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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 WHO Blood 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.

Assessment criteriA for nAtionAl blood regulAtory systems 01

Contents

Authors and Acknowledgements .....................................................................................................................................................................................02Abbreviations ....................................................................................................................................................................................................................................................03Glossary ......................................................................................................................................................................................................................................................................04Introduction......................................................................................................................................................................................................................................................... 07

Section A. Essential elements ............................................................................................................................................................................................. 091. 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 .............................................................................................................................................................................................................10Applicable to blood, blood components, plasma-derived medicinal products, associated substances, and medical devices including in vitro diagnostics

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

Applicable to blood and blood components including plasma for fractionation

4. Licensing and/or registration of manufacturers and distributors of plasma-derived medicinal products ...............16Applicable to plasma-derived medicinal products

5. Approval of blood and blood components (product and/or process approval) ...................................................................................18Applicable to blood and blood components including plasma for fractionation

6. Approval of plasma-derived medicinal products ..............................................................................................................................................................20Applicable to plasma-derived medicinal products

7. Regulatory oversight of associated substances and medical devices including in vitro diagnostics .............................22Applicable to associated substances and medical devices including in vitro diagnostics

8. Access to a laboratory independent of manufacturers ..............................................................................................................................................23Applicable to blood, blood components, plasma-derived medicinal products, associated substances, and medical devices including in vitro diagnostics

9. Control of clinical trials ..........................................................................................................................................................................................................................26Applicable to blood, blood components, plasma-derived medicinal products, associated substances, and medical devices including in vitro diagnostics

10. System for lot release of plasma-derived medicinal products .............................................................................................................................28Applicable to plasma-derived medicinal products and donor screening tests

11. Regulatory inspections and enforcement activities .....................................................................................................................................................30Applicable to blood, blood components, plasma-derived medicinal products, associated substances, and medical devices including in vitro diagnostics

12. Vigilance systems ..........................................................................................................................................................................................................................................32Applicable to blood, blood components, plasma-derived medicinal products, associated substances, and medical devices including in vitro diagnostics

13. Ensuring traceability and record keeping by manufacturers for all regulated products .............................................................34Applicable to blood, blood components, plasma-derived medicinal products, associated substances, and medical devices including in vitro diagnostics

14. International cooperation .....................................................................................................................................................................................................................34Applicable to blood, blood components, plasma-derived medicinal products, associated substances, and medical devices including in vitro diagnostics

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

02

Authors and AcknowledgementsThe drafting group was formed of Members of the WHO Blood Regulators Network (BRN) and the WHO Blood Products and Related Biologicals programme, Quality Assurance and Safety: Medicines, World Health Organization:

Dr I Prosser, Dr G Smith, Therapeutic Goods Administration, Australia; Dr P Ganz, Dr F Agbanyo, Health Canada, Canada; Dr P Zorzi, Dr I Sainte-Marie, AFSSAPS, France; Professor R Seitz, Dr M Heiden, Paul Ehrlich Institut, Germany; Dr C Schärer, 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 this tool. The first 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 supported for consideration by WHO Member States. Over 90 national regulatory agencies were represented in the Conference.

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

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

Blood Bank Directorate, Ministry of Public Health, Afghanistan; Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (ANMAT), Argentina; Scientific Center of Drug and Medical Technologies Expertise (SCDMTE), Armenia; European Commission, Directorate General for Health and Consumer Affairs (SANCO), Belgium; Gerência Geral de Sangue, outros Tecidos, Células e Órgãos, Agência Nacional de Vigilância Sanitária (ANVISA), Brazil; Department of Drug Registration, State Food and Drug Adminstration, China (People’s Republic of); Instituto Nacional de Salud (INS) and Instituto Nacional de Vigilancia de Medicamentos y Alimentos (INVIMA), Ministerio de la Protección Social, Colombia; Centro para el Control Estatal de la Calidad de los Medicamentos (CECMED), Cuba; Danish Medicines Agency, Denmark; The Minister’s Technical Office, Ministry of Health, Egypt; Laboratory Services Department, Food and Drugs Board, Ghana; Central Drugs Standard Control Organization, Ministry of Health and Familiy Welfare, India; National Agency of Drug and Food Control (NADFC), Indonesia; Food and Drug Organization, Iran (Islamic Republic of); Division of Blood and Blood Products, Ministry of Health, Labour and Welfare, Japan; National Blood Service, Ministry of Health, Latvia; Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS), Mexico; Department of Health and Social Affairs, Micronesia (Federated States of); Department of Drug Administration (DDA), Ministry of Health and Population, Nepal; Medicines Evaluation Board, the Netherlands; Centro Nacional de Diagnóstico y Referencia (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 Salud Pública y Bienestar Social, Paraguay; Centre for Product Registration, National Pharmaceutical Control Bureau, 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, Ministère de la Santé, 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 Medical Sciences, Ministry of Public Health, Thailand; Sharjah Blood Transfusion & Research Centre, Ministry of Health, United Arab Emirates.

Assessment criteriA for nAtionAl blood regulAtory systems 03

All comments received were reviewed by the drafting group and a final proposed version was submitted to the 62nd Expert Committee on Biological Standardization (ECBS). Special thanks are due to the Members of 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 Griffiths, Biologics and Genetic Therapies Directorate, Health Canada, Canada; Mrs T Jivapaisarnpong, Institute of Biological Products, Department of Medical Sciences, Ministry of Public Health, Thailand; Dr H Klein, National Institutes of Health, USA; Dr P Minor, National Institute for Biological Standards and Control, UK; Dr F M Moftah, National Blood Transfusion Service, Ministry of 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 (People’s Republic of).

For further information contact:Programme Manager

Blood Products and Related Biologicals Quality Assurance and Safety: Medicines

Department of Essential Medicines and Health Products World Health Organization

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

Assessment criteriA for nAtionAl blood regulAtory systems 05

GlossaryThe WHO Expert Committee on Biological Standardization adopted the following definitions for the purpose of this report.

ApprovalA decision to authorize marketing of a drug by a national regulatory authority. The mechanism by which a regulatory authority ensures that there is compliance with regulatory requirements and standards that assure quality, safety and efficacy for all blood products and/or processes and establishments involved in collecting blood donations and/or manufacturing blood products. A regulatory approval is generally a precondition for marketing of a blood product. Associated medical devicesAll devices involved in donor testing and/or manufacturing activities.

Associated substances and materialsAll 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 be prepared by various separation methods and under such conditions can be used either directly for therapeutic purposes or for further processing or manufacturing.

Blood establishmentAny 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 transfusion or further industrial manufacturing.

Blood productAny therapeutic substance derived from human blood, including whole blood, blood components and plasma-derived medicinal products.

Core functionA specific function through which the regulatory system assures quality, safety and efficacy of blood products.

DistributorAny 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 is fundamentally related to the system’s ability to effectively ensure quality, safety and efficacy of blood products.

Good clinical practice (GCP)A standard for the design, conduct, performance, monitoring, auditing, recording, analysing and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity and confidentiality 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. Similar criteria for safety, quality and efficacy should be met as for blood and blood components.

06

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 final products or services that consistently meet appropriate specifications and compliance with defined regulations.

Legislation A legal instrument of government that defines laws which govern a particular subject matter, e.g. regulation of quality, safety and efficacy of medicines. Laws define the roles, rights and obligations of all parties involved in the subject matter in general terms (see also Regulations).

Licensing Authorization by the national regulatory authority for the manufacture, importation, exportation, or distribution of medical products.

Manufacturer Any natural or legal person (structure, facility or body) with responsibility for any aspect of the following activities 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 productAny therapeutic product derived from human plasma and produced by an industrial-scale manufacturing process 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 ensures that steps, processes, procedures and policies related to quality activities are being followed.

Registration A procedure under which information regarding the identification, location(s) and scope of activities of all parties involved in manufacturing or supplying a medicinal product and associated medical devices and substances is submitted to the regulatory authority in order to comply with administrative requirements before starting, continuing or amending relevant activities.

Regulations Legislative instruments of government that provide more prescriptive information regarding compliance with relevant legislation. Regulations are specifically designed to provide the legal framework and details necessary to achieve the administrative and technical goals of legislation.

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

Sponsor An individual, company, institution or organization that takes responsibility for the initiation, management and/or financing of a drug submission or clinical trial.

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

Assessment criteriA for nAtionAl blood regulAtory systems 07

IntroductionBlood transfusion is an indispensable, potentially life-saving medical intervention, and blood products such 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 equitable access 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 are met for production of blood products and monitoring of blood safety. Consequently, as a pillar for the establishment of safe blood programmes globally, WHO has advocated for the establishment and sustenance 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 unequal access globally to blood products, particularly plasma-derived products, leaving many patients without needed transfusions and many of those with severe congenital and acquired disorders without adequate plasma-derived treatments. In this resolution, the World Health Assembly urged Member States “to take 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 of regulatory authorities in order to ensure that regulatory control in the area of quality and safety of blood products across the entire transfusion chain meets internationally recognized standards.”

Purpose and application of the documentThe purpose of this document is to provide a tool to assist capacity building of national regulatory authorities (NRAs) for the regulation of blood and blood products. Ancillary to the existence of NRAs to regulate activities assuring the provision of safe blood products, there is currently a need to develop criteria defining 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 functions which 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 both developed and developing countries, an assessment tool that reflects international best practices in blood regulation could serve to highlight strengths of the NRA while identifying gaps or areas for future development. In addition, adoption of global criteria by NRAs could promote international convergence of regulations, which can have a beneficial impact on global safety and availability of blood products.

To promote these objectives, this document identifies the essential elements and core regulatory functions that should be present in an effective NRA to assure the quality, safety and efficacy 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 essential elements and core functions that are intended to help NRAs assess their performance in the regulation of blood and blood products and prioritize efforts to address any gaps that are identified.

Understanding and use of the documentTo achieve the aim of an international best practice national blood regulatory framework, a set of integrated general and specific regulatory functions have been identified that are applicable to all aspects of blood product regulation, from the collection of source material through to the quality control of the final product, and covering not only blood products but also associated substances and medical devices, including in vitro diagnostics. Section A of this document identifies essential elements that are necessary to establish the legal basis, authority and general characteristics of the NRA. Section B identifies specific 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 and that in some countries the specific 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 functions may be applicable regardless of the intended use of the blood (e.g. for transfusion purposes or for further manufacturing use). However, regulatory structures should be designed in such a way as to avoid fragmentation and uncoordinated delegation.

08

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 these criteria could also serve as a useful means to highlight strengths of NRA programmes for regulation of blood products while identifying gaps or areas for future development. National authorities are encouraged to use the assessment criteria as a roadmap towards evolving a best practice blood regulatory system.

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

It is also recognized that single required criteria may not formally be fulfilled even by regulators with proven effectiveness, but that underlying relevant safety issues can be met by other means. This offers the opportunity to compare different ways of ensuring safety of blood products and points out areas where refinement of the assessment criteria may need to be considered.

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

Assessment criteriA for nAtionAl blood regulAtory systems 09

Sect

ion

A. E

ssen

tial e

lem

ents

1.

Natio

nal r

egul

ator

y sys

tem

Appl

icab

le to

blo

od, b

lood

com

pone

nts,

pla

sma-

deriv

ed m

edic

inal

pro

duct

s, a

ssoc

iate

d su

bsta

nces

, and

med

ical

dev

ices

incl

udin

g in

vitr

o di

agno

stic

s

Mai

n cr

iteria

rela

ted

to th

e el

emen

tR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

1.1.

A c

ompr

ehen

sive

lega

l (s

tatu

tory

) bas

is e

xist

s fo

r es

tabl

ishm

ent o

f a re

gula

tory

sy

stem

app

licab

le to

blo

od,

bloo

d co

mpo

nent

s, p

lasm

a-de

rived

pro

duct

s, a

ssoc

iate

d su

bsta

nces

, and

med

ical

de

vice

s in

clud

ing

in v

itro

diag

nost

ics.

RR R R R R R S

1.1.

1.

Prov

isio

ns fo

r the

mai

n re

gula

tory

func

tions

can

be

iden

tified

and

are

up

to d

ate.

1.1.

2.

The

regu

latio

ns o

r the

ir ad

apta

tions

take

into

con

side

ratio

n de

velo

pmen

ts in

the

field

of b

lood

an

d re

late

d te

chno

logi

es.

1.1.

3.

Regu

latio

ns h

ave

been

est

ablis

hed

and

are

avai

labl

e; th

ey a

re in

telli

gibl

e to

thos

e th

at n

eed

to

com

ply

with

or e

nfor

ce th

em, a

nd th

e w

ays

of c

omm

unic

atio

n us

ed a

re a

dequ

ate.

1.1.

4.

