Guidance for procurementof in vitro diagnostics andrelated laboratory items
and equipment

Guidance for procurementof in vitro diagnostics andrelated laboratory items
and equipment

Guidance for procurement of in vitro diagnostics and related laboratory items and equipment
ISBN 978-92-4-151255-8
This publication supersedes the manual that was published in 2013 under the title “Manual for procurement of diagnostics and related
laboratory items and equipment”.
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CONTENTS
Abbreviations

3

Glossary

4

Scope and intended audience

6

Acknowledgments

6

Introduction
How best practices for procurement benefits programmess
Where to deploy in vitro diagnostic medical devices, including testing at point-of-care77
7

Users of IVDs
Needs assessment

9
9
9
11
12
12
12
13
14
17

Standardization and harmonization

How to quantify procurement demand and make procurement decisions
Budgeting
Product selection for procurement
Quality specifications
Product specifications (performance and operational characteristics)
Performance characteristics of IVDs
Operational characteristics of IVDs
Specific issues related to IVDs that require equipment

Testing strategies, validation of testing algorithms, and standardization and harmonization
Standardized testing strategies for specific testing objectives
Product selection - validated testing algorithms

Equipment MaintenancePost-market surveillance, including lot testing and complaint reporting
Monitoring complaints, including adverse events
Lot testing

Procurers of IVDs
Sourcing vendors
Embargos

Bid solicitation

Methods of solicitation
Solicitation documentation

Bid evaluation

Bid response
Evaluation of substantially responsive bids
Contracting

Quantifying procurement demand
Monitoring procurement practices
Evaluating supplier performance

Manufacturers of IVDs
Delivery of goods
Installation, training, maintenanceRequirements for installation
Training requirements
MaintenanceWarranty
Post-market surveillance
Decommissioning IVDs

17

18
18
18
18
19
20
20
21
21
21
21
21
21
23
23
24
24
26
26
26
27
27
27
27
27
27
28
28
29

iii

National regulatory authorities for IVDs
Regulatory approvals
Post-market surveillance

30
30
31

WHO
WHO prequalification assessment

32
32
32
32
32
32
33
33

Eligibility for WHO prequalification assessment
Product dossier review
Inspection of the site of manufacture
Independent evaluation of performance and operational characteristics
Final prequalification decision

Post-market surveillance for WHO prequalified products

iv

Donations

34

References

35

Annexes
Annex 1. Checklist for 12 key aspects for needs assessment for instruments and analysers
Annex 2. Methodology for product selection – using the principles of verification
Annex 3. INCOTERMS 2010

36
36
37
40

GUIDANCE FOR PROCUREMENT OF IN VITRO DIAGNOSTICS AND RELATED LABORATORY ITEMS AND EQUIPMENTABBREVIATIONS
CD4
CFR
CIF
CLIA
CLSI
ECL
EIA
ELISA
EOI
EQA
EQAS
FSCA
FSN
GAVI Alliance
GFATM
ICB
IMDRF
INCOTERM
ISO
ITB
IVD
LTA
NAT
NGO
NRA
NRL
OD/CO
OTIF
PEPFAR
PO
POCT
PMI
PMS
PSM
QA
QC
QMS
RDT
RFP
RFQ
SOP
SOW
TCO
TOR
UN
WHO

CD4 T-lymphocyte
cost and freight
cost insurance and freightchemiluminescence immunoassay
Clinical and Laboratory Standards Instituteelectrochemiluminescence immunoassay
enzyme immunoassay
enzyme-linked immunosorbent assay
expression of interest
external quality assessment
external quality assessment scheme
field safety corrective action
field safety notice
The Global Alliance for Vaccines and Immunization
The Global Fund to fight AIDS, Tuberculosis and Malariainternational competitive bidding
International Medical Device Regulators Forum
International Commercial Terms
International Standards Organization
invitation to bid
in vitro diagnostic medical device
long term agreement
nucleic acid testing
nongovernmental organisation
national regulatory authority (for medical products)
national reference laboratory
optical density to cut-off
on time and in fullPresident's Emergency Plan for AIDS Reliefpurchase order
point of care testing
President’s Malaria Initiative
post-market surveillance
procurement and supply management
quality assurance
quality control
quality management system
rapid diagnostic tests
request for proposal
request for quote
standard operating procedure
scope of work
total cost of ownershipterms of reference
United Nations
World Health Organizationv

GLOSSARYvi

AnalyteA substance or chemical constituent that is analyzed (identified or measured) by
the assay, e.g. polyclonal or monoclonal antibodies or antigen

Analyser

Equipment that consume reagents, consumables and produce a test result. Usually
repaired and maintained by service contracts.

Ancillary equipment

Freezer, washers, readers, incubators, etc. Usually repaired and serviced by incountry biomedical engineers.

Cleaning

Process to remove any type of contamination, visible or not.

Consumables

Items that are used once during testing and are not reused e.g. gloves, pipette tips,
etc.

Decontamination

Procedure that eliminates or reduces microbial or toxic agents to a safe level withrespect to the transmission of infection or other adverse effects.

Disinfection

Process to reduce the number of microorganisms but not usually of bacterial
spores, without necessarily killing or removing all organisms, usually from nonliving objects such as laboratory equipment or laboratory benches.

DurablesItems that can be reused for multiple tests such as glassware, plastic ware, etc.

Equipment

Items such as analysers that may be used for a range of specific assays and generallaboratory equipment such as centrifuges, pipettes and incubators

External quality assessment

A programme designed to assess laboratory performance, i.e. assessment of
the quality of the entire testing process from collection of specimen, the testingprocedure, to the reporting of testing results. Usually composed of one or moreof the following activities: site visits, participation in external quality assessment
schemes/proficiency testing and inter-laboratory comparison.

Hazardous waste

Waste that is potentially harmful to human beings, property or the environment.
E.g. used reagent strips contaminated with human blood, reagent solution
containing sodium azide, decommissioned instruments containing heavy metals.
Includes waste that is flammable, combustible, ignitable, corrosive, toxic, reactive,
injurious or infectious.

In vitro diagnostic medical
device (IVD)

A medical device, used alone or in combination, intended by the manufacturer forthe examination of specimens derived from the human body solely or principally
to provide information for diagnostic, monitoring or compatibility purposes. For
example, IVDs can be used for the following test purposes: diagnosis, screening,monitoring, predisposition, prognosis, prediction, determination of physiologicalstatus. IVDs also include reagents, calibrators, control materials and specimen
receptacles.
Note: Rapid diagnostics tests, enzyme immunoassays, nucleic acid testing
technologies, are all examples of IVDs.

Life-cycle

All phases in the life of a IVD, from the initial conception to final decommissioning
and disposal.

Manufacturer

Any natural or legal person with responsibility for design and/or manufacture of
an IVDs with the intention of making the IVD available for use, under their name;whether or not such an IVD is designed and/or manufactured by that person
themselves or on their behalf by another person(s).

Point of care testing

Also referred to as near-patient testing. Testing that is performed near or at thesite of the patient leading to a possible change in the care of the patient. Testing
performed outside of a central laboratory environment, generally near to, or at thesite of the patient.

GUIDANCE FOR PROCUREMENT OF IN VITRO DIAGNOSTICS AND RELATED LABORATORY ITEMS AND EQUIPMENTProcurement and supply
management

A systematic activity that ensures the continuous quality and availability of
products through optimal procurement planning, storage and distribution frommanufacturer to the end-user.

Quality assurance

Part of quality management focused on providing confidence that quality
requirements have been met. A comprehensive set of policies, procedures andpractices used to monitor the entire testing process of a testing service and toensure that the testing site results are reliable.
Note: QA includes monitoring; evaluating; taking corrective actions, if necessary
based on evaluations; and monitoring corrective actions for the testing services
preanalytical, analytical and post analytical activities. These activities include, but
are not limited to, recordkeeping, calibration and maintenance of equipment,
quality control, proficiency testing and training.

Quality control

Part of quality management focused on fulfilling quality requirements. The set ofprocedures designed to monitor the test method and the results to ensure test
system performance. QC includes testing control materials, charting the results, andanalyzing sources of error, and evaluating and documenting and remedial action
take as a result of this analysis.
Note: QC does not control for the provision of correct testing results but rather
indicates the test system (assay) has worked correctly.

Quality management system

A management system that directs and controls an organization with regard
to quality, comprising an organizational structure, procedures, processes andresources.

Quality improvement

Part of quality management, focused on increasing the ability to fulfil quality
requirements.

Reagents

Part of an IVD that produces a signal via a chemical or electrochemical reaction,
which allows the quantity to be detect and its value measured in a specimen.
A substance that produces a chemical reaction in a specimen that allows for ananalyte to be detected and measured. E.g. specific reagents for CD4 enumeration,
as well as general reagents such as ethanol , methanol, sodium chloride, etc.

Risk management

Each manufacturer shall establish and maintain an ongoing process of risk
management which involves the entire product lifecycle, from the conception
to decommission, to identify the hazards associated to an IVD, to estimate andevaluate the risks involved, to control the risks and evaluate the effectiveness ofestablished controls. This program shall include the following elements: analysis,
assessment, control and risk monitoring.

Sensitivity

Ability of an IVD to identify the presence of a target marker associated with aparticular disease or condition.

Specificity

Ability of an IVD to recognize the absence of a target marker associated with aparticular disease or condition.

Sterilization

Process to render a medical device (or other item) as free of viable microorganisms
through inactivation of microbiological contaminants.

Supplier

A participant in the procurement process either as a contractor or as an entity thatmakes a submission (bid or offer).

Vendor

A potential or actual Supplier or provider of goods, services and/or works. A
Vendor may take various forms, including an individual person, a company(whether privately or publicly held), a partnership, a government agency or anongovernmental organisation.

WHO Prequalification of In
Vitro Diagnostics

An assessment of the safety, performance/operational characteristics andmanufacturing quality of in vitro diagnostics, as performed by WHO.

vii

SCOPE AND INTENDED
AUDIENCE

The purpose of Guidance for Procurement of Diagnostics
and Related Laboratory Items and Equipment is to provide
information on procurement processes specific to HIV
and HIV-related in vitro diagnostics, laboratory items
and equipment. This guidance is not intended to replace
existing guidelines on basic procurement processes but
rather to enhance and extend current processes to include
specific issues related to diagnostics and related items/
equipment that are considered essential to ensure highquality testing services.
The intended audience are WHO Member States including
programme managers, end-users, procurement officers; staff
in United Nations (UN) agencies; and non-governmentalorganizations (NGOs) who conduct the selection and useof in vitro diagnostics and related laboratory items andequipment.
Users of this guidance who procure with financial resourcesfrom multilateral or bilateral agencies or sources otherthan national funds will be obliged to follow the rules,
regulations and policies of the funding organization. As

viiisuch there may be certain guidance that is different to theguidance set down in this document.
Finally, the country programmes themselves should be theultimate decision makers for procurement decisions.
See section 6 (bibliography) for further useful reading.

ACKNOWLEDGMENTS

This document was originally conceived and written by
Anita Sands. David Whybrew and Judy McCloud of Crown
Agents provided input in the initial development stage.
Paula Fernandes of Global Scientific Solutions for Health(GHSS) edited “the Manual for procurement of diagnostics
and related laboratory items and equipment” and provided
additional technical input. Jason Williams, Peter Smith andFarouk Umaru assisted Anita Sands to write this document.
René Becker-Burgos, Diane Bell, Sue Best, Katrien Fransen,
Vincent Habiyambere, Lisa Hedman, Francesco Marinucci,
Trevor Peter, Lorenzo Witherspoon and Bibiana Zamaro
reviewed and provided input into this document.

GUIDANCE FOR PROCUREMENT OF IN VITRO DIAGNOSTICS AND RELATED LABORATORY ITEMS AND EQUIPMENTINTRODUCTION
How best practices for procurement benefits programmess
Testing programmes strive to procure products that areappropriate for the intended setting of use at the most
reasonable price to ensure that testing is accessible for
all who need it. When procurement is not conducted inaccordance with documented best practices, the products
procured may not be appropriate for use by the intended
user or for the intended setting. Therefore, the qualityof procurement practices have a direct impact on theeffectiveness of programme funding for testing services, forexample, when analysers are purchased that require more
highly trained staff or when rapid diagnostic tests (RDTs) areprocured that are not validated for capillary whole blood
specimens. Poorly conducted procurement has a hugeprogrammatic impact if stability of products and allowableshelf life for labile reagents are not foreseen as part of the
procurement process. Currently, many testing programmes
procure their annual needs to avoid repeating an often
long and complex procurement process. This guidance
aims to highlight the necessary factors to consider when
procuring in vitro diagnostic medical devices (IVDs) andother laboratory items.
It has been documented that without sound procurement
policy, ten recurring challenges are likely to present
including: lack of adherence to existing procurement policy,
misalignment with service delivery policy, tiers of testing
network not defined, effective coordinating body lacking,inadequate equipment maintenance and data availability,
managing frequent shifts in technology, human resources,
competing priorities, and political agendas. (Williams J. etal., 2016)
Therefore, it is critical that laboratory policies, procurement
policies and treatment guidelines are aligned so as toprovide a responsive and appropriate service to clients.

Where to deploy in vitro diagnostic medical devices, including
testing at point-of-care
Tiered and integrated testing networks are fundamental
to ensure accessibility and equity in clinical testing for
diagnosis and surveillance of disease and monitoring oftreatment, see Figure 1. An integrated testing network can
maximise the impact of limited resources by providing
appropriate testing services tailored to the required scopeand capacity of each facility. At the national level, services
may be targeted towards disease surveillance, training,
evaluation, quality assurance, and testing. Conversely, atthe peripheral level, the focus may be on early detectionof diseases of public health importance using simpler
diagnostic tools such as microscopy and RDTs. District andtertiary levels offering expanded diagnostic capacity andscope would serve as referral centres for more complex
diagnoses referred from the peripheral levels.
Point-of-care testing is emerging as an indispensable partof national disease control programmes. Certain IVDs are
suited for use at point-of-care, particularly those that don’t
require phlebotomy or cold chain storage of reagents thatare robust in adverse environments and for which results
can be returned quickly to effect a decision for a given
patient. The terminology of point-of-care test or device
can be misleading as a product category, as it is where the
IVD is used that determines if testing is at point-of-care ornear to point-of-care, rather than certain properties of aparticular IVD. It is critical that testing undertaken at pointof-care be included, and therefore supported, by the tiered
testing network.
Each country will define the scope of testing services
through a network that meets their clinical needs andexpectations. It is advisable to assess aspects of thelaboratory network including, but not limited to: disease
patterns, existing supply chain infrastructure and function,
laboratory services, infrastructure and personnel.

1Introduction
Figure 1. Illustrative example of the tiered testing network

Lab-NAT/CLIA/ECL/EIA/WB/RDT

4

Lab-NAT/POC-NAT/CLIA/ECL/EIA/WB/
RDT

3Provincial/regional
Senior laboratory specialists / technicians

POC-NAT/EIA/RDT

2

DistrictLaboratory technicians

RDT

1

Primary care
Health-care workers, trained lay providers

0Community/outreachCommunity workers, trained lay
providers

RDT

National
Senior laboratory specialists

Facilitybased
testing

Non-facilitybased
testing

Source: Short, medium, long term product development priorities in HIV-related diagnostics. WHO expert meeting report.
Geneva: World Health Organization; 2012
Note: with evolving technology development, POC-NAT may soon be possible at Level 1 health facilities.

