who - who prequalification of medicines programme update for 2006

7/31/2019 WHO - WHO Prequalification of Medicines Programme Update for 2006

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2WHO PREQuALiFicAtiOn PROGRAMME

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The Programme was launched in 2001, in partnership with

UNAIDS, UNICEF and the UN Population Fund, with support

rom the World Bank. Its ocus was tackling the quality

problems commonly associated with medicines or treating

HIV/AIDS, malaria and tuberculosis (TB).

Product dossiers relating to products for treatingHIV/AIDS, malaria and tuberculosis (TB) productswere examined in each session and also betweensessions. A total of 496 assessment reports (linkedto 435 different products) were written duringthe six assessment sessions, representing a 45%increase over the number of reports (342) writtenduring 2005.

insPEctiOns

Forty-nine inspections were carried out (comparedwith 52 in 2005, when the inspection capacity of the

Programme was slightly higher), as follows:

17 inspections (compared with 20 in 2005) ofthe manufacturing sites of nished productmanufacturers

10 inspections (the same number as in 2005) of

the manufacturing sites of active pharmaceuticalingredients (APIs) 15 inspections (compared with 14 in 2005) of

contract research organizations (CROs) 7 inspections (compared with 8 in 2005) of

quality control laboratories (QCLs), mostly inAfrica.

An overview of inspections performed, listing

manufacturing sites, CROs and QCLs that complywith WHO norms and standards regarding good

manufacturing practice (GMP), good clinicalpractice (GCP) and good laboratory practice (GCP),respectively, continues to be maintained on theprequalication web-site (http://www.who.int/prequal/).

Table 1: Details o dossier assessments carried out in 2006

Number o assessment sessions in Copenhagen 6

Number o assessment days 42

Total number o assessment reports produced 496

Number o assessment reports produced on HIV/AIDS products 389

Number o assessment reports produced on TB products 78

Number o assessments produced on malaria products 29

Quality problems with medicines or treating

HIV/AIDS, malaria and TB

HIV/AIDS: For people living with HIV/AIDS,

antiretroviral products oer hope o prolonged

survival yet they are not available in sufcient

quality or quantity where they are needed most.

Malaria: Data rom a recent WHO survey in six

Arican countries showed that 1065% o sampled

antimalarial chloroquin tablets contained too little

active ingredient. The poor quality o frst-line

treatments is contributing to drug resistance and

treatment ailure.

TB: Many generic anti-TB medicines have serious

quality deects, due to their poor manuacturing

quality. Also, bioequivalence has oten not been

proved.


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WHO PREQuALiFicAtiOn PROGRAMME

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Then in 2006, the Programme laid the groundwork or

prequaliying medicines and commodities or reproductive

health. This was in response to the act that, in many

developing countries, the need or amily planning and

reproductive health services remains urgent. For example,

130 million couples wishing to use modern contraception

do not have access to amily planning services, and

340 million new cases o treatable sexually transmitted

inections occur each year. Moreover, provision o

reproductive health is oten hampered by lack o reliable

and good-quality supplies o medicines and commodities.

And international donor support or reproductive health

supplies is decreasing as a percentage o need and

o use. As a result, reproductive health medicines and

commodities are increasingly being unded and purchased

by national governments. But they do not always have

the necessary regulatory and procurement capacity or

ensuring sae, eective and adequate supplies.

Considerable assistance with inspections wasreceived from PIC/S1 member countries. WHO ishoping to encourage an increased number of PIC/Smember countries to work with the Programme.France provided signicant inspection support.Its own national medicines regulatory agency(NMRA) (Agence franaise de Scurit sanitairedes Produits de Sant (AFSSAPS)) has individualinspection units for nished product, CRO and

API inspections and so can make inspectors readilyavailable for the nished product, CRO and APIinspections conducted by the Programme. (Franceis one of the relatively few countries with signicantCRO inspection expertise.) In 2006, the FrenchMinistry of Health, AFSSAPS and WHO concluded

an agreement whereby France provides technicalsupport for the Programmes inspection activities.

Of the inspections carried out in developing countries,90% included participation not only of PIC/S

inspectors, but also of up to three local inspectors.