Legi

slat

ion

exis

ts th

at d

efine

s th

erap

eutic

pro

duct

s fo

r hum

an u

se to

be

regu

late

d, a

nd

esta

blis

hes

stan

dard

s of

qua

lity,

safe

ty a

nd e

ffica

cy fo

r:a.

bl

ood,

blo

od c

ompo

nent

s an

d pl

asm

a-de

rived

pro

duct

s;b.

as

soci

ated

sub

stan

ces

and

med

ical

dev

ices

incl

udin

g in

vitr

o di

agno

stic

s.

1.1.

5.

Legi

slat

ion

exis

ts th

at p

rovi

des

a le

gal b

asis

for t

he re

spon

sibl

e N

RA to

per

form

the

esse

ntia

l fu

nctio

ns.

1.1.

6.

Legi

slat

ion

enab

les

the

appr

opria

te in

stitu

tions

to is

sue

regu

latio

ns.

1.1.

7.

The

deve

lopm

ent o

f reg

ulat

ions

incl

udes

the

oppo

rtun

ity fo

r pub

lic c

onsu

ltatio

n.

1.2.

The

legi

slat

ion

assi

gns

the

enfo

rcem

ent o

f reg

ulat

ions

re

gard

ing

the

prod

ucts

co

vere

d in

1.1

to o

ne o

r m

ore

resp

onsi

ble

regu

lato

ry

auth

oriti

es.

RR R R

1.2.

1.

The

com

pete

nt a

utho

ritie

s in

volv

ed in

the

regu

lato

ry s

yste

m fo

r blo

od, b

lood

com

pone

nts,

pla

sma-

deriv

ed p

rodu

cts,

ass

ocia

ted

subs

tanc

es, a

nd m

edic

al d

evic

es in

clud

ing

in v

itro

diag

nost

ics

are

clea

rly id

entifi

ed a

nd c

an b

e na

med

for e

ach

of th

e re

gula

tory

func

tions

.

1.2.

2.

The

resp

onsi

bilit

ies,

func

tions

and

the

orga

niza

tion

of e

ach

of th

ese

auth

oriti

es a

re c

lear

ly

defin

ed, i

n pa

rtic

ular

as

rega

rds

the

scop

e of

the

regu

latio

n (re

gula

tory

func

tions

) the

y ha

ve u

nder

th

eir c

ontro

l.

1.2.

3.

The

activ

ities

of t

he v

ario

us a

utho

ritie

s in

volv

ed a

re c

oord

inat

ed a

nd s

uper

vise

d by

an

adm

inis

trativ

e m

echa

nism

.* R

=req

uire

d; S

=sug

gest

ed

10

2.

Natio

nal r

egul

ator

y aut

horit

yAp

plic

able

to b

lood

, blo

od c

ompo

nent

s, p

lasm

a-de

rived

med

icin

al p

rodu

cts,

ass

ocia

ted

subs

tanc

es, a

nd m

edic

al d

evic

es in

clud

ing

in v

itro

diag

nost

ics

Mai

n cr

iteria

rela

ted

to th

e el

emen

tR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

2.1.

The

re is

inde

pend

ence

of

the

regu

lato

ry a

utho

rity

in

deci

sion

-mak

ing.

RR R R R R S

2.1.

1.

A cl

ear d

ivis

ion

of ro

les

and

resp

onsi

bilit

ies

is im

plem

ente

d be

twee

n th

e N

RA, b

lood

es

tabl

ishm

ents

, man

ufac

ture

rs a

nd d

istri

buto

rs, r

eflec

ting

inde

pend

ence

of t

he re

gula

tory

sy

stem

.

2.1.

2.

Acco

unta

bilit

ies

for d

ecis

ion-

mak

ing

are

clea

r.

2.1.

3.

Inte

rnal

pol

icy

on p

oten

tial c

onfli

cts

of in

tere

st fo

r sta

ff ex

ists

.

2.1.

4.

NRA

man

agem

ent a

nd a

sses

smen

t act

iviti

es (i

nclu

ding

use

of e

xper

t com

mitt

ees)

nev

er in

clud

e re

pres

enta

tives

from

man

ufac

ture

rs o

r lic

ence

hol

ders

.

2.1.

5.

A co

de o

f con

duct

for r

egul

ator

y st

aff e

xist

s.

2.1.

6.

Writ

ten

proc

edur

es fo

r mee

tings

with

man

ufac

ture

rs, d

istri

buto

rs a

nd o

ther

spo

nsor

s ex

ist.

2.2.

The

NR

A ha

s es

tabl

ishe

d an

in

stitu

tiona

l dev

elop

men

t pl

an.

SS S S

2.2.

1.

The

NRA

has

an

inst

itutio

nal d

evel

opm

ent p

lan,

whi

ch is

impl

emen

ted

and

upda

ted.

2.2.

2.

The

deve

lopm

ent p

lan

incl

udes

: vis

ion;

stra

tegi

c ob

ject

ives

; tim

elin

e an

d de

adlin

e fo

r tar

get

impl

emen

tatio

n; in

dica

tors

; fun

ctio

ns a

nd/o

r dut

ies

of th

e N

RA; o

ngoi

ng s

taff

train

ing

plan

; re

sour

ces

need

ed; i

nfor

mat

ion

and/

or c

omm

unic

atio

n st

rate

gy; a

nd a

hum

an re

sour

ce

deve

lopm

ent p

lan.

2.2.

3.

Perfo

rman

ce in

dica

tors

are

est

ablis

hed

and

used

for m

onito

ring

atta

inm

ent o

f obj

ectiv

es.

Assessment criteriA for nAtionAl blood regulAtory systems 11

2.

Natio

nal r

egul

ator

y aut

horit

yAp

plic

able

to b

lood

, blo

od c

ompo

nent

s, p

lasm

a-de

rived

med

icin

al p

rodu

cts,

ass

ocia

ted

subs

tanc

es, a

nd m

edic

al d

evic

es in

clud

ing

in v

itro

diag

nost

ics

Mai

n cr

iteria

rela

ted

to th

e el

emen

tR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

2.3.

The

NR

A ha

s ad

equa

te

reso

urce

s to

car

ry o

ut it

s fu

nctio

ns p

rope

rly a

nd to

en

forc

e re

gula

tory

func

tions

.

RR R R R R R S S

2.3.

1.

An a

dequ

ate

num

ber o

f tra

ined

sta

ff an

d bu

dget

ary

prov

isio

ns e

xist

for a

ll es

sent

ial f

unct

ions

.

2.3.

2.

All s

taff

mem

bers

hav

e ap

prop

riate

qua

lifica

tions

to c

ondu

ct re

gula

tory

act

iviti

es a

nd a

re p

rovi

ded

with

tim

ely,

rele

vant

and

regu

larly

upd

ated

trai

ning

.

2.3.

3.

Task

s an

d re

spon

sibi

litie

s of

sta

ff m

embe

rs a

re w

ell d

efine

d.

2.3.

4.

Mec

hani

sms

are

in p

lace

to e

nsur

e th

at th

ose

perfo

rmin

g re

gula

tory

func

tions

hav

e su

ffici

ent a

nd

curr

ent e

xper

tise

in s

peci

aliz

ed a

reas

.

2.3.

5.

Polic

ies

and

proc

edur

es e

xist

for r

ecru

itmen

t and

sel

ectio

n of

ext

erna

l exp

erts

and

the

man

agem

ent o

f exp

ert a

dvis

ory

com

mitt

ees,

incl

udin

g po

tent

ial c

onfli

ct o

f int

eres

t.

2.3.

6.

An a

gree

men

t bet

wee

n th

e N

RA a

nd e

xter

nal e

xper

ts d

efini

ng ro

les

and

resp

onsi

bilit

ies

is

esta

blis

hed.

2.3.

7.

The

sour

ces

of fu

ndin

g of

the

resp

onsi

ble

auth

oriti

es p

erfo

rmin

g re

gula

tory

func

tions

are

defi

ned.

2.3.

8.

Writ

ten

crite

ria fo

r sel

ectio

n an

d re

crui

tmen

t of r

egul

ator

y st

aff a

re d

efine

d.

12

2.

Natio

nal r

egul

ator

y aut

horit

yAp

plic

able

to b

lood

, blo

od c

ompo

nent

s, p

lasm

a-de

rived

med

icin

al p

rodu

cts,

ass

ocia

ted

subs

tanc

es, a

nd m

edic

al d

evic

es in

clud

ing

in v

itro

diag

nost

ics

Mai

n cr

iteria

rela

ted

to th

e el

emen

tR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

2.4.

A q

ualit

y m

anag

emen

t sys

tem

(Q

MS)

is in

pla

ce.

SS S S S S S S

2.4.

1.

A QM

S is

impl

emen

ted

by th

e N

RA fo

r all

its c

ore

func

tions

as

spec

ified

bel

ow.

2.4.

2.

Budg

etar

y pr

ovis

ions

are

mad

e fo

r im

plem

enta

tion

and

mai

nten

ance

of t

he Q

MS.

2.4.

3.

A qu

alifi

ed q

ualit

y m

anag

er is

des

igna

ted

as re

spon

sibl

e fo

r the

impl

emen

tatio

n of

the

QMS.

2.4.

4.

The

docu

men

tatio

n ne

eded

to e

stab

lish,

impl

emen

t and

mai

ntai

n th

e QM

S is

defi

ned

(qua

lity

man

ual,

SOPs

, etc

.).

2.4.

5.

The

QMS

is b

ased

on

reco

gniz

ed in

tern

atio

nal s

tand

ards

.

2.4.

6.

The

QMS

is c

ertifi

ed o

r acc

redi

ted

by e

xter

nal b

odie

s.

2.4.

7.

An in

tern

al a

nd e

xter

nal a

udit

and

revi

ew s

yste

m e

xist

s as

wel

l as

evid

ence

that

cor

rect

ive

and

prev

entiv

e ac

tions

are

take

n as

a re

sult

of m

onito

ring

and/

or a

udits

.

2.5.

Tra

nspa

renc

y an

d ac

coun

tabi

lity

are

ensu

red.

RR R R S S

2.5.

1.

Lega

lly-s

peci

fied,

con

fiden

tial a

nd tr

ade

secr

et in

form

atio

n is

ava

ilabl

e fo

r int

erna

l use

and

de

cisi

on-m

akin

g. H

owev

er, a

ll ot

her i

nfor

mat

ion

is p

ublic

ly a

vaila

ble

and

kept

up

to d

ate.

2.5.

2.

List

ing

of a

utho

rized

pro

duct

s an

d co

mpa

nies

is m

ade

avai

labl

e w

here

nee

ded.

2.5.

3.

Info

rmat

ion

on s

anct

ions

, rec

alls

and

pub

lic h

ealth

war

ning

s is

pub

licly

ava

ilabl

e.

2.5.

4.

Info

rmat

ion

on d

ecis

ions

is a

vaila

ble

and

easi

ly a

cces

sibl

e to

the

publ

ic a

nd in

clud

es n

egat

ive

deci

sion

s in

sel

ecte

d ca

ses

(may

var

y de

pend

ing

on n

atio

nal r

egul

atio

n).

2.5.

5.

An o

ppor

tuni

ty fo

r int

erac

tion

betw

een

the

NRA

and

sta

keho

lder

s is

giv

en.

* R=r

equi

red;

S=s

ugge

sted

Assessment criteriA for nAtionAl blood regulAtory systems 13

Sect

ion

B. C

ore

func

tions

3.

Lice

nsin

g and

/or r

egist

ratio

n of

blo

od es

tabl

ishm

ents

Appl

icab

le to

blo

od a

nd b

lood

com

pone

nts

incl

udin

g pl

asm

a fo

r fra

ctio

natio

n

Mai

n cr

iteria

rela

ted

to th

e fu

nctio

nR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

3.1.

Leg

isla

tive

auth

ority

exi

sts

to re

quire

regi

stra

tion

and/

or li

cens

ing

of b

lood

es

tabl

ishm

ents

, and

for

enfo

rcem

ent p

ower

.

RR R

3.1.

1.

Legi

slat

ion

and/

or re

gula

tion

exis

t tha

t req

uire

a b

lood

est

ablis

hmen

t tha

t int

ends

to c

olle

ct,

test

, pro

cess

, sto

re, m

anuf

actu

re, d

istri

bute

, im

port

or e

xpor

t blo

od a

nd b

lood

com

pone

nts

to b

e au

thor

ized

, acc

redi

ted,

regi

ster

ed o

r lic

ense

d by

the

desi

gnat

ed N

RA.

3.1.

2.

The

NRA

has

the

auth

ority

to ta

ke re

gula

tory

act

ion

(e.g

. rev

oke,

sus

pend

the

licen

ce) i

f the

es

tabl

ishm

ent d

oes

not c

ompl

y w

ith re

gula

tory

requ

irem

ents

.

3.2.

A li

cens

ing

and/

or re

gist

ratio

n sy

stem

is e

stab

lishe

d an

d op

erat

iona

l for

blo

od

esta

blis

hmen

ts.

RR R R R S S

3.2.

1.

Activ

ities

that

are

dec

entra

lized

or d

eleg

ated

to o

ther

age

ncie

s or

aut

horit

ies

follo

w th

e st

anda

rds,

gu

idel

ines

and

pro

cedu

res

as a

gree

d by

the

cent

ral r

egul

ator

y au

thor

ity, a

nd a

repo

rtin

g m

echa

nism

is e

stab

lishe

d be

twee

n th

e re

spon

sibl

e au

thor

ities

.

3.2.

2.

Requ

ired

regi

stra

tion

and/

or li

cenc

e ap

plic

atio

ns a

re a

sses

sed

by th

e N

RA b

ased

on

writ

ten

guid

elin

es.

3.2.

3.

A lis

t of a

ll lic

ense

d an

d/or

regi

ster

ed b

lood

est

ablis

hmen

ts is

mai

ntai

ned

and

mad

e av

aila

ble

whe

re n

eede

d.

3.2.

4.

Advi

ce fo

r app

lican

ts is

ava

ilabl

e on

the

cont

ent,

form

at, r

equi

rem

ents

and

pro

cedu

res

to fo

llow

in

orde

r to

subm

it a

requ

ired

regi

stra

tion

and/

or a

pplic

atio

n fo

r an

esta

blis

hmen

t lic

ence

.

3.2.

5.

Faci

lity

docu

men

tatio

n (e

.g. s

ite m

aste

r file

, qua

lifica

tion

of a

resp

onsi

ble

pers

on) i

s su

bmitt

ed a

s pa

rt o

f a re

quire

d re

gist

ratio

n an

d/or

app

licat

ion

for a

n es

tabl

ishm

ent l

icen

ce a

nd is

ass

esse

d to

dem

onst

rate

that

the

faci

lity

is s

uita

ble

for t

he a

ctiv

ities

to b

e pe

rform

ed (e

.g. b

lood

col

lect

ion,

do

nor s

cree

ning

, tes

ting,

sto

rage

, etc

.).

3.2.

6.

Rene

wal

per

iods

for a

n es

tabl

ishm

ent l

icen

ce a

nd/o

r reg

istra

tion

are

defin

ed a

nd c

onsi

sten

t with

m

echa

nism

s of

sur

veill

ance

.

14

3.

Lice

nsin

g and

/or r

egist

ratio

n of

blo

od es

tabl

ishm

ents

Appl

icab

le to

blo

od a

nd b

lood

com

pone

nts

incl

udin

g pl

asm

a fo

r fra

ctio

natio

n

Mai

n cr

iteria

rela

ted

to th

e fu

nctio

nR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

3.3.

Sig

nific

ant c

hang

es to

an

esta

blis

hmen

t lic

ence

and

/or

regi

stra

tion

are

subm

itted

and

as

sess

ed b

y th

e N

RA

prio

r to

impl

emen

tatio

n.

RR S

3.3.

1.

Chan

ges

are

asse

ssed

bas

ed o

n th

e ty

pe o

f cha

nge.

3.3.

2.

Writ

ten

guid

elin

es fo

r app

lican

ts a

re a

vaila

ble

that

defi

ne th

e ty

pes

and

scop

es o

f cha

nges

and

do

cum

enta

tion

requ

ired.

3.4.

Com

plia

nce

with

the

prin

cipl

es

of g

ood

man

ufac

turin

g pr

actic

e (G

MP)

is a

sses

sed

as p

art o

f the

est

ablis

hmen

t lic

ensi

ng a

nd/o

r reg

istr

atio

n pr

oces

s.

RR R R

3.4.

1.

Com

plia

nce

with

app

licab

le p

rinci

ples

of G

MP

is a

con

ditio

n fo

r mai

ntai

ning

an

esta

blis

hmen

t lic

ence

and

/or r

egis

tratio

n an

d fo

r app

rova

l of s

igni

fican

t cha

nges

.

3.4.

2.

Nat

iona

l GM

P an

d go

od d

istri

butio

n pr

actic

e (G

DP)

prin

cipl

es a

re p

ublis

hed

and

are

cons

iste

nt

with

or b

ased

on

reco

gniz

ed s

tand

ards

for t

he m

anuf

actu

ring

and

dist

ribut

ion

of b

lood

and

blo

od

com

pone

nts.

3.4.

3.

Perio

dic

insp

ectio

ns a

ccor

ding

to G

MP

and

GD

P pr

inci

ples

are

car

ried

out f

or s

uper

visi

on o

f blo

od

esta

blis

hmen

ts. F

or in

spec

tions

car

ried

out a

broa

d:a.

th

ere

is a

n ag

reem

ent w

ith o

ther

NRA

’s fo

r exc

hang

e of

insp

ectio

n re

port

s an

d/or

ce

rtifi

cate

s; o

rb.

a

list o

f ref

eren

ce c

ount

ries

and/

or a

genc

ies

who

se c

ertifi

cate

s an

d de

cisi

ons

are

acce

pted

exi

st; o

rc.

si

te in

spec

tions

are

car

ried

out a

broa

d.

3.5.

QM

S re

quire

men

ts a

re

esta

blis

hed

for a

ll fu

nctio

ns

perf

orm

ed b

y bl

ood

esta

blis

hmen

ts.

RR

3.5.

1.

The

esse

ntia

l com

pone

nts

for a

QM

S ar

e co

vere

d.

Assessment criteriA for nAtionAl blood regulAtory systems 15

3.

Lice

nsin

g and

/or r

egist

ratio

n of

blo

od es

tabl

ishm

ents

Appl

icab

le to

blo

od a

nd b

lood

com

pone

nts

incl

udin

g pl

asm

a fo

r fra

ctio

natio

n

Mai

n cr

iteria

rela

ted

to th

e fu

nctio

nR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

3.6.

Ass

essm

ent o

f com

plia

nce

with

sta

ndar

ds re

gard

ing

dono

r sel

ectio

n cr

iteria

and

te

stin

g of

don

atio

ns is

par

t of

the

esta

blis

hmen

t lic

ensi

ng

and/

or re

gist

ratio

n pr

oces

s (a

ltern

ativ

ely

this

requ

irem

ent

can

be m

et u

nder

Cor

e fu

nctio

n 5)

.

RR R R R

3.6.

1.

Com

plia

nce

with

nat

iona

l sta

ndar

ds is

a c

ondi

tion

for m

aint

aini

ng a

n es

tabl

ishm

ent l

icen

ce.

3.6.

2.

Nat

iona

l sta

ndar

ds a

re p

ublis

hed

and

are

cons

iste

nt w

ith o

r bas

ed o

n re

cogn

ized

sta

ndar

ds fo

r bl

ood

and

bloo

d co

mpo

nent

s.

3.6.

3.

Insp

ectio

ns a

re c

arrie

d ou

t for

che

ckin

g co

mpl

ianc

e w

ith th

ese

natio

nal s

tand

ards

.

3.6.

4.

Defi

ned

proc

edur

es a

re in

pla

ce fo

r tak

ing

actio

n in

inst

ance

s of

any

non

conf

orm

ity.

* R=r

equi

red;

S=s

ugge

sted

16

4.

Lice

nsin

g and

/or r

egist

ratio

n of

man

ufac

ture

rs a

nd d

istrib

utor

s of p

lasm

a-de

rived

med

icin

al p

rodu

cts

Appl

icab

le to

pla

sma-

deriv

ed m

edic

inal

pro

duct

s

Mai

n cr

iteria

rela

ted

to th

e fu

nctio

nR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

4.1.

Leg

isla

tive

auth

ority

exi

sts

to re

quire

regi

stra

tion

and/

or li

cens

ing

of m

anuf

actu

rers

an

d di

strib

utor

s of

pla

sma-

deriv

ed p

rodu

cts,

and

for

enfo

rcem

ent p

ower

.

RR R

4.1.

1.

Legi

slat

ion

and/

or re

gula

tion

exis

t tha

t req

uire

man

ufac

ture

rs a

nd d

istri

buto

rs o

f pla

sma-

deriv

ed

prod

ucts

that

inte

nd to

man

ufac

ture

, dis

tribu

te, i

mpo

rt o

r exp

ort p

lasm

a-de

rived

pro

duct

s to

be

regi

ster

ed a

nd/o

r lic

ense

d by

the

desi

gnat

ed N

RA.

4.1.

2.

The

NRA

has

aut

horit

y to

take

regu

lato

ry a

ctio

n (e

.g. r

evok

e, s

uspe

nd th

e lic

ence

) if t

he c

ompa

ny

does

not

com

ply

with

regu

lato

ry re

quire

men

ts.

4.2.

A li

cens

ing

and/

or re

gist

ratio

n sy

stem

is e

stab

lishe

d an

d op

erat

iona

l for

man

ufac

ture

rs

and

dist

ribut

ors

of p

lasm

a-de

rived

pro

duct

s.

RR R R R S S

4.2.

1.

Activ

ities

that

are

dec

entra

lized

or d

eleg

ated

to o

ther

age

ncie

s or

aut

horit

ies

follo

w th

e st

anda

rds,

gu

idel

ines

and

pro

cedu

res

as a

gree

d by

the

cent

ral r

egul

ator

y au

thor

ity, a

nd a

repo

rtin

g m

echa

nism

is e

stab

lishe

d be

twee

n th

e re

spon

sibl

e au

thor

ities

.

4.2.

2.

Requ

ired

regi

stra

tion

and/

or li

cenc

e ap

plic

atio

ns a

re a

sses

sed

by th

e N

RA b

ased

on

writ

ten

guid

elin

es.

4.2.

3.

A lis

t of a

ll lic

ense

d an

d/or

regi

ster

ed m

anuf

actu

rers

and

dis

tribu

tors

is m

aint

aine

d an

d m

ade

avai

labl

e w

here

nee

ded.

4.2.

4.

Advi

ce fo

r app

lican

ts is

ava

ilabl

e on

the

cont

ent,

form

at, r

equi

rem

ents

(dep

endi

ng o

n th

e ac

tiviti

es) a

nd p

roce

dure

s to

follo

w in

ord

er to

sub

mit

a re

quire

d re

gist

ratio

n an

d/or

app

licat

ion

for a

n es

tabl

ishm

ent l

icen

ce.

4.2.

5.

Faci

lity

docu

men

tatio

n (e

.g. s

ite m

aste

r file

, key

per

sonn

el, q

ualifi

catio

n of

a re

spon

sibl

e pe

rson

) is

sub

mitt

ed a

s pa

rt o

f a re

quire

d re

gist

ratio

n an

d/or

app

licat

ion

for a

n es

tabl

ishm

ent l

icen

ce a

nd

is a

sses

sed

to d

emon

stra

te th

at th

e fa

cilit

y is

sui

tabl

e fo

r the

act

iviti

es to

be

perfo

rmed

.

4.2.

6.

Rene

wal

per

iods

for a

n es

tabl

ishm

ent l

icen

ce a

nd/o

r reg

istra

tion

are

defin

ed a

nd c

onsi

sten

t with

m

echa

nism

s of

sur

veill

ance

.

Assessment criteriA for nAtionAl blood regulAtory systems 17

4.

Lice

nsin

g and

/or r

egist

ratio

n of

man

ufac

ture

rs a

nd d

istrib

utor

s of p

lasm

a-de

rived

med

icin

al p

rodu

cts

Appl

icab

le to

pla

sma-

deriv

ed m

edic

inal

pro

duct

s

Mai

n cr

iteria

rela

ted

to th

e fu

nctio

nR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

4.3.

Sig

nific

ant c

hang

es to

an

esta

blis

hmen

t lic

ence

and

/or

regi

stra

tion

are

subm

itted

and

as

sess

ed b

y th

e N

RA

prio

r to

impl

emen

tatio

n.

RR S

4.3.

1.

Chan

ges

are

asse

ssed

bas

ed o

n th

e ty

pe o

f cha

nge.

4.3.

2.

Writ

ten

guid

elin

es fo

r app

lican

ts a

re a

vaila

ble

that

defi

ne th

e ty

pes

and

scop

es o

f cha

nges

and

do

cum

enta

tion

requ

ired.

4.4.

Com

plia

nce

with

prin

cipl

es

of G

MP

and

GD

P is

ass

esse

d as

par

t of t

he e

stab

lishm

ent

licen

sing

and

/or r

egis

trat

ion

proc

ess.

RR R R

4.4.

1.

Com

plia

nce

with

app

licab

le p

rinci

ples

of G

MP

and

GD

P is

a c

ondi

tion

for m

aint

aini

ng a

n es

tabl

ishm

ent l

icen

ce a

nd/o

r reg

istra

tion

and

for a

ppro

val o

f sig

nific

ant c

hang

es.

4.4.

2.

Nat

iona

l GM

P an

d G

DP

stan

dard

s ar

e pu

blis

hed

and

are

cons

iste

nt w

ith o

r bas

ed o

n re

cogn

ized

st

anda

rds

for t

he m

anuf

actu

ring

and

dist

ribut

ion

of p

lasm

a-de

rived

pro

duct

s.

4.4.

3.

Perio

dic

insp

ectio

ns a

ccor

ding

to G

MP

and

GD

P pr

inci

ples

are

car

ried

out f

or s

uper

visi

on o

f m

anuf

actu

rers

and

dis

tribu

tors

of p

lasm

a-de

rived

pro

duct

s. F

or in

spec

tions

car

ried

out a

broa

d:a.

th

ere

is a

n ag

reem

ent w

ith o

ther

NRA

s fo

r exc

hang

e of

insp

ectio

n re

port

s an

d/or

ce

rtifi

cate

s; o

rb.

a

list o

f ref

eren

ce c

ount

ries

and/

or a

genc

ies

who

se c

ertifi

cate

s an

d de

cisi

ons

are

acce

pted

exi

st; o

rc.

si

te in

spec

tions

are

car

ried

out a

broa

d.

4.5.

QM

S re

quire

men

ts a

re

esta

blis

hed

for a

ll fu

nctio

ns

perf

orm

ed b

y m

anuf

actu

rers

an

d di

strib

utor

s.

RR

4.5.

1.

The

esse

ntia

l com

pone

nts

for a

QM

S ar

e co

vere

d.

* R=r

equi

red;

S=s

ugge

sted

18

5.

Appr

oval

of b

lood

and

blo

od co

mpo

nent

s (pr

oduc

t and

/or p

roce

ss a

ppro

val)

Appl

icab

le to

blo

od a

nd b

lood

com

pone

nts

incl

udin

g pl

asm

a fo

r fra

ctio

natio

n

Mai

n cr

iteria

rela

ted

to th

e fu

nctio

nR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

5.1.

Leg

al p

rovi

sion

s ex

ist f

or a

sy

stem

to e

nsur

e qu

ality

, sa

fety

and

effi

cacy

of b

lood

an

d bl

ood

com

pone

nts.

RR R

5.1.

1.

An a

ppro

val s

yste

m is

requ

ired

that

incl

udes

any

impo

rted

pro

duct

s.

5.1.

2.

The

NRA

has

the

auth

ority

to is

sue

an a

ppro

val,

to s

uspe

nd it

and

to w

ithdr

aw it

if th

e pr

oduc

t is

cons

ider

ed u

nsaf

e or

doe

s no

t com

ply

with

regu

lato

ry re

quire

men

ts.

5.2.

A s

yste

m fo

r ens

urin

g qu

ality

, sa

fety

and

effi

cacy

of b

lood

an

d bl

ood

com

pone

nts

is

esta

blis

hed

and

oper

atio

nal.

RR R R S S R

5.2.

1.

The

capa

bilit

y ex

ists

to p

erfo

rm s

cien

ce-b

ased

risk

ass

essm

ents

and

risk

man

agem

ent.

5.2.

2.

Spec

ifica

tions

rela

ted

to q

ualit

y, sa

fety

and

effi

cacy

of b

lood

and

blo

od c

ompo

nent

s ar

e de

fined

an

d un

der t

he s

uper

visi

on o

f the

NRA

.

5.2.

3.

The

criti

cal s

tand

ards

for p

rodu

ct m

anuf

actu

ring

are

lega

lly b

indi

ng a

nd in

clud

e do

nor s

elec

tion,

la

bora

tory

test

ing,

com

pone

nt p

repa

ratio

n, s

tora

ge, i

ssua

nce,

trac

king

, tra

cing

, rec

ord

keep

ing,

an

d sa

fe d

ispo

sal o

f uni

ts n

ot m

eetin

g sp

ecifi

catio

ns fo

r use

in tr

ansf

usio

n.

5.2.

4.

Proc

edur

es to

reco

gniz

e ex

cept

ions

are

cle

arly

defi

ned

(e.g

. if c

olle

cted

by

a m

edic

al p

ract

ition

er

for a

spe

cific

ther

apeu

tic p

urpo

se).

5.2.

5.

Requ

irem

ents

and

sta

ndar

ds a

re b

ased

on

inte

rnat

iona

lly re

cogn

ized

sta

ndar

ds.

5.2.

6.

Plas

ma

for f

ract

iona

tion

mee

ts in

tern

atio

nally

reco

gniz

ed s

tand

ards

.

5.3.

Don

or s

elec

tion

and

defe

rral

cr

iteria

are

est

ablis

hed

as

appr

opria

te to

the

inte

nded

us

e of

the

com

pone

nt.

RR R

5.3.

1.

Don

or s

elec

tion

and

defe

rral

crit

eria

(tem

pora

ry a

nd p

erm

anen

t def

erra

ls) t

ake

into

acc

ount

the

heal

th o

f the

don

or a

nd th

e sa

fety

and

sui

tabi

lity

of th

e do

natio

n co

nsis

tent

with

cur

rent

sci

ence

.

5.3.

2.

Mec

hani

sms

for r

egul

arly

revi

ewin

g an

d up

datin

g th

e do

nor s

elec

tion

and

defe

rral

crit

eria

are

in

plac

e an

d ta

ke in

to c

onsi

dera

tion

the

deve

lopm

ent o

f iss

ues

that

mig

ht h

ave

a ne

gativ

e im

pact

on

the

qual

ity a

nd s

afet

y of

blo

od a

nd b

lood

com

pone

nts,

e.g

. epi

dem

iolo

gica

l situ

atio

n or

em

ergi

ng

dise

ases

.

Assessment criteriA for nAtionAl blood regulAtory systems 19

5.

Appr

oval

of b

lood

and

blo

od co

mpo

nent

s (pr

oduc

t and

/or p

roce

ss a

ppro

val)

Appl

icab

le to

blo

od a

nd b

lood

com

pone

nts

incl

udin

g pl

asm

a fo

r fra

ctio

natio

n

Mai

n cr

iteria

rela

ted

to th

e fu

nctio

nR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

5.4.

Tra

nsm

issi

ble-

dise

ase

test

ing

requ

irem

ents

are

est

ablis

hed

as a

ppro

pria

te to

the

inte

nded

us

e of

the

com

pone

nt.

RR R

5.4.

1.

Mec

hani

sms

for r

egul

arly

revi

ewin

g (e

.g. b

y qu

alifi

ed e

xper

ts in

epi

dem

iolo

gy) a

nd u

pdat

ing

the

test

ing

requ

irem

ents

are

in p

lace

.

5.4.

2.

Epid

emio

logi

cal d

ata

rega

rdin

g th

e pr

eval

ence

and

inci

denc

e of

infe

ctio

us d

isea

se m

arke

rs in

bl

ood

dono

rs a

re a

vaila

ble

and

regu

larly

upd

ated

.

5.5.

Lab

ellin

g re

quire

men

ts a

re

esta

blis

hed.

RR R S S

5.5.

1.

Each

blo

od c

ompo

nent

has

a u

niqu

e an

d cl

ear i

dent

ifier

and

is fu

lly tr

acea

ble.

5.5.

2.

Orig

inal

labe

lling

and

sig

nific

ant a

men

dmen

ts a

re s

ubm

itted

to th

e N

RA a

nd a

sses

sed

prio

r to

impl

emen

tatio

n.

5.5.

3.

Prod

uct l

abel

ling

incl

udes

info

rmat

ion

on th

e ris

ks a

nd b

enefi

ts o

f pro

duct

use

.

5.5.

4.

Requ

irem

ents

are

bas

ed o

n in

tern

atio

nally

reco

gniz

ed s

tand

ards

.

5.6.

An

appr

oval

sys

tem

for b

lood

an

d bl

ood

com

pone

nts

is

oper

atio

nal.

RR S S S S

5.6.

1.

Asse

ssm

ent e

xist

s th

at in

clud

es re

leva

nt a

spec

ts o

f qua

lity,

safe

ty a

nd w

here

app

licab

le e

ffica

cy

of b

lood

and

blo

od c

ompo

nent

s.

5.6.

2.

Gui

delin

es fo

r app

lican

ts e

xist

on

the

cont

ent,

form

at a

nd p

roce

dure

s to

follo

w in

ord

er to

sub

mit

an a

pplic

atio

n fo

r app

rova

l.

5.6.

3.

Writ

ten

guid

elin

es fo

r ass

essm

ent o

f app

licat

ions

are

impl

emen

ted.

5.6.

4.

Appe

al p

roce

dure

s ar

e in

pla

ce.

5.6.

5.

An a

sses

smen

t rep

ort i

s pr

epar

ed a

nd u

sed

as a

refe

renc

e fo

r dec

isio

n.

5.7.

The

re is

a re

quire

men

t for

m

anuf

actu

ring

chan

ges

to b

e su

bmitt

ed a

nd a

sses

sed

by th

e re

gula

tory

aut

horit

y.

SS S

5.7.

1.

Writ

ten

guid

elin

es fo

r app

lican

ts a

re a

vaila

ble

that

defi

ne th

e ty

pes

and

scop

es o

f cha

nges

and

do

cum

enta

tion

requ

ired.

5.7.

2.

Writ

ten

guid

elin

es fo

r ass

essm

ent e

xist

bas

ed o

n th

e ty

pe o

f cha

nge

(e.g

. sig

nific

ant,

notifi

able

, ad

min

istra

tive)

.

5.8.

App

ropr

iate

ass

essm

ent

expe

rtis

e is

ava

ilabl

e.R

R S

5.8.

1.

Acce

ss to

exp

erts

with

rele

vant

qua

lifica

tions

and

exp

erie

nce

(inte

rnal

and

/or e

xter

nal)

is a

ssur

ed

for a

sses

smen

t of b

lood

and

blo

od c

ompo

nent

s (p

recl

inic

al, c

linic

al a

nd q

ualit

y da

ta).

5.8.

2.

Writ

ten

proc

edur

es fo

r sel

ectio

n, m

anag

emen

t, an

d us

e of

ext

erna

l exp

erts

are

in p

lace

.* R

=req

uire

d; S

=sug

gest

ed

20

6.

Appr

oval

of p

lasm

a-de

rived

med

icin

al p

rodu

cts

Appl

icab

le to

pla

sma-

deriv

ed m

edic

inal

pro

duct

s

Mai

n cr

iteria

rela

ted

to th

e fu

nctio

nR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

6.1.

Leg

al p

rovi

sion

for a

m

arke

ting

appr

oval

sys

tem

ex

ists

to e

nsur

e th

e qu

ality

, sa

fety

and

effi

cacy

of p

lasm

a-de

rived

pro

duct

s.

RR R

6.1.

1.

Mar

ketin

g ap

prov

al is

requ

ired

for p

lasm

a-de

rived

pro

duct

s, in

clud

ing

impo

rted

pro

duct

s.

6.1.

2.

The

NRA

has

the

auth

ority

to is

sue

mar

ketin

g ap

prov

al fo

r pla

sma-

deriv

ed p

rodu

cts,

to s

uspe

nd

an a

ppro

val a

nd to

with

draw

it if

the

prod

uct i

s co

nsid

ered

uns

afe

or d

oes

not c

ompl

y w

ith

regu

lato

ry re

quire

men

ts.

6.2.

A m

arke

ting

appr

oval

sys

tem

fo

r pla

sma-

deriv

ed p

rodu

cts

is

esta

blis

hed

and

oper

atio

nal.

RR R R R R S S S

6.2.

1.

The

capa

bilit

y ex

ists

to p

erfo

rm s

cien

ce-b

ased

risk

ass

essm

ents

and

risk

man

agem

ent.

6.2.

2.

Ther

e is

a re

quire

men

t for

the

appl

ican

t to

incl

ude

a lis

t of a

ll th

e bl

ood

esta

blis

hmen

ts th

at

colle

cted

the

plas

ma

used

in th

e pr

oduc

t.

6.2.

3.

Spec

ifica

tions

rela

ted

to th

e qu

ality

and

saf

ety

of p

lasm

a fo

r fra

ctio

natio

n ar

e de

fined

and

und

er

the

supe

rvis

ion

of th

e N

RA.

6.2.

4.

Sele

ctio

n, d

efer

ral a

nd tr

ansm

issi

ble-

dise

ase

test

ing

requ

irem

ents

for p

lasm

a do

nors

are

es

tabl

ishe

d (s

ee C

riter

ia 5

.3 a

nd 5

.4).

6.2.

5.

Advi

ce fo

r app

lican

ts is

ava

ilabl

e on

the

cont

ent,

form

at a

nd p

roce

dure

s to

follo

w in

ord

er to

su

bmit

an a

pplic

atio

n fo

r mar

ket a

utho

rizat

ion.

6.2.

6.

Appe

al p

roce

dure

s ar

e in

pla

ce.

6.2.

7.

The

natio

nal c

ontro

l lab

orat

ory

(NCL

) is

invo

lved

in a

sses

smen

t as

appr

opria

te.

6.2.

8.

Writ

ten

proc

edur

es fo

r sel

ectio

n, m

anag

emen

t, an

d us

e of

ext

erna

l exp

erts

are

ava

ilabl

e.

Assessment criteriA for nAtionAl blood regulAtory systems 21

6.

Appr

oval

of p

lasm

a-de

rived

med

icin

al p

rodu

cts

Appl

icab

le to

pla

sma-

deriv

ed m

edic

inal

pro

duct

s

Mai

n cr

iteria

rela

ted

to th

e fu

nctio

nR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

6.3.

Ass

essm

ent o

f app

licat

ions

fo

r mar

ket a

utho

rizat

ion

is

impl

emen

ted.

RR R S S S

6.3.

1.

Asse

ssm

ent o

f qua

lity,

safe

ty a

nd e

ffica

cy o

f pla

sma-

deriv

ed p

rodu

cts

is p

erfo

rmed

, inc

ludi

ng

asse

ssm

ent o

f the

effe

ctiv

enes

s of

mea

sure

s us

ed b

y m

anuf

actu

rers

to in

activ

ate

and/

or re

mov

e tra

nsm

issi

ble

path

ogen

s.

6.3.

2.

Proc

edur

es to

reco

gniz

e ex

cept

ions

are

cle

arly

defi

ned.

6.3.

3.

Asse

ssm

ent r

epor

ts a

re p

repa

red

and

used

as

a re

fere

nce

for d

ecis

ion-

mak

ing.

6.3.

4.

Writ

ten

crite

ria e

xist

for r

ecog

nitio

n of

oth

er N

RA’s

repo

rts

and/

or d

ecis

ions

(if a

pplic

able

).

6.3.

5.

Writ

ten

guid

elin

es fo

r ass

essm

ent o

f app

licat

ions

are

ava

ilabl

e.

6.4.

The

re is

a re

quire

men

t for

ch

ange

s to

be

subm

itted

an

d as

sess

ed b

y th

e re

gula

tory

aut

horit

y pr

ior t

o im

plem

enta

tion.

RR S S

6.4.

1.

Chan

ges

are

asse

ssed

bas

ed o

n th

e ty

pe o

f cha

nge.

6.4.

2.

Writ

ten

guid

elin

es fo

r app

lican

ts a

re a

vaila

ble

that

defi

ne th

e ty

pes

and

scop

es o

f cha

nges

and

do

cum

enta

tion

requ

ired.

6.4.

3.

Writ

ten

guid

elin

es fo

r ass

essm

ent a

re a

vaila

ble

base

d on

the

type

of c

hang

e.

6.5.

App

ropr

iate

ass

essm

ent

expe

rtis

e ex

ists

.R

R6.

5.1.

Ac

cess

to e

xper

ts (i

nter

nal a

nd/o

r ext

erna

l) fo

r ass

essm

ent o

f pla

sma-

deriv

ed p

rodu

cts

(pre

clin

ical

, clin

ical

and

qua

lity

data

) is

assu

red,

and

list

s ex

ist o

f sta

ff an

d/or

exp

erts

with

re

leva

nt q

ualifi

catio

ns a

nd e

xper

ienc

e.

6.6.

Cle

ar a

nd c

ompr

ehen

sive

in

form

atio

n on

aut

horiz

ed

plas

ma-

deriv

ed p

rodu

cts

is

avai

labl

e.

RR R S

6.6.

1.

The

prod

uct i

nfor

mat

ion

mad

e av

aila

ble

is a

ppro

ved.

6.6.

2.

A su

mm

ary

of p

rodu

ct c

hara

cter

istic

s (S

PC) o

r equ

ival

ent i

nfor

mat

ion

is a

vaila

ble

for a

ll pl

asm

a-de

rived

pro

duct

s.

6.6.

3.

SPC-

like

info

rmat

ion

is re

gula

rly u

pdat

ed a

nd p

ublic

ly a

vaila

ble.

6.7.

A li

st o

f aut

horiz

ed p

rodu

cts

exis

ts.

RR S

6.7.

1.

A lis

t of a

utho

rized

pro

duct

s is

mad

e av

aila

ble

whe

re n

eede

d.

6.7.

2.

A lis

t of a

utho

rized

pro

duct

s is

pub

licly

ava

ilabl

e.* R

=req

uire

d; S

=sug

gest

ed

22

7.

Regu

lato

ry ov

ersig

ht of

ass

ocia

ted

subs

tanc

es a

nd m

edic

al d

evic

es in

clud

ing i

n vit

ro d

iagn

ostic

sAp

plic

able

to a

ssoc

iate

d su

bsta

nces

and

med

ical

dev

ices

incl

udin

g in

vitr

o di

agno

stic

s

Mai

n cr

iteria

rela

ted

to th

e fu

nctio

nR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

7.1.

Leg

al p

rovi

sion

s ex

ist f

or

regu

lato

ry o

vers

ight

of

the

rele

vant

ass

ocia

ted

subs

tanc

es a

nd m

edic

al

devi

ces.

RR R R R

7.1.

1.

Prem

arke

t rev

iew

and

app

rova

l is

requ

ired

for i

n vi

tro d

iagn

ostic

s an

d sc

reen

ing

test

kits

use

d fo

r do

nor s

elec

tion,

test

ing

of b

lood

and

blo

od c

ompo

nent

s fo

r the

rape

utic

use

, and

/or f

or fu

rthe

r m

anuf

actu

ring

of p

lasm

a-de

rived

pro

duct

s (e

.g. t

ests

for d

onor

hae

mog

lobi

n, te

sts

for i

nfec

tious

di

seas

e m

arke

rs).

7.1.

2.

Prem

arke

t rev

iew

and

app

rova

l is

requ

ired

for m

edic

al d

evic

es in

volv

ed in

the

man

ufac

ture

of

bloo

d co

mpo

nent

s (e

.g. a

pher

esis

mac

hine

s).

7.1.

3.

Prem

arke

t rev

iew

and

app

rova

l is

requ

ired

for a

ssoc

iate

d su

bsta

nces

(e.g

. ant

icoa

gula

nts,

ad

ditiv

e so

lutio

ns).

7.1.

4.

The

NRA

has

the

enfo

rcem

ent p

ower

to in

vest

igat

e an

d ac

t aga

inst

mar

kete

d pr

oduc

ts a

nd

invo

lved

com

pani

es th

at d

o no

t com

ply

with

the

requ

irem

ents

.

7.2.

Sys

tem

s fo

r pre

mar

ket

revi

ew a

nd a

ppro

val o

f as

soci

ated

sub

stan

ces

and

rele

vant

med

ical

dev

ices

are

es

tabl

ishe

d an

d op

erat

iona

l.

RR R R R S

7.2.

1.

The

capa

bilit

y ex

ists

to p

erfo

rm s

cien

ce-b

ased

risk

ass

essm

ents

and

risk

man

agem

ent.

7.2.

2.

Prem

arke

t rev

iew

incl

udes

an

asse

ssm

ent o

f qua

lity,

safe

ty a

nd e

ffect

iven

ess.

7.2.

3.

Advi

ce fo

r app

lican

ts o

n co

nten

t (da

ta re

quire

men

ts),

form

at, a

nd p

roce

dure

s fo

r sub

mitt

ing

an

appl

icat

ion

exis

ts.

7.2.

4.

If de

cent

raliz

ed, r

oles

and

resp

onsi

bilit

ies

of th

e bo

dies

invo

lved

are

defi

ned

and

ther

e is

a

mec

hani

sm fo

r inf

orm

atio

n ex

chan

ge b

etw

een

the

cont

rol a

utho

rity

and

the

NRA

.

7.2.

5.

Writ

ten

guid

elin

es fo

r pro

duct

ass

essm

ents

exi

st.

7.3.

App

ropr

iate

ass

essm

ent

expe

rtis

e is

ava

ilabl

e.

RR S

7.3.

1.

Acce

ss to

exp

erts

with

rele

vant

qua

lifica

tions

and

exp

erie

nce

(inte

rnal

and

/or e

xter

nal)

for

asse

ssm

ent o

f blo

od a

nd b

lood

com

pone

nts

(pre

clin

ical

, clin

ical

and

qua

lity

data

) is

esta

blis

hed.

7.3.

2.

Writ

ten

proc

edur

es fo

r sel

ectio

n, m

anag

emen

t and

use

of e

xter

nal e

xper

ts a

re in

pla

ce.

* R=r

equi

red;

S=s

ugge

sted

Assessment criteriA for nAtionAl blood regulAtory systems 23

8.

Acce

ss to

a la

bora

tory

inde

pend

ent o

f man

ufac

ture

rsAp

plic

able

to b

lood

, blo

od c

ompo

nent

s, p

lasm

a-de

rived

med

icin

al p

rodu

cts,

ass

ocia

ted

subs

tanc

es, a

nd m

edic

al d

evic

es in

clud

ing

in v

itro

diag

nost

ics

Mai

n cr

iteria

rela

ted

to th

e fu

nctio

nR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

8.1.

Acc

ess

by th

e N

RA

to a

na

tiona

l con

trol

labo

rato

ry

(NCL

) ind

epen

dent

of

the

man

ufac

ture

r(s)

is

esta

blis

hed.

RR R R S

8.1.

1.

Polic

y an

d op

erat

iona

l agr

eem

ents

are

in p

lace

for u

se o

f any

ext

erna

l con

trol l

abor

ator

ies.

8.1.

2.

Adeq

uate

test

ing

plan

s, te

stin

g pr

oced

ures

and

rela

ted

docu

men

tatio

n ar

e av

aila

ble.

8.1.

3.

Resp

onsi

bilit

ies

for t

estin

g in

the

pre-

licen

sing

and

pos

t-lic

ensu

re p

erio

d ar

e cl

early

defi

ned.

8.1.

4.

The

NCL

is in

volv

ed in

defi

ning

the

spec

ifica

tions

and

ana

lytic

al m

etho

ds d

urin

g as

sess

men

t of

mar

ketin

g au

thor

izat

ions

.

8.2.

App

ropr

iate

org

aniz

atio

n an

d fin

anci

al s

uppo

rt fr

om

man

agem

ent e

nsur

e th

e im

plem

enta

tion

of a

dequ

ate

test

ing

prog

ram

mes

(inc

ludi

ng

docu

men

tatio

n) u

sing

ap

prop

riate

equ

ipm

ent,

and

qual

ified

and

exp

erie

nced

st

aff.

RR R R R S S

8.2.

1.

Writ

ten

test

ing

proc

edur

es a

nd re

late

d do

cum

enta

tion

are

in p

lace

.

8.2.

2.

A re

-test

pol

icy

is e

stab

lishe

d.

8.2.

3.

A st

rate

gy fo

r the

intro

duct

ion

and

valid

atio

n of

new

or i

mpr

oved

test

s ex

ists

.

8.2.

4.

Repo

rtin

g an

d is

suan

ce to

the

NRA

of a

ll cr

itica

l res

ults

incl

udin

g ou

t of s

peci

ficat

ions

han

dlin

g is

im

plem

ente

d.

8.2.

5.

Doc

umen

t con

trol i

s es

tabl

ishe

d.

8.2.

6.

SOPs

, tes

t pro

cedu

res,

sam

ple

hand

ling

and

data

man

agem

ent a

re o

rgan

ized

.

8.3.

An

exte

rnal

ly a

ccre

dite

d qu

ality

man

agem

ent s

yste

m

(QM

S) is

in p

lace

in th

e la

bora

tory

.

SS S

8.3.

1.

A qu

ality

pol

icy

and

qual

ity m

anua

l exi

st.

8.3.

2.

A qu

alifi

ed q

ualit

y m

anag

er is

des

igna

ted

and

a QM

S is

in o

pera

tion.

24

8.

Acce

ss to

a la

bora

tory

inde

pend

ent o

f man

ufac

ture

rsAp

plic

able

to b

lood

, blo

od c

ompo

nent

s, p

lasm

a-de

rived

med

icin

al p

rodu

cts,

ass

ocia

ted

subs

tanc

es, a

nd m

edic

al d

evic

es in

clud

ing

in v

itro

diag

nost

ics

Mai

n cr

iteria

rela

ted

to th

e fu

nctio

nR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

8.4.

Equ

ipm

ent d

ocum

enta

tion

is

in p

lace

.R

R R S S S

8.4.

1.

Calib

ratio

n an

d m

aint

enan

ce s

ched

ules

are

ava

ilabl

e.

8.4.

2.

Valid

atio

n pr

otoc

ols

are

avai

labl

e.

8.4.

3.

Equi

pmen

t sel

ectio

n pr

oces

ses

are

docu

men

ted

and

uniq

ue e

quip

men

t ide

ntifi

catio

n (ID

) is

in

plac

e.

8.4.

4.

Com

mis

sion

ing

reco

rds

(i.e.

inst

alla

tion

and

qual

ifica

tion)

are

ava

ilabl

e.

8.4.

5.