Quality of testing

Any site conducting testing using IVDs should operate
within a quality management system, see Figure 2. There
are twelve components of a quality management system
where a quality management system defines a systematic
approach to ensuring quality of testing through useof standard operating procedures, management of
documents and records, implementation of process(quality) control, and participation in external quality
assessment (through proficiency testing and on-site
supervision). The quality system must also extend to
appropriate physical infrastructure, procedures forpurchasing and inventory, equipment maintenance,
customer service, human resource management andreview including pre-service and in-service competencybased training, and continual process improvement(otherwise known as quality improvement).
Source: ISO 15189:2012 Medical laboratories -Requirements for quality and competence, International
Standards Organization, 2012

Figure 2. Twelve components of a quality management system
Organization

Personnel

Equipment

Purchasing & inventory

Process control

Information management

Documents & records

Occurence management

Assessment

Process improvement

Customer service

Facilities & safety!

2

GUIDANCE FOR PROCUREMENT OF IN VITRO DIAGNOSTICS AND RELATED LABORATORY ITEMS AND EQUIPMENTStandardization and harmonization
The 2008 “Maputo Declaration on strengthening oflaboratory systems”1 called on governments, donors, andimplementing partners to ensure a commitment to work
collaboratively, and in close coordination with national
authorities to support sustainable laboratory systemstrengthening efforts. Moreover, to create a unified andaligned national laboratory network that responds to the
public health needs of governments. Standardization efforts
shape procurement policies and procurement practice,aiming to create efficient and rational use of reagentsand instrumentation, streamlining of product selectionand equipment maintenance approaches, and simplify
forecasting and quantification.
There are many benefits in harmonization andstandardization, but efforts can be challenging due to theimplications of evolving diagnostic coverage and shifts inclinical needs that occur as part of health response efforts,
health system maturation, existing procurement policies,
policy and guideline adherence, as well as changes inexisting demographic and morbidity demands. Therefore,
attempts at harmonization and standardization should not
overlook the requirement to recognize that these efforts
are dynamic and require frequent reviews is an importantprinciple to address as part of all standardization efforts andshould inform forward planning initiatives (see Figure 3).

6

iew

1

Rev

As
se
ss

Conso
findinglidates

In order to conduct or update a needs assessment for
instruments and analysers, a checklist of 12 key aspects for
procurement should be referenced, see Annex 1.

Figure 3. The dynamic process of country-driven harmonization andstandardization

4

M
An OH
do d p ap
cu ol prom icy va
en
l
tat
ion

2

A needs assessment must take into account the testing
requirements at each level of any health system. Healthfacilities will vary within country, particularly in terms ofhuman resource capacity, infrastructure, and client needs.
It is important to ensure that procurement is aligned withcountry preferences through adherence to laboratory
policies, minimum packages of care, and national care andtreatment guidelines. In particular, national laboratory
harmonization and standardization efforts should
be observed and, if necessary, procurement practice
should be unified with policy by ensuring that clinical,
programmatic, and laboratory development and service
delivery expectations are current and are responsive to theevolving public health demands.

Disseminateand implem
ent

Needs assessment

Harmonization and standardization policies should not be
considered static. Reviews should occur periodically but
implementation progress and technology updates can bereviewed more frequently as part of national quantification
efforts. As systems and clinical demands shift, technology
advances, and existing instruments age and become
obsolete, national instrument lists and testing profile
updates are required to align service delivery expectations
and ensure the ability to provide such services.

5

USERS OF IVDS

3

d
ase
ce b ationnez
Evidndardista

A harmonization and standardization plan is a countrydriven initiative supported by a multi-stakeholder approach
usually conducted in a workshop setting through aconsensus driven process. Firstly, a national test menu isdeveloped, defined by tiered health care level. This effort
should include clinicians and programme managers, aswell as laboratory staff and procurement officers to ensurethat the diagnostic needs are clearly defined. Then, theproposed test menu is reviewed by laboratory technicalexperts, to establish appropriate methodologies to be
employed to provide such services. Efforts then focus on
the development of a proposed harmonized instrument
list by tiered level, the necessary ancillary equipment
requirements, and staffing required to respond to thedefined testing menu. All workshop activities conclude by
developing a way-forward approach in advancing the final
harmonization proposal and defining future procurement

1 Maputo Declaration to to Strengthen Laboratory Systems. Brazzaville, World Health Organization Regional Officefor Africa, 2008. Accessed on 12 October 2016 at http://www.who.int/diagnostics_laboratory/Maputo-Declaration_2008.pdf

3

Users of IVDs
practice, see Figure 4. Critically, the outcome of theworkshop must be accepted at the policy level in order for
it to be effective and implementable.
When implemented, standardization efforts streamline
product selection, and therefore, procurement processes
become more efficient, enabling economies of scale.
A rationalized test menu may simplify equipment
maintenance, facilitate quality assurance (particularly
external quality assessment) and post-market surveillanceas performance can be compared across different testingsites using the same IVDs and allow standardized trainingof personnel. This can hereby reduce the total cost ofownership over time. Standardization can be of most benefit
for analytes where there are multiple test procedures andhigh levels of instrument diversity, e.g. haematology andclinical chemistry.
It is important to note that standardization should not
imply reducing competitiveness, assuming that limiting

the number of instruments will lead to sole and single
sourcing of instruments and reagents. Harmonization andstandardization policies must be dynamic. Ongoing review
and evaluation of testing services, instrument performance,
as well as vendor performance guides the harmonizationand standardization policy over time. Approved lists of
instruments and vendors will shift based on technology andperformance, potentially encouraging improved service andfurther competition.
It is critical to foresee instrument retirement or redeployment
as a mechanism to maintain ongoing flexibility intechnologies and test capacity within the network. Without
clarity and national policy on how to retire or redeploy
instruments, an inflexibility is created in the market that
inhibits entry of technologies with better pricing, better
terms and conditions, and diminishes competition. How
to transition from one technology to another must be
considered as part of procurement planning and later
contracting methodology.

Figure 4. Developing a harmonization and standardization plan (Williams J. et al., 2016)
Process

Phase 1
Source: National Care andTreatment Guidelines
Laboratory Strategic Plans
etc...
Phase 2

Testing profile
defined by tieredlevel

1. Clinical programs and laboratory engagement existing review and refinement of testing services

Policy stakeholders, implementers,
clinicians, program, procurement,
biomedical engineers,laboratorians (all levels)

Testing
methodologies
defined

2. Informed testing protocols - influenced byexisting HR, infrastructure, and instrumentation

Procurement , biomedical
engineers, laboratorians (alllevels)

1. Instrument
coverage defined

2. Instrument
evaluation criteria
defined

3. Instrument
selection process
defined4. Evidence
based selection
established by tier

3. Evidence based instrument reduction process*Ancillary equipment
needs establishedby tier

4. Define minimum ancillary equipment needs on
testing methodology and instrument selection

Human resource
demands
established by tier

5. Define minimum human resource requirements
based on testing methodology and instrument
selection

MOH approval and policy dissemination

4

Involvement*Evidence based approach:
Review of existing instrument
specifications, national laboratory
quantification data (service
statistics, consumption, anddemographic data), instrument
inventories, and commodity
distribution data. Can be used toestablish site level demand andexisting instrument utilization,
as well as instrument testing
contributions by brands to inform
selection.

Policy stakeholders, implementers, clinicians, program, procurement, biomedical engineers,laboratorians (all levels) - timeline required with roles and responsibilities defined

GUIDANCE FOR PROCUREMENT OF IN VITRO DIAGNOSTICS AND RELATED LABORATORY ITEMS AND EQUIPMENTHow to quantify procurement demand and make procurement
decisions
Quantification is the broad concept that includes
forecasting and supply planning i.e. “How much will be
procured and when will it be delivered.” It entails estimating
the quantities and costs of reagents, equipment andconsumables required. Quantification determines when
products must be delivered to ensure uninterrupted supply
by taking into account the expected demand, unit costs,
stock already on order, expired stock and other wastage,
freight, logistics, insurance and other costs, lead times andbuffer stocks. The total commodity requirements and costs
are calculated and compared with the available financial
resources to determine the final quantities to procure.2

Figure 5. Elements of quantification

ForecastingÌ Æ

Quantification

Supplyplanning

Additional reagents should be foreseen for the purposesof quality assurance, including lot verification testing,internal/external quality control and external quality
assessment.

stock-outs and wastage of supplies through under orover forecasting. Repeat testing due to invalid or nonreturnable results should be accounted for, and re-tested
when recommended programmatically to confirm a result
before initiating treatment.

Standardization as described above should be a prerequisite
for quantification. Each step of standardization andquantification (forecasting and supply planning) should
proceed with input of all relevant national authorities
including testing programmes and laboratories, theregulatory authority or other entity that decides onimportation of IVDs, and local procurement agencies, aswell as implementing partners such as financing agencies
and international procurement agencies. It is critical thatthe quantification step is used to optimize usage of existing
analysers already placed within the country, including
those which may be used by other testing programmes.
Certain multi-disease analysers are capable of utilising
reagents for multiple pathogens, e.g. anti-HIV and antiHCV or HIV TNA and HCV RNA. Therefore, different testing
programmes should coordinate their testing needs andharmonize service and maintenance packages.

To increase forecasting accuracy, it is important tocollect multiple data sets and use mixed forecasting
methodologies for comparative purposes. Relying solely
on one methodology will ultimately limit validation
efforts and reduce forecasting accuracy. Efforts should bemade to employ a mixed method approach. For existing
programmes, demographic and morbidity based forecasting
efforts and procurement history should be complemented
with service level test numbers and consumption based
forecasts. For new programme start-ups where historicalservice or consumption data is not available, demographic
and morbidity may be the sole option.

Forecasting is “How much is needed, in quantities and cost,to meet the health demand of the population?” This means
estimating the expected consumption of commodities
based on historical consumption, service statistics,
morbidity and/or demographic data or assumptions
when data are unavailable, to calculate the quantities ofcommodities needed to meet demand during a particulartime frame.3 It is a projection that is usually made for a
12-month period. The lack of high quality demand data
contributes greatly to low quality forecasts and resultant
2 Adapted from Promising Practices Quantification: Forecasting and Supply Planning http://siapsprogram.org/
publication/promising-practices-in-supply-chain-management/
3 Adapted from Promising Practices Quantification: Forecasting and Supply Planning http://siapsprogram.org/
publication/promising-practices-in-supply-chain-management/

Conducting multi-method forecasts can assist in measuringlaboratory service delivery capacity and supply chain
performance, and provide insights into the ability of alaboratory network to respond to overall programmatic
expectations. By comparing expected demographic/morbidity estimates against past procurement and service
statistics, programmatic gaps in service delivery and excess
capacity can be quickly identified for targeted interventions.
Comparing service statistics against consumption or
issues data can identify wastage or inefficiencies in theexisting supply chain. It is also possible to identify broader
network issues related to general service delivery, as
well as measuring the cost implications and determining
approaches to create greater efficiencies.
Supply Planning is the final output of quantification, supply
planning details the quantities required to fill the supply

5

Users of IVDs
pipeline, costs, lead times, and arrival dates of shipments toensure optimal procurement and delivery schedules.4
USAID and Clinton Health Access Initiative (CHAI)
developed ForLab (Forlabtool.com)– a laboratorycommodities quantification software application. The
software requires some level of training which can beprovided upon request through CHAI and USAID via
the Global Health Supply Chain, Procurement Supply
Management (GHSC PSM) mechanism.

Budgeting
Any budget for testing services should consider thefollowing four components:• Infrastructure and other administrative overheads oroperating costs;• Personnel (salary, benefits, training);• Reagents, consumables, durables, other supplies; and• Equipment (analysers, ancillary equipment, otherequipment).
The costs of test kits, reagents and associated consumables(e.g. for specimen collection, for waste disposal, biosafety)
will be incurred as repeating costs. A quantification exercise
can help to ascertain the quantities of each item that are
required. Whereas the cost of an analyser may be oneoff if managed as a capital purchase or nil if a reagent
rental agreement is made whereby a higher unit cost forreagents is off-set by no cost for the analyser. Agreements
for leasing of analysers will generally result in less cost for
the equipment budget.
Where equipment purchase becomes an option, costshould also consider installation costs, as well as ongoing preventive and corrective maintenance. Certain
equipment such as biosafety cabinets, autoclaves, andwater purification systems might require modification ofexisting infrastructure and specialised installation andvalidation, as well as annual certifications. This would
need to be accounted for in the total cost of ownership.
Certain analysers may require dedicated physical spaceor reinforced work benches, and dust-free environments
through sealed windows and door jambs.

When practicable, it is advisable that certain testing
programme may be funded across more than one diseaseprogrammes, e.g. HIV and antenatal care, HIV and hepatitis
C or B, and HIV and tuberculosis. These programmes may
be supported by domestic financing such as national healthinsurance and/or co-payments by end-users. Similarly,
bilateral and multilateral agencies may choose to support
some or all of the national testing programme.

Product selection for procurement
The methodology for product selection will depend on the
procurement procedure used: 1) open tendering or 2) solesourced with adequate justification such as harmonisation/
standardization or validated testing algorithms.
Figure 6 outlines the approach as to how product selection
fits within the process for uptake of IVDs.
The following sections will outline the following
specifications that should be considered for productselection:• quality specifications• product specifications (performance and operational
specifications)

Quality specifications
It is critical the specifications indicate the requirements for
quality assurance of product. With several exceptions, few
national authorities have the capacity to evaluate the quality

Figure 6. Product selection procedure
Needs assessment– who needs to betested and where

National
registration of IVDs

End-users might also contemplate to extend the
manufacturer’s warranty for certain analysers. Consideringthat the lifespan of most analysers at least three (five) years,
negotiations to extend the manufacturer’s warranty at thetime of purchasing and installation will likely result in costsavings and efficiencies in running analysers over time.

Select testing strategy– how to test

WHO
prequalification
Product selection- select IVDs to use
within the testing
strategy
Conformity
assessment by anotherregulatory authority;or Approval for use byanother country

Procurement of IVDs
4 Adapted from Promising Practices Quantification: Forecasting and Supply Planning http://siapsprogram.org/
publication/promising-practices-in-supply-chain-management/

6

GUIDANCE FOR PROCUREMENT OF IN VITRO DIAGNOSTICS AND RELATED LABORATORY ITEMS AND EQUIPMENT

of products intended for procurement, and therefore relyon performance and operational characteristics to guidedecisions on product selection. Procurement specifications
should include some consideration of products that havebeen approved by (i.e. conforms to requirements of )WHO Prequalification of In Vitro Diagnostics or any of thefounding members of Global Harmonization Task Force5(GHTF), see Table 1 for additional details.
Assessments of IVDs conducted by WHO prequalification
and GHTF founding members provide an additional quality
assessment over and above the nationally led productevaluation processes which will generally be restricted to anassessment of performance and operational characteristics
only.
It should be noted that different regulatory versions of
products are manufactured, meaning that a productpresented for tender is not necessarily identical to thatapproved by the regulatory authority, with respect to all
manufacturing procedures, processes and equipment,
product code and labelling.
Table 1 provides information on the types of certificatesthat may be provided as part of tendering processes, theseshould be examined for validity and where possible verified
with the certifying body.