Number of inspections of each type

API/GMP

CRO

FP/GMP

QCL

10

15

17

7

Number of inspections by type, for HIV/AIDS products

API

CRO

FP

Total number

6

8

6

20

Number of inspections by type, for TB products

API

CRO

FP

Total number

3

5

5

13

Number of inspections by type, for malaria products

API

CRO

FP

Total number

1

2

6

9

Number of quality control laboratory inspections

Pre-audit inspections

Laboratory inspections

Total number

5

2

7

Table 2: Numbers and types o inspections carried out in 2006

API active pharmaceutical ingredientCRO contract research organizationFP fnished productGCP good clinical practiceGMP good manuacturing practiceQCL quality control laboratory


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HOW dOEs tHE PROGRAMME WORk?

The Prequalifcation Programme makes a solid, scientifc

assessment based on WHO prequalifcation guidelines,

that are in line with internationally harmonized standards

o the quality o both generic and patented medicines.

The process begins with submission to WHO, by a

pharmaceutical manuacturer, o an Expression o Interest

(EOI), together with a product dossier. The saety, quality

and efcacy inormation contained in the product dossier

is examined by two WHO-appointed assessors. Both

assessors must approve its contents. I they disagree, or

i the product is particularly complex, additional assessors

are consulted. When the dossier is close to approval,

inspection o the manuacturing site(s) (o the active

pharmaceutical ingredient and the fnished product) is

organized.

PREQuALiFicAtiOn OF PROducts FORHiv/AiDS

Forty-two antiretroviral (ARV) products wereprequalied (29 of which were generics), bringingthe number of HIV-related products on the list ofprequalied products to 154. Of the 42 products,17 had been approved or tentatively approved bythe US Food and Drug Administration (US FDA),and one product had been tentatively approved byHealth Canada.

During the six dossier assessment sessions,389 assessment reports, linked to 334 HIV/AIDS-related products were written, representing anincrease of 75% over the gure for 2005. TwelveGMP inspections were carried out for HIV/AIDSmedicines, including three three-year re-inspections

and six inspections for ARV APIs. Eight inspectionsof CROs were conducted, corresponding to 10bioequivalence studies of HIV/AIDS medicines.

Country Number of inspectors

Australia

Austria

Canada

France

Italy

Netherlands

SingaporeSwitzerland

United Kingdom

4

1

2

25

2

1

53

4

Table 3: Participation o PIC/S inspectors in inspections in 2006

Country Number of inspections

Belgium

Cameroon

Canada

China

France

Ghana

IndiaKenya

Madagascar

Malaysia

Niger

South Arica

Switzerland

Uganda

United States

1

1

1

6

1

1

281

1

1

1

3

1

1

1

Table 4: Number o inspections carried out per country in 2006


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Qaly orol of ARv

Post-approval monitoring of the quality of

prequalied products continued to be undertaken.(For an example, please seeJournal of GenericMedicines article mentioned on page 11.) In 2006,the Programme participated in a large sampling/quality-control testing programme of ARV products,as well as in some smaller initiatives relating toinvestigation into safety and quality complaintsregarding products that have not been prequalied.

PREQuALiFicAtiOn OF PROducts FOR tb

By the end of 2004, a total of eight TB productshad been prequalied. However, no additionalTB products were prequalied in 2005 or

2006. This was due to continued failure of

manufacturers to comply with prequalicationrequirements. Strategies for improving compliancewere maintained. These included increasedcommunication with manufacturers, regarding, forexample, the benets of prequalication, and rapidprovision of feedback concerning the quality oftheir products. Scientic advice, especially relatingto bioequivalence and efcacy/safety was alsoprovided to manufacturers. This advice includedrecommendations regarding clinical study design,choice of comparator products2 and review of

submitted protocols.

Although no TB products were prequalied

in 2006, the interest of TB manufacturers inprequalication of their products denitely grew.This interest was reected in the 50% increasein the number of assessment reports that wereproduced: 78 assessment reports, linked to 70 TBproducts (as opposed to 50 assessment reportslinked to around 50 products in 2005).

Ad hoc assessments of product dossiers continuedto be undertaken by the PrequalicationProgramme as a service to the Global Drug Facility(GDF).3 These assessments consumed considerableresources (in terms of assessor and nancial input).Since the GDF initiative has only partly achievedits objectives, these ad hoc assessments will be

reviewed in 2007. Part of the problem stems fromthe fact that the available products are of relativelypoor quality.

Inspection o a CRO is sometimes also necessary. Products

submitted or prequalifcation are oten multi-source

generics. In such cases, therapeutic equivalence with an

innovator (brand-name) product is verifed by perorming

a bioequivalence study. Such studies are generally carried

out by an independent CRO, which must thereore also be

inspected and approved.

The results positive or negative o dossier

assessments and inspections are communicated to

manuacturers and CROs. This technical eedback (which is

provided ree o charge) has proved to be o great practical

value because it helps manuacturers and CROs to improve

the quality o their products and clinical studies.


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Eight GMP inspections were carried out for TBproducts, including two three-year re-inspections

and three inspections of manufacturers of TBproduct APIs. Five inspections of CROs wereconducted that corresponded to 11 bioequivalencestudies for TB products.

Three of the inspections of API manufacturerswere carried out in cooperation with the InspectionProgramme of the Certication of SuitabilityProcedure, organized by the European Directorate forthe Quality of Medicines of the Council of Europe.

PREQuALiFicAtiOn OF PROducts FOR

MALARiA

During the six dossier assessment sessions inCopenhagen, 29 assessment reports, linked to31 products were written (in comparison with73 reports, linked to more than 40 malaria productsin 2005). This drop in assessment reports was dueto the drop in number of new submissions. It alsoreected the slow progress made by manufacturersin addressing deciencies identied by assessmentscarried out in 2005.

Several dossiers for malaria products werewithdrawn by manufacturers, following revision

of WHO treatment guidelines. The withdrawalsconcerned products that were not included inWHOs new treatment guidelines for artemisinin-

based combination therapies.4

Seven GMP inspections were carried out for malariaproducts, including one three-year inspectionand one manufacturing site inspection. Two CROinspections were conducted, corresponding to twobioequivalence studies of malaria products.

In common with the manufacturers of TB products,scientic advice relating to bioequivalence andefcacy/safety was provided to manufacturersof malaria products. This advice includedrecommendations regarding clinical study design,choice of comparator products and review ofsubmitted protocols.

Additionally, a comprehensive summary ofpre-clinical artemisinin toxicity (i.e. the results of

experimental studies in animals and cell cultures)was posted on the Prequalication Programmeweb-site as an aid to manufacturers compiling

Prequalifcation o QCLs ollows similar procedures. A

QCL must respond to an EOI and submit a laboratory

inormation fle or assessment. I the fle is approved, the

laboratory is then inspected to veriy that its quality control

activities are sufciently rigorous or monitoring medicines

quality.

QCLs are not only inspected but also assisted to reach

prequalifcation status through provision o customized

technical guidance and assistance in the orm o

inventory audits to improve laboratory management

and practice.

QCLs are vital to ongoing quality control o prequalifed

products. That is, they check the quality o medicines

circulating on the market. In the case o medicines

that have previously been prequalifed, they check that

the prequalifed medicines continue to comply with

internationally determined and agreed standards or

pharmaceutical saety, efcacy and quality.


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dossiers for artemisinin products. The Noteto Applicants Expressing Interest in SupplyingArtemisinin Containing Drug Products:Bioequivalence, or Safety and Efcacy Issues wasrevised accordingly.

Five antimalarials are now included on the list of

prequalied products.

PREQuALiFicAtiOn OF REPROductivE

HEALtH PROducts

The rst Expression of Interest (EOI) forreproductive health products was published on theProgramme web-site in October 2006. Additionaladvice to manufacturers on how to compile adossier for a reproductive health product, forexample, on choice of comparator products, wasalso posted on the prequalication web-site.

PREQuALiFicAtiOn OF QcL

QCLs started to be prequalied in 2005, whenthree QCLs were prequalied two university-based QCLs in South Africa and a nationalpharmaceutical QCL in Algeria. All are listed on the

prequalication web-site.

The dossier assessments and inspections are carried out

by qualifed, external experts rom national medicines

regulatory agencies (NMRAs), mostly rom countries

that are members o the Pharmaceutical Inspection

Cooperation/Scheme (PIC/S). They provide assessment and

inspection support to a core team at WHO headquarters.

(See also the reerence to PIC/S on page 3.)

Prequalifcation Programme activities and products prequalifedNumberin 2005

Numberin 2006

Percentageincrease ordecrease

between 2005and 2006

Dossier assessments

Assessment sessions in Copenhagen 9 6 33.3

Number o assessment days 45 42 6.6

Total number o assessment reports 342 496 +45

Number o assessment reports on HIV/AIDS-related products 222 389 +75

Number o assessment reports on TB products 50 78 +56Number o assessment reports on malaria products 70 29 59.6

Inspections 52 49 5.7

Inspections o manuacturing sites o fnished product manuacturers 20 17 15

Inspections o manuacturing sites o active pharmaceutical ingredients 10 10 No change

Inspections o contract research organizations 14 15 +7.1

Inspections o national pharmaceutical quality control laboratories (QCLs) 8 7 12.5

Products, laboratories prequalifed

Total number o products prequalifed 32 44 +38

Number o HIV/AIDS products prequalifed 29 42 +44.8

Number o TB products prequalifed 0 0 No change

Number o malaria products prequalifed 1 2 +100

Number o QCLs prequalifed 3 0 100

Table 5: Summary o Prequalifcation Programme activities, and products prequalifed, or 2005 and 2006


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By the end of 2006, 18 laboratories had expressed

interest in gaining approval; and 15 of them hadsubmitted a Laboratory Information File, the rststage of the process. Five pre-audit inspections ofnational pharmaceutical QCLs5 were carried out all in Africa as a means of providing guidanceon improvements needed in laboratory practice and

management.

Progress in prequalifying additional QCLs has beenslow. The laboratories prequalied in 2005 werealready operating at or close to the levels requiredfor prequalication. But it has become clear thatthose laboratories now seeking prequalicationstatus will require considerable technical assistancefrom the Programme, and must commit to making

substantial operational improvements themselves.Technical assistance has been delivered to several

national QCLs, including to laboratories in Ethiopiaand Tanzania.

tRAininG WORksHOPs On PREQuALiFicAtiOn

issuEs

Recognizing the importance of capacity buildingthrough training and hands-on practice, theprequalication team organized several trainingworkshops on prequalication issues during 2006.

These workshops provided tuition on generalor specic technical issues for larger groups,

including staff from NMRAs and QCLs, and frommanufacturers or other private companies. (Allworkshop materials can be found on the on theprequalication web-site at http://www.who.int/prequal/.)

Such workshops include group sessions withtask work. Efforts are made to ensure open andcollegial communication between manufacturers

and the presenters, who themselves are assessorsor inspectors working with the PrequalicationProgramme. The overall aim is to promote mutualunderstanding concerning quality and efcacy/safetyissues. Feedback on the workshops held to date hasbeen very positive: they are seen as a catalyst for

increasing capacity to ensure medicines quality. Fourworkshops were held in 2006, as follows:

Worhop : Gl, cha

January (5 days)Subject: Pharmaceutical quality, GMP andbioequivalence, with a focus on artemisinines.

The Programme actively seeks the participation o

regulatory sta rom less well resourced NMRAs in

Arica, Asia, Latin America, and the countries o central

and eastern Europe, in dossier assessment sessions and

inspections. Such participation constitutes valuable on-

the-job training. Additionally, workshops are organized or

regulatory sta (including QCL sta) and manuacturers

to alert them to common problems identifed during the

manuacture and development o generic medicines

or HIV/AIDS, TB and malaria. By these means, valuable

knowledge on medicines quality, efcacy and saety issues

is transmitted. As a result, the capacity o manuacturers

to produce good-quality generic products is increasing,

as is the capacity o NMRAs and QCLs to monitor

pharmaceutical quality.

Full details o the prequalifcation procedures and

prequalifed products can be ound at: http://www.who.

int/prequal/


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Worhop 2: Hao, ve nam

January (3 days)Subject: Pharmaceutical quality and bioequivalence.

Worhop : Par, Frae

March (2 days)Subject: GCP seminar for inspectors participating in

the WHO Prequalication Programme.

Worhop : dar-e-salam, ue Repl of

tazaa

August (5 days)Subject: Pharmaceutical quality, GMP and

bioequivalence, with a focus on artemisinines.

tRAnsPAREncY AbOut MEdicinEs QuALitY

The Programme pays particular attention toincreasing transparency around quality issuesrelating to generic medicines. Informationcollected and results obtained during assessmentsand inspections are (subject to condentialityrequirements) made publicly available throughWHO prequalication web-pages and publishedreports.

WHO Public Assessment and Inspection Reportsare a major means of communication. (In 2004,

the World Health Assembly requested that WHOsprequalication activities be made more transparent,including making assessment reports and inspectionreports publicly available.) A standardized formatis used for producing WHO Public AssessmentReports (WHOPARs). WHOPARs are posted onthe prequalication website (with priority beinggiven to xed-dose combination products). Theweb-site includes guidance for manufacturersregarding these reports and information on howthe reports are compiled by the prequalication

team. (When submitting a product dossier forassessment, manufacturers must include specieddocumentation for inclusion in the WHOPARthat will later be compiled on their product.) A

standardized format is also used for WHO PublicInspection Reports (WHOPIRs), which are likewiseposted on the prequalication web-site.

During 2006, 11 WHOPARs for specic productsand 24 WHOPIRs, covering all types of inspections,

were produced.

WHO bEnEFits FROM PREQuALiFicAtiOn?

People at risk rom and/or inected with HIV/AIDS,

TB and/or malaria: For HIV/AIDS patients, in particular,

scaled-up access to medicines o assured quality is

leading to a vastly improved quality o lie. It is also helping

to reduce wasted expenditure on substandard medicines,

be this at household level or medicines purchased

by individuals and their amilies, at national level or

medicines purchased by central medical stores, or at the

level o global treatment initiatives. In other words, more

patients are being treated optimally.


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uPdAtE On EXistinG cOLLAbORAtiOn

copehage Hiv Programme

The collaboration initiated in 2005 with theCopenhagen HIV Programme (CHIP), basedin Denmarks Hvidovre University Hospital,continues. Activities focus on reviewing safety andefcacy information relating to ARV products andcontained in WHOPARs. Standardized texts onsafety and efcacy for APIs and API combinationsare developed and published, together withthe corresponding WHOPAR, for prequaliedproducts. The collaboration is helping to promoteconsistency of clinical information about ARVproducts, as well as to reduce the timeline forprovision of acceptable and useful summaries of

product characteristics.

us FdA a oher reglaory ahore

A number of HIV products approved or tentativelyapproved by the US FDA were added to the list ofproducts prequalied by WHO. These additionsrelied on the scientic assessment and inspectionsconducted by the US FDA. Information exchangebetween the two organizations is in accordance with acondentiality agreement that was nalized in 2005.

Collaboration also continues to be developed withthe European Commission and the EuropeanMedicines Evaluation Agency, particularly on

sharing and exchanging inspection-relatedinformation.

NMRAs: In resource-limited settings, in particular,

the Prequalifcation Programme is helping medicines

regulatory sta to increase their technical capacity to

monitor and ensure the quality o medicines, particularly

those or treating HIV/AIDS, TB and malaria. This includes

developing greater understanding o: dossier assessment

or new generic medicines; good manuacturing practice

(GMP) adherence and GMP inspection; and how to

overcome problems resulting rom poor manuacturing

practices. For NMRA Programme participants rom

developed countries, the principal beneft is a greater

understanding o regulatory problems in resource-poor

settings and problems encountered by pharmaceutical

manuacturers outside their jurisdictions.

QCLs: For unctional developing country QCLs, benefts

include increased capacity to assess the quality o

medicines samples, not simply or medicines or treating

HIV/AIDS, TB and malaria, but medicines in general.


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Pharmaceutical manuacturers in developing

countries: The capacity o this very diverse group to

produce medicines o assured quality, efcacy and saety

is being enhanced, in turn reducing reliance on imports,

and increasing opportunities or export. Manuacturers

have already been assisted in improving the quality

o their dossier submission. An increased number o

generic medicines manuacturers now routinely submit

dossiers that include sufcient detail regarding proo

o saety, efcacy and quality. In short, the Programme

oers manuacturers a tremendous opportunity to obtain

technical guidance ree o charge, that is o the highest

calibre and that might otherwise be unavailable to them.

PubLicAtiOns And inFORMAtiOn

An article (Ongoing monitoring of antiretroviral

products as part of WHOs Prequalication Projecton post-approval monitoring of prequaliedproducts by T.G. Dekker, A.J. van Zyl, O. Gross,I. Tasevska I, M. Stahl, M.L. Rabouhans andL. Rgo) was published in theJournal of GenericMedicines (Vol. 3(2):69105, January 2006).

The prequalication website (http://www.who.int/prequal/) was updated frequently in 2006. Newlyