who_oms - 2012 - assessment criteria for national blood regulatory systems

8/14/2019 WHO_OMS - 2012 - Assessment Criteria for National Blood Regulatory Systems

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World Health Organization 2012

All rights reserved. Publications of the World Health Organization are available on the WHO web site (www.who.int) or can be purchased fromWHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail:[email protected]).

Requests for permission to reproduce or translate WHO publications whether for sale or for noncommercial distribution should beaddressed to WHO Press through the WHO web site (http://www.who.int/about/licensing/copyright_form/en/index.html).

The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever onthe part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerningthe delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be fullagreement.The mention of specic companies or of certain manufacturers products does not imply that they are endorsed or recommended by the

World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names ofproprietary products are distinguished by initial capital letters.

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This publication contains the collective views of an international group of experts and does not necessarily represent the decisions or thepolicies of the World Health Organization.

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The assessment criteria for national blood regulatory systems were adopted by the WHO

Expert Committee on Biological Standardization at its sixty-second meeting, held in Geneva

from 17 to 21 October 2011. The document contains the collective views of the WHOBlood Regulators Network. It was developed in response to a request from WHO and the

International Conference of Drug Regulatory Authorities for an assessment tool to assist

capacity building of national regulatory authorities for the regulation of blood and blood

products.

The tool is intended to help Member States to identify gaps and priorities when developing

capacity building programmes, and support the introduction of regulation of blood products.

Establishment of such regulation was recommended in the 2010 World Health Assembly

resolution (WHA63.12) on the availability, quality and safety of blood products.


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ASS ESS MEN T CRI TER IA FOR NAT ION AL BLO OD REG ULA TOR Y S YS TEM S 01

Contents

Authors and Acknowledgements.....................................................................................................................................................................................02Abbreviations ....................................................................................................................................................................................................................................................03Glossary ......................................................................................................................................................................................................................................................................04

Introduction.........................................................................................................................................................................................................................................................07

Section A. Essential elements .............................................................................................................................................................................................09

1. National regulatory system ..................................................................................................................................................................................................................09

Applicable to blood, blood components, plasma-derived medicinal products,associated substances, and medical devices including in vitro diagnostics

2. National regulatory authority .............................................................................................................................................................................................................10


Section B. Core functions ............................................................................................................................................................................................................133. Licensing and/or registration of blood establishments............................................................................................................................................13

Applicable to blood and blood components including plasma for fractionation4. Licensing and/or registration of manufacturers and distributors of plasma-derived medicinal products...............16

Applicable to plasma-derived medicinal products5. Approval of blood and blood components (product and/or process approval) ...................................................................................18

Applicable to blood and blood components including plasma for fractionation6. Approval of plasma-derived medicinal products ..............................................................................................................................................................20

Applicable to plasma-derived medicinal products7. Regulatory oversight of associated substances and medical devices including in vitro diagnostics .............................22Applicable to associated substances and medical devices including in vitro diagnostics8. Access to a laboratory independent of manufacturers ..............................................................................................................................................23


9. Control of clinical trials ..........................................................................................................................................................................................................................26


10. System for lot release of plasma-derived medicinal products .............................................................................................................................28

Applicable to plasma-derived medicinal products and donor screening tests11. Regulatory inspections and enforcement activities .....................................................................................................................................................30


12. Vigilance systems ..........................................................................................................................................................................................................................................32


13. Ensuring traceability and record keeping by manufacturers for all regulated products .............................................................34


14. International cooperation .....................................................................................................................................................................................................................34


Bibiliography ......................................................................................................................................................................................................................................................35


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02

Authors and Acknowledgements

The drafting group was formed of Members of the WHO Blood Regulators Network (BRN) and the WHOBlood Products and Related Biologicals programme, Quality Assurance and Safety: Medicines, WorldHealth Organization:

Dr I Prosser, Dr G Smith, Therapeutic Goods Administration, Australia; Dr P Ganz, Dr F Agbanyo, HealthCanada, Canada; Dr P Zorzi, Dr I Sainte-Marie, AFSSAPS, France; Professor R Seitz, Dr M Heiden,Paul Ehrlich Institut, Germany; Dr C Schrer, Dr M Jutzi, Swissmedic, Switzerland; Dr J Epstein,Dr G Michaud, Food and Drug Administration, USA; Dr A Padilla, World Health Organization

Existing WHO evaluation templates for vaccines and medicinal products were consulted in developing thistool. The rst consolidated draft was discussed at the Blood and Blood Products Workshop of the 14th

International Conference of Drug Regulatory Authorities (ICDRA), Singapore, 2010, where it was supportedfor consideration by WHO Member States. Over 90 national regulatory agencies were represented in theConference.

Through a global consultation process involving all WHO regions, regulators were encouraged tocontribute their self-assessments and comments on the usefulness of the tool to help towards itsnalization. Thanks are due to the WHO Regional Ofces for their support in this process.

Valuable inputs in the form of comments and self-assessment feedback were received from the followingnational agencies (in alphabetical order by country):

Blood Bank Directorate, Ministry of Public Health, Afghanistan; Administracin Nacional deMedicamentos, Alimentos y Tecnologa Mdica (ANMAT), Argentina; Scientic Center of Drug and Medical

Technologies Expertise (SCDMTE), Armenia; European Commission, Directorate General for Health andConsumer Affairs (SANCO), Belgium; Gerncia Geral de Sangue, outros Tecidos, Clulas e rgos, AgnciaNacional de Vigilncia Sanitria (ANVISA), Brazil; Department of Drug Registration, State Food and Drug

Adminstration, China (Peoples Republic of); Instituto Nacional de Salud (INS) and Instituto Nacional deVigilancia de Medicamentos y Alimentos (INVIMA), Ministerio de la Proteccin Social, Colombia; Centropara el Control Estatal de la Calidad de los Medicamentos (CECMED), Cuba; Danish Medicines Agency,Denmark; The Ministers Technical Ofce, Ministry of Health, Egypt; Laboratory Services Department,

Food and Drugs Board, Ghana; Central Drugs Standard Control Organization, Ministry of Health andFamiliy Welfare, India; National Agency of Drug and Food Control (NADFC), Indonesia; Food and DrugOrganization, Iran (Islamic Republic of); Division of Blood and Blood Products, Ministry of Health,Labour and Welfare, Japan; National Blood Service, Ministry of Health, Latvia; Comisin Federal para

la Proteccin contra Riesgos Sanitarios (COFEPRIS), Mexico; Department of Health and Social Affairs,Micronesia (Federated States of); Department of Drug Administration (DDA), Ministry of Health andPopulation, Nepal; Medicines Evaluation Board, the Netherlands; Centro Nacional de Diagnstico yReferencia (CNDR), Ministerio de Salud de Nicaragua (MINSA), Nicaragua; National Agency for Food and

Drug Administration and Control (NAFDAC), Nigeria; Programa Nacional de Sangre, Ministerio de SaludPblica y Bienestar Social, Paraguay; Centre for Product Registration, National Pharmaceutical ControlBureau, Ministry of Health, Malaysia; Korea Food and Drug Administration (KFDA), Republic of Korea;Saudi Food and Drug Authority, Saudi Arabia; Direction de la Pharmacie et des Laboratoires, Ministre de

la Sant, Senegal; Medicines and Medical Devices Agency, Serbia; Department of Health, South Africa;National Drug Quality Control Laboratory, Medicines and Poisons Board, Sudan; Medical Products Agency,

Sweden; Ministry of Health, Syrian Arab Republic; Institute of Biological Products, Department of MedicalSciences, Ministry of Public Health, Thailand; Sharjah Blood Transfusion & Research Centre, Ministry ofHealth, United Arab Emirates.


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All comments received were reviewed by the drafting group and a nal proposed version was submitted to

the 62nd Expert Committee on Biological Standardization (ECBS). Special thanks are due to the Membersof the ECBS, who provided valuable advice and agreed to the adoption of this document:

Dr J Epstein, Center for Biologics Evaluation and Research, Food and Drug Administration,USA; Dr E Grifths, Biologics and Genetic Therapies Directorate, Health Canada, Canada;

Mrs T Jivapaisarnpong, Institute of Biological Products, Department of Medical Sciences, Ministry ofPublic Health, Thailand; Dr H Klein, National Institutes of Health, USA; Dr P Minor, National Institutefor Biological Standards and Control, UK; Dr F M Moftah, National Blood Transfusion Service, Ministryof Health, Egypt; Dr J Petricciani, International Association for Biologicals, USA; Dr LS Slamet,

National Agency of Drug and Food Control (NADFC), Indonesia; Dr P Strengers, Sanquin Foundation,the Netherlands; Professor H Yin, Center for Drug Evaluation, State Food and Drug Administration,China (Peoples Republic of).

For further information contact:

Programme ManagerBlood Products and Related Biologicals

Quality Assurance and Safety: MedicinesDepartment of Essential Medicines and Health Products

World Health Organization


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04

Abbreviations

AE adverse event

AR adverse reaction

BRN WHO Blood Regulators Network

ECBS WHO Expert Committee on Biological Standardization

GCP good clinical practice

GDP good distribution practice

GMP good manufacturing practice

ICDRA International Conference of Drug Regulatory Authorities

NCL national control laboratory

NRA national regulatory authority

QMS quality management system

SOP standard operating procedure

SPC summary of product characteristics


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Glossary

The WHO Expert Committee on Biological Standardization adopted the following denitions for the

purpose of this report.

Approval

A decision to authorize marketing of a drug by a national regulatory authority. The mechanism by whicha regulatory authority ensures that there is compliance with regulatory requirements and standards thatassure quality, safety and efcacy for all blood products and/or processes and establishments involved

in collecting blood donations and/or manufacturing blood products. A regulatory approval is generally aprecondition for marketing of a blood product.Associated medical devices

All devices involved in donor testing and/or manufacturing activities.

Associated substances and materials

All substances or materials involved in manufacturing of blood products, including anticoagulants,additive solutions and storage solutions. These materials are regulated as drugs in some jurisdictions.

Blood component1

A constituent of blood (erythrocytes, leukocytes, platelets, cryoprecipitate and plasma) that can beprepared by various separation methods and under such conditions can be used either directly fortherapeutic purposes or for further processing or manufacturing.

Blood establishment

Any structure, facility or body that is responsible for any aspect of the collection, testing, processing,storage, release and/or distribution of human blood or blood components when intended for transfusionor further industrial manufacturing.

Blood product

Any therapeutic substance derived from human blood, including whole blood, blood components andplasma-derived medicinal products.

Core function

A specic function through which the regulatory system assures quality, safety and efcacy of blood

products.

Distributor

Any facility that engages in distribution, including storage, importation or exportation of blood products,which may include wholesalers.

Essential elementA basic characteristic of a regulatory system as a whole (such as a legal basis for its activities,enforcement power, independence of the regulator from the regulated parties etc.), which isfundamentally related to the systems ability to effectively ensure quality, safety and efcacy of blood

products.

Good clinical practice (GCP)

A standard for the design, conduct, performance, monitoring, auditing, recording, analysing and reportingof clinical trials that provides assurance that the data and reported results are credible and accurate, andthat the rights, integrity and condentiality of trial subjects are protected.

1 Stem cells may or may not be included in the scope of the regulatory activity of the competent authority for blood and blood products. Similarcriteria for safety, quality and efcacy should be met as for blood and blood components.


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Good distribution practice (GDP)

The part of quality assurance that ensures the quality of a pharmaceutical product is maintained by means of

adequate control of all activities which occur throughout the distribution process.

Good manufacturing practice (GMP)All elements in the established practice that will collectively lead to nal products or services that

consistently meet appropriate specications and compliance with dened regulations.

LegislationA legal instrument of government that denes laws which govern a particular subject matter, e.g.

regulation of quality, safety and efcacy of medicines. Laws dene the roles, rights and obligations of all

parties involved in the subject matter in general terms (see also Regulations).

LicensingAuthorization by the national regulatory authority for the manufacture, importation, exportation, ordistribution of medical products.

ManufacturerAny natural or legal person (structure, facility or body) with responsibility for any aspect of the followingactivities in relation to blood products: collection, testing, processing, storage, packaging, labelling,release, and/or distribution.

National regulatory authority (NRA)

National regulatory authorities (also called national medicines regulatory authorities) are legally-established bodies that promulgate medicines regulations and enforce them.

Plasma-derived medicinal product

Any therapeutic product derived from human plasma and produced by an industrial-scale manufacturingprocess that pools multiple units. Also called plasma derivatives or plasma-derived products.

Quality management system (QMS)A management system that directs and controls an organization with respect to quality, and that ensuresthat steps, processes, procedures and policies related to quality activities are being followed.

Registration

A procedure under whichinformation regarding the identication, location(s) and scope of activities of allparties involved in manufacturing or supplying a medicinal product and associated medical devices andsubstances is submitted to the regulatory authority in order to comply with administrative requirementsbefore starting, continuing or amending relevant activities.

Regulations

Legislative instruments of government that provide more prescriptive information regarding compliance

with relevant legislation.Regulations are specically designed to provide the legal framework and detailsnecessary to achieve the administrative and technical goals of legislation.

Standard operating procedure (SOP)Denes a prescriptive document that outlines how an activity is carried out.

SponsorAn individual, company, institution or organization that takes responsibility for the initiation, managementand/or nancing of a drug submission or clinical trial.

Vigilance

A mechanism of oversight involving an organized system for gathering safety information. This termencompasses pharmacovigilance, haemovigilance and materiovigilance.


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Introduction

Blood transfusion is an indispensable, potentially life-saving medical intervention, and blood productssuch as clotting factors and some immunoglobulins are designated by WHO as essential medicines.However, the inherent risks of blood and the complexity of providing adequate, timely and equitableaccess to safe blood products require an organized national or regional blood regulatory system. Within

that system, a competent blood products regulatory authority assures that appropriate standards aremet for production of blood products and monitoring of blood safety. Consequently, as a pillar for theestablishment of safe blood programmes globally, WHO has advocated for the establishment andsustenance of strong national regulatory authorities (NRAs) both in developed and developing countries.

In 2010, in resolution WHA63.12, the World Health Assembly expressed its concern about the unequalaccess globally to blood products, particularly plasma-derived products, leaving many patients withoutneeded transfusions and many of those with severe congenital and acquired disorders without adequateplasma-derived treatments. In this resolution, the World Health Assembly urged Member States totake all the necessary steps to update their national regulations on donor assessment and deferral,the collection, testing, processing, storage, transportation and use of blood products, and operation ofregulatory authorities in order to ensure that regulatory control in the area of quality and safety of bloodproducts across the entire transfusion chain meets internationally recognized standards.

Purpose and application of the document

The purpose of this document is to provide a tool to assist capacity building of national regulatoryauthorities (NRAs) for the regulation of blood and blood products. Ancillary to the existence of NRAs toregulate activities assuring the provision of safe blood products, there is currently a need to developcriteria dening best practices or attributes of national blood regulatory systems globally for activities

related to regulation of blood products. This document provides a description of elements and functionswhich may support the creation of an appropriate blood regulatory system where none exists so far,and which may also be used as a tool to assess strengths and gaps of established systems. For bothdeveloped and developing countries, an assessment tool that reects international best practices in

blood regulation could serve to highlight strengths of the NRA while identifying gaps or areas for futuredevelopment. In addition, adoption of global criteria by NRAs could promote international convergence ofregulations, which can have a benecial impact on global safety and availability of blood products.

To promote these objectives, this document identies the essential elements and core regulatory

functions that should be present in an effective NRA to assure the quality, safety and efcacy of blood

and blood products, as well as associated substances and medical devices including in vitro diagnostics.Additionally, this document provides major criteria, indicators and associated ratings for the essentialelements and core functions that are intended to help NRAs assess their performance in the regulation ofblood and blood products and prioritize efforts to address any gaps that are identied.

Understanding and use of the document

To achieve the aim of an international best practice national blood regulatory framework, a set ofintegrated general and specic regulatory functions have been identied that are applicable to all aspects

of blood product regulation, from the collection of source material through to the quality control of thenal product, and covering not only blood products but also associated substances and medical devices,

including in vitro diagnostics. Section A of this document identies essential elements that are necessary

to establish the legal basis, authority and general characteristics of the NRA. Section B identies

specic core functions of the NRA that are necessary for comprehensive oversight of blood products,

related substances and medical devices. It is recognized that the functions may be interdependent andthat in some countries the specic functions captured in this document may not be within the scope

of one national blood regulatory authority but may be captured by other national authorities or other

acceptable mechanisms to achieve compliance to the assessment criteria. Some regulatory functionsmay be applicable regardless of the intended use of the blood (e.g. for transfusion purposes or forfurther manufacturing use). However, regulatory structures should be designed in such a way as to avoidfragmentation and uncoordinated delegation.


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This document provides the main criteria and indicators for each essential element and core function.The criteria and indicators provide a framework that will identify areas for improvement to governments,particularly in developing countries. A self-assessment or external assessment process using thesecriteria could also serve as a useful means to highlight strengths of NRA programmes for regulationof blood products while identifying gaps or areas for future development. National authorities areencouraged to use the assessment criteria as a roadmap towards evolving a best practice bloodregulatory system.