Important note: Although conforming to certain
internationally recognised standards for pre-market
assessment and post-market surveillance which may
increase confidence, users should be aware that false
certificates have been identified and some issuingbodies may not meet international standards of rigour
in their assessment process. It is therefore critical thatnational authorities through their regulatory bodies
conduct post-market surveillance on IVDs. See separate
WHO guidance on this topic at http://www.who.int/
diagnostics_laboratory/postmarket/en/

Product specifications (performance and operational characteristics)
Product specifications are detailed statements of thebuyer’s requirements covering both the technical andcommercial attributes that the product must satisfy forbuyer acceptance. Minimum performance and operational
criteria should be agreed for diagnostics to be selected foreach level of the tiered testing network. These can be used
to build minimum technical specifications for tendering
processes.
Specifications must be clearly written to ensure accurate
procurement that represents the highest quality for thebest price/value. There must be sufficient detail to award
the contract to the best and most appropriate vendor(manufacturer/supplier/distributor). Specifications must be
clear and concise, and must avoid marketing jargon.

5 Founding members of the Global Harmonization Task Force as Australia, Canada, European Union, Japan, USA

Table 1. Examples of stringent regulatory assessment
Regulatory jurisdiction

Risk class6

Documentary evidence

European Union

Annex II, List AEC Full Quality Assurance Certificate
EC Production Quality Assurance Certificate
EC Type-Examination Certificate

United States Food and Drug Administration

Class III

PMA letter or BLA license

Health Canada

Class IV

Medical Device Licence and summary report for a Class IV IVD
CMDCAS-issued ISO 13485 Certificate

Therapeutic Goods Administration, Australia

Class 4

TGA Licence for Manufacture
TGA Issued ISO 13485 Certificate
AUST R Number
TGA Full Quality Assurance Certificate
TGA Type-Examination Certificate
TGA Production Quality Assurance Certificate

Japan Ministry of Health, Labour and Welfare

Class IIIJMHLW Minister’s Approval
JMHLW License for Manufacturer (seizo-gyo-kyoka)
JMHLW Recognised Foreign Manufacturer (gaikoku seizogyosya nintei)

Note: WHO prequalification public report issued by WHO Prequalification Team would also be considered as stringent review. Financing agencies may also conductcertain types of quality assessment of IVDs.

7

Users of IVDs
For users who need more information on procurement
specifications, WHO and its partners have developed apractical tool6. When conducting an assay, a range ofadditional consumables and/or reagents may be required,this tool provides a list of these items for each product listed.
It is regularly updated to keep up with changes for inclusionof new IVDs and removal of obsolete IVDs.
For basic descriptions of the most commonly usedcategories of IVDs, see Table 2 for additional details.

Performance characteristics of IVDs
Minimum acceptable performance criteria must be agreed
at national level between care/treatment programmes
and laboratory programmes and include the following
characteristics, as appropriate for the particular category,see Table 3 for additional details.

If the product has been approved by the country of sale
and/or has been evaluated by the national referencelaboratory in the country of sale, these performance data
should be available. If data is unavailable, the list of WHO
prequalified IVDs should be referred to where a link to
the WHO prequalification public report can be assessed.
WHO Prequalification of In Vitro Diagnostics provides
an independent assessment of the safety, quality andperformance of commercially available IVDs.
In certain circumstances, neither in-country evaluation
nor WHO prequalification may have been conducted for
an IVD submitting for tender. In these circumstances, data
and documentation submitted by the vendor may be
used to review compliance with expected performance
characteristics.

6 Specifications and quantities for efficient procurement of essential equipment and laboratory commodities for HIV.
Retrieved 12 October 2016 from http://www.who.int/hiv/pub/amds/amds_equipment-commodities-forecast/en/

Table 2. Formats of selected IVDs
Type

FormatSpecimen type

Immunofiltration (vertical flow)

Serum, plasma, venous/capillary whole blood

Immunochromatographic (lateral flow)

Serum, plasma, venous/capillary whole blood, oral fluid

Serology IVDs
Rapid diagnostic tests
Simple assays
Immunoassays

Confirmatory assays

Indirect solid-phase enzyme immunoassays (e.g. comb assays) Serum, plasma
Agglutination

Serum, plasma

Enzyme immunoassay (microtitre plate)

Serum, plasma

Enzyme immunoassay (simple immunoanalysers)

Serum, plasma

Chemiluminescence and electrochemiluminescence
immunoanalysers
Western blot, line immunoassays

Serum, plasma
Serum, plasma

Nucleic acid testing (NAT) technologies• Polymerase chain reaction (PCR) including
reverse transcriptase PCR (RT-PCR)• Branched DNA (bDNA)• Transcription mediated amplification (TMA)• Nucleic acid sequence-based amplification(NASBA)

Qualitative NAT technologies for use at or near to point-of-care Venous/capillary whole blood
Qualitative NAT technologies for use in laboratories
Quantitative NAT technologies for use at or near to point-ofcare
Quantitative NAT technologies for use in laboratories

Venous whole blood, dried blood spot (capillary/venous whole
blood)
Venous whole blood, dried blood spot (capillary/venous whole
blood), plasma
Venous whole blood, dried blood spot (capillary/venous whole
blood), plasma

Flow cytometry (CD4 enumeration technologies)
Single platform flow cytometer
Dual-platform flow cytometer8

Dedicated flow cytometers for use at or near to point-of-care

Venous/capillary whole blood

Dedicated flow cytometers for use in laboratories

Venous whole blood

Flow cytometers for use in laboratories

Venous whole blood

GUIDANCE FOR PROCUREMENT OF IN VITRO DIAGNOSTICS AND RELATED LABORATORY ITEMS AND EQUIPMENT

Use of HIV serological assays
For individuals over 18 months of age, HIV is typically diagnosed through the detection of HIV antibodies (a serologicalmarker) and/or HIV p24 antigen rather than direct detection of the components of the virus itself (virological markers).
Serological assays used for HIV diagnosis detect HIV-1/2 antibodies, with fourth generation serological assays
incorporating detection of both HIV-1/2 antibodies and HIV p24 antigen. When HIV testing cannot discern a diagnosis,
supplemental assays may be used, such as assays that detect HIV p24 antigen only or assays that can detect specifictypes of HIV-1 and HIV-2 antibodies.
Use of CD4 enumeration technologies
Immunological techniques such as CD4 enumeration are often used to monitor the immunological response to HIV
infection as a predictor of disease progression, and in management of opportunistic infections.
Use of HIV nucleic acid testing (NAT) technologies
For HIV early infant diagnosis (under 18 months of age), virological assays including nucleic acid testing (NAT)
technologies and ultrasensitive p24 antigen enzyme immunoassays may be used to diagnose HIV infection.
Nucleic acid testing is also used for monitoring purposes such as to monitor viral suppression, i.e. the virological responseto antiretroviral therapy (ART).

Table 3. Performance characteristics for HIV IVDs related to their intended use
Serology assays for diagnosis
Clinical sensitivity
Analytical sensitivity
Clinical specificity
Invalid rate/runInter-reader variability, if subjectively readCD4 enumeration for monitoring
Intra-assay variation
Inter-assay variation
Inter-instrument variation
Carry-over studies
Invalid rate
Trueness of measurement: bias, misclassification
Nucleic acid testing technologies (NAT) for diagnosis – infant and adult
Clinical sensitivity
Analytical sensitivity
Clinical specificity
Invalid rate
Trueness of measurement: misdiagnosis
For all claimed specimen types
Nucleic acid testing technologies (NAT) for monitoring
Intra-assay variation
Inter-assay variation
Inter-instrument variation
Linearity
Invalid rate
Analytical sensitivity for subtypes
Limit of detection
Limit of quantification
Robustness
Trueness of measurement: bias, misclassification rate, specificity
For all claimed specimen types

9

Users of IVDs

Table 4. Operational characteristics for HIV IVDs
Operational characteristics
Specimen type
According to product’s instructions for use

Venous whole blood

Capillary whole blood

Serum

Oral fluid

Plasma (including specific anticoagulants)

Dried blood spots

Any stabilizers used

Plasma separator devices

Detection typeCombined or discriminatory detection of antibodies
Combined or discriminatory detection of antigen and antibodies
Single platform flow cytometer
Qualitative or quantitative detection of nucleic acid
Subtype detection
Relevant subtypes to be detectedGroups M (including A, B, C, D, F, G, H, J, K, AG, AE) N, O

Incubation period
Minimum reading time

May range from read immediately up to 30 minutes, after addition of specimen/buffer

Maximum reading time

May range from 10 minutes up to 60 minutes, after addition of specimen/buffer

Ease of use
Consider combination of the following aspects

Specimen collection requirements, e.g. finger-stick whole blood or venous whole blood by venepuncture
Number of steps in the test procedure

Number of steps that require precision

If visually read, ease of reading the test band, line, spot, If visually read, ease of interpretation of testing results,
e.g. few faint bands
e.g. more bands = more complicatedExtent of infrastructure required at testing sites
Are there any infrastructure requirements that would
prohibit use of certain assays?

Refrigeration for storage of reagents

Refrigeration of reconstituted reagents and controls

Electricity/generator

Temperature-controlled work space

Storage/stability
Transport requirements for reagents (temperature,
Any product tolerance excursion ranges accepted during transit? Any specialized shipping requirements?
humidity)
In-use stability for specific reagents (temperature, humidity) Any specific requirements once reagents are opened or once the specimen is added to test device/cartridge?
Equipment/consumables required but not provided in the test kit
Reasonable exclusions from the test kit - can these beobtained from the manufacturer/distributor or obtained
separately?

Lancets, alcohol swabs, cotton wool for finger-stick
Blood collection equipment for venous whole blood
whole blood
Other general laboratory consumables: gloves, pipettes, etc.

Specimen throughput and individual testing service delivery models
Throughput per operator/provider

For RDTs, ≤10 specimens per hour per operator with limited laboratory infrastructure
For EIAs, ≥40 specimens per day per operator with standard laboratory infrastructure

NAT

For POCT, depends on instrument but usually no more than 1-2 specimens per hour per operator
For laboratory, depends on instrument but usually no more than 24 specimens per run per operator

CD4 enumeration

For POCT, depends on instrument but usually no more than 4 specimens per hour per operator
For laboratory, depends on instrument but usually no more than 24 specimens per run per operator

Technical skill of staff conducting testing
Number of precision steps required

E.g. counting of multiple drops, timing of steps required, use of precision pipette, interpretation of results

Phlebotomy required

Venepuncture for serum/plasma

Quality control, including procedural controls

10

Serology

RDT: Control line appears when human specimen is added (i.e. qualitative IgG control, likely not to indicate
adequate volume of specimen) AND/OR
RDT: Control line appears when reagents only are added (i.e. does not indicate addition of human specimen)
EIA: Colour control upon addition of specimen and/or certain reagents

NAT

Amplification control, quantification control, contamination control, dilution of specimen

CD4 enumeration

Control beads

Availability of internal test kit controls and external quality
control specimens

Compatibility with quality control materials; some are available but separate from test kit.

GUIDANCE FOR PROCUREMENT OF IN VITRO DIAGNOSTICS AND RELATED LABORATORY ITEMS AND EQUIPMENTOperational characteristics of IVDs
The operational aspects of diagnostics are equally as
important as the performance characteristics, and thus
both must be considered in product selection, and withintechnical specifications. Consideration should be given to
the platform, costs and logistics required to perform theassay including but not limited to the following, see Table 4
for additional details.

Specific issues related to IVDs that require equipment
Laboratory equipment can be divided into several broad
categories:• Analysers – those that consume reagents, consumables
and produce a test result. Usually repaired andmaintained by service contracts.
• Ancillary equipment – freezer, washers, readers,incubators, etc. Usually repaired and serviced by incountry biomedical engineers.
• Other equipment – biosafety cabinets, autoclaves,water purification systems. Requires infrastructure
modifications, installation and validation, as well as
annual certifications.
Increasingly laboratory information management systems(LIMS), and connectivity-related equipment and softwareare being deployed to testing services. These should beconsidered when conducting procurement, particularly as
an aid for integration between disease programmes that
may use the same analyser. It will be critical to determine
the compatibility of analyzers with built-in connectivity
solutions to existing LIMS i.e. their ability to interface with
open source LIMS.

Analysers can be further classified as closed systems andopen systems. Closed systems are those analysers which
use manufacturer-specific reagents only. Closed systems
may be advantageous due to the use of specific reagentsthat are validated by the manufacturer to assure accuracy
and reproducibility of test results and maintenance ofequipment integrity and warranty. Open systems are thoseanalysers that use reagents from other manufacturers. These
are sometimes referred to as open polyvalent platforms.
These open systems must be validated by the end-user
before testing commences.
The major benefit of an open system is the potential for
lower cost reagents, see Table 5 for additional details.

Table 5. Comparison of open and closed systems (analysers)
Closed Systems
Advantages

Disadvantages

Greater control over reagent quality

Reagents are single or sole-sourced

Tighter inventory control may be required Increased commodity diversity across thelaboratory network
Required use of vendor specific controls
and service providers
Open systems
Advantages

Disadvantages

Increased competition for reagents

Potential for lower quality

Decreased difficulty in obtaining stock

Potential for greater variability in test
results

Reduced commodity diversity – ability
to share products across multiple open
platforms

Specifically for procurement of laboratory-based IVDs
Reagents are items that generally require specific adherence to cold chain with very narrow range of temperature
tolerance/excursion. Reagent transport and storage temperatures usually range from 2° to 8°C but can be as low as -10°and -25° C, depending on the reagent. It is important to recognize that standard cold chain transport packaging canmaintain these levels of temperature control for upwards of 72 hours without repackaging, although frozen reagents
create further challenges due to the requirement for viable dry ice. Any delays at customs or with a shipping agent
could place these high cost items immediately at risk upon arrival in-country. Once in-country, these products mustthen be transported either to a centralized facility for wider distribution, or directly to the end user facilities within thecold chain range specified by the manufacturer.
To ensure commodity viability, it is recommended prior to selecting and procuring a specific analyser to:• Understand cold chain requirements for reagents;• Address any existing logistics challenges associated with the importing and distribution of such reagents, prior to
instrument procurement and deployment decisions being made;• Ensure roles and responsibilities are clearly delineated, with responsible parties held accountable for lost product if
cold chain is compromised;• Ensure that manufacturers are engaged to provide possible logistics and infrastructure support, even if analyser are
donated;• Ensure proper storage facilities, transport procedures, and policies are in place to avoid the potential of significant
loss of product due to breaks in cold chain between the procurement agent and the end user;• Whenever possible, ensure in-country distributors of such products are used, with direct deliveries to end users tofurther reduce risk of product loss and liability; and• Ensure close coordination between the national authorities, laboratory personnel, implementing partners,
procurement agencies, and commodity distribution and other logistics services to ensure that all logistics challenges
are addressed for this product type.
11

Users of IVDs
Testing strategies, validation of testing algorithms, andstandardization and harmonization
Countries should have developed national policies andstrategic plans7 for testing services, including laboratorybased testing services, other health facilities andcommunity-based settings. National guidance will provide
the expected scope and standardization of testing services.
It is important to remember that considerable heterogeneityof testing needs will exist within a single country, and so asingle testing algorithm may not fit all needs.
National authorities and technical experts should be
consulted to ensure that any proposed selection of specificproducts is harmonized with the relevant national policies
including policies on standardization and national validated
testing algorithms, as described below.

Standardized testing strategies for specific testing objectives
WHO recommends standardized testing strategies tomaximize the accuracy of diagnosis while minimizing costand increasing simplicity. A testing strategy describes
a testing sequence for a specific objective, taking into
consideration the presumed disease prevalence in the
population. Whereas, a testing algorithm describes the
specific branded products (assays) that will be used withina given testing strategy.

This terminology can be applied to a variety of testing
objectives, e.g. testing strategy for diagnosis of HIV
infection, testing strategy for monitoring the responseto antiretroviral therapy, etc.
Standardized testing strategies should apply equally
to facility-based testing (for example, in laboratories,
stand-alone testing sites, clinical facilities and othertesting services) and non-facility-based testing (forexample, community-based testing conducted outsideof the conventional health facilities). All personnel who
perform testing, including specimen collection, the testingprocedure and reporting of results should adhere to these
testing strategies. This includes both laboratory staff andother health workers who are trained for these tasks,
including through task sharing.
Refer to the relevant WHO guidance on testing strategies
for specific testing objectives, e.g. WHO consolidated
guidelines on HIV testing services, WHO consolidated
guidelines on viral hepatitis testing services, WHOlaboratory diagnosis of sexually transmitted infections,
including human immunodeficiency virus, etc.

Product selection - validated testing algorithms
Once a testing strategy has been selected, the products to
be used must be validated as a testing algorithm – anotherform of standardization through product selection. Productselection at national level should be conducted by thenational reference laboratory or another facility designatedby national authorities for this task. Such studies should
validate a product or combination of products, as they will
be used within a standardized testing strategy.
A pre-selection of candidate assays should be selectedtaking into account the considerations for desired quality
specification, and product specifications (performanceand operational characteristics). For testing strategies thatuse more than one assay (e.g. HIV diagnosis), it is critical toensure that assays do not share common false reactivity
for the same specimens. Therefore, selection of assays withdifferent antigen preparations should be considered as apreliminary step. Although, it is acknowledged that thisinformation is rather difficult to obtain and increasingly,
original manufacturers sell semi-finalized or finalized
product to other manufacturers who re-assemble test kits
as re-branders/re-labellers. This practice makes it difficult
to determine the exact provenance of diagnostics, andtherefore, predict common false results between assays.
Validated testing algorithms are preferable at each levelof the health system with additional products available as
back-up options, in case of stock-outs, certain defective
lots or product failures. Where a nationally validated testingalgorithm exists, only assays that are part of the algorithm
should be procured unless otherwise indicated, with
sufficient justification, by national authorities.
See annex 2, for guidance on how to conduct a verification
study for product selection.

Equipment MaintenancePreventive equipment maintenance should be scheduled
on a daily, monthly, quarterly, and annual basis, dependingon the type of analyser/equipment. Some tasks, as listed
in the instructions for use accompanying the analyser
should be performed by the operator and be part of the
training at the time of installation. It is important thatstandard operating procedures (SOPs) are developed
for all equipment maintenance with associated records
maintained. Failure to perform required operator preventive
equipment maintenance may invalidate the maintenancecontract. More complex tasks may require supplierapproved trained and certified service personnel.

7 WHO guidance on development of national strategic laboratory policy and plans http://www.wpro.who.int/
health_technology/documents/docs/Nationalhealthlab2_0F38.pdf

12GUIDANCE FOR PROCUREMENT OF IN VITRO DIAGNOSTICS AND RELATED LABORATORY ITEMS AND EQUIPMENT

It is imperative that end-users are aware of the terms
and conditions of preventive maintenance contracts
for analysers and equipment that has been assigned
to them. Ensuring that vendors conduct equipment
maintenance activities that have been contracted, isalso required.

Post-market surveillance, including lot testing and complaint
reporting
Ensuring continuous product quality and compliancewith minimum performance criteria through post-market
surveillance is another necessary part of the procurement
cycle. Post-market surveillance of IVDs empowers national
authorities (and WHO) to detect, investigate, communicate
and contain events that threaten public health security andto take appropriate action. Post-market surveillance can bedivided into reactive and proactive measures.
Reactive - Information on quality, safety or performanceof an IVD on the market is collected reactively throughnotification by users and evaluation by manufacturers ofcomplaints (including adverse events). The reactive natureof this statement refers to the fact that the problem has
already occurred, and may have affected a clinical decision.
Proactive - Additional information on quality, safety or
performance may also be collected proactively throughlot verification testing. This relates to proactively trying to

identify a problem before it affects a clinical decision. Lot
verification testing is conducted after shipment to the buyer(countries) and can be performed both pre-distribution andpost-distribution to end-users.
Manufacturers should also collect post-market surveillancethrough actively gathering evidence from the literatureon their product or similar products, through seeking
feedback from customers, and post-market clinical follow
up. This is a critical aspect that will not be widely covered inthis guidance as has been published elsewhere8. Figure 7
illustrates the post-market surveillance processes for IVDs.
Health facilities that perform testing within a functional
quality management system are more likely to be able
to detect substandard lots of reagents and faulty or
malfunctioning equipment.
An experienced end-user may often be able to identify
problems related to the diagnostic and/or related laboratory
equipment. Daily quality assurance measures will assist
the user to obtain information about potential quality
problems; routine quality control (QC) e.g. with test kits
controls provided within the test kit and/or available frommanufacturers separately, or external QC material; regularparticipation in external quality assessment schemes(EQAS); equipment maintenance schedules as well as other
QA measures such as good recordkeeping and competencybased training.

Figure 7. Post-market surveillance for in vitro diagnostics

Any class of IVD

Reactive PMS

Proactive PMS

Evaluation of EQA/QC data

Lot verification testing

Pre-distribution

Post-distribution

Complaint
Possible Field Safety
Corrective Action
Possible issuance of Field Safety Notice
8 WHO. Guidance on post-market surveillance for in vitro diagnostics. Geneva. 2015. http://www.who.int/diagnostics_laboratory/postmarket/en/13

Users of IVDs
The following quality indicators should be monitored, as
appropriate:• Percentage of defective consumables e.g. specimentransfer pipettes, lancets;• Percentage of invalid test devices (if single use devices
such as RDTs);• Percentage of invalid runs (disaggregated by error
codes);• Percentage of equipment breakdown and respective
down time• Percentage of out-of-range QC results; and• Percentage of discrepant results within a testingalgorithm consisting of two or more assays.

Monitoring complaints, including adverse events
Complaints about product quality and performance can besubmitted to the relevant regulatory authority, and to WHO
if the product is WHO prequalified, for follow-up and action9.
Manufacturers are obliged to investigate reports of poor
performance as part of their quality systems requirements.
Complaints may include:• Administrative/contractual complaints or inquiries
related to any aspect of the procurement contract not
fulfilled e.g. agreed delivery time not adhered to, agreed
guaranteed shelf life upon delivery not adhered to,incorrect product and/or quantity delivered, etc.
• Technical complaints, affecting the safety, quality or
performance of an IVD, for example: malfunction or
deterioration in the characteristics or performance,
inadequate design or manufacture; inaccuracy inthe labelling, inappropriate instructions for use and/or promotional materials, or any other issues might
be reported that result in a significant public healthconcern. Information about such issues may become
available in other ways than through reporting (forexample through literature and other scientificdocumentation).
Adverse events should be reported in any of the following
circumstances:
1. When an incident leads to death of a patient, user orother person.
2. When an incident leads to serious deterioration in
health of a patient, user or other person (also known asserious injury).
3. No death or serious deterioration in health occurs but
the event might lead to death or serious deteriorationin health.
4. When an incident might happen as a consequence ofa medical decision or action taken or not taken on the
9 For more information and IVD complaint reporting forms in English and French
see the WHO website http://www.who.int/diagnostics_laboratory/procurement/complaints/en/index.html

14basis of results given by the IVD, typically:• Misdiagnosis:• Delayed diagnosis;• Delayed treatment;• Inappropriate treatment;• Transfusion of inappropriate (contaminated)materials including blood products, tissues or organs.
5. Use errors that did result in death or serious deteriorationin health or that have a negative trend with the potential
for death or serious deterioration in state of health or
public threat.
Users should document any problems using information
taken from the testing logbook/register and inventory
records including affected product code(s), affected lot
number(s) and expiry date(s), serial number of affected
instrument, affected consignments or test kits, affected
users, and any measures taken, including taking
photographs of affected test devices and/or test kits toillustrate the complaint.
If a field safety corrective action (FSCA) is required, it isusually communicated to affected users in the form of a
Field Safety Notice (FSN). It is critical that procurers areaware of any relevant FSN that might affect products they
have procured.
A FSCA may include:• Return of an IVD to the manufacturer or its
representative;• IVD modification (retrofitting an instrument, changes
to labelling or instructions for use, software updates,
modification to clinical management of a patient
through re-testing affected patients or with closer
clinical supervision) ;• IVD exchange;• IVD destruction; or• Advice given by the manufacturer regarding the use of
the IVD (e.g. where the IVD is no longer on the market or
has been withdrawn but could still possibly be in use).

Lot testing
To ensure that IVDs continue to meet their specifications,manufacturer must assure that in-process and final quality
control lot release testing is conducted. As a complementarymeasure, national regulatory authorities have the mandate
to arrange proactive lot verification testing including:• Pre-distribution to testing sites (when a consignmentof test kits arrives in country); and• Post-distribution to testing sites (after the lot has alreadybeen in use).
See later section for national regulatory authorities for
guidance on lot verification testing.

GUIDANCE FOR PROCUREMENT OF IN VITRO DIAGNOSTICS AND RELATED LABORATORY ITEMS AND EQUIPMENTPROCURERS OF IVDSThe United Nations Commission on International Trade
Law (UNCITRAL) developed the Model Law on Public
Procurement that countries, organizations and private
entities are encouraged to adopt. The UNCITRAL provides
detailed definitions and regulatory framework that should
be reviewed by readers of this guidance.
The following methods may be used to procure IVDs, andrelated products:• International competitive bidding; or• Restricted bidding.

When procuring a range of laboratory products, it may
be possible, and more efficient, to break down the list of
products into functional lots to enable suppliers to bid on
ranges of products offered. For example, a single lot may
contain larger ancillary equipment such as autoclaves,centrifuges and ultralow temperature freezers, whereas
a second lot may contain small consumables such as
gloves and pipette tips. The laboratory product market isfragmented such that not all suppliers will have the capacity
to bid on all lots. Breaking items down into lots provides
the greatest opportunity to receive high quality products
at the lowest price.

Embargos
Standard procurement practices rely on international
competitive bidding. However, due to the highlyspecialized nature of certain IVDs, and particularly
analysers, bidding may need to be restricted to products stated innational standardization exercises and/or national validated testingalgorithms. It is essential that such restricted bidding befully justified with written evidence for selection such asa national validated testing algorithm study.

However, there may be certain categories of consumables,
durables and auxiliary equipment10 that may be purchased
through competitive bidding.

Sourcing vendors
Potential vendors (manufacturers, suppliers anddistributors) should be identified through a fully transparent
process. Due to the wide range of IVDs and their suppliers,
it is pertinent to pre-select suppliers. Pre-selection, as
defined according to the UNCITRAL procurement law is: “ …
to identify, prior to solicitation, a limited number of suppliers
or contractors that best meet the qualification criteria for the
procurement concerned”11.
Regardless of whether vendor pre-selection is employed ornot, certain information should be collected and evaluatedto ensure that the vendor is commercially viable andcapable of supplying to the terms of the bid. This would
usually take place in the context of the bid evaluation.
Methods for sourcing vendors include:• Publication of a request for expressions of interest (EOI);• Communication with technical organizations such as
WHO or other relevant bodies;• Invitation of specific vendors based upon market
research.

10 See glossary for examples.
11 United Nations Commission on International Trade Law. 2011. UNCITRAL Model Law on Public Procurement.
Accessed on 12 April 2013 at http://www.uncitral.org/pdf/english/texts/procurem/ml-procurement-2011/
ML_Public_Procurement_A_66_17_E.pdf

During vendor selection, any embargos enforced by thecountry of sale and intended use should be noted. Any
embargo should be stated in the bidding documents
or at the very least, bidding documents should carry astatement requiring vendors to check legal obligations forinternational trade.

Bid solicitation
The method of bid solicitation (invitation) will vary according
to the rules of the procuring organisation. The following
section conforms to guidance set out in the United Nations
Procurement Manual. However, certain donors and other
implementing partners may have specific procurement
guidelines and conditions for countries benefitting fromtheir funding.

Methods of solicitation
The method of solicitation may vary according to the
product type, see Table 6.

Table 6. Three methods of solicitation for international bidding
Bid solicitation

Criteria

Request for Quotation (RFQ) For procurement of simple, uncomplicated goods withstandard specifications (with smaller value, less than
US$ 40 000).
Invitation to Bid (ITB)
For procurement of simple, uncomplicated goods andservices of standard specifications (with larger value,
in excess of US$ 40 000).
Request for Proposal (RFP) For procurement that cannot be quantitatively or
qualitatively expressed in sufficient details to permit
use of ITB.

Only in exceptional circumstances would a deviationfrom these methods of solicitation be permissible. Suchdecisions should be made with respect to rules of thenational authorities and/or funding agencies.

Solicitation documentation
The solicitation documentation should contain a number

15

Users of IVDs

Table 7. Key considerations for bid solicitation documents
Element

Consideration

Quality management
system specifications

Provision of appropriate quality management systems for manufacture, e.g. ISO 13485 Medical devices -- Quality management systems -- Requirements
for regulatory purposes for IVDs, ISO 9000 series for other laboratory products, etc. Evidence of meeting WHO prequalification requirements in the form of avalid WHO prequalification public report may also be accepted. Certain financing agencies may have their own quality policies.
Product specifications Minimal acceptable criteria for performance and operational characteristics for IVDs and the accepted method for authenticating such claims, e.g.
manufacturer’s instructions for use, performance evaluation report from national reference laboratory, conformity assessment report, WHO prequalification
public report, etc.

Delivery terms

Should not refer to brand names, product codes or be specific for branded items unless the sole-source bidding is in effect. In case of sole-source bidding,documented justification should be part of the bidding documents, and the bid submission. For example, IVDs that have been validated as part of a national
testing algorithm require sole sourcing so the technical specifications should include the brand name, product code and regulatory version to be supplied.
Inclusion of expected date of delivery in calendar days (e.g. 60 days) at place of delivery as per INCOTERMS 2015.

Guaranteed shelf life
upon delivery

Guaranteed shelf life upon delivery differs from shelf life upon manufacture. It is important to specify required shelf life upon delivery in the bid
solicitation documents.
For IVDs, it is generally accepted that the reagents have a minimum of 80% of the shelf life upon delivery remaining at the time of delivery.
For example, a rapid diagnostic test may have claimed shelf life upon manufacturer of 24 months. The manufacturer may decide to only agree to aguaranteed shelf life upon delivery of 18 months, this allows for rotating stockpile of product within their warehouse. Therefore, they would need to supply
product with at least 14 ½ months.
However, this guarantee is highly dependent on the INCOTERM that is selected, see Annex 3. For example, if EXW then the responsibility for the product is nolonger on the seller (manufacturer) when the buyer picks up the goods from the factory. The seller therefore, can control how long it takes for the goods toarrive at the end user. If using so-called longer INCOTERMS such as CPT, CIP, DAT, DAP, DDP, the guaranteed shelf life upon delivery will be easier for the seller(manufacturer) to control.