Oper

atio

n m

anua

ls a

nd lo

gs e

xist

.

8.5.

Hum

an re

sour

ce m

anag

emen

t is

impl

emen

ted.

RR S S

8.5.

1.

Qual

ified

and

exp

erie

nced

sta

ff m

embe

rs w

ith d

efine

d re

spon

sibi

litie

s an

d co

mpe

tenc

ies

are

avai

labl

e.

8.5.

2.

A st

aff t

rain

ing

plan

is d

evel

oped

and

impl

emen

ted.

8.5.

3.

The

impa

ct o

f sta

ff tra

inin

g is

mon

itore

d.

8.6.

An

audi

t and

revi

ew s

yste

m

exis

ts.

SS S S

8.6.

1.

Com

preh

ensi

ve in

tern

al a

udit

and

revi

ew s

yste

ms

are

in p

lace

.

8.6.

2.

Doc

umen

tatio

n of

act

ions

take

n as

a re

sult

of a

udits

is a

vaila

ble.

8.6.

3.

The

labo

rato

ry is

aud

ited

by e

xter

nal o

rgan

izat

ions

.

8.7.

A v

alid

atio

n po

licy

for t

he

intr

oduc

tion

of te

sts

is

impl

emen

ted.

RR R

8.7.

1.

A va

lidat

ion

prog

ram

me

for n

on-c

ompe

ndia

l tes

ts is

ava

ilabl

e.

8.7.

2.

Proc

edur

es e

xist

for t

rans

fers

of v

alid

ated

met

hods

(i.e

. bet

wee

n th

e m

anuf

actu

rer a

nd th

e re

gula

tor).

8.8.

A g

ener

al s

afet

y pr

ogra

mm

e ex

ists

.R

R R S

8.8.

1.

List

s of

haz

ardo

us s

ubst

ance

s ar

e av

aila

ble.

8.8.

2.

Resp

onsi

ble

staf

f mem

bers

are

des

igna

ted.

8.8.

3.

A fu

ll sa

fety

pro

gram

me

exis

ts.

Assessment criteriA for nAtionAl blood regulAtory systems 25

8.

Acce

ss to

a la

bora

tory

inde

pend

ent o

f man

ufac

ture

rsAp

plic

able

to b

lood

, blo

od c

ompo

nent

s, p

lasm

a-de

rived

med

icin

al p

rodu

cts,

ass

ocia

ted

subs

tanc

es, a

nd m

edic

al d

evic

es in

clud

ing

in v

itro

diag

nost

ics

Mai

n cr

iteria

rela

ted

to th

e fu

nctio

nR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

8.9.

A p

olic

y fo

r use

of r

efer

ence

st

anda

rds

and

reag

ents

exi

sts.

RR R R S

8.9.

1.

Acce

ss to

a c

atal

ogue

(lis

t, sp

ecifi

catio

ns a

nd s

ourc

es) a

nd re

gula

r sup

ply

syst

em fo

r sta

ndar

ds

and

refe

renc

e m

ater

ials

is im

plem

ente

d.

8.9.

2.

Appr

opria

te u

se o

f ref

eren

ce m

ater

ials

is e

nsur

ed.

8.9.

3.

Use

of re

agen

ts o

f ass

ured

qua

lity

(e.g

. gra

des)

is e

nsur

ed.

8.9.

4.

A sy

stem

is in

pla

ce to

est

ablis

h an

d qu

alify

nat

iona

l ref

eren

ce s

tand

ards

in in

tern

atio

nal u

nits

(IU

s).

8.10

. Dat

a tr

ends

are

mon

itore

d an

d an

alys

ed.

RR R S

8.10

.1. R

esul

ts o

f ref

eren

ce m

ater

ials

are

mon

itore

d.

8.10

.2. R

esul

ts a

re c

ompa

red

with

thos

e of

the

man

ufac

ture

r.

8.10

.3. L

abor

ator

y re

sults

are

mon

itore

d an

d tre

nds

are

asse

ssed

.

8.11

. Par

ticip

atio

n in

inte

rnat

iona

l pr

ofici

ency

sch

emes

and

co

llabo

rativ

e st

udie

s is

or

gani

zed.

SS

8.11

.1. R

egul

ar p

artic

ipat

ion

(dat

e of

last

par

ticip

atio

n, s

cope

, pro

duct

(s),

coor

dina

ting

inst

itutio

n) is

or

gani

zed.

8.12

. Reg

ulat

ory

outc

ome

of

test

ing

is a

naly

sed

and

used

as

a ba

sis

for d

ecis

ion-

mak

ing.

RR R R

8.12

.1. C

ompl

ianc

e w

ith a

utho

rized

spe

cific

atio

ns is

che

cked

.

8.12

.2. R

esul

ts a

re c

ompa

red

with

thos

e of

the

man

ufac

ture

r.

8.12

.3. C

orre

ctiv

e ac

tion

is in

itiat

ed in

cas

e of

non

-com

plia

nce.

* R=r

equi

red;

S=s

ugge

sted

26

9.

Cont

rol o

f clin

ical

tria

lsAp

plic

able

to b

lood

, blo

od c

ompo

nent

s, p

lasm

a-de

rived

med

icin

al p

rodu

cts,

ass

ocia

ted

subs

tanc

es, a

nd m

edic

al d

evic

es in

clud

ing

in v

itro

diag

nost

ics

Mai

n cr

iteria

rela

ted

to th

e fu

nctio

nR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

9.1.

App

licab

le le

gal p

rovi

sion

for

the

regu

latio

n of

bio

med

ical

re

sear

ch in

hum

an s

ubje

cts

exis

ts.

RR R R R R

9.1.

1.

An a

utho

rizat

ion

syst

em fo

r clin

ical

tria

ls is

requ

ired.

9.1.

2.

The

scop

e an

d re

quire

men

ts fo

r reg

ulat

ion

of c

linic

al tr

ials

are

defi

ned.

9.1.

3.

The

NRA

has

the

enfo

rcem

ent p

ower

for t

he a

utho

rizat

ion,

sus

pens

ion

and

with

draw

al o

f clin

ical

tri

als.

9.1.

4.

Lega

l pro

visi

ons

are

in p

lace

to a

ssur

e an

eth

ical

ove

rsig

ht o

f clin

ical

tria

ls.

9.1.

5.

Com

plia

nce

with

prin

cipl

es o

f goo

d cl

inic

al p

ract

ice

(GCP

) is

man

dato

ry.

9.2.

A s

yste

m fo

r aut

horiz

atio

n of

cl

inic

al tr

ials

is o

pera

tiona

l.R

R R R S S S S

9.2.

1.

A sy

stem

is e

stab

lishe

d fo

r clin

ical

tria

l ass

essm

ent a

nd a

utho

rizat

ion.

9.2.

2.

An in

spec

tion

syst

em is

est

ablis

hed

to v

erify

com

plia

nce

with

the

prin

cipl

es o

f GCP

.

9.2.

3.

Expe

rtis

e is

ava

ilabl

e fro

m w

ithin

or o

utsi

de th

e N

RA.

9.2.

4.

Writ

ten

guid

elin

es fo

r ass

essm

ent o

f clin

ical

tria

ls a

nd c

hang

es a

re im

plem

ente

d.

9.2.

5.

Writ

ten

guid

elin

es a

nd fo

rms

on th

e da

ta re

quire

men

ts, t

he fo

rmat

and

pro

cedu

res

for s

ubm

ittin

g a

clin

ical

tria

l app

licat

ion

are

avai

labl

e to

spo

nsor

s.

9.2.

6.

Prov

isio

n fo

r sci

entifi

c ad

vice

(e.g

. pre

clin

ical

and

clin

ical

) on

the

desi

gn o

f clin

ical

tria

ls o

r iss

ues

rela

ted

to th

e su

bmis

sion

of a

ppro

pria

te d

ata

is in

pla

ce.

9.2.

7.

Ther

e ar

e w

ritte

n gu

idel

ines

for G

CP.

Assessment criteriA for nAtionAl blood regulAtory systems 27

9.

Cont

rol o

f clin

ical

tria

lsAp

plic

able

to b

lood

, blo

od c

ompo

nent

s, p

lasm

a-de

rived

med

icin

al p

rodu

cts,

ass

ocia

ted

subs

tanc

es, a

nd m

edic

al d

evic

es in

clud

ing

in v

itro

diag

nost

ics

Mai

n cr

iteria

rela

ted

to th

e fu

nctio

nR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

9.3.

Dat

a re

quire

men

ts fo

r clin

ical

tr

ial a

pplic

atio

ns a

re d

efine

d.R

R R R

9.3.

1.

Prod

uctio

n an

d qu

ality

con

trol o

f the

clin

ical

can

dida

te m

ater

ial (

e.g.

pro

duct

cha

ract

eriz

atio

n,

labo

rato

ry s

peci

men

s) a

re in

clud

ed.

9.3.

2.

Prov

isio

n fo

r pre

clin

ical

dat

a ex

ists

.

9.3.

3.

Asse

ssm

ent o

f the

clin

ical

tria

l pro

toco

l with

resp

ect t

o pa

tient

saf

ety

and

info

rmed

con

sent

is

perfo

rmed

.

9.4.

Ass

uran

ce o

f eth

ical

ove

rsig

ht

exis

ts.

RR S S S

9.4.

1.

A sy

stem

of i

ndep

ende

nt e

thic

al re

view

and

app

rova

l exi

sts

in a

ccor

danc

e w

ith th

e pr

inci

ples

of

GCP.

9.4.

2.

Ethi

cs c

omm

ittee

s (e

.g. t

he In

stitu

tiona

l Rev

iew

Boa

rd) a

re fo

rmal

ly d

efine

d, in

clud

ing

thei

r co

mpo

sitio

n.

9.4.

3.

The

ethi

cs c

omm

ittee

s in

clud

e m

embe

rs e

xter

nal t

o th

e co

ncer

ned

inst

itutio

n.

9.4.

4.

The

role

s an

d du

ties

of e

thic

s co

mm

ittee

s to

ove

rsee

clin

ical

tria

ls a

re o

utlin

ed.

* R=r

equi

red;

S=s

ugge

sted

28

10. S

yste

m fo

r lot

rele

ase o

f pla

sma-

deriv

ed m

edic

inal

pro

duct

sAp

plic

able

to p

lasm

a-de

rived

med

icin

al p

rodu

cts

and

dono

r scr

eeni

ng te

sts

Mai

n cr

iteria

rela

ted

to th

e fu

nctio

nR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

10.1

. Leg

al p

rovi

sion

s fo

r offi

cial

lo

t rel

ease

cer

tifica

tion

are

in

plac

e.

RR R S

10.1

.1.

The

NRA

has

the

auth

ority

to is

sue

lot r

elea

se c

ertifi

cate

s an

d th

e en

forc

emen

t pow

er to

su

spen

d or

revo

ke lo

t rel

ease

.

10.1

.2.

The

NRA

has

the

lega

l aut

horit

y to

per

form

lot r

elea

se a

nd/o

r hav

e in

pla

ce a

pol

icy

and

crite

ria

for a

ccep

tanc

e of

lot r

elea

se p

erfo

rmed

by

anot

her N

RA (e

.g. a

lot r

elea

se c

ertifi

cate

from

the

coun

try

of o

rigin

).

10.1

.3.

Writ

ten

crite

ria fo

r exe

mpt

ion

from

lot r

elea

se e

xist

.

10.2

. A

lot r

elea

se s

yste

m is

es

tabl

ishe

d an

d op

erat

iona

l.R

R R R R R R R S

10.2

.1.

Lot

rele

ase

prot

ocol

s an

d pr

oced

ures

are

est

ablis

hed

and/

or a

ccep

tanc

e of

lot r

elea

se

perfo

rmed

by

anot

her N

RA is

in p

lace

.

10.2

.2.

Lot r

elea

se is

bas

ed a

t a m

inim

um o

n re

view

of s

umm

ary

lot-s

peci

fic d

ata.

10.2

.3.

Qual

ified

sta

ff m

embe

rs (i

.e. s

taff

with

rele

vant

qua

lifica

tions

, tra

inin

g an

d ex

perie

nce)

are

av

aila

ble

to p

erfo

rm lo

t rel

ease

.

10.2

.4.

Test

ing

polic

y an

d te

st p

roto

cols

incl

udin

g ac

cept

ance

crit

eria

are

defi

ned.

10.2

.5.

Reco

rds

on lo

t rel

ease

are

mai

ntai

ned.

10.2

.6.

Proc

edur

es fo

r com

mun

icat

ion

with

the

prod

uct m

anuf

actu

rer a

re d

efine

d.

10.2

.7.

Writ

ten

proc

edur

es a

nd g

uide

lines

(inc

ludi

ng te

mpl

ates

of c

ertifi

cate

s), c

heck

lists

, and

/or

SOPs

are

dev

elop

ed a

nd u

sed

to re

view

sum

mar

y lo

t pro

toco

ls a

nd a

re im

plem

ente

d fo

r the

lot

rele

ase

proc

ess.

10.2

.8.

Test

ing

proc

edur

es a

re e

xter

nally

acc

redi

ted.

Assessment criteriA for nAtionAl blood regulAtory systems 29

10. S

yste

m fo

r lot

rele

ase o

f pla

sma-

deriv

ed m

edic

inal

pro

duct

sAp

plic

able

to p

lasm

a-de

rived

med

icin

al p

rodu

cts

and

dono

r scr

eeni

ng te

sts

Mai

n cr

iteria

rela

ted

to th

e fu

nctio

nR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

10.3

. A q

ualit

y m

anag

emen

t sy

stem

for o

ffici

al lo

t rel

ease

is

impl

emen

ted.

RR S S

10.3

.1.

The

labo

rato

ry th

at p

erfo

rms

lot r

elea

se w

ithin

or f

or th

e N

RA c

ompl

ies

with

Cor

e fu

nctio

n 8.

10.3

.2.

Appr

opria

te d

ata

colle

ctio

n an

d an

alys

is (e

.g. l

ot-to

-lot c

onsi

sten

cy, t

rend

ana

lysis

) is

impl

emen

ted.

10.3

.3.

Cont

inua

l rev

iew

and

sci

entifi

c di

alog

ue e

xist

with

the

man

ufac

ture

rs a

nd p

rodu

ct re

view

exp

erts

on

issu

es o

f qua

lity

test

resu

lts.

10.4

. Acc

ess

to p

rodu

ct-re

late

d do

cum

enta

tion

to g

uide

pa

rtic

ular

are

as o

f scr

utin

y in

lo

t rel

ease

is p

ossi

ble.

RR R R R

10.4

.1.

App

rove

d re

leva

nt m

arke

ting

auth

oriz

atio

n an

d its

upd

ates

are

ava

ilabl

e.

10.4

.2.

Acce

ss to

com

plai

nts

and

adve

rse

even

t (AE

) rep

orts

is p

ossi

ble.

10.4

.3.

Acce

ss to

the

man

ufac

ture

r’s b

atch

reco

rds

is p

ossi

ble.

10.4

.4.

Acce

ss to

insp

ectio

n re

port

s is

pos

sibl

e.* R

=req

uire

d; S

=sug

gest

ed

30

11. R

egul

ator

y ins

pect

ions

and

enfo

rcem

ent a

ctivi

ties

Appl

icab

le to

blo

od, b

lood

com

pone

nts,

pla

sma-

deriv

ed m

edic

inal

pro

duct

s, a

ssoc

iate

d su

bsta

nces

, and

med

ical

dev

ices

incl

udin

g in

vitr

o di

agno

stic

s

Mai

n cr

iteria

rela

ted

to th

e fu

nctio

nR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

11.1

. Leg

al p

rovi

sion

exi

sts

to

insp

ect p

rem

ises

whe

re

regu

late

d ac

tiviti

es a

re

perf

orm

ed in

ord

er to

ass

ess

and

enfo

rce

com

plia

nce

with

the

appl

icab

le la

ws,

re

gula

tions

and

sta

ndar

ds.

RR R R R R R

11.1

.1.

A m

anda

te e

xist

s fo

r ins

pect

ions

by

the

NRA

and

enf

orce

men

t of c

ompl

ianc

e w

ith p

rinci

ples

of

GM

P, G

DP

and

othe

r sta

ndar

ds.

11.1

.2.

App

licab

le s

tand

ards

and

pra

ctic

es a

re d

efine

d in

lega

l pro

visi

ons.

11.1

.3.

The

NRA

has

the

auth

ority

to ta

ke e

nfor

cem

ent a

ctio

n ag

ains

t the

acc

ount

able

com

pani

es o

r pe

rson

s th

at a

re n

ot in

com

plia

nce.

11.1

.4.

The

NRA

has

the

auth

ority

to s

ampl

e pr

oduc

ts, m

anuf

actu

ring

mat

eria

ls a

nd re

cord

s if

nece

ssar

y.

11.1

.5.

The

NRA

has

the

auth

ority

to re

call

prod

ucts

.

11.1

.6.

Pro

visi

ons

exis

t for

con

flict

of i

nter

est a

nd c

onfid

entia

lity.

11.2

. Ins

pect

ion

and

enfo

rcem

ent

syst

ems

are

esta

blis

hed

and

oper

atio

nal.

RR R R R R

11.2

.1.

Est

ablis

hed

polic

ies

and

prog

ram

mes

exi

st fo

r con

duct

ing

insp

ectio

ns o

f all

regu

late

d ac

tiviti

es.

11.2

.2.

An in

spec

tion

plan

exi

sts

with

ade

quat

e hu

man

and

fina

ncia

l res

ourc

es fo

r con

duct

ing

insp

ectio

ns a

t app

ropr

iate

inte

rval

s.

11.2

.3.

The

NRA

mai

ntai

ns fi

les

of e

ach

insp

ectio

n, in

clud

ing

the

insp

ectio

n re

port

and

fina

l dec

isio

ns

take

n.

11.2

.4.

Ther

e is

an

esta

blis

hed

proc

ess

for a

ppro

pria

te re

gula

tory

act

ion

to a

ddre

ss in

spec

tiona

l fin

ding

s (e

.g. r

ecal

l of p

rodu

cts,

am

ende

d lic

ence

s).

11.2

.5.

If th

e m

echa

nism

is a

dopt

ed, p

rovi

sion

s ex

ist f

or a

ccep

tanc

e of

ext

erna

l ins

pect

orat

es a

ccor

ding

to

inte

rnat

iona

lly re

cogn

ized

sta

ndar

ds.

Assessment criteriA for nAtionAl blood regulAtory systems 31

11. R

egul

ator

y ins

pect

ions

and

enfo

rcem

ent a

ctivi

ties

Appl

icab

le to

blo

od, b

lood

com

pone

nts,

pla

sma-

deriv

ed m

edic

inal

pro

duct

s, a

ssoc

iate

d su

bsta

nces

, and

med

ical

dev

ices

incl

udin

g in

vitr

o di

agno

stic

s

Mai

n cr

iteria

rela

ted

to th

e fu

nctio

nR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

11.3

. Ins

pect

ors

with

app

ropr

iate

ex

pert

ise

and

qual

ifica

tions

ar

e av

aila

ble.

RR R S

11.3

.1.

Ins

pect

ors

have

the

appr

opria

te e

xper

tise

and

train

ing

to c

ondu

ct in

spec

tions

of b

lood

es

tabl

ishm

ents

, and

man

ufac

ture

rs a

nd d

istri

buto

rs o

f pla

sma-

deriv

ed p

rodu

cts.

11.3

.2.

Trai

ning

of i

nspe

ctor

s in

clud

es s

peci

fic a

spec

ts re

late

d to

the

activ

ities

of r

elev

ant

esta

blis

hmen

ts.

11.3

.3.

Use

of a

team

app

roac

h is

pos

sibl

e in

ord

er to

incl

ude

spec

ializ

ed k

now

ledg

e an

d ex

pert

ise

in

spec

ific

prod

ucts

whe

re n

eede

d.

11.4

. A q

ualit

y m

anag

emen

t sy

stem

is im

plem

ente

d th

at is

co

nsis

tent

with

inte

rnat

iona

l pr

inci

ples

for p

harm

aceu

tical

an

d re

late

d in

spec

tora

tes.

RR S S

11.4

.1.

Writ

ten

proc

edur

es e

xist

for c

ondu

ctin

g in

spec

tions

(ins

pect

ion

man

ual)

and

follo

win

g-up

on

defic

ienc

ies

and/

or v

iola

tions

.

11.4

.2.

An e

stab

lishe

d pr

oced

ure

(e.g

. per

iodi

c in

tern

al a

nd e

xter

nal a

udits

) exi

sts

to m

onito

r the

in

spec

tion

proc

ess.

11.4

.3.

Mon

itorin

g of

tim

elin

es a

nd in

dica

ted

actio

ns is

impl

emen

ted.

11.5

. A re

call

syst

em e

xist

s w

ith

mec

hani

sms

to e

nsur

e th

e pr

oper

dis

posi

tion

of b

lood

, bl

ood

com

pone

nts,

pla

sma-

deriv

ed p

rodu

cts,

ass

ocia

ted

subs

tanc

es, a

nd m

edic

al

devi

ces

incl

udin

g in

vitr

o di

agno

stic

s.

RR R R R

11.5

.1.

Polic

y an

d pr

oced

ures

for a

reca

ll sy

stem

incl

udin

g pr

oduc

t dis

posi

tion

exis

t.

11.5

.2.

The

reca

ll sy

stem

is b

ased

on

defin

ed a

ctio

n an

d do

cum

ente

d co

mm

unic

atio

n to

the

appr

opria

te

leve

l of t

he d

istri

butio

n sy

stem

.

11.5

.3.

A fe

edba

ck m

echa

nism

exi

sts

to c

onfir

m th

at a

ppro

pria

te a

ctio

n (in

clud

ing

dest

ruct

ion

whe

n ne

cess

ary)

has

bee

n ta

ken

at a

ll ap

prop

riate

leve

ls.

11.5

.4.

Full

lot t

race

abili

ty is

in p

lace

.* R

=req

uire

d; S

=sug

gest

ed

32

12. V

igila

nce s

yste

ms

Appl

icab

le to

blo

od, b

lood

com

pone

nts,

pla

sma-

deriv

ed m

edic

inal

pro

duct

s, a

ssoc

iate

d su

bsta

nces

, and

med

ical

dev

ices

incl

udin

g in

vitr

o di

agno

stic

s

Mai

n cr

iteria

rela

ted

to th

e fu

nctio

nR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

12.1

. Leg

al p

rovi

sion

s fo

r a

natio

nal v

igila

nce

syst

em

exis

t.

RR R R

12.1

.1.

The

NRA

has

a le

gal m

anda

te a

nd e

nfor

cem

ent p

ower

for m

anda

tory

repo

rtin

g el

emen

ts o

f the

na

tiona

l vig

ilanc

e sy

stem

.

12.1

.2.

The

NRA

has

the

auth

ority

to s

peci

fy re

port

ing

of a

dver

se e

vent

s (A

Es) a

nd a

dver

se re

actio

ns

(ARs

) with

in th

e na

tiona

l vig

ilanc

e sy

stem

.

12.1

.3.

Auth

ority

exi

sts

to re

quire

the

mar

ketin

g au

thor

izat

ion

hold

er to

per

form

a s

peci

fic s

tudy

of

safe

ty a

nd/o

r effe

ctiv

enes

s in

the

post

-mar

ketin

g pe

riod.

12.2

. N

atio

nal v

igila

nce

syst

ems

for t

he m

onito

ring

and

man

agem

ent o

f AE

and

AR a

re e

stab

lishe

d an

d op

erat

iona

l.

RR R S S S

12.2

.1.

Role

s an

d re

spon

sibi

litie

s of

the

key

part

ies,

the

NRA

, and

sur

veill

ance

sta

ff in

volv

ed in

AE

and

AR m

onito

ring

and

man

agem

ent a

ctiv

ities

are

cle

arly

defi

ned

and

docu

men

ted.

12.2

.2.

Gui

delin

es e

xist

and

are

pub

lishe

d an

d ac

cess

ible

(i.e

. dis

tribu

ted

or a

vaila

ble

whe

n ne

eded

) to

all s

taff

invo

lved

in A

E an

d AR

sur

veill

ance

.

12.2

.3.

Gui

delin

es in

clud

e th

e fo

llow

ing:

a.

obje

ctiv

es o

f the

sys

tem

;b.

a

list o

f AEs

and

ARs

to b

e re

port

ed;

c.

case

defi

nitio

ns fo

r all

AEs

and

ARs

to b

e re

port

ed;

d.

info

rmat

ion

on h

ow to

repo

rt A

Es a

nd A

Rs fo

r all

bloo

d, b

lood

com

pone

nts,

pla

sma-

deriv

ed p

rodu

cts,

ass

ocia

ted

subs

tanc

es, a

nd m

edic

al d

evic

es in

clud

ing

in v

itro

diag

nost

ics

(i.e.

who

sho

uld

repo

rt, h

ow, w

here

and

whe

n re

port

s sh

ould

be

sent

);e.

th

e pr

oces

s fo

r ana

lysi

ng d

ata

and

prov

idin

g fe

edba

ck to

rele

vant

sta

ff an

d ke

y pa

rtie

s;f.

the

proc

ess

for i

nves

tigat

ing

and

resp

ondi

ng to

ser

ious

AEs

and

ARs

(inc

ludi

ng w

ho

shou

ld b

e in

cha

rge

of th

e in

vest

igat

ion)

;g.

th

e pr

oces

s fo

r inf

orm

ing

patie

nts,

par

ents

, the

com

mun

ity a

nd c

ount

ry (w

here

rele

vant

) of

the

findi

ngs

of a

n in

vest

igat

ion

and

rele

vant

act

ions

.

12.2

.4.

A st

anda

rdiz

ed re

port

ing

form

exi

sts

with

com

preh

ensi

ve in

form

atio

n to

mon

itor A

Es a

nd A

Rs.

12.2

.5.

A sy

stem

is e

stab

lishe

d fo

r pro

vidi

ng p

erio

dic

feed

back

on

AEs

and

ARs,

incl

udin

g su

mm

ary

and

spec

ific

inve

stig

atio

n re

port

s fro

m th

e na

tiona

l to

all l

evel

s (in

clud

ing

heal

th fa

cilit

y le

vel).

Assessment criteriA for nAtionAl blood regulAtory systems 33

12. V

igila

nce s

yste

ms

Appl

icab

le to

blo

od, b

lood

com

pone

nts,

pla

sma-

deriv

ed m

edic

inal

pro

duct

s, a

ssoc

iate

d su

bsta

nces

, and

med

ical

dev

ices

incl

udin

g in

vitr

o di

agno

stic

s

Mai

n cr

iteria

rela

ted

to th

e fu

nctio

nR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

12.3

. Gui

danc

e on

AE

and

AR

mon

itorin

g an

d m

anag

emen

t is

pro

vide

d to

app

ropr

iate

st

aff.

SS

12.3

.1.

Gui

delin

es a

nd te

mpl

ates

on

AE a

nd A

R re

port

ing

and

mon

itorin

g ar

e pr

ovid

ed to

app

ropr

iate

st

aff d

ealin

g w

ith A

E an

d AR

.

12.4

. The

re is

dem

onst

rate

d ca

paci

ty to

det

ect,

inve

stig

ate

and

take

act

ion

rega

rdin

g si

gnifi

cant

AEs

and

AR

s.

RR R R R R S

12.4

.1.

The

NRA

is re

gula

rly in

form

ed o

f dat

a re

leva

nt to

the

qual

ity a

nd s

afet

y of

blo

od p

rodu

cts

incl

udin

g:

a.

bloo

d tra

nsfu

sion

saf

ety;

b.

trans

mis

sibl

e di

seas

e su

rvei

llanc

e da

ta;

c.

devi

ce fa

ilure

s.

12.4

.2.

Man

ufac

ture

rs a

re re

quire

d to

info

rm th

e N

RA o

f any

new

saf

ety

issu

es o

r mar

ketin

g an

d/or

re

gula

tory

dec

isio

ns ta

ken

in o

ther

cou

ntrie

s.

12.4

.3.

Proc

edur

es fo

r ini

tiatin

g co

rrec

tive

and/

or re

gula

tory

act

ion

(e.g

. rec

all)

are

avai

labl

e.

12.4

.4.

Ther

e is

doc

umen

ted

capa

city

to in

vest

igat

e AE

s an

d AR

s, fo

r exa

mpl

e:a.

ro

utin

e re

port

ing

of A

Es a

nd A

Rs a

ccor

ding

to e

stab

lishe

d gu

idel

ines

and

/or

SOP

s;b.

a

clea

r und

erst

andi

ng a

nd a

dequ

ate

train

ing

amon

g ke

y pa

rtie

s of

resp

ectiv

e ro

les

and

resp

onsi

bilit

ies;

c.

acce

ss to

reso

urce

s (p

erso

nnel

, lab

orat

ory)

to c

ondu

ct c

ompr

ehen

sive

inve

stig

atio

ns.

12.4

.5.

Case

inve

stig

atio

ns a

re ti

mel

y an

d co

mpl

ete,

for e

xam

ple:

a.

timel

ines

are

est

ablis

hed

for p

rom

pt in

vest

igat

ion

and

prel

imin

ary

repo

rtin

g re

late

d to

se

rious

adv

erse

reac

tions

;b.

in

vest

igat

ion

is th

orou

gh a

nd fi

ndin

gs a

re c

lear

ly d

escr

ibed

.

12.4

.6.

Ther

e is

a d

emon

stra

ted

repo

rtin

g sy

stem

(act

ive

or p

assi

ve, s

entin

el o

r uni

vers

al) w

ith

satis

fact

ory

sens

itivi

ty, f

or e

xam

ple:

a.

annu

al n

umbe

r of r

epor

ts;

b.

repo

rtin

g ra

te;

c.

brea

kdow

n of

repo

rts

by ty

pes

of A

E, a

ge g

roup

, dis

trict

s et

c.* R

=req

uire

d; S

=sug

gest

ed

34

13. E

nsur

ing t

race

abili

ty a

nd re

cord

keep

ing b

y man

ufac

ture

rs fo

r all

regu

late

d pr

oduc

tsAp

plic

able

to b

lood

, blo

od c

ompo

nent

s, p

lasm

a-de

rived

med

icin

al p

rodu

cts,

ass

ocia

ted

subs

tanc

es, a

nd m

edic

al d

evic

es in

clud

ing

in v

itro

diag

nost

ics

Mai

n cr

iteria

rela

ted

to th

e fu

nctio

nR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

13.1

. The

NR

A en

sure

s th

at

stan

dard

s fo

r tra

ceab

ility

an

d re

cord

kee

ping

are

in

pla

ce fo

r all

aspe

cts

of m

anuf

actu

ring

and

dist

ribut

ion.

RR R

13.1

.1.

A re

quire

men

t exi

sts

for m

anuf

actu

rers

to im

plem

ent m

etho

ds a

nd m

aint

ain

reco

rds

that

ena

ble

trace

abili

ty, i

nclu

ding

:a.

fo

r man

ufac

ture

rs o

f blo

od p

rodu

cts,

trac

eabi

lity

from

don

or to

reci

pien

t and

vic

e ve

rsa;

b.

ensu

ring

the

inte

grity

of m

anuf

actu

ring

reco

rds

and

com

plet

enes

s of

dis

tribu

tion

reco

rds.

13.1

.2.

Proc

edur

es fo

r rec

ord

keep

ing

and

rete

ntio

n pe

riods

defi

ned

by th

e N

RA a

re a

vaila

ble.

* R=r

equi

red;

S=s

ugge

sted

14. I

nter

natio

nal c

oope

ratio

nAp

plic

able

to b

lood

, blo

od c

ompo

nent

s, p

lasm

a-de

rived

med

icin

al p

rodu

cts,

ass

ocia

ted

subs

tanc

es, a

nd m

edic

al d

evic

es in

clud

ing

in v

itro

diag

nost

ics

Mai

n cr

iteria

rela

ted

to th

e fu

nctio

nR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

14.1

. A n

atio

nal p

olic

y to

faci

litat

e in

tern

atio

nal c

oope

ratio

n an

d ha

rmon

izat

ion

is

impl

emen

ted.

SS S S

14.1

.1.

A n

atio

nal p

olic

y an

d/or

stra

tegy

on

inte

rnat

iona

l int

erac

tions

exi

st, e

.g. i

nfor

mat

ion

shar

ing

on

prod

uct a

ppro

vals

, saf

ety

data

and

pol

icy

initi

ativ

es.

14.1

.2.

Agr

eem

ents

exis

t bet

ween

the

NRA

and

oth

er in

tern

atio

nal o

rgan

izatio

ns a

nd re

gula

tory

au

thor

ities

.

14.1

.3.

The

NRA

par

ticip

ates

in in

tern

atio

nal h

arm

oniz

atio

n in

itiat

ives

and

foru

ms.

14.2

. Sh

arin

g of

risk

info

rmat

ion

with

inte

rnat

iona

l or

gani

zatio

ns a

nd o

ther

re

gula

tory

aut

horit

ies

is

impl

emen

ted.

RR S S S S

14.2

.1.

Abi

lity

is s

how

n by

the

NRA

to p

artic

ipat

e in

inte

rnat

iona

l ris

k m

anag

emen

t effo

rts

whe

n ne

eded

.

14.2

.2.

The

NRA

has

the

abili

ty to

eng

age

in in

tern

atio

nal r

isk

asse

ssm

ent w

hen

need

ed, e

.g. a

cces

s to

ep

idem

iolo

gica

l dat

a, e

xper

tise

in ri

sk a

sses

smen

t.

14.2

.3.

The

capa

city

or e

xper

tise

to a

cces

s ep

idem

iolo

gica

l dat

a an

d fo

rmal

ly a

sses

s ris

ks is

ava

ilabl

e.

14.2

.4.

Doc

umen

ted

proc

edur

es fo

r the

tim

ely

shar

ing

of ri

sk in

form

atio

n in

tern

atio

nally

exi

st.

14.2

.5.

Reco

rds

are

kept

of r

isk

info

rmat

ion

that

has

bee

n ex

chan

ged.

* R=r

equi

red;

S=s

ugge

sted

14. I

nter

natio

nal c

oope

ratio

nAp

plic

able

to b

lood

, blo

od c

ompo

nent

s, p

lasm

a-de

rived

med

icin

al p

rodu

cts,

ass

ocia

ted

subs

tanc

es, a

nd m

edic

al d

evic

es in

clud

ing

in v

itro

diag

nost

ics

Mai

n cr

iteria

rela

ted

to th

e fu

nctio

nR

atin

g*

Indi

cato

rs re

late

d to

the

mai

n cr

iteria

Mai

n cr

iteria

Indi

cato

r

14.1

. A n

atio

nal p

olic

y to

faci

litat

e in

tern

atio

nal c

oope

ratio

n an

d ha

rmon

izat

ion

is

impl

emen

ted.

SS S S

14.1

.1.

A n

atio

nal p

olic

y an

d/or

stra

tegy

on

inte

rnat

iona

l int

erac

tions

exi

st, e

.g. i

nfor

mat

ion

shar

ing

on

prod

uct a

ppro

vals

, saf

ety

data

and

pol

icy

initi

ativ

es.

14.1

.2.

Agr

eem

ents

exis

t bet

ween

the

NRA

and

oth

er in

tern

atio

nal o

rgan

izatio

ns a

nd re

gula

tory

au

thor

ities

.

14.1

.3.

The

NRA

par

ticip

ates

in in

tern

atio

nal h

arm

oniz

atio

n in

itiat

ives

and

foru

ms.

14.2

. Sh

arin

g of

risk

info

rmat

ion

with

inte

rnat

iona

l or

gani

zatio

ns a

nd o

ther

re

gula

tory

aut

horit

ies

is

impl

emen

ted.

RR S S S S

14.2

.1.

Abi

lity

is s

how

n by

the

NRA

to p

artic

ipat

e in

inte

rnat

iona

l ris

k m

anag

emen

t effo

rts

whe

n ne

eded

.

14.2

.2.

The

NRA

has

the

abili

ty to

eng

age

in in

tern

atio

nal r

isk

asse

ssm

ent w

hen

need

ed, e

.g. a

cces

s to

ep

idem

iolo

gica

l dat

a, e

xper

tise

in ri

sk a

sses

smen

t.

14.2

.3.

The

capa

city

or e

xper

tise

to a

cces

s ep

idem

iolo

gica

l dat

a an

d fo

rmal

ly a

sses

s ris

ks is

ava

ilabl

e.

14.2

.4.

Doc

umen

ted

proc

edur

es fo

r the

tim

ely

shar

ing

of ri

sk in

form

atio

n in

tern

atio

nally

exi

st.

14.2

.5.

Reco

rds

are

kept

of r

isk

info

rmat

ion

that

has

bee

n ex

chan

ged.

* R=r

equi

red;

S=s

ugge

sted

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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 Health Organization, 2007 (WHO Technical Report Series, No. 941, Annex 4).

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Resolution WHA63.12. Availability, safety and quality of blood products. In: Sixty-third World Health Assembly, Geneva, 17-21 May 2010, Volume 1, Resolutions. Geneva, World Health Organization, 2010 (WHA63/2010/REC/1).

WHO good manufacturing practices for blood establishments. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations. Forty-fifth report. Geneva, World Health Organization, 2011 (WHO Technical Report Series, No. 961, Annex 4).

WHO good manufacturing practices: main principles for pharmaceutical products. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations. Forty-Fifth Report Geneva, World Health Organization, 2011 (WHO Technical Report Series, No. 961, Annex 3).

Supplementary guidelines on good manufacturing practices: validation. WHO Expert Committee on Specifications for Pharmaceutical Preparations. Fortieth Report. Geneva, World Health Organization, 2006 (WHO Technical Report Series, No. 937, Annex 4).

WHO good manufacturing practices for sterile pharmaceutical products. WHO Expert Committee on Specifications for Pharmaceutical Preparations. Forty-Fifth Report Geneva, World Health Organization, 2011 (WHO Technical Report Series, No. 961, Annex 6).

Catalogue of the WHO International Biological Reference Preparations: blood products and related substances (http://www.who.int/entity/bloodproducts/catalogue/en/index.html).