It is recognized that many national blood regulatory systems will not be able to meet all the criteriaand indicators listed in this document. The criteria and indicators are therefore organized into thoseconsidered as being required (R) and thus necessary in order to be effective as a blood regulator, andthose that are considered as being desirable or suggested (S) to achieve a blood regulatory system ofinternational best practice.

It is also recognized that single required criteria may not formally be fullled even by regulators with

proven effectiveness, but that underlying relevant safety issues can be met by other means. This offersthe opportunity to compare different ways of ensuring safety of blood products and points out areaswhere renement of the assessment criteria may need to be considered.

With experiences gained, future versions of these assessment criteria are expected to betteraccommodate effective alternatives, or may suggest the need for additional guidance, such as forprioritization of efforts.


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Sectio

nA.

Essentialele

ments

1.

Nat

ionalregulatorysystem

Applicabletoblood,

bloodcomponents,

plasma-derivedmedicinalproducts

,associatedsubstances,

andmedicaldevicesincludinginvitrodiagnostics

Maincriteriarelatedtotheelement

Rating*

Indicatorsrelatedtothemaincriteria

Ma

in

crite

ria

Indicator

1.1.Aco

mprehensivelegal

(statutory)basisexistsfor

esta

blishmentofaregulatory

systema

pplicabletoblood,

bloo

dcomponents,plasma-

derivedproducts,associated

subs

tances,andmedical

devicesincludinginvitro

diag

nostics.

R

R R R R R R S

1.1.1.

Provisionsf

orthemainregulatoryfunctionsc

anbeidentiedandareuptodate.

1.1.2.Theregulat

ionsortheiradaptationstakeinto

considerationdevelopmentsinth

eeldofblood

andrelated

technologies.

1.1.3.Regulations

havebeenestablishedandarea

vailable;theyareintelligibletotho

sethatneedto

complywith

orenforcethem,andthewaysof

communicationusedareadequa

te.

1.1.4.Legislation

existsthatdenestherapeuticpro

ductsforhumanusetoberegula

ted,and

establishes

standardsofquality,safetyande

fcacyfor:

a.

blo

od,bloodcomponentsandplasm

a-derivedproducts;

b.

associatedsubstancesandmedical

devicesincludinginvitrodiagnost

ics.

1.1.5.Legislation

existsthatprovidesalegalbasisfortheresponsibleNRAtoperform

theessential

functions.

1.1.6.Legislation

enablestheappropriateinstitutionstoissueregulations.

1.1.7.

Thedevelopmentofregulationsincludesthe

opportunityforpublicconsultation

.

1.2.Thelegislationassignsthe

enfo

rcementofregulations

rega

rdingtheproducts

cove

redin1.1tooneor

moreresponsibleregulatory

auth

orities.

R

R R R

1.2.1.Thecompetentauthoritiesinvolvedinthereg

ulatorysystemf

orblood,bloodco

mponents,plasma-

derivedproducts,associatedsubstances,andmedicaldevicesincludinginvitrodiagnosticsare

clearlyiden

tiedandcanbenamedforeach

oftheregulatoryfunctions.

1.2.2.Theresponsibilities,functionsandtheorganizationofeachoftheseauthorities

areclearly

dened,inparticularasregardsthescopeof

theregulation(regulatoryfunctions)theyhaveunder

theircontro

l.

1.2.3.Theactivitiesofthevariousauthoritiesinvolvedarecoordinatedandsupervisedbyan

administrat

ivemechanism.

*R=required

;S=suggested


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2.

Nat

ionalregulatoryauthority

Applicabletoblood,

bloodcomponents,





Rating*


Ma

in

crite

ria

Indicator

2.1.Ther

eisindependenceof

theregulatoryauthorityin

decision-making.

R

R R R R R S

2.1.1.Acleardivisionofrolesandresponsibilitiesis

implementedbetweentheNRA,blood

establishments,manufacturersanddistributors,reectingindependenceoftheregulatory

system.

2.1.2.Accountabilitiesfordecision-makingareclear.

2.1.3.Internalpolicyonpotentialconictsofinteres

tforstaffexists.

2.1.4.NRAmanag

ementandassessmentactivities

(includinguseofexpertcommitte

es)neverinclude

representativesfromm

anufacturersorlicenc

eholders.

2.1.5.Acodeofconductforregulatorystaffexists.

2.1.6.Writtenproceduresformeetingswithmanufa

cturers,distributorsandotherspo

nsorsexist.

2.2.TheNRAhasestablishedan

institutionaldevelopment

plan

.

S

S S S

2.2.1.TheNRAha

saninstitutionaldevelopmentpla

n,whichisimplementedandupd

ated.

2.2.2.Thedevelopmentplanincludes:vision;strate

gicobjectives;timelineanddeadlinefortarget

implementa

tion;indicators;functionsand/or

dutiesoftheNRA;ongoingstafftrainingplan;

resourcesn

eeded;informationand/orcomm

unicationstrategy;andahumanr

esource

developmentplan.

2.2.3.Performanc

eindicatorsareestablishedandu

sedformonitoringattainmentof

objectives.


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2.

Nat


Applicabletoblood,

bloodcomponents,





Rating*


Ma

in

crite

ria

Indicator

2.3.TheNRAhasadequate

reso

urcestocarryoutits

func

tionsproperlyandto

enfo

rceregulatoryfunctions.

R

R R R R R R S S

2.3.1.Anadequat

enumberoftrainedstaffandbud

getaryprovisionsexistforallesse

ntialfunctions.

2.3.2.Allstaffme

mbershaveappropriatequalicationstoconductregulatoryactivitie

sandareprovided

withtimely,

relevantandregularlyupdatedtraining.

2.3.3.Tasksandr

esponsibilitiesofstaffmembersa

rewelldened.

2.3.4.Mechanism

sareinplacetoensurethatthoseperformingregulatoryfunctions

havesufcientand

currentexpertiseinspecializedareas.

2.3.5.Policiesand

proceduresexistforrecruitment

andselectionofexternalexpertsandthe

manageme

ntofexpertadvisorycommittees,

includingpotentialconictofinterest.

2.3.6.AnagreementbetweentheNRAandexternal

expertsdeningrolesandrespon

sibilitiesis

established

.

2.3.7.

Thesourcesoffundingoftheresponsibleauthoritiesperformingregulatoryfun

ctionsaredened.

2.3.8.Writtencriteriaforselectionandrecruitmentofregulatorystaffaredened.


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12

2.

Nat


Applicabletoblood,

bloodcomponents,





Rating*


Ma

in

crite

ria

Indicator

2.4.Aqu

alitymanagementsystem

(QMS)isinplace.

S

S S S S S S S

2.4.1.AQMSisim

plementedbytheNRAforallitsc

orefunctionsasspeciedbelow.

2.4.2.BudgetaryprovisionsaremadeforimplementationandmaintenanceoftheQM

S.

2.4.3.AqualiedqualitymanagerisdesignatedasresponsiblefortheimplementationoftheQMS.

2.4.4.Thedocumentationneededtoestablish,implementandmaintaintheQMSisd

ened(quality

manual,SO

Ps,etc.).

2.4.5.TheQMSis

basedonrecognizedinternationa

lstandards.

2.4.6.TheQMSis

certiedoraccreditedbyexternalbodies.

2.4.7.

Aninternal

andexternalauditandreviewsystemexistsaswellasevidencetha

tcorrectiveand

preventiveactionsaretakenasaresultofmonitoringand/oraudits.

2.5.Tran

sparencyand

acco

untabilityareensured.

R

R R R S S

2.5.1.Legally-specied,condentialandtradesecretinformationisavailableforinter

naluseand

decision-making.However,allotherinformationispubliclyavailableandkeptuptodate.

2.5.2.Listingofauthorizedproductsandcompaniesismadeavailablewhereneeded

.

2.5.3.Information

onsanctions,recallsandpublich

ealthwarningsispubliclyavailable.

2.5.4.Information

ondecisionsisavailableandeas

ilyaccessibletothepublicandincludesnegative

decisionsin

selectedcases(mayvarydepend

ingonnationalregulation).

2.5.5.AnopportunityforinteractionbetweentheNR

Aandstakeholdersisgiven.

*R=required

;S=suggested


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Sectio

nB.

Corefunctions

3.

Lic

ensingand/orregistration

ofbloodestablishments

Applicabletobloodandbloodcomponentsincludingplasmaforfractionation

Maincriteriarelatedtothefunction

Rating*


Ma

in

crite

ria

Indicator

3.1.Legi

slativeauthorityexists

tore

quireregistration

and/orlicensingofblood

esta

blishments,andfor

enfo

rcementpower.

R

R R

3.1.1.Legislation

and/orregulationexistthatrequireabloodestablishmentthatintendstocollect,

test,proces

s,store,manufacture,distribute,importorexportbloodandbloodcomponentstobe

authorized,

accredited,registeredorlicensed

bythedesignatedNRA.

3.1.2.TheNRAha

stheauthoritytotakeregulatoryaction(e.g.revoke,suspendthelicence)ifthe

establishmentdoesnotcomplywithregulatoryrequirements.

3.2.Alic


systemi

sestablished

and

operationalforblood

esta

blishments.

R

R R R R S S

3.2.1.Activitiesth

ataredecentralizedordelegated

tootheragenciesorauthoritiesfo

llowthestandards,

guidelinesandproceduresasagreedbythec

entralregulatoryauthority,anda

reporting

mechanism

isestablishedbetweentherespo

nsibleauthorities.

3.2.2.Requiredre

gistrationand/orlicenceapplicationsareassessedbytheNRAbas

edonwritten

guidelines.

3.2.3.Alistofalllicensedand/orregisteredbloode

stablishmentsismaintainedand

madeavailable

whereneed

ed.

3.2.4.Advicefora

pplicantsisavailableontheconte

nt,format,requirementsandprocedurestofollowin

ordertosubmitarequiredregistrationand/orapplicationforanestablishment

licence.

3.2.5.Facilitydocumentation(e.g.sitemasterle,q

ualicationofaresponsibleperso

n)issubmittedas

partofarequiredregistrationand/orapplicationforanestablishmentlicenceandisassessed

todemonst

ratethatthefacilityissuitablefor

theactivitiestobeperformed(e.g

.bloodcollection,

donorscree

ning,testing,storage,etc.).

3.2.6.Renewalpe

riodsforanestablishmentlicence

and/orregistrationaredeneda

ndconsistentwith

mechanism

sofsurveillance.


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14

3.

Lic





Rating*


Ma

in

crite

ria

Indicator

3.3.Sign

icantchangestoan

esta

blishmentlicenceand/or

registrationaresubmittedand

asse

ssedbytheNRApriorto

implementation.

R

R S

3.3.1.Changesar

eassessedbasedonthetypeofc

hange.

3.3.2.Writtenguid

elinesforapplicantsareavailable

thatdenethetypesandscopes

ofchangesand

documenta

tionrequired.

3.4.Com

pliancewiththeprinciples

ofgoodmanufacturing

prac

tice(GMP)isassessed

aspartoftheestablishment

licen

singand/orregistration

proc

ess.

R

R R R

3.4.1.Compliance

withapplicableprinciplesofGMP

isaconditionformaintainingan

establishment

licenceand

/orregistrationandforapprovalo

fsignicantchanges.

3.4.2.NationalGM

Pandgooddistributionpractice(GDP)principlesarepublishedandareconsistent

withorbasedonrecognizedstandardsforthemanufacturinganddistributionofbloodandblood

component

s.

3.4.3.Periodicins

pectionsaccordingtoGMPandGDPprinciplesarecarriedoutforsupervisionofblood

establishments.Forinspectionscarriedouta

broad:

a.

thereisanagreementwithotherNRAsforexchangeofinspectionreportsand/or

certicates;or

b.

alistofreferencecountriesand/orag

encieswhosecerticatesanddec

isionsare

acce

ptedexist;or

c.

siteinspectionsarecarriedoutabroad

.

3.5.QMS

requirementsare

esta

blishedforallfunctions

performedbyblood

esta

blishments.

R

R

3.5.1.

TheessentialcomponentsforaQMSarecovered.


19/40


3.

Lic





Rating*


Ma

in

crite

ria

Indicator

3.6.Asse

ssmentofcompliance

with

standardsregarding

dono

rselectioncriteriaand

testingofdonationsispartof

theestablishmentlicensing

and/orregistrationprocess

(alte

rnativelythisrequirement

canbemetunderCore

func

tion5).

R

R R R R

3.6.1.Compliance

withnationalstandardsisacond

itionformaintaininganestablishmentlicence.

3.6.2.Nationalstandardsarepublishedandareconsistentwithorbasedonrecogniz

edstandardsfor

bloodandb

loodcomponents.

3.6.3.Inspections

arecarriedoutforcheckingcompliancewiththesenationalstanda

rds.

3.6.4.Denedpro

ceduresareinplacefortakingac

tionininstancesofanynonconfor

mity.

*R=required

;S=suggested


20/40

16

4.

Lice

nsingand/orregistration

ofmanufacturersanddist

ributorsofplasma-derived

medicinalproducts

Applicabletoplasma-derivedmedicinal

products


Rating*


Ma

in

crite

ria

Indicator

4.1.Legi

slativeauthorityexists

tore

quireregistrationand/

orlicensingofmanufacturers

and

distributorsofplasma-

derivedproducts,andfor

enfo

rcementpower.

R

R R

4.1.1.Legislation

and/orregulationexistthatrequiremanufacturersanddistributors

ofplasma-derived

productsth

atintendtomanufacture,distribu

te,importorexportplasma-derive

dproductstobe

registereda

nd/orlicensedbythedesignated

NRA.

4.1.2.TheNRAha

sauthoritytotakeregulatoryaction(e.g.revoke,suspendthelicence)ifthecompany

doesnotco

mplywithregulatoryrequirements.

4.2.Alic


systemi

sestablishedand

oper

ationalformanufacturers

and

distributorsofplasma-

derivedproducts.

R

R R R R S S

4.2.1.Activitiesth

ataredecentralizedordelegated

tootheragenciesorauthoritiesfo

llowthestandards,

guidelinesandproceduresasagreedbythec

entralregulatoryauthority,anda

reporting

mechanism

isestablishedbetweentherespo

nsibleauthorities.

4.2.2.Requiredre

gistrationand/orlicenceapplicationsareassessedbytheNRAbas

edonwritten

guidelines.

4.2.3.Alistofalllicensedand/orregisteredmanufacturersanddistributorsismainta

inedandmade

availablewhereneeded.

4.2.4.Advicefora


nt,format,requirements(depend

ingonthe

activities)a

ndprocedurestofollowinorderto

submitarequiredregistrationan

d/orapplication

foranestablishmentlicence.

4.2.5.Facilitydocumentation(e.g.sitemasterle,k

eypersonnel,qualicationofaresponsibleperson)

issubmittedaspartofarequiredregistration

and/orapplicationforanestablishmentlicenceand

isassessed

todemonstratethatthefacilityis

suitablefortheactivitiestobepe

rformed.

4.2.6.Renewalpe

riodsforanestablishmentlicence

and/orregistrationaredeneda

ndconsistentwith

mechanism

sofsurveillance.


21/40


4.

Lice

nsingand/orregistration

ofmanufacturersanddist

ributorsofplasma-derived

medicinalproducts


products


Rating*


Ma

in

crite

ria

Indicator

4.3.Sign

icantchangestoan

esta

blishmentlicenceand/or

registrationaresubmittedand

asse

ssedbytheNRApriorto

implementation.

R

R S

4.3.1.Changesar


hange.

4.3.2.Writtenguid



ofchangesand

documenta

tionrequired.

4.4.Com

pliancewithprinciples

ofGMPandGDPisassessed

aspartoftheestablishment

licen

singand/orregistration

proc

ess.

R

R R R

4.4.1.Compliance

withapplicableprinciplesofGMP

andGDPisaconditionformaint

ainingan

establishmentlicenceand/orregistrationandforapprovalofsignicantchanges.

4.4.2.NationalGM

PandGDPstandardsarepublish

edandareconsistentwithorbas

edonrecognized

standardsf

orthemanufacturinganddistribu

tionofplasma-derivedproducts.

4.4.3.Periodicins

pectionsaccordingtoGMPandGDPprinciplesarecarriedoutforsupervisionof

manufacturersanddistributorsofplasma-derivedproducts.Forinspectionscarriedoutabroad:

a.

thereisanagreementwithotherNRAsforexchangeofinspectionreportsand/or

certicates;or

b.

alistofreferencecountriesand/orag

encieswhosecerticatesanddec

isionsare

acce

ptedexist;or

c.

siteinspectionsarecarriedoutabroad

.

4.5.QMS

requirementsare

esta

blishedforallfunctions

performedbymanufacturers

and

distributors.

R

R

4.5.1.

TheessentialcomponentsforaQMSarecovered.

*R=required

;S=suggested


22/40

18

5.

App

rovalofbloodandbloodcomponents(productand/orprocessapproval)



Rating*


Ma

in

crite

ria

Indicator

5.1.Lega

lprovisionsexistfora

systemt

oensurequality,

safe

tyandefcacyofblood

and

bloodcomponents.

R

R R

5.1.1.Anapprovalsystemi

srequiredthatincludesanyimportedproducts.

5.1.2.TheNRAha

stheauthoritytoissueanapprov

al,tosuspenditandtowithdrawitiftheproductis

considered

unsafeordoesnotcomplywithre

gulatoryrequirements.

5.2.Asystemf

orensuringquality,

safe

tyandefcacyofblood

and

bloodcomponentsis

esta

blishedandoperational.

R

R R R S S R

5.2.1.Thecapabilityexiststoperforms

cience-basedriskassessmentsandriskmana

gement.

5.2.2.Specicatio

nsrelatedtoquality,safetyandefcacyofbloodandbloodcompon

entsaredened

andunderthesupervisionoftheNRA.

5.2.3.Thecritical

standardsforproductmanufacturingarelegallybindingandincludedonorselection,

laboratorytesting,componentpreparation,storage,issuance,tracking,tracing,recordkeeping,

andsafedisposalofunitsnotmeetingspeci

cationsforuseintransfusion.

5.2.4.Procedures

torecognizeexceptionsareclearlydened(e.g.ifcollectedbyame

dicalpractitioner

foraspeci

ctherapeuticpurpose).

5.2.5.Requirementsandstandardsarebasedonin

ternationallyrecognizedstandard

s.

5.2.6.Plasmaforfractionationmeetsinternationallyrecognizedstandards.

5.3.Donorselectionanddeferral

crite

riaareestablishedas

appr

opriatetotheintended

useofthecomponent.

R

R R

5.3.1.Donorselectionanddeferralcriteria(temporaryandpermanentdeferrals)take

intoaccountthe

healthofth

edonorandthesafetyandsuitab

ilityofthedonationconsistentwithcurrentscience.

5.3.2.Mechanism

sforregularlyreviewingandupda

tingthedonorselectionanddeferralcriteriaarein

placeandtakeintoconsiderationthedevelop

mentofissuesthatmighthavea

negativeimpacton

thequalityandsafetyofbloodandbloodcom

ponents,e.g.epidemiologicalsitu

ationoremerging

diseases.


23/40


5.

App

rovalofbloodandbloodcomponents(productand/orprocessapproval)



Rating*


Ma

in

crite

ria

Indicator

5.4.Tran

smissible-diseasetesting

requ

irementsareestablished

asappropriatetotheintended

useofthecomponent.

R

R R

5.4.1.Mechanism

sforregularlyreviewing(e.g.byqualiedexpertsinepidemiology)a

ndupdatingthe

testingrequ

irementsareinplace.

5.4.2.Epidemiologicaldataregardingtheprevalenc

eandincidenceofinfectiousdise

asemarkersin

blooddonorsareavailableandregularlyupdated.

5.5.Labe

llingrequirementsare

esta

blished.

R

R R S S

5.5.1.Eachblood

componenthasauniqueandclearidentierandisfullytraceable.

5.5.2.Originallab

ellingandsignicantamendmentsaresubmittedtotheNRAandas

sessedpriorto

implementa

tion.

5.5.3.Productlab

ellingincludesinformationonthe

risksandbenetsofproductuse.

5.5.4.Requirementsarebasedoninternationallyre

cognizedstandards.

5.6.Ana

pprovalsystemf

orblood

and

bloodcomponentsis

oper

ational.

R

R S S S S

5.6.1.Assessmen

texiststhatincludesrelevantaspectsofquality,safetyandwherea

pplicableefcacy

ofbloodan

dbloodcomponents.

5.6.2.Guidelinesforapplicantsexistonthecontent

,formatandprocedurestofollow

inordertosubmit

anapplicationforapproval.

5.6.3.Writtenguid

elinesforassessmentofapplicat

ionsareimplemented.

5.6.4.Appealproc

eduresareinplace.

5.6.5.Anassessm

entreportispreparedandusedasareferencefordecision.

5.7.Ther

eisarequirementfor

man

ufacturingchangestobe

subm

ittedandassessedbythe

regu

latoryauthority.

S

S S

5.7.1.

Writtenguid



ofchangesand

documenta

tionrequired.

5.7.2.

Writtenguid

elinesforassessmentexistbasedonthetypeofchange(e.g.signicant,notiable,

administrative).

5.8.Appropriateassessment

expe

rtiseisavailable.

R

R S

5.8.1.Accesstoexpertswithrelevantqualications

andexperience(internaland/ore

xternal)isassured

forassessm

entofbloodandbloodcomponents(preclinical,clinicalandquality

data).

5.8.2.Writtenproceduresforselection,management,anduseofexternalexpertsare

inplace.

*R=required

;S=suggested


24/40

20

6.

App

rovalofplasma-derivedmedicinalproducts


products


Rating*


Ma

in

crite

ria

Indicator

6.1.Lega

lprovisionfora

marketingapprovalsystem

existstoensurethequality,

safe

tyandefcacyofplasma-

derivedproducts.

R

R R

6.1.1.Marketinga

pprovalisrequiredforplasma-derivedproducts,includingimported

products.

6.1.2.TheNRAha

stheauthoritytoissuemarketing

approvalforplasma-derivedprod

ucts,tosuspend

anapprovalandtowithdrawitiftheproductisconsideredunsafeordoesnotc

omplywith

regulatoryr

equirements.

6.2.Amarketingapprovalsystem

forp

lasma-derivedproductsis

esta


R

R R R R R S S S

6.2.1.Thecapabilityexiststoperforms


gement.

6.2.2.Thereisarequirementfortheapplicanttoincludealistofallthebloodestablishmentsthat

collectedth

eplasmausedintheproduct.

6.2.3.Specicatio

nsrelatedtothequalityandsafet

yofplasmaforfractionationared

enedandunder

thesupervisionoftheNRA.

6.2.4.Selection,d

eferralandtransmissible-disease

testingrequirementsforplasmadonorsare

established

(seeCriteria5.3and5.4).

6.2.5.Advicefora


nt,formatandprocedurestofollo

winorderto

submitana

pplicationformarketauthorizatio

n.

6.2.6.Appealproc

eduresareinplace.

6.2.7.

Thenationa

lcontrollaboratory(NCL)isinvolv

edinassessmentasappropriate.

6.2.8.Writtenproceduresforselection,management,anduseofexternalexpertsare

available.


25/40


6.

App

rovalofplasma-derivedmedicinalproducts


products


Rating*


Ma

in

crite

ria

Indicator

6.3.Asse

ssmentofapplications

form

arketauthorizationis

implemented.

R

R R S S S

6.3.1.Assessmen

tofquality,safetyandefcacyofplasma-derivedproductsisperformed,including

assessmen

toftheeffectivenessofmeasures

usedbymanufacturerstoinactiv

ateand/orremove

transmissib

lepathogens.

6.3.2.Procedures

torecognizeexceptionsareclearlydened.

6.3.3.Assessmen

treportsarepreparedanduseda

sareferencefordecision-making.

6.3.4.WrittencriteriaexistforrecognitionofotherN

RAsreportsand/ordecisions(ifapplicable).

6.3.5.Writtenguid

elinesforassessmentofapplicat

ionsareavailable.

6.4.Ther

eisarequirementfor

chan

gestobesubmitted

and

assessedbythe

regu

latoryauthoritypriorto

impl

ementation.

R

R S S

6.4.1.Changesar


hange.

6.4.2.Writtenguid



ofchangesand

documenta

tionrequired.

6.4.3.Writtenguid

elinesforassessmentareavailab

lebasedonthetypeofchange.


expe

rtiseexists.

R

R

6.5.1.Accesstoexperts(internaland/orexternal)forassessmentofplasma-derivedproducts

(preclinical,clinicalandqualitydata)isassured,andlistsexistofstaffand/orexpertswith

relevantqu

alicationsandexperience.

6.6.Clea

randcomprehensive

informationonauthorized

plasma-derivedproductsis

available.

R

R R S

6.6.1.Theproductinformationmadeavailableisap

proved.

6.6.2.Asummary

ofproductcharacteristics(SPC)o

requivalentinformationisavailab

leforallplasma-

derivedproducts.

6.6.3.SPC-likeinformationisregularlyupdatedand

publiclyavailable.

6.7.Alis

tofauthorizedproducts

exists.

R

R S

6.7.1.

Alistofauthorizedproductsismadeavailablewhereneeded.

6.7.2.

Alistofauthorizedproductsispubliclyavailable.

*R=required

;S=suggested


26/40

22

7.

Reg

ulatoryoversightofassociatedsubstancesandmedicaldevicesincludinginvitrodiagnostics

Applicabletoassociatedsubstancesandmedicaldevicesincludinginvitro

diagnostics


Rating*


Ma

in

crite

ria

Indicator

7.1.Lega

lprovisionsexistfor

regu

latoryoversightof

therelevantassociated

subs

tancesandmedical

devices.

R

R R R R

7.1.1.

Premarketreviewandapprovalisrequiredforinvitrodiagnosticsandscreeningtestkitsusedfor

donorselec

tion,testingofbloodandbloodcomponentsfortherapeuticuse,an

d/orforfurther

manufacturingofplasma-derivedproducts(e

.g.testsfordonorhaemoglobin,te

stsforinfectious

diseasema

rkers).

7.1.2.

Premarketreviewandapprovalisrequiredformedicaldevicesinvolvedinthem

anufactureof

bloodcomp

onents(e.g.apheresismachines)

.

7.1.3.

Premarketreviewandapprovalisrequiredforassociatedsubstances(e.g.anticoagulants,

additivesolutions).

7.1.4.

TheNRAha

stheenforcementpowertoinvestigateandactagainstmarketedproductsand

involvedcompaniesthatdonotcomplywitht

herequirements.

7.2.Systemsforpremarket

revie

wandapprovalof

asso

ciatedsubstancesand

relevantmedicaldevicesare

esta


R

R R R R S

7.2.1.

Thecapabilityexiststoperforms


gement.

7.2.2.

Premarketreviewincludesanassessmentof

quality,safetyandeffectiveness.

7.2.3.

Advicefora

pplicantsoncontent(datarequirements),format,andproceduresforsubmittingan

application

exists.

7.2.4.

Ifdecentralized,rolesandresponsibilitiesofthebodiesinvolvedaredenedan

dthereisa

mechanism

forinformationexchangebetwee

nthecontrolauthorityandtheNR

A.

7.2.5.

Writtenguidelinesforproductassessmentse

xist.


expe

rtiseisavailable.

R

R S

7.3.1.

Accesstoe

xpertswithrelevantqualications

andexperience(internaland/ore

xternal)for

assessmen

tofbloodandbloodcomponents

(preclinical,clinicalandqualityda

ta)isestablished.

7.3.2.

Writtenproceduresforselection,managementanduseofexternalexpertsare

inplace.

*R=required

;S=suggested


27/40


8.

Acc

esstoalaboratoryindependentofmanufacturers

Applicabletoblood,

bloodcomponents,





Rating*


Ma

in

crite

ria

Indicator

8.1.Acce

ssbytheNRAtoa

nationalcontrollaboratory

(NCL

)independentof

themanufacturer(s)is

esta

blished.

R

R R R S

8.1.1.Policyando

perationalagreementsareinplaceforuseofanyexternalcontrollaboratories.

8.1.2.Adequatete

stingplans,testingproceduresandrelateddocumentationareavailable.

8.1.3.Responsibilitiesfortestinginthepre-licensingandpost-licensureperiodareclearlydened.

8.1.4.TheNCLisinvolvedindeningthespecicationsandanalyticalmethodsduringassessmentof

marketinga

uthorizations.

8.2.Appropriateorganization

and

nancialsupportfrom

man

agementensurethe

impl

ementationofadequate

testingprogrammes(including

docu

mentation)using

appr

opriateequipment,and

qualiedandexperienced

staff.

R

R R R R S S

8.2.1.Writtentest

ingproceduresandrelateddocum

entationareinplace.

8.2.2.Are-testpo

licyisestablished.

8.2.3.Astrategyfortheintroductionandvalidationofneworimprovedtestsexists.

8.2.4.Reportinga

ndissuancetotheNRAofallcriticalresultsincludingoutofspecicationshandlingis

implemente

d.

8.2.5.Documentcontrolisestablished.

8.2.6.SOPs,testprocedures,samplehandlinganddatamanagementareorganized.

8.3.Ane

xternallyaccredited

qual

itymanagementsystem

(QMS)isinplaceinthe

labo

ratory.

S

S S

8.3.1.Aqualitypo

licyandqualitymanualexist.

8.3.2.Aqualiedqualitymanagerisdesignatedand

aQMSisinoperation.


28/40

24

8.

Acc


Applicabletoblood,

bloodcomponents,





Rating*


Ma

in

crite

ria

Indicator

8.4.Equipmentdocumentationis

inpl

ace.

R

R R S S S

8.4.1.Calibration

andmaintenanceschedulesarea

vailable.

8.4.2.Validationp

rotocolsareavailable.

8.4.3.Equipment

selectionprocessesaredocumen

tedanduniqueequipmentidenti

cation(ID)isin

place.

8.4.4.Commissioningrecords(i.e.installationandq

ualication)areavailable.

8.4.5.Operationm

anualsandlogsexist.

8.5.Hum

anresourcemanagement

isim

plemented.

R

R S S

8.5.1.Qualiedan

dexperiencedstaffmemberswithdenedresponsibilitiesandcom

petenciesare

available.

8.5.2.Astafftrain

ingplanisdevelopedandimplem

ented.

8.5.3.Theimpact

ofstafftrainingismonitored.

8.6.Ana

uditandreviewsystem

exists.

S

S S S

8.6.1.Comprehen

siveinternalauditandreviewsystemsareinplace.

8.6.2.Documenta

tionofactionstakenasaresulto

fauditsisavailable.

8.6.3.Thelaboratoryisauditedbyexternalorganiza

tions.

8.7.Avalidationpolicyforthe

intro

ductionoftestsis

impl

emented.

R

R R

8.7.1.

Avalidation

programmefornon-compendialt

estsisavailable.

8.7.2.

Procedures

existfortransfersofvalidatedme

thods(i.e.betweenthemanufacturerandthe

regulator).

8.8.Age

neralsafetyprogramme

exists.

R

R R S

8.8.1.Listsofhaz

ardoussubstancesareavailable.

8.8.2.Responsiblestaffmembersaredesignated.

8.8.3.Afullsafety

programmeexists.


29/40


8.

Acc


Applicabletoblood,

bloodcomponents,





Rating*


Ma

in

crite

ria

Indicator

8.9.Apo

licyforuseofreference

stan

dardsandreagentsexists.

R

R R R S

8.9.1.Accesstoa

catalogue(list,specicationsand

sources)andregularsupplysyste

mf

orstandards

andreferen

cematerialsisimplemented.

8.9.2.Appropriate

useofreferencematerialsisensured.

8.9.3.Useofreag

entsofassuredquality(e.g.grade

s)isensured.

8.9.4.

Asystemis

inplacetoestablishandqualifyn

ationalreferencestandardsininte

rnationalunits

(IUs).

8.10.Dat

atrendsaremonitored

and

analysed.

R

R R S

8.10.1.Resultsofr

eferencematerialsaremonitored.

8.10.2.Resultsare

comparedwiththoseofthemanu

facturer.

8.10.3.Laboratory

resultsaremonitoredandtrendsareassessed.

8.11.Participationininternational

pro

ciencyschemesand

collaborativestudiesis

org

anized.

S

S

8.11.1.Regularpar

ticipation(dateoflastparticipatio

n,scope,product(s),coordinating

institution)is

organized.

8.12.Reg

ulatoryoutcomeof

testingisanalysedand

use

dasabasisfordecision-

making.

R

R R R

8.12.1.Compliance

withauthorizedspecicationsischecked.

8.12.2.Resultsare

comparedwiththoseofthemanu

facturer.

8.12.3.Correctivea

ctionisinitiatedincaseofnon-co

mpliance.

*R=required

;S=suggested


30/40

26

9.

Con

trolofclinicaltrials

Applicabletoblood,

bloodcomponents,





Rating*


Ma

in

crite

ria

Indicator

9.1.Applicablelegalprovisionfor

theregulationofbiomedical

rese

archinhumansubjects

exists.

R

R R R R R

9.1.1.Anauthorizationsystemf

orclinicaltrialsisre

quired.

9.1.2.Thescopeandrequirementsforregulationofclinicaltrialsaredened.

9.1.3.TheNRAha

stheenforcementpowerforthea

uthorization,suspensionandwith

drawalofclinical

trials.

9.1.4.Legalprovisionsareinplacetoassureaneth

icaloversightofclinicaltrials.

9.1.5.Compliance

withprinciplesofgoodclinicalpr

actice(GCP)ismandatory.

9.2.Asystemf

orauthorizationof

clinicaltrialsisoperational.

R

R R R S S S S

9.2.1.Asystemis

establishedforclinicaltrialasses

smentandauthorization.

9.2.2.Aninspectionsystemi

sestablishedtoverifycompliancewiththeprinciplesofGCP.

9.2.3.Expertiseis

availablefromw

ithinoroutsidetheNRA.

9.2.4.Writtenguid

elinesforassessmentofclinicaltrialsandchangesareimplemented.

9.2.5.Writtenguid

elinesandformsonthedatarequirements,theformatandproceduresforsubmitting

aclinicaltrialapplicationareavailabletospo

nsors.

9.2.6.Provisionfo

rscienticadvice(e.g.preclinical

andclinical)onthedesignofclinicaltrialsorissues

relatedtothesubmissionofappropriatedata

isinplace.

9.2.7.

Therearew

rittenguidelinesforGCP.


31/40


9.

Con

trolofclinicaltrials

Applicabletoblood,

bloodcomponents,





Rating*


Ma

in

crite

ria

Indicator

9.3.Data

requirementsforclinical

trial

applicationsaredened.

R

R R R

9.3.1.Production

andqualitycontroloftheclinicalc

andidatematerial(e.g.productch

aracterization,

laboratoryspecimens)areincluded.

9.3.2.Provisionfo

rpreclinicaldataexists.

9.3.3.Assessmen

toftheclinicaltrialprotocolwithrespecttopatientsafetyandinformedconsentis

performed.

9.4.Assu

ranceofethicaloversight

exists.

R

R S S S

9.4.1.

Asystemof

independentethicalreviewanda

pprovalexistsinaccordancewiththeprinciplesof

GCP.

9.4.2.Ethicscommittees(e.g.theInstitutionalReviewBoard)areformallydened,inc

ludingtheir

composition.

9.4.3.Theethicscommitteesincludemembersexte

rnaltotheconcernedinstitution.

9.4.4.Therolesanddutiesofethicscommitteestooverseeclinicaltrialsareoutlined.

*R=required

;S=suggested


32/40

28

10.

Systemf

orlotreleaseofplasm

a-derivedmedicinalproducts


productsanddonorscreeningtests


Rating*


Ma

in

crite

ria

Indicator

10.1.Leg

alprovisionsforofcial

lot

releasecerticationarein

place.

R

R R S

10.1.1.

TheNRAhastheauthoritytoissuelotrelea

secerticatesandtheenforcementpowerto

suspendorrevokelotrelease.

10.1.2.

TheNRAhasthelegalauthoritytoperformlotreleaseand/orhaveinplacea

policyandcriteria

foracceptanceoflotreleaseperformedbyanotherNRA(e.g.alotreleasecerticatefromt

he

countryoforigin).

10.1.3.

Writtencr

iteriaforexemptionfroml

otreleaseexist.

10.2.Alotreleasesystemi

s

est

ablishedandoperational.

R

R R R R R R R S

10.2.1.

Lotreleas

eprotocolsandproceduresareestablishedand/oracceptanceoflotrelease

performedbyanotherNRAisinplace.

10.2.2.

Lotreleas

eisbasedataminimumo

nreviewofsummarylot-specicdata.

10.2.3.

Qualiedstaffmembers(i.e.staffwithrelevantqualications,trainingandex

perience)are

availabletoperforml

otrelease.

10.2.4.

Testingpo

licyandtestprotocolsincludinga

cceptancecriteriaaredened.

10.2.5.

Recordso

nlotreleasearemaintained.

10.2.6.

Proceduresforcommunicationwiththepro

ductmanufactureraredened.

10.2.7.

Writtenproceduresandguidelines(includin

gtemplatesofcerticates),check

lists,and/or

SOPsare

developedandusedtoreviewsum

marylotprotocolsandareimplementedforthelot

releaseprocess.

10.2.8.

Testingpr

oceduresareexternallyaccredited.


33/40


10.

Systemf

orlotreleaseofplasm

a-derivedmedicinalproducts


productsanddonorscreeningtests


Rating*


Ma

in

crite

ria

Indicator

10.3.Aqualitymanagement

sys

temforofciallotrelease

isimplemented.

R

R S S

10.3.1.

Thelaboratorythatperformslotreleasewit

hinorfortheNRAcomplieswithC

orefunction8.

10.3.2.

Appropria

tedatacollectionandanalysis(e.g.lot-to-lotconsistency,trendanalysis)is

implemen

ted.

10.3.3.

Continualreviewandscienticdialogueexistwiththemanufacturersandpro

ductreviewexperts

onissues

ofqualitytestresults.

10.4.Acc

esstoproduct-related

doc

umentationtoguide

par

ticularareasofscrutinyin

lotreleaseispossible.

R

R R R R

10.4.1.

Approved

relevantmarketingauthorizationanditsupdatesareavailable.

10.4.2.

Accessto

complaintsandadverseevent(AE

)reportsispossible.

10.4.3.

Accessto

themanufacturersbatchrecords

ispossible.

10.4.4.

Accessto

inspectionreportsispossible.

*R=required

;S=suggested


34/40

30

11.

Reg

ulatoryinspectionsanden

forcementactivities

Applicabletoblood,

bloodcomponents,





Rating*


Ma

in

crite

ria

Indicator

11.1.Leg

alprovisionexiststo

inspectpremiseswhere

reg

ulatedactivitiesare

per

formedinordertoassess

and

enforcecompliance

withtheapplicablelaws,

reg

ulationsandstandards.

R

R R R R R R

11.1.1.

Amandat

eexistsforinspectionsbytheNRAandenforcementofcompliance

withprinciplesof

GMP,GDP

andotherstandards.

11.1.2.

Applicablestandardsandpracticesarede

nedinlegalprovisions.

11.1.3.

TheNRAhastheauthoritytotakeenforcem

entactionagainsttheaccountablecompaniesor

personsthatarenotincompliance.

11.1.4.

TheNRAhastheauthoritytosampleproducts,manufacturingmaterialsandrecordsif

necessary.

11.1.5.

TheNRAhastheauthoritytorecallproducts.

11.1.6.

Provisionsexistforconictofinterestandc

ondentiality.

11.2.Inspectionandenforcement

sys

temsareestablishedand

ope

rational.

R

R R R R R

11.2.1.

Establishedpoliciesandprogrammesexist

forconductinginspectionsofallregulatedactivities.

11.2.2.

Aninspec

tionplanexistswithadequatehumanandnancialresourcesforco

nducting

inspectionsatappropriateintervals.

11.2.3.

TheNRAmaintainslesofeachinspection,includingtheinspectionreportandnaldecisions

taken.

11.2.4.

Thereisa

nestablishedprocessforappropr

iateregulatoryactiontoaddressinspectional

ndings(e.g.recallofproducts,amendedlicences).

11.2.5.

Ifthemec

hanismi

sadopted,provisionsexistforacceptanceofexternalinspectoratesaccording

tointerna

tionallyrecognizedstandards.


35/40


11.

Reg

ulatoryinspectionsanden

forcementactivities

Applicabletoblood,

bloodcomponents,





Rating*


Ma

in

crite

ria

Indicator

11.3.Inspectorswithappropriate

exp

ertiseandqualications

are

available.

R

R R S

11.3.1.

Inspectorshavetheappropriateexpertisea

ndtrainingtoconductinspectionsofblood

establishments,andmanufacturersanddis

tributorsofplasma-derivedprodu

cts.

11.3.2.

Trainingo

finspectors

includes

specic

aspe

cts

related

to

the

activities

ofrele

vant

establishments.

11.3.3.

Useofateama

pproachispossibleinorder

toincludespecializedknowledge

andexpertisein

specicproductswhereneeded.

11.4.Aqualitymanagement

systemi

simplementedthatis

con

sistentwithinternational

prin

ciplesforpharmaceutical

and

relatedinspectorates.

R

R S S

11.4.1.

Writtenproceduresexistforconductinginspections(inspectionmanual)andfollowing-upon

decienci

esand/orviolations.

11.4.2.

Anestablishedprocedure(e.g.periodicinte

rnalandexternalaudits)existsto

monitorthe

inspectionprocess.

11.4.3.

Monitorin

goftimelinesandindicatedactionsisimplemented.

11.5.Arecallsystemexistswith

me

chanismstoensurethe

pro

perdispositionofblood,

bloodcomponents,plasma-

der

ivedproducts,associated

sub

stances,andmedical

dev

icesincludinginvitro

diagnostics.

R

R R R R

11.5.1.

Policyand

proceduresforarecallsystemin

cludingproductdispositionexist.

11.5.2.Therecall

systemi

sbasedondenedactionanddocumentedcommunicationtotheappropriate

levelofthedistributionsystem.

11.5.3.Afeedbac

kmechanismexiststoconrmtha

tappropriateaction(includingde

structionwhen

necessary

)hasbeentakenatallappropriatelevels.

11.5.4.Fulllottra

ceabilityisinplace.

*R=required

;S=suggested


36/40

32

12.

Vigilancesystems

Applicabletoblood,

bloodcomponents,





Rating*


Ma

in

crite

ria

Indicator

12.1.Leg

alprovisionsfora

nat

ionalvigilancesystem

exist.

R

R R R

12.1.1.

TheNRAhasalegalmandateandenforcem

entpowerformandatoryreportin

gelementsofthe

nationalv

igilancesystem.

12.1.2.

TheNRAhastheauthoritytospecifyreportingofadverseevents(AEs)andad

versereactions

(ARs)with

inthenationalvigilancesystem.

12.1.3.

Authorityexiststorequirethemarketingauthorizationholdertoperforma

specicstudyof

safetyand/oreffectivenessinthepost-marketingperiod.

12.2.Nationalvigilancesystems

for

themonitoringand

ma

nagementofAEand

AR

areestablishedand

ope

rational.

R

R R S S S

12.2.1.

Rolesand

responsibilitiesofthekeyparties

,theNRA,andsurveillancestaffinvolvedinAEand

ARmonitoringandmanagementactivitiesa

reclearlydenedanddocumente

d.

12.2.2.

Guidelinesexistandarepublishedandaccessible(i.e.distributedoravailablewhenneeded)to

allstaffin

volvedinAEandARsurveillance.

12.2.3.

Guidelinesincludethefollowing:

a.objectivesofthesystem;

b.a

listofAEsandARstobereported;

c.ca

sedenitionsforallAEsandARs

tobereported;

d.in

formationonhowtoreportAEsan

dARsforallblood,bloodcompon

ents,plasma-

derivedproducts,associatedsubsta

nces,andmedicaldevicesinclud

inginvitro

diagnostics(i.e.whoshouldreport,

how,whereandwhenreportssho

uldbesent);

e.th

eprocessforanalysingdataandprovidingfeedbacktorelevantstaffandkeyparties;

f.th

eprocessforinvestigatingandrespondingtoseriousAEsandARs(

includingwho

sh

ouldbeinchargeoftheinvestiga

tion);

g.th

eprocessforinformingpatients,parents,thecommunityandcountry(whererelevant)

ofthendingsofaninvestigationandrelevantactions.

12.2.4.

Astandar

dizedreportingformexistswithco

mprehensiveinformationtomonitorAEsandARs.

12.2.5.

Asystemisestablishedforprovidingperiod

icfeedbackonAEsandARs,inclu

dingsummaryand

specicin

vestigationreportsfromt

henatio

naltoalllevels(includinghealthfacilitylevel).


37/40


12.

Vigilancesystems

Applicabletoblood,

bloodcomponents,





Rating*


Ma

in

crite

ria

Indicator

12.3.Gui

danceonAEandAR

monitoringandmanagement

isp

rovidedtoappropriate

staff.

S

S

12.3.1.

GuidelinesandtemplatesonAEandARrep

ortingandmonitoringareprovide

dtoappropriate

staffdealingwithAEandAR.

12.4.The

reisdemonstrated

cap

acitytodetect,

investigateandtakeaction

reg

ardingsignicantAEsand

ARs.

R

R R R R R S

12.4.1.

TheNRAisregularlyinformedofdatareleva

nttothequalityandsafetyofbloodproducts

including:

a.bloodtransfusionsafety;

b.transmissiblediseasesurveillancedata;

c.devicefailures.

12.4.2.

Manufact

urersarerequiredtoinformt

heN

RAofanynewsafetyissuesorma

rketingand/or

regulatorydecisionstakeninothercountrie

s.

12.4.3.

Proceduresforinitiatingcorrectiveand/orregulatoryaction(e.g.recall)areavailable.

12.4.4.

Thereisd

ocumentedcapacitytoinvestigate

AEsandARs,forexample:

a.ro

utinereportingofAEsandARsac

cordingtoestablishedguidelinesand/orSOPs;

b.a

clearunderstandingandadequatetrainingamongkeypartiesofrespectiverolesand

re

sponsibilities;

c.accesstoresources(personnel,lab

oratory)toconductcomprehensiveinvestigations.

12.4.5.

Caseinve

stigationsaretimelyandcomplete,forexample:

a.timelinesareestablishedforpromp

tinvestigationandpreliminaryrep

ortingrelatedto

se

riousadversereactions;

b.in

vestigationisthoroughandndingsareclearlydescribed.

12.4.6.

Thereisa

demonstratedreportingsystem(activeorpassive,sentineloruniversal)with

satisfacto

rysensitivity,forexample:

a.annualnumberofreports;

b.re

portingrate;

c.breakdownofreportsbytypesofAE

,agegroup,districtsetc.

*R=required

;S=suggested


38/40

34

13.

Ens

uringtraceabilityandreco

rdkeepingbymanufacturersforallregulatedproduc

ts

Applicabletoblood,

bloodcomponents,





Rating*


Ma

in

crite

ria

Indicator

13.1.The

NRAensuresthat

sta

ndardsfortraceability

and

recordkeepingare

inp

laceforallaspects

ofm

anufacturingand

distribution.

R

R R

13.1.1.

Arequirementexistsformanufacturerstoimplementmethodsandmaintainrecordsthatenable

traceability,including:

a.

form

anufacturersofbloodproducts,traceabilityfromd

onortorecipientandviceversa;

b.

ensuringtheintegrityofmanufacturin

grecordsandcompletenessofdistributionrecords.

13.1.2.

ProceduresforrecordkeepingandretentionperiodsdenedbytheNRAarea

vailable.

*R=required

;S=suggested

14.

Inte

rnationalcooperation

Applicabletoblood,

bloodcomponents,





Rating*


Ma

in

crite

ria

Indicator

14.1.An

ationalpolicytofacilitate

internationalcooperation

and

harmonizationis

imp

lemented.

S

S S S

14.1.1.

Anationalpolicyand/orstrategyoninterna

tionalinteractionsexist,e.g.inform

ationsharingon

productapprovals,safetydataandpolicyin

itiatives.

14.1.2.

Agreemen

tsexistbetweentheNRAandothe

rinternationalorganizationsandregulatory

authoritie

s.

14.1.3.

TheNRAparticipatesininternationalharmo

nizationinitiativesandforums.

14.2.Sharingofriskinformation

withinternational

org

anizationsandother

reg

ulatoryauthoritiesis

imp

lemented.

R

R S S S S

14.2.1.

Abilityiss

hownbytheNRAtoparticipatein

internationalriskmanagementeffortswhen

needed.

14.2.2.

TheNRAhastheabilitytoengageininterna

tionalriskassessmentwhenneeded,e.g.accessto

epidemiologicaldata,expertiseinriskassessment.

14.2.3.

Thecapacityorexpertisetoaccessepidemiologicaldataandformallyassess

risksisavailable.

14.2.4.

Documen

tedproceduresforthetimelysharingofriskinformationinternationallyexist.

14.2.5.

Recordsa

rekeptofriskinformationthatha

sbeenexchanged.

*R=required

;S=suggested


39/40

Bibliography

WHO requirements for the collection, processing and quality control of blood, blood components andplasma derivatives. In: WHO Expert Committee on Biological Standardization. Forty-third report. Geneva,World Health Organization, 1994 (WHO Technical Report Series, No. 840, Annex 2).

WHO guidelines on viral inactivation and removal procedures intended to assure the viral safety of humanblood plasma products. In: WHO Expert Committee on Biological Standardization. Fifty-second report.Geneva, World Health Organization, 2004 (WHO Technical Report Series, No. 924, Annex 4).

WHO recommendations for the production, control and regulation of human plasma for fractionation.In: WHO Expert Committee on Biological Standardization. Fifty-sixth report. Geneva, World HealthOrganization, 2007 (WHO Technical Report Series, No. 941, Annex 4).

Recommendations of the 14th International Conference of Drug Regulatory Authorities (ICDRA),Singapore, 30 November3 December 2010. WHO Drug Information Vol. 25, No. 1, 2011 (http://www.who.int/medicines/publications/druginformation/en/index.html).

Resolution WHA63.12. Availability, safety and quality of blood products. In:

who_oms - 2012 - assessment criteria for national blood regulatory systems

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