandbyresearchinstitutes,

suchasOswaldoCruzFoundation,wherepathogensofhigh

riskaretheobjectofresearch.Howeverthereisneither

spe-cificlegislationnorregulationsforthisissueinthecountryyet.

Currently,theonlyformaldocumentthatdealswiththisin

BrazilistheNIT-DICLA-061,tothebestofourknowledge.The

lackofofficiallegislationandregulationsonbiosecuritywithin

nationalleveljustifiesinsomeextentthenon-complianceby

theCollectionregardingthissubject.

Foritem11(additionalrequirementstoABNTNBRISO/IEC

17025standardfortheaccreditationtestinglaboratoriesfrom

BRC) mostof therequirements were metor partlymet by

theFungalCollection(Fig.3).Therequirementsthatwerenot

metreferredtotheissuesrelated,ingeneral,totheincident

responseplanandsecurityscreeningofthestaffmembers.

RequirementsthattheCollectionpartlymetwererelated

toadjustmentsneededintheManagementSystemofthe

Col-lection,suchaspreparationofahealthandsafetyplanaswell

asthecontrolofinformationofthebiologicalmaterial,both

aspectsarerelatedtobiosecurity.

Mostoftherequirementsrelatedtoitem12(Applicationof

ABNTISOGUIA34incombination withABNTNBRISO/IEC

17025 standard for the accreditation of reference material

producers from BRC) were met (Fig. 3). The requirements

that were not met referred to aspects related, in general,

to training on biosecurity, regular risk assessment,

biolog-ical material delivery, internal audit and critical analysis.

Whereastherequirementsthatwerepartlymetbythe

Col-lectionconcernedquarantine,suitabilityoftheenvironment,

visitorcontrol,documentinginventory control,adequacyof

thedocumentationprovidedtoABNTISOGUIA31(Reference

materials-Contentsofcertificatesandlabels)andcontrolof

biologicalmaterialsupply.Therewerenorequirementsthat

didnotapply.

Foritem13(AdditionalrequirementstoABNTISOGUIA34

accreditationofreferencematerialsproducersfromBRC)the

Collectionmetorpartlymetmostoftherequirements(Fig.3).

Therequirementsthatwerenotmetwererelatedgenerallyto

visitorcontrolandincidentresponseplan,whichwerealready

identifiedpreviously,anddataexchange.Whilethe

require-mentsthattheCollectionpartlymetreferredtoinformation

onaccesslevel,definitionofabiosecurityagent,strictcontrol

ofthechainofcustody,whichareaspectsalreadyidentified

regardingitem11,besidesriskassessmentoftheinformation

anddatabase.

BasedonthisassessmentconductedintheFungal

Collec-tionbyinternalauditandchecklistapplicationaproposalfor

itsadequacytoABNTISOGUIA34:2012waspreparedfocusing

mainlyonmanagementoftheproductionprocess.

TheorganizationalstructureofINCQSwillhavetochange

in order to insert the reference material producer and to

defineresponsibilitiesfortheproductionofreference

mate-rials.Additionally,thequalitypolicyofINCQSwillhavetobe

revisedtocoverotherissuesrelatedtoABNTISOGUIA34:2012.

Following these modifications, all documents of INCQS

ManagementSystemwillhavetobemodifiedconcerningits

scopeinordertoincludetherequirementsofABNTISOGUIA

34:2012.Some of the technical procedures will have to be

reviewedand otherswillhavetobeestablishedinorderto

complywithABNTISOGUIA34:2012.

Analyzes ofroot causes will have tobe performed and

the corrective actions relating to non-conformities of the

internal auditreport 002/2013 willhave to be determined.

Consequently,theproposedcorrectiveactionswillhavetobe

implemented.

Regardingthechecklistapplication,theitemsthatdidnot

meetandpartlymettherequirementswillhavetobe

evalu-atedandcorrectiveactionsalsowillhavetobedetermined.

Aftertheimplementationofalltheseproposedcorrective

actions,theeffectivenessoftheseactionswillhavetobe

ver-ifiedbyanewinternalauditintheFungalCollectionhaving

ascriteriatheABNTNBRISO/IEC17025:2005andABNTISO

GUIA34:2012,includingalltechnicalrequirements.Fora

bet-terresult,itissuggestedtheinclusionofastatisticalexpert

andamycologistintheauditteam.

Onlyafter evaluating the resultsof this new audit will

be possible to forward the necessary documentation to

Cgcre/InmetrofortherequestoftheFungalCollection

accredi-tationascertifiedreferencematerialproducerinthebiological

area.AndifthisCollectionisaccrediteditwillbeapioneerin

Brazilinthismodality.

Basedontheanalyzesoftheresultsobtainedbythe

appli-cationofNIT-DICLA-061aproposalofcorrectiveactionswas

alsosetinordertopreparetheCollectionfortheaccreditation

byCgcre/Inmetroofthetestingandreferencematerial

pro-ductionactivitiesperformedbytheBRC and,consequently,

withinthescope oftheFiocruz HealthBRC project.

There-fore,thestepsdefinedabovewerealsofollowedfortheFungal

CollectionadequacyregardingNIT-DICLA-061.

The compliance of most of the requirements, such as

the implementation of policies, procedures and forms for

records,dependsontheactionoftheFungalCollectionitself,

manyoftheseadjustmentsarealreadyincourse.However,

issues of infrastructure and personnel availability for the

productionofreference materials,both aspectsconsidered

weaknesses, deserve special attention by the Direction of

INCQS.

RegardingNIT-DICLA-061application,thereweresome

dif-ficultiesinunderstandingsomeoftheitems.Sincethiswas

thefirsttimethattheNIT-DICLA-061wasappliedina

micro-bial collection, the critical analysis ofall its requirements

allowedtheverificationofdifficultiesofunderstanding and

ofimplementation.Therefore,thisstudywillhelpTC-BRCto

improvethisnewnormandtoworkinitsnewversion.

Fromthisassessmentitisalsoconcludedthattheissues

related to Biosecurity are considered critical aspects and

deservespecialattentionfromallpartiesinvolved,including

theDirectionofINCQS,theFiocruzAdministration,TC-BRC

andtheBrazilianFederalGovernment.

The implementation of these documents in the Fungal

Collectionanditsaccreditationasareferencematerial

pro-ducerinthebiologicalarea,willbringconfidencetotheresults

issuedbyinstitutionsthatusethecertifiedreference

materi-alsproducedbythisCulturecollection aswell asthe other

services provided as BRC, contributing significantly to the

Brazilianscientificresearch,epidemiologicalsurveillanceand

biotechnologicaldevelopment,besidesreducingdependency

onimportedcertifiedreferencematerials.Theimportanceof

thisautonomymustbeconsideredregardingthehighcostsof

biologicalreferencematerialsimportationandthetechnical

andsanitarybarriers.

Additionally, thiswork canbeapilotfortheproduction

ofothercertifiedreferencematerialsinthebiologicalareain

the country,sincethereisnocertificate referencematerial

produceraccreditedinBrazil.Italsocouldbeusedbyother

col-lectionsandlaboratoriesfromFiocruzandbyotherpublicand

privateinstitutionsofBrazilthathaveinterestinproducing

referencematerialsinthebiologicalarea.

Duetotheconfidentialnatureoftheaudit,thecorrective

actionsdesignedforthenonconformitiesdetectedduringthis

studywerenotdescribedinthispaper.However,theputative

solutionsforthenon-compliancesareprovidedin

supplemen-tarymaterialthatincludetemplateofthedocumentsusedin

this work,whichcanberequestedbyemailtothe address

vdquali@incqs.fiocruz.br.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

Acknowledgments

TheauthorsthankRenataMartinsHortaBorgesforthe

fun-damentalinsightsinmomentsofdoubt.

r

e

f

e

r

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n

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