Clauses with a priceimpactConsideration of "total
cost of ownership"
Provision for
installation, training,
maintenanceWarranties

Regulatory versions

Provision for staggered deliveries should be considered when guaranteed shelf life is short and annual procurement is favoured. Staggered deliveries allow
for annual purchase of diagnostics under a single procurement contract but with multiple delivery times. For example, annual supply of HIV RDTs could bedelivered in quarterly intervals to ensure best guaranteed shelf life and avoid the need for large storage areas. The additional costs for shipping should be
off-set against wastage due to expired products.
These will include but are not limited to: insurance, INCOTERMS (transfer of ownership), warranties, guarantees, distributor or agent fees.
Total Cost of Ownership (TCO) refers to all costs relating to the acquired product whether direct or indirect, fixed or variable. TCO may include final price(distributor’s share), upgrade, storage, supplies, additional operating costs, disposal costs, volume discounts, internal processing costs, etc.
Explicit provision for installation, then pre-service and in-service training. Explicit provision for preventive and corrective maintenance schedules for the
expected lifespan of the analyser/equipment.
Warranties are usually required for ancillary and other large laboratory equipment. A warranty requires the manufacturer (or vendor) to ensure
manufacturing faults are rectified within a specified time period, usually 12 months. Warranties usually include provision for equipment repair that includes
parts and labour and/or total replacement where necessary. Warranties should not be expected to cover problems related to poor/incorrect installation, if
not performed by the vendor or vendor-specified agent, use or maintenance. The exact nature of the warranty should be clearly specified in the contract.
Which regulatory version will be supplied and which regulatory version was used to generate evidence to meet the technical specifications.

of necessary elements to ensure a successful, transparent
and unbiased bidding process, see Table 7.
Sole-source justification
In some cases, no or too few in-country suppliers exist to
make open competitive bidding a realistic option. While this
scenario is undesirable, it may exist where manufacturers
have exclusive agreements with a sole distributor or where
few products are registered. Reagents for closed systems
will require sole-source justification. If there is a direct
request for a specific assay or analyser, there would need
to be evidence to show that brand selection is justified ina fair and open manner. An important consideration in thejustification of specific products is their inclusion in national
policy and/or guidelines.
INCOTERMS and insurance

used to govern procurement contracts by defining the
responsibilities and liabilities of the buyer and the seller. It
is a series of three letter trade terms to communicate tasks,
costs, when risk passes from the seller to the buyer, andwhen delivery legally occurs.
INCOTERMS must be specified for each product or range of
products and are particularly important in consideration of
the complex shipping and storage requirements of IVDs.
For example, maintenance of cold-chain storage must be
assured for the duration of the shipping and distribution
process can be assured using the correct INCOTERMS.
Some products are very sensitive to fluctuations inenvironmental conditions and cold packing or dry ice may
require replenishment during shipping. Responsibility fortransportation and storage conditions should be madeclear by indicating the specific INCOTERM on the bidding
documents, see Annex 3.

INCOTERMS are commercial terms established by
the International Chamber of Commerce which are

16

GUIDANCE FOR PROCUREMENT OF IN VITRO DIAGNOSTICS AND RELATED LABORATORY ITEMS AND EQUIPMENTThe contract should ensure that the vendor (seller)
has responsibility until the products have reached thedelivery point and that the delivery point should beclearly defined.
The procuring organisation must have appropriate
insurance for all products, including reagents, equipment,
consumables and durables throughout the transportationand storage process. This is especially important when the
INCOTERM states that vendor (seller) responsibility ends
when the consignment is delivered to the port of entry as
the designated place. Complex requirements for customs
clearance may be required and the correct storage of goods
must be observed while waiting for the goods to clear.
Certain goods will require transportation at specified
temperatures. The specified transportation and storage
temperatures must be ensured at all times. If cold chain
storage is not specified, goods will usually be transported
as general cargo. Caution should be taken to ensure
goods such as reagents remain within temperature ranges
validated by their manufacturer. In some cases, IVDs arevalidated as stable at 2 to 30 °C, yet storage facilities intropical climates may exceed such temperatures.
For some settings, goods are delivered from the port ofentry to a centralised warehouse (e.g. central medical
stores). From this point, the goods are distributed to testingsites according to demand and pre-determined delivery
schedules. It is particularly important that sellers and/or
buyers have insurance on storage facilities throughout the
supply chain.
Central medical stores should have standard operatingprocedures in place for storage of IVDs including
reagents, durables, consumables, equipment, andanalysers.

Bid evaluation
Clear directions on the bidding process must be provided in
the solicitation documents and must be adhered to strictly.
Receipt of bids must be carried out in a transparent andconsistent manner and must ensure fairness to all bidders.
Bids may be received by hardcopy and can be stored inelectronic format.
Commercial and technical evaluation of the bids should be
performed separately. The bid evaluation committee should
consist of a specialist evaluator for each of these parts i.e.
a technical evaluation team and a commercial evaluation
team, consisting each of at least two or more appropriately
qualified members. The technical and commercial parts ofthe bid can be evaluated concurrently at the discretion of
the bid evaluation committee.

Quality and appropriateness for the intended purpose
should be the primary evaluation criteria. A product that
does not conform to minimum quality standards or is not
appropriate for the intended use should never be procured,
no matter the price. Once quality, safety, performance, andappropriateness have been determined, UN practices canbe followed: (1) best value for money, (2) fairness, integrity
and transparency, (3) effective international competition,and (4) the interest of the end-user.
The bid evaluation is separated into three stages:
1. The bid response;
2. Preliminary examination of bids;
3. Evaluation of substantially responsive bids.

Bid response
Bids must be opened at the time specified in the solicitation
documents and all participating vendors are permitted to
be present. At the opening, bids must fulfil the requirements
set out in the solicitation documents. Minor corrections
that do not affect the substance of the bid may be madeat this time.
The procurer can reject a bid at this stage if:• Bidder is not qualified;• Bidder does not accept required minor corrections;• Bid is not fully responsive;• Bid is abnormally low; or• Unfair competitive advantage or conflicts of interest arefound.
Successful bid responses are registered and will then passto the next stage of bid evaluation. Unsolicited submissions
should be rejected.
Important note: Negotiations between procurer (buyer)
and vendor (seller) must never occur with respect to any
tender as this represents unfair advantage during/after
the tendering process.

Preliminary examination of bids
This preliminary review of bids examines eligibility,
completeness, errors, legal validity, bid validity, bid security,
plus substantial responsiveness to commercial and technicalspecifications. It is usual to confirm that each vendor
responded completely to every lot. A preliminary review
may be made of the technical specifications. At this stage,a check is made to verify that required documentation
is present to support the bid evaluation. The quality andcorrectness of that documentation is further assessed in
the next stage.

17

Procurers of IVDs
Evaluation of substantially responsive bids
After preliminary review and initial qualification, each bid isclosely reviewed and the technical, quality and performance
characteristics of offered goods are evaluated. Quality andappropriateness for the intended use are primary criteria.
Price comparisons should only be made after the technicalreview.
Evaluation criteria are based upon technical specifications
and commercial requirements. It is important to ensure
evaluation criteria are measureable and objective, where
possible. A bid may be found non-responsive, and therefore
be disqualified at any stage of the evaluation process.
Any reasons for disqualification should be made andincorporated into the final bid evaluation report. In general,the pool of substantially responsive bids that make it to thepost-qualification stage is likely to be small.
The lowest evaluated responsive bidder must be establishedi.e. the post-qualified bidder with the lowest price that offers
best value for money. Domestic preference and prevailing
import duties on goods may also be considered at the
final stage of the decision process. In cases where the
manufacturer rather than the manufacturer’s distributor
or agent submits a bid, it is important to ensure prices areprovided taking into account local fees and charges. Pricetransparency is important to ensure financial resources are
sufficient to cover all procurement costs.
All bidding vendors should be informed of the final decision;
selection or rejection.
Commercial considerations of the vendor
The commercial viability of the manufacturer andsustainability of the product or technology must be
examined. Reagents and technical support for diagnostic
platforms should be available for the working life of theanalyser or equipment.12 Commercial considerations of
the vendor are important especially for procurement ofclosed systems . The procurer, in conjunction with technicalexperts, must assess the potential risks such changes inplatform technology, discontinuation of future technicalsupport, and financial stability of manufacturer/ supplier/
distributor and therefore long term viability.
The prior commercial track record of manufacturer (orvendor) must be examined to ensure capacity to deliver
reagents on-time in-full, and provision of post-sales
technical support. It may be that in-country agentsor distributors carry out some or all of these tasks onbehalf of the manufacturer. Some common example
commercial specifications include: evidence of previous
12 See Definitions

18

large transactions, ability to maintain supply of reagents atspecified temperatures during transit, prior experience withcountry of supply or equivalent setting, etc.

Contracting
The contractual process begins once a bid has been
awarded. It is important that both legal and technicalexpertise is involved in the development of contracts forlaboratory products, particularly for analysers. The methodof contracting may vary and will depend on the nature of
product, see Table 7.

Table 8. Types of procurement contracting
Contract type Considerations
Purchase order(PO)

POs are reserved for low value procurements, usually less than
US$ 4,000. Terms and conditions are set forth within the PO whichconstitutes a legally binding contract between seller and buyer.
Any related documents must be clearly indicated and suppliedwith the PO.
Customized
Due to the complexity of laboratory products, customized
contracts
contracts that are individually worded (as opposed to a setof Standardized provisions) are usually required. Customized
contracts required detailed written information/ instructions thatclearly define the obligations of both seller and buyer.
Systems contract, These types of contract are used for products that may be required
blanket POs
on a recurring basis or over an extended period of time. The
and long term
buyer enters a mutual arrangement with a supplier (the seller)
agreements (LTA) to provide goods or services with quantities to be determinedat prescribed prices or pricing provisions. Long-term purchaseagreements are common practice to ensure a reliable source of
supply goods and services at the lowest price 14
This is most suitable for instrument-based IVDs whereby reagentsand consumables need to be replenished.
13

Customized contracts usually contain the following
information:• an overarching document containing specificcontractual provisions agreed between seller and buyer;• relevant portions of the solicitation documents
including specifications, terms of reference or scope ofwork;• the vendor’s submission including best and final offer
provided in response to the tender.
Long term agreements (LTAs) are designed to facilitate
rapid processing of requests for procurement. LTAs are
particularly effective when the same goods (reagents andconsummables) are required repeatedly over a periodof time. Even without an accurate forecast, LTAs can beleveraged to negotiate lower pricing, more assured supply,
improved service and maintenance terms, and a greater
investment in suppliers servicing a market in a consistentmanner. One potential disadvantage which is a drop in
prices can be mitigated by re-negotiating the LTA terms
on an annual or biennial basis. These types of contract
require continuous close monitoring. Generally, an LTA
13 Definition adapted from UNDP website http://www.undp.org.tr/Gozlem2.aspx?WebSayfaNo=240#5

GUIDANCE FOR PROCUREMENT OF IN VITRO DIAGNOSTICS AND RELATED LABORATORY ITEMS AND EQUIPMENTFigure 8. Key elements of a contract
Order of Precedence

Liquidated damages
clause and additional
insurances

Specifications,
TOR, SOW

Performance security

Contract
duration/term
Vendorresponsibilities
Buyer
responsibilities

Warranties
Key Elementsof aContract

Contract amendment
or modification

Contract monitoringand supervision

Notice provision

Reportingrequirements

Signatures of parties

Payment terms andmethods

Identification ofpartieswith a supplier for a prequalified product (if IVD) or witha prequalified supplier (if durable or consumable) is mostdesirable. Other benefits of an LTA include protection
against unreasonable increases in price for the same
product and saves costly and time-consuming procurement
processes and procedures.
A LTA can be made for the period of one to five years
depending on the product and the volatility in the market.
Entering into a LTA when it is presumed that prices may
decrease may be unwise, however, it usually guards
against unreasonable price increases that may result froma monopolisation. A term of 1-2 years is generally mostsuitable to weigh the pros and cons of the IVD market.
The following Figure 8 illustrates key elements that may be
included in a contract14. Each element should be carefully
considered and appropriate language included in thecontract to ensure protection for both buyer and seller.
Failure to address common issues and establish a planfor unforeseen circumstances may lead to lengthy court
proceedings and substantial financial loss.
The method of payment must be clearly defined of that isthat suited the contract including handling fees, insurance,
payment terms and general and/or specialised terms andconditions that should be considered and especially where
reagent require cold-chain conditions during transport.

14 Adapted from United Nations. 2010. United Nations Procurement Manual, Revision 6. Retrieved 13 April, 2013 fromhttp://www.un.org/Depts/ptd/pdf/pmrev6.pdf

Contracts should ensure a clause for rejection or refusalof goods that do not conform to the specifications, as
stated in the bidding documents. Payment of goods should
not been deemed as acceptance of goods. Specific terms
and conditions may also be stated in the contract suchas guaranteed shelf life upon delivery, manufacturing
standards, lot testing requirements, etc. In addition, a
critical part of the procurement contract is to ensure the
manufacturer conducts post-market surveillance as part oftheir regulatory obligations.

Lot testing conducted independently of the manufacturer
may be used to flag potential for “out of specification”
goods. Such testing must follow a standard operatingprocedure that is suited to the testing objective. Any
testing data that is generated should be forwarded tothe manufacturer as a complaint. All components ofthe test kit should be verified as part of lot testing, e.g.
lancets, specimen transfer devices, instructions for use,packaging. For further guidance, see WHO Post-Market
Surveillance of In Vitro Diagnostics, 2015 http://www.who.
int/diagnostics_laboratory/postmarket/en/Contracting for equipment
Analysers and ancillary laboratory equipment may bepurchased using the following methods:
1. Outright purchase;
2. Lease; and3. Reagent rental.
“Purchasers should carefully evaluate acquisition contracts to
identify minimum volume commitments, service requirements,
training that is included, user support, warranty provisions
and reagent pricing discounts. Negotiation of these elementsin the contract is required to guarantee that the best value
and the lowest costs are obtained from the vendor. Everything
in the contract is negotiable. The input of the Ministry of
Health officials would be desirable in the procurement andnegotiation for laboratory equipment, service, reagents, andsupplies”.15
Outright purchasing relates to the complete acquisition ofa piece of equipment or an analyser. Outright purchasing
may be the most practical method for ancillary equipment
such as centrifuges, pipettes, refrigerators, heating blocks,
etc. However, reagent rental and leasing options may beefficient for analysers such as those for clinical chemistry,
haematology, and serology, where the platform costs are
15 p.12, Consultation on Technical and Operational Recommendations for Clinical Laboratory Testing Harmonizationand Standardization: Meeting Report page 12. Access 29 May 2013 at http://www.who.int/management/facility/
laboratory/Maputo_Meeting_Report_7_7_08.pdf

19

Procurers of IVDs
considerable and platforms must be maintained (preventive
and corrective) regularly to ensure functionality. A reagent
rental agreement provides greater incentive for the vendor(seller) to ensure the equipment is functional as payment isbased upon test throughput (see Table 8).
16

Reagent rental is a most attractive option when an allin pricing option is negotiated. All-in pricing refers to
the cost per returnable result for the reagents, certain
consummables, the analyser, service/maintenance andtraining.

Quantifying procurement demand
End-users will typically undertake a quantification exercise
to establish a 12-month forecast for all commodities.

Monitoring procurement practices
A wide range of indicators may be monitored i.e. routinely
tracked over time through either a specific system formonitoring or existing data sources. Effective monitoring
allows for better evaluation of the effectiveness of
procurement procedures, and therefore impact onprogrammes. The following indicators have been developed
for pharmaceutical procurement and supply systems but
could be adapted to meet the needs of IVD procurement:• Product selection in accordance with nationalguidelines/national validated testing algorithms;

•
•
•
•

Consumption;
Procurement efficiency in terms of pricing, supplierperformance and port clearance;
Quality control; andDistribution and inventory control in terms of loss, andminimum stock levels.

Evaluating supplier performance
Evaluating the supplier is an integral component of the
procurement cycle. It is necessary to collate information
concerning each consignment in accordance with theprinciples of On-Time In-Full (OTIF) as an indicator of
performance, including:• if the goods must be delivered in acceptable condition;• if orders are full and complete;• if guaranteed shelf life is delivered;• if complaints are handled appropriately; and• if responses to breakdowns dealt with efficiently.
Data should be collected continuously and for eachconsignment and across the period of the procurement
contract, preferably by the procuring entity. The degreeof implementation of the contacted details for service andmaintenance can vary. It is critical that the supplier’s ability
conduct service and maintenance in a timely manner ismonitored.

Table 8. Types of procurement contracting17
Purchase

Lease

Reagent rental

More substantial initial cash outlay

Minimal initial cash outlay

Minimal initial cash outlay

Risk of obsolescence, after more than
5 years

Less risk of obsolescence, unless lease term is more than 5 years

Equipment expense can be
depreciated. Can be used as a trade-in
for upgraded models (rarely).
Equipment must be decontaminatedand decommissioned at some point
Reagent cost must be negotiatedconsidering the capital outlay forequipment purchase.

Equipment can be returned after the l12 month ease period, andupgraded for a new model. Allows for trying out the equipment
before buying it.
Difficulties exporting (returning) analysers from certain countries.

Less risk of obsolescence, unless contract does not allow for
upgradesVendors may be reluctant to set up agreements in resource-limited settings, will be dependent on how testing programmes are financed.
Equipment can be upgraded for a new model during the contract.

Equipment issues regarding import and export (return) are similar
as for leasing
Total cost is higher than purchase due to financing arrangement; a Total cost is higher than purchase due to financing arrangement,
buy-out option may exist.
as for lease; a buy-out option may exist. Predictable fixed costs permonth.
Reagent pricing must be negotiated separately from the lease based Cost of equipment, reagents and service is spread across each test,on volumes
payment is a fixed amount on a per returnable result basis. So
reagent costs (price per test) are higher. May also be negotiated as
all in pricing.
Volume commitments must be accurate as these are the basis for
pricing
Most desirable for changing technologies and high-cost systems due
to risk of obsolescence in 5 years

16 Table is adapted from Consultation on Technical and Operational Recommendations for Clinical Laboratory Testing
Harmonization and Standardization: Meeting Report page 12. Access 29 May 2013 at http://www.who.int/
management/facility/laboratory/Maputo_Meeting_Report_7_7_08.pdf

20

GUIDANCE FOR PROCUREMENT OF IN VITRO DIAGNOSTICS AND RELATED LABORATORY ITEMS AND EQUIPMENTMANUFACTURERS OF IVDS

the manufacturer). The vendor must ensure that required
calibration and/or QC reagents, where necessary, havebeen ordered and arrive in a timely manner. Details of all
installation requirements must be included in the contract.
Successful installation of the equipment according to the
manufacturer’s specifications must be documented.

Delivery of goods

Training requirements

Manufacturers through their suppliers (distributors andagents) play an important role in the procurement process.
Certain aspects usually outlined in procurement contracts
are described in this section.

Timely delivery of the expected goods can be measured
as On-Time In-Full (OTIF) in the following terms: if the
expected product as ordered was delivered, if the quantity
was delivered as ordered, at the place specified by the Buyer,
and at the time expected. If delivery is delayed past the timeagreed or if the goods do not match those ordered, testing
programmes may incur a stock-out or shortage of supplies.
Certain customs procedures may occur at port/airport ofentry, all means necessary should be taken to minimise
these delays including thorough knowledge of importation
requirements in countries of destination.

Installation, training, maintenanceAll contracts related to analyser/equipment installation,
training and maintenance must be considered as part ofthe procurement process. It is expected that there must
be an explicit provision in the procurement contractfor installation, pre-service and in-service training, andpreventive and corrective maintenance schedules for the
expected lifespan of the analyser/equipment. Contracts
should cover a minimum of two years, in addition to
the usual one-year manufacturer’s warranty, but should
preferably be longer. The initial contract should be made at
the time of procurement (as part of vendor requirements
and detailed specifications). Contract extensions beyond
the initial time period should be made well in advanceand ensure manufacturer approved service personnel areprovided.
The terms of installation and training must be negotiatedin advance of purchasing. The need for and intensity of
training will depend upon the number and competency ofstaff, as well as expected staff turnover.

Requirements for installation
General equipment and analysers should be installedby appropriately qualified staff. The vendor must be
contractually obligated to provide manufacturer-approved
installation either through the manufacturer, by the vendor
themselves or using an in-country agent (sub-contracted by

Training requirements must be specified in the contract.
The vendor is obliged to train laboratory personnel in thecalibration, operation, (basic preventive maintenance andrepair) of particularly analysers such as haematology, clinicalchemistry, serology, etc. Training is usually divided into preservice and in-service (meaning on-going) training, in orderto maintain an acceptable level of proficiency, it is crucial
that staff be appropriately trained and refresher training
regularly provided. High quality training results in improved
equipment operation and less frequent breakdown. Recordsof such training must be retained.

MaintenanceAll equipment must be must be regularly maintained withboth preventive and corrective schedules, irrespective of
the claims made by vendors. In all circumstances, basic
regular maintenance can prolong the lifetime of equipment.
Preventive and corrective maintenance must be specified
in the contract.

HELPFUL PUBLICATION: The WHO Maintenance
Manual for Laboratory Equipment, 2nd edition gives an
overview of the technical requirements for installation,
use and maintenance for ancillary and other laboratory
equipment.
Other aspects that should be considered as part of the
procurement process are:
• Provision for upgrades, particularly for software;• Trouble-shooting;• Replacement spare parts;• Labour and travel; and• Loaner instruments in event of instrument breakdown
or instrument swap-out, in case of some analysers thatare used at point of care.
It is essential to define and negotiate these additional
maintenance costs up front, preferably as part of thecontract. If a separate contract is made for maintenance,
the reliability of the vendor should be used to determine
if these services will be paid for upfront or only after theservice has been completed.

21

Manufacturers of IVDs
Warranty

Figure 9. Complaint handling for post-market surveillance

A warranty is a commitment made by the supplier toreplace goods, usually instruments (analysers and ancillaryequipment), within a certain period of time at no additionalcost, when a quality or performance issue arises.

Post-market surveillance

Reactive post-market
surveillance

Complaint received and classified

Manufacturers should implement an effective postmarket surveillance system with both active and passive
collection of post-market information, including complaints.
Manufacturers must establish a documented procedure
for a feedback system to provide early warning of quality
problems and for corrective action/preventive action.
Reactive post-market surveillance comprises of complainthandling by the manufacturer through the following steps:
1. Classify complaint;
2. Conduct root cause analysis;
3. Take corrective action.
A field safety corrective action (FSCA) is an action takenby the manufacturer to reduce certain risks related touse of a given IVD. Such problems include malfunction or
deterioration affecting the performance or operational
characteristics of an IVD, as well as any inadequacy in the
instructions for use which might lead or might have led tothe death of a patient, user or other individual or to a serious
deterioration in his/her state of health.
When the need for a FSCA of an IVD has been established,
the manufacturer of the affected product assumes the
responsibility for recovery of the goods and implementationof the corrective action. WHO and the relevant NRAs may
assist by monitoring the overall action.

Root cause analysis

Possible Field Safety Corrective
ActionPossible issuance of Field Safety Notice

FSCA may include:• Return of an IVD to the manufacturer or its representative(product recall);• IVD modification (such as revised instructions for use);• IVD exchange (with new instrument);• IVD destruction (product recall);• Advice given by the manufacturer regarding the use of
the IVD (e.g. where the IVD is no longer on the market or
has been withdrawn but could still possibly be in use).

Standards that are applicable to post-market surveillance
Manufacturers of IVDs are expected to adhere to available international standards such as ISO 2859:2006 Sampling
procedures for inspection by attributes series and ISO 3951: 2013 Sampling procedures for inspection by variables series toverify the safety, quality and performance of each lot manufactured of their products.
Manufacturers are obliged to perform quality control lot release as part of the requirements of ISO 13485:2003 Medical
devices -- Quality management systems -- Requirements for regulatory purposes, which states that there must be adequate
monitoring and measurement of product and evidence of conformity with an agreed upon acceptance criteria. Where
manufacturers purchase key components for the product, these components must be verified to ensure they meet
specified purchasing requirements. Furthermore, there must be a process to identify and control product that does notconform to requirements and to prevent its unintended use or delivery.
In assessing the need for field safety corrective action, the manufacturer is advised to use the methodology described in
the standards: ISO 14971:2007 Medical devices - Application of risk management to medical devices and “Implementationof risk management principles and activities within a Quality Management System” (GHTF/SG3/N15R8).

22

GUIDANCE FOR PROCUREMENT OF IN VITRO DIAGNOSTICS AND RELATED LABORATORY ITEMS AND EQUIPMENT• Any serious adverse event should be reported by the
manufacturer to the relevant national regulatory
authority within their respective timelines (and to
WHO within 10 days).
• Any moderate adverse event or change in trend of mild adverse
events should be reported by the manufacturer to therelevant national regulatory authority within theirrespective timelines (and to WHO within 30 days).
• All complaints (both administrative and technicalincluding serious, moderate and mild adverse events)
to be reported by the manufacturer annually to therelevant NRA.
As soon as it is received, any complaint must be classified
by the manufacturer as part of the risk management filefor the product. The degree of risk will determine thetimeline for action, and who should be informed. The
requirement for root cause analysis will remain, irrespectiveof the classification.

Decommissioning IVDs
Even after sale of an IVD, the manufacturer has theobligation to ensure that any risks related to use of the IVD
throughout its life cycle (i.e. installation, use and disposalof the IVD) are managed through their risk management
framework. This means that the manufacturer is responsible
for ensuring that their product can be disposed of in a safemanner. This responsibility of the manufacturer should be
accounted for in the procurement contract.
There are a range of reasons for an IVD to be disposed of, orotherwise decommissioned, including:• Single-use IVDs that are disposed after use, such as ananti-HIV-1/2 RDT;
• Due to unacceptable levels of wear and damage or
unreliability;• Under instruction for field safety corrective action(FSCA) issued by the manufacturer (e.g. IVD return
through a recall to manufacturer or IVD destruction byuser under instruction from manufacturer);• Obsolescence of technology; and• Reagents or consumables that are no longer
commercially available.
Different categories of IVDs will have different safety
considerations when the device is disposed of, see Table 9
for additional details.

Table 9. Decommission or disposal of different types of IVDs
Category of IVD

Example of IVD

Safety consideration

Disposable, single use Reagents or test kits.
Auxiliary equipment

Analysers

Chemical and biologicalsafety of the user, patientand environment
Centrifuge, vortex, pipette,
Biological, electrical safety
microplate washer and reader, of the user, patient andincubator, microscopes,
environment
heating plates, etc.
Dedicated equipment
Electrical, chemical,
for clinical chemistry,
biological safety of the user,
haematology, serology,
patient and environment
nucleic acid testing (NAT).

Whereby, biological safety refers to measures taken toprotect the user, patient and environment from any biologicalsource of contamination. Universal precautions refers toan approach to infection control to treat all human bloodand certain human body fluids as if they were known to be
infectious for HIV, HBV and other bloodborne pathogens.
Biological safety can be achieved through a variety of means
such as disinfection (using antimicrobial agents, other thanantibiotics or antiseptics), sterilization (using autoclave), anduse of other biocides. Most practically, single-use HIV-1/2
RDTs could be autoclaved or incinerated prior to disposal.
Chemical safety refers to measures taken to protect theuser, patient and environment from any harmful effects ofchemical exposure.
Radiation safety refers to measures taken to protect theuser, patient and environment from the harmful effects ofradiation.
Electrical safety refers to measures taken to protect theuser, patient and environment from the harmful effects ofelectrical malfunction.
Although, the final responsibility for disposal of an IVD
rests with the manufacturer, the practicalities of how nondisposable IVDs such as auxiliary equipment or analysers
are decommissioned might be affected by how the IVDs
were procured. For example, under reagent rental or leasing
options, a clause should be inserted into the procurement
contract to ensure that equipment to be decommissioned isdecontaminated and removed safely by the manufacturer ina timely manner. For procurement as an outright purchase,the manufacturer should assist the user to decontaminate
and dispose of the equipment in the most environmentallyfriendly manner possible.

Figure 10. Life cycle of an IVD
Design,includingvalidation

Manufacture,includingpackaging andlabellingUse, including
installationPost-market
surveillance,
includingvigilance

Disposal,includingdecomission

23

National Regulatory Authorities for IVDs
NATIONAL REGULATORYAUTHORITIES FOR IVDS
Regulatory approvals17
Regulation, specifically for IVDs, can be non-exhaustive
and may be poorly enforced, particularly for resourcelimited settings. Manufacturers are obliged to seek national
registration in markets where they intend to market theirproduct. The procedure for national registration with therelevant regulatory authority begins the procedure toapprove a product for sale and use, bearing in mind thatnational registration may not always confer stringent and/or sufficient regulatory control. Adequate pre-market
assessment should be conducted by national authorities
through national regulatory authorities and nationalreference laboratories.
A range of documentation that may be offered as evidenceof safety, quality and performance to determine productregistration, and later, decisions on product selection. These
include certificates issued by conformity assessment bodies,
audit reports, and study reports.

Regulators that are founding members of Global
Harmonization Task Force (GHTF) will consider if there isa high potential for unreasonable risks created by the useof the product, but when used only in their jurisdiction.
Therefore, the stringency of pre-market assessment is thendetermined by the level of risks the diagnostic poses whenutilized in the population of the regulator. For example,
if the product is used to screen blood donations for HIV,the individual and public health risk is considered high,and therefore most regulatory authorities will undertakea stringent pre-market assessment. But importantly, a
product that is not considered one that poses a high risk
in many well-regulated settings, may indeed be a high riskin another setting, such examples are malaria RDTs andCD4 enumeration technologies. In most countries with astringent and effective regulatory authority, malarial disease
has a minor impact on that jurisdiction’s population. As such,pre-market assessment of quality, safety and performanceby the regulator is often minimal in comparison with, forexample, diagnostics for HCV, HBV or HIV.
However, the level and stringency of assessment may
not be the same across product categories. For example,
assessment of HIV RDTs has been well established in many
countries, while introduction of CD4 technologies that can

18

Table 10. Regulatory approvals for diagnostics
Type of regulatory approval

Details

Regulatory approval in country of manufacture

Approval in the country of origin, i.e. where the product is manufactured, either approval for sale and use in the country of
manufacture or approval for export only19.

Regulatory approval in country of intended use

Regulatory approval by other national
authorities

Approval by implementing partners andfunding agencies

Regulatory requirements “for export only” are less stringent than “for sale and use”. Approval “for export only” does not provide
evidence of sufficient regulatory review of safety, quality and performance.
Approval of diagnostics that are manufactured elsewhere and imported, approval for sale and use in the country of intended
use conducted by national authorities. Assessment by national authorities (national regulatory authority or national referencelaboratory) includes studies to validate national testing algorithms, and other performance evaluations and studies to gather
clinical evidence.
Global efforts towards harmonization of regulatory approaches have led to internationally accepted standards for a risk-based
approach for the pre-market assessment of safety, quality and performance of diagnostics. Assessments undertaken by the WHO
Prequalification Team - Diagnostics and regulatory authorities that are founding members of the Global Harmonization Task
Force i.e., European Commission, Health Canada, US Food and Drug Administration, Australian Therapeutic Goods Administration,
Japan’s Ministry of Health, Labour and Welfare and Pharmaceuticals and Medical Devices Agency (PMDA) could be considered for
categories of diagnostics that are stringently assessed.
Given the slight differences in regulatory requirements, manufacturers may supply different regulatory versions of the “same”
product such as versions for markets with stringent regulatory controls and versions for markets with little or no regulatory
control, the latter are often referred to as “rest of world” regulatory versions. Therefore, a less-regulated or un-regulated versionof seemingly the same product may be supplied without any assurance that same quality controlled components and procedures
were used to manufacture the product to be procured.
Implementing partners and multilateral/bilateral donors may have their own quality assurance policies and/or their own
mechanisms for assessing diagnostics for procurement such as Global Fund, UNITAID and USAID, etc.

17 Approval is otherwise known as registration, certification or licensing, hereafter referred to as approval in thisdocument.
18 Sometimes referred to as a “Certificate of Free Sale”

24

GUIDANCE FOR PROCUREMENT OF IN VITRO DIAGNOSTICS AND RELATED LABORATORY ITEMS AND EQUIPMENT

be used at point-of-care has been hampered by lack ofstandardized assessment procedures.
As a minimum, the technical specifications must state
the exact nature of the regulatory approval required from thecountry of origin and from the country of intended saleand use. Supportive documentation must be submitted
as part of the bidding process to verify the exact
regulatory status of the product that will be procured.

Given the range in differences between regulatory versionsof seemingly the same product, national authorities should
pay special attention to the regulatory version marketedin their jurisdiction. For instance, if a change is made toa regulatory version in another jurisdiction, how would
this impact other regulatory versions. For post-market
surveillance, are mechanisms in place to allow for reportingof incidents that have occurred with a different regulatory
version in a different jurisdiction.

should be agreed upon between the national authorities
and the procurer beforehand and may be risk-based
depending on the value and/or volume of the consignment.
A panel of biological specimens should be tested on
an appropriately collected sample of tests from a given
consignment received. Acceptability criteria must be
assigned and a process in place to handle products that
do not comply to pre-determined technical specifications.
It may be useful to monitor lot to lot variation over timewith the same specimen panel to identify any shifts ortrends in test performance that could foreseeably impact
the test result.
Sampling of tests from field conditions
In addition to pre-distribution lot verification testing,samples may be taken at regular intervals throughout
the year and tested accordingly, as appropriate based on
the above mentioned risk approach taking into accountexcursion of recommended storage temperatures.

Post-market surveillance

Field Safety Corrective Action

Lot testing of consignments

If the need for a field safety corrective action (FSCA) has
been taken by the manufacturer to reduce certain risks
related to use of a given IVD, the regulatory authority should
help to enforce the recommended actions.

To ensure that IVDs continue to meet their specifications,
national regulatory authorities have the mandate to arrange
proactive lot verification testing including:• Pre-distribution to testing sites (when a consignmentof test kits arrives in country); and• Post-distribution to testing sites (after the lot has alreadybeen in use).
Pre-distribution lot verification testing should take place
in a nationally designated facility, usually the nationalreference laboratory, before the consignment is released for
distribution nationally. The sampling interval and procedure

FSCA may include:• Return of an IVD to the manufacturer or its representative(product recall);• IVD modification (such as revised instructions for use);• IVD exchange (with new instrument);• IVD destruction (product recall);• Advice given by the manufacturer regarding the use of
the IVD (e.g. where the IVD is no longer on the market or
has been withdrawn but could still possibly be in use).

25

WHO
WHO
WHO prequalification assessment
WHO prequalification assessment fills a gap for somenational regulatory authorities by assessing the quality,
safety and performance of in vitro diagnostics that are mostsuited for use in resource-limited settings.
The final WHO prequalification assessment outcome
depends on:
1. Results of the dossier review and acceptance of thecorrective action plan, if required.
2. Results of the site inspection(s) and acceptance of thecorrective action plan, if required.
3. Meeting the minimum acceptance criteria on thelaboratory evaluation.

Eligibility for WHO prequalification assessment
WHO determines whether an application will be eligible forprequalification assessment based on (1) WHO eligibility
criteria and (2) programmatic suitability. Products that havealready undergone a stringent regulatory assessment bycertain regulatory authorities may proceed to an abridged
WHO prequalification assessment. If so, submission of a
product dossier for WHO review is not required. However,abridged WHO prequalification assessment still requires
the conduct of the laboratory evaluation and a shortened
inspection that leverages the findings of previous
inspections.

Product dossier review
A product dossier contains documentation and data
to demonstrate that the IVD conforms to the Essential
Principles of Safety and Performance of Medical
Devices. Guidance issued from the International Medical
Device Regulators Forum (IMDRF) (formerly the Global
Harmonization Task Force) is considered the international
best practice related to regulation of medical devices,
including IVDs. Other standards and guidance issued by
the International Organization for Standardization (ISO)and Clinical and Laboratory Standards Institute (CLSI) can
provide specific information on specialized areas such asstability testing for IVDs. The product dossier requested by
WHO should be submitted according to the “Instructions
for compilation of a product dossier” (http://www.who.int/
diagnostics_laboratory/evaluations/PQDxInfo/en/)
The WHO prequalification assessment reviews theperformance and use of IVDs specifically from theperspective of WHO Member States, that is, stability, risk
assessment and instructions for use. National regulatory

26

authorities (NRAs) undertaking stringent review may notreview these aspects in the same way. WHO rates any
non-conformities, and the manufacturer is expected tofile a corrective action plan that outlines how and whenrequirements will be met.

Inspection of the site of manufacture
The WHO inspection schedule is divided into stages:
Stage

Content

Stage 1

Evaluation of readiness for inspection through desktop
review of quality documentation or a brief on-site
inspection.
Initial full on-site inspection to determine
implementation of the quality management system,
facility and warehousing, competence of staff, criticalsuppliers including outsourced activities, internal audit
and management commitment or review. Also, withdossier assessor attends the inspection to confirm aspectsof the dossier.
Confirmation of implementation of the corrective action
plan submitted in response to Stage 2 inspection; may or
may not require another on-site inspection.
Risk-based; at least annual reporting required.

Stage 2

Follow-up
Surveillance
Re-inspection

Risk-based; conducted after 3−5 years holding WHO
prequalification.

All sites inspected must meet prequalification requirements
and must demonstrate:
1. a fully implemented quality management system(design, development and manufacturing including
quality control, storage and distribution);
2. risk management;
3. product stability;
4. routine manufacturing;
5. sufficient capacity to ensure reliable delivery.

Independent evaluation of performance and operational characteristics
WHO conducts performance evaluations, whereby eachproduct is tested on a worldwide-sourced clinical specimen
reference panel, commercially acquired seroconversion
panels and panels of specimens containing low antibody
titers and antigen concentrations. These evaluations aim
to assess technical and performance characteristics suchas diagnostic sensitivity and diagnostic specificity, as well
as seroconversion and low titer sensitivity relative to thoseof other assays of similar format.
Manufacturers send one or more production lots to WHO
Collaborating Centres or other laboratories designatedby WHO to conduct the evaluation testing. WHO issues
a technical report of the performance and operational
characteristics and determines if the assay meets WHO
prequalification requirements. Specific minimum
acceptance criteria are applied to each assay format, see
Table 11, Table 12, Table 13.

GUIDANCE FOR PROCUREMENT OF IN VITRO DIAGNOSTICS AND RELATED LABORATORY ITEMS AND EQUIPMENTTable 11. Minimum acceptable performance for HIV serology
assays for WHO prequalification
Characteristic

RDT

EIA

Sensitivity

>99%

100%

Specificity

>98%

>98%

Inter-reader variability

<5%

N/A

Invalid rate

<5%

<5%

Table 12. Minimum acceptable performance for HCV serology
assays for WHO prequalification
Characteristic

RDT

EIA

Sensitivity

>98%

100%

Specificity

>97%

>98%

Inter-reader variability

<5%

N/A

Invalid rate

<5%

<5%

Table 13. Minimum acceptable performance for HBsAg
serology assays for WHO prequalification
Characteristic

RDT

EIA

Sensitivity

>99%

100%

Analytical sensitivity for screeningof donations AND for testing ofasymptomatic and symptomatic
individuals for diagnostic purposes
Analytical sensitivity for testing ofasymptomatic and symptomatic
individuals for diagnostic purposes
Specificity

LoD< 0.13 IU/mL

LoD < 0.13 IU/mL

LoD < 4 IU/mL

LoD < 4 IU/mL

>98%

>98%

Inter-reader variability

<5%

N/A

Invalid rate

<5%

<5%

Final prequalification decision
When the prequalification decision has been made, WHOissues a public report, and the product is added to the listof WHO prequalified products. It is, therefore, eligible for
WHO and UN procurement as well as direct procurementby countries, and other implementing partners anddonors such as UNITAID and Global Fund. In the postprequalification stage, the manufacturer is obliged to
conduct post-market activities to continue to assure thequality, safety and performance of a WHO-prequalified
IVD. The manufacturer is also obligated to notify WHO of

any changes to the product or the quality management
system, so that these may be evaluated to determine any
implication for their listing as WHO-prequalified.

Post-market surveillance for WHO prequalified products
The purpose of post-market surveillance is to protect
individual health and public health through continued
surveillance of IVDs once they are placed on the market. Postmarket activities ensure that manufacturers are aware of any
event that may affect the quality, safety or performance of
their assay. Manufacturers must then evaluate and assess
any residual risks and, as appropriate, take risk mitigation
measures. Figure 7 shows the components of post-market
surveillance.
A centralized collection of post-market data on WHOprequalified IVDs enables coordinated action in WHO
Member States and ensures traceability of information. These
post-market data include results from pre-distribution andpost-distribution lot verification testing as well as complaints
and evaluation data. Regulators and users submit these postmarket data to WHO in the form of lot testing reports and IVD
complaint forms. National regulatory authorities, procurers
and implementing partners, such as nongovernmentalorganizations, are notified of certain reports of adverse
events through vigilance information exchange.
Other actions that WHO might take on post-market
information include:• post-market surveillance information exchange withnational regulatory authorities• post-market surveillance information exchange with
manufacturers• publishing post-market surveillance information on
WHO’s website• additional surveillance of the IVD concerned• removal of the product from the list of WHO-prequalified
IVDs, if needed• inspection of the manufacturing site to ensure that
corrective or preventive action as a result of any
complaint has been implemented.
WHO’s Guidance for post-market surveillance of in vitro
diagnostics provides further information. (http://www.who.
int/diagnostics_laboratory/postmarket/en/)27

DONATIONS

Many countries are faced with decisions concerning
acceptance of donated equipment, both new and secondhand. Some donations may not be registered or supported
in country and may not be listed in national guidelinesthat describe standardization and harmonisation policies.
Donated products should be refused if they do not conformto existing national policies including testing algorithms
and closed testing systems.
Donations of reagents close to expiry should be consideredin the context of work load and capacity for storage anddistribution. It is important that countries understandthe supply chain constraints for dealing with close-toexpiry products and set minimum acceptance criteria. The
appropriate disposal of expired product can be more costly
than the purchase price.

28

The WHO Guidelines on Donation of Medical Equipment
may be used as a guide in addition to the following caveats.
Donated equipment must be part of the PSM plan and/or
national guidelines and thus potential donors of equipment
should be involved in national laboratory planning
processes. Countries should have clear national policies
about donations of diagnostics and other perishable
reagents. If a donation is to go ahead, the donors should
send the equipment specifications to the laboratory
ahead of delivery (to ensure that the necessary physicalinfrastructure is present). Donated equipment and reagentsshould have at least 50% of their useful life remaining at
the time of donation. Donated equipment should follow
the usual procurement process to ensure that adequate
reagents and supplies are procured, that installation,
maintenance (preventive and corrective) and training arealso procured. Equipment retirement (decommissioning)procedures should be developed and followed for donatedand other equipment.

GUIDANCE FOR PROCUREMENT OF IN VITRO DIAGNOSTICS AND RELATED LABORATORY ITEMS AND EQUIPMENTREFERENCES

ISO 13485 Medical devices -- Quality management systems-- Requirements for regulatory purposes
ISO 15190 Medical laboratories — Requirements for safety
ISO 14971 Medical devices — Application of risk
management to medical devices
WHO. Manual for procurement of diagnostics andrelated laboratory items and equipment, 1st edition (2ndedition under preparation). Geneva. 2013. http://www.
who.int/diagnostics_laboratory/procurement/131024_
procurement_of_diagnostics_finalversion.pdf
WHO. Post-market surveillance of in vitro diagnostics.
Geneva. 2015 http://www.who.int/diagnostics_laboratory/
postmarket/150819_pms_guidance_final_version.pdf?ua=1
WHO. Specifications and quantities for efficient procurementof essential equipment and laboratory commodities forHIV. Geneva. 2015. 2nd edition. Accessed 27 May 2016
from http://www.who.int/hiv/pub/amds/amds_equipmentcommodities-forecast/en/
WHO. Guidance on development of national strategiclaboratory policy and plans. Manila Accessed 27 May
2016 from http://www.wpro.who.int/health_technology/
documents/docs/Nationalhealthlab2_0F38.pdf

WHO. Consolidated guidelines on HIV testing services.
Geneva. 2015. Accessed 27 May 2016 at http://www.who.
int/hiv/pub/guidelines/hiv-testing-services/en/
WHO. Consolidated guidelines on viral hepatitis testing
services. Geneva. Publication forthcoming in 2016.
WHO. Laboratory diagnosis of sexually transmitted
infections. Geneva. 2013. Accessed 27 May 2016 at
http://www.who.int/reproductivehealth/publications/rtis/9789241505840/en/
European Commission, DG Health and Consumers (SANCO).
Guidelines on medical devices vigilance system (MEDDEV
2.12-1 rev 8). January 2013. http://ec.europa.eu/growth/
sectors/medical-devices/index_en.htm
MHRA. Management of In Vitro Diagnostic Medical Devices.
December 2013. https://www.gov.uk/government/
uploads/system/uploads/attachment_data/file/371813/
Management_of_In_Vitro_Diagnostic_Medical_Devices.pdf
MHRA. Management and use of IVD point of care test
devices. December 2013. https://www.gov.uk/government/
uploads/system/uploads/attachment_data/file/371800/
In_vitro_diagnostic_point-of-care_test_devices.pdf
Williams J, Umaru F, Edgil D, Kuritsky J. Progress inharmonizing tiered HIV laboratory systems: challenge andopportunities in 8 African countries. Global Health: Scienceand Practice, 2016, 4(3):467-80.

29

Annexes
ANNEXES
Annex 1. Checklist for 12 key aspects for needs assessment for instruments and analysers
The following checklist may be used to assess new instrument or analyser procurement.
1. Is the product on the nationally approved list, e.g. national registration, national standardization list?
2. Is the request to replace existing old instruments? If yes, is there an instrument replacement strategy?
3. If these instruments are for new locations, is there an instrument deployment plan for the proposed instrument?
4. What is the current estimated diagnostic capacity for this particular instrument type in country?
5. What is the diagnostic burden at the proposed sites? Is the instrument selected appropriate, based an instrument
capacity vs. diagnostic demand?
6. Is there suitable infrastructure at the proposed sites - any additional peripheral needs?
7. Is there expected service delivery expansion at the proposed sites? (scale up)
8. Have the additional costs of reagents, staff training, and maintenance been considered - what are the funding sourcesand estimated costs?
9. Will the instrument require an extended warranty after its warranty expires?
10. Is a local Authorized Manufacturer Distributor available to service the instrument?
11. Is there a Maintenance Service Agreement (MSA) in place for similar instruments you have currently on-hand? If yes,is the MSA still valid and who is managing the Agreement?
12. Is an equipment inventory list available for similar instruments on-hand? If so, was an inventory conducted in the past
12 months with updated serial numbers and site locations?
General principles for all categories of equipment
Criteria
Laboratory infrastructure

30

Considerations• Constant/intermittent/no electricity• Capacity of an uninterruptible power supply to run analyser or alternatively to “save” a result for test in-progress
Environmental conditions• Temperature and humidity for storage of reagents• Operating temperatures and humidity in the testing area
• Dust-free testing area
Safety• Consider biological, chemical, electrical safety to the user, to the patient, to other people in the vicinity, and to the environment
Staff skills level and training• Number of precision steps required, including need for phlebotomy• Computer literacy required
Simplicity of operation (ease of use)
• Number of precision steps required, including need for phlebotomy• Computer literacy required
Maintenance and calibration• Preventive maintenance that can be carried out by operator, or by supplier. Certain daily maintenance carried out by the operator,
requirementswith less frequent scheduled maintenance carried out by the supplier.
• Corrective maintenance that can be carried out by operator, or by supplier• Calibration needs when instrument is moved, can be carried out by operator or by supplier• Inclusion of the costs for maintenance (both preventive and corrective) and calibration - might be certain trade-offs for relatively
cheap instruments for use of POC
Supplier/vendor support• Procurement contracting (possibility for long term agreements, reagent rental, etc.)• Availability and reliability (in-country and/or within region) for: technical support (maximum testing down-time permitted)• pre-service and in-service training
Total cost of ownership• Inclusive of entire testing system which includes reagents and consumables, analysers, and other equipment• Cost of preventive/corrective maintenance and training• Consider cost of changing from one IVD or analyser to another, cost of re-training, re-writing SOPs, etc.
Additional specific considerations for analysers
Criteria
Considerations
Specimen type
• Serum, plasma (check any restrictions on anticoagulants), venous whole blood, capillary (fingerstick/heelstick whole blood), oral
fluid, sputum, etc.
Stability (transport, storage, in use) for• Temperature and relative humidity validated by manufacturer
reagents, controls and calibrators• Shelf-life upon manufacture• Shelf-life upon delivery, to be negotiated within procurement contract
Test menu available• Consider scalability for various volumes• For example:- more than one serological marker, anti-HIV/anti-HCV- more than one immunological marker,- more than one molecular marker, HIV RNA/HCV RNA/HBV DNA
Quality control (QC)
• Internal quality control mechanisms• Availability of external quality control material, e.g. artificial controls, control beads, etc.
External quality assessment (EQA)• Compatibility with existing programmes for EQA/proficiency testing (inter-laboratory comparison)
Workload of testing service• Expected turn-around-time• Expected specimen through-put• Ability to batch test runs, or notConnectivity• Data management capability; interface capability
Availability of back-up methods• If analyser is unusable, is a loaner analyser made available?

Annex 2. Methodology for product selection – using the principles of verification
National programmes may wish to maintain the option of performing a small-scale laboratory verification study, and/or point-of-use verification study to determine that the product (or testing algorithm) performs well before widespreadroll-out.
1. For qualitative IVDs such as RDTs (where a qualitative result is taken from an quantitative scale), the difference between
the new candidate testing algorithm(s) and the pre-existing status quo testing algorithm should be verified.
2. For quantitative IVDs such as viral load, verification of precision and estimation of bias can be used to determine if theassay is operating in accordance with manufacturer’s claims.

Qualitative assays
Panel of specimens for verification of product performance should include specimens that react near to the cut-off. These
will have the most value in challenging the qualitative accuracy of the candidate testing algorithm(s).
Prepare three specimens, one that is at the cutoff, then one that is 20% above the cutoff and one that is 20% below the cutoff.
• One specimen with +1 reactivity intensity on a scale of 0 to 3.
• One specimen with inconclusive (+/-) reactivity intensity on a scale of 0 to 3.
• One specimen with +2 reactivity intensity on a scale of 0 to 3.
Test each of the three specimens up to 40 times (40 replicates per specimen) on both the new candidate testing algorithm(s)and the status quo testing algorithm. More than one operator can conduct testing and this may provide for even more
representative data.
Compare the rate of false positive or false negative results for each of the testing algorithms, per operator. Given thatthe target value for each specimen will be generated through characterisation according to the status quo for the three
specimens used (2x HIV-positive and HIV-negative), then run experiment to obtain overall mean value and the overall
mean’s standard error.

Quantitative assays
Verification of precision can be evaluated by repeated measurements of two or more specimens over at least 5 days in one
run/testing session (generating at least 25 replicates per specimen on each assay). More than one operator can conduct
the testing, and this may provide for even more representative data. Testing does not have to take place on consecutive
calendar days. However, to ensure to ensure that specimen integrity is assured aliquot and freeze specimens, and thaw
each day so that aliquots are subjected to identical storage conditions. If aliquots are stored at 2 to 8 °C, then the aliquots
might have different properties by day 5 of storage.
Control materials should be run, if available. If either the positive or negative controls do not give the expected results,
the run is rejected and the results are not accepted for the verification study. If more than one invalid run, cease testing
and contact manufacturer.
Review data generated each day to check for outliers, out of range results, and pre-analytical errors such as transcription,
specimen mix-ups, clots, insufficient specimen volume. Do not reject if the result just seem aberrant.
Determine the allowable bias (i.e. what is clinically acceptable, which is generally 100% concordance). Compare each assay
with the target value.

31

Annexes
Phase 1: Prepare for verification study
a. Determine candidate testing algorithms to be verified
From the following lists of quality assured IVDs and in accordance with national requirements:• List of national registered in vitro diagnostics; and• WHO list of for prequalified in vitro diagnostics; and/or• List of products eligible for procurement under donor arrangements.
By choosing assays that are WHO prequalified or other approved by other agencies conducting stringent regulatory
assessment, assays have been assessed to determine if the manufacturer has sufficient validation and verification data to
support the claims they have made about the performance and operational characteristics for the product.

Therefore, the aim of the verification study is not to repeat an evaluation of diagnostic accuracy (for diagnostic sensitivity
and diagnostic specificity) but rather to determine if the testing algorithm(s) works as well as the status quo testingalgorithm that has been in place.

Combinations of RDTs to diagnose HIV infection must be shown to not share false (incorrect) test results for the same
specimens.
b. Request test kits
It is the responsibility of the study principle investigator to obtain sufficient number of tests from one lot of each assay
from the manufacturer (or distributor in the country of study). These test kits should be stored in conditions stated in the
manufacturer’s instructions for use. Any additional consumables that are required to perform each of the assays must areavailable.
c. Recruit specimens for the verification study
See above for qualitative and quantitative assays
Serum/plasma specimens will be used for their ease and ability to be collected in larger volumes. As the manufacturer will
have validated the candidate assay on other specimen types such as capillary whole blood, if it is claimed in the instructions
for use, as part of the validation and verification studies. The validation panel should be stored according to the instructionsof the panel provider which will usually be -20 °C or -80 °C.
Phase 2: Conduct verification study
a. Study site
The verification study may be conducted in any setting, as designated by national authorities. Ideally firstly in a laboratory
setting, then at point of use settings.
b. Study staff
All testing providers (operators) should follow standard operating procedures, and be trained in the performance ofeach candidate assay with adequate documentation in the form of standard operating procedures and standardized runworksheets. Accurate recordkeeping is crucial, and it should be emphasized that transcription errors are common. Each
operator testing the candidate assays should be blinded to the expected reference result for each of the specimens.
c. Verification specimen panel
Each specimen of the verification panel should be labelled with specimen ID numbers that do not reveal their expectedreference result. All candidate testing algorithms should be tested on the same verification panel, preferably by the same
operator. It is critical to be judicious when using the verification panel, aliquots should only be removed when needed. It
is preferable to test all assays with the same specimen on the same day, this will reduce inter-aliquot variability.

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GUIDANCE FOR PROCUREMENT OF IN VITRO DIAGNOSTICS AND RELATED LABORATORY ITEMS AND EQUIPMENT

d. Results interpretation
Results for visually read assays (RDTs, other simple assays)
Ideally, a second reader should make a blinded rereading of any visually read assay after the first reader (usually theoperator) has read and recorded the overall test result. In addition, the intensity of the test line/band should be recorded.
• If the two readers interpret the test results the same way, then the status of the specimen is recorded as is.
• If the two readers do not agree, a third reader should adjudicate on the reading. With the majority reading taken.
If a result cannot be conclusively reached, the result should be recorded as inconclusive and the specimen retested on a
new test device from the same lot. These should be included in the data analysis as a misdiagnosed specimen.
Results for instrument based assays (EIA, CLIA, ECL)
Certain immunoassays will display an OD/CO ratio that is within the grey zone, according to the manufacturer’s instructions
for use (usually 0.90 – 1.10). These specimens should be repeated in duplicate on the same lot. These should be includedin the data analysis as a misdiagnosed specimen.
Invalid results
For RDTs, invalid test results are typically when the control line does not appear, irrespective if the test line appears or not,and when high background colour completely obscures the result window. Other anomalies should also be recorded suchas streaking across the membrane, non-migration of specimen, debris on the membrane, etc.
For instrument-based assays (including immunoassays such as EIA, CLIA, ECL), invalid results or invalid runs occur when
the internal and/or external test kit controls (HIV negative, HIV positive) are not within the acceptance range specified in
the manufacturer’s instructions for use.
All invalid results should be recorded in the data analysis.
e. Study data analysis
If the initial testing result does not agree with the expected reference result, the specimen in question should be tested
again in duplicate on the same lot.
• If the same result is observed, then the result is recorded as not in accordance with the reference result and isincluded in the data analysis. For example, if a HIV-1 subtype O specimen is found non-reactive by a candidate
testing algorithm, the specimen would be repeated on the same testing algorithm (same lots), if the specimen is still
non-reactive, then the assay does not detect that HIV-1 subtype O specimen, i.e. disagreement with the expectedreference result.
• If the results remain discrepant from the reference result, the result is recorded as discrepant and the result is includedin the data analysis. For example, if a HIV-1 subtype O specimen is found non-reactive by a candidate assay, thespecimen would be repeated on the same assay (same lot), if the specimen is then found to be reactive, then results
are discrepant for detection of HIV-1 subtype O specimen, i.e. initially false non-reactive, final reactive result.
f. Study results
The results of the verification study should remain valid for a period of 3-5 years.

Phase 3: Monitor implementation of the testing algorithm(s)a. Implement the newly proposed testing algorithm in parallel with an existing algorithm for a period of two weeks forhigh throughput testing sites or four weeks for low throughput testing sites. Data should be collected on the rate ofreported HIV-inconclusive status and the rate of invalid test results (no more than 5% is acceptable) and any comments
related to test procedures or other operational characteristics should be documented. A discrepancy rate of >1%
between new and existing algorithms is significant and requires investigation and possible repeat of the validation
study.
b. Monitoring of the testing algorithm(s) should continue in keeping with quality systems principles.

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Annexes
Annex 3. INCOTERMS 2010
Abbreviation

Full Name

Implications

Applicable to all modes of transport

DAT

Ex Works(..named place)
Free Carrier(..named place)
Carriage paid to(.. named destination)
Carriage and insurance paid to(.. named place of destination)
Deliver at terminal

DAP

Delivered at place

DDP

Delivery duty paid

EXW
FCA
CPT
CIP

Applicable to sea and inland waterway transport
FAS
Free alongside ship
FOB
CFR
CIF

34

Free on Board(…named port of shipment)
Cost and freight
Cost, insurance and freight(.. named place of destination)

The Seller fulfils their obligations to deliver when the goods are made available at the Seller’s premises. The Buyer
must bear all the costs and risks involved in taking the goods from the Seller’s premises to the destination.
The Seller’s obligation to deliver occurs when he is handed over the goods, cleared for export, into the charge of thecarrier named by the Buyer at the named place.
The Seller pays the freight for the carriage of the goods to the named destination. The risk of loss or damage istransferred to the Buyer when the goods have been delivered into the custody of the carrier.
The Seller’s responsibility is the same as under CPT expect they must also obtain and pay for insurance against the
Buyer’s risk of loss or damage.
Transfer to the Buyer of responsibility for loss or damage occurs when the goods are placed at the disposal of theBuyer in a named terminal at the place of destination.
Delivery and transfer of risk occur when the goods are placed at the disposal of the Buyer on the arriving means oftransport.
The Seller is responsible for delivering the goods to the named place in the country of importation, including paying
all duties, taxes, customs.
The Seller has fulfilled their obligations when the goods have been placed alongside the vessel at the port of
shipment. From that moment, the Buyer is responsible for all costs and risks.
The Buyer is responsible for all costs and risks once the goods have passed over the ship’s rail at the port of export.
The Seller must pay the costs and freight necessary to take the good to the named port of destination. The risks ofloss or damage transfer to the Buyer when the goods pass over the ship’s rail at the port of shipment.
The Seller has the same obligations as under CFR but is also required to provide insurance against the Buyer’s risk ofloss or damage to the goods during transit.

GUIDANCE FOR PROCUREMENT OF IN VITRO DIAGNOSTICS AND RELATED LABORATORY ITEMS AND EQUIPMENTCONTAC T
Department of Essential Medicinesand Health Products
World Health Organization
20 Avenue Appia
CH-1211 Geneva 27
Switzerland
E-mail: diagnostics@who.int
www.who.int/diagnostics_laboratory

978 92 4 151255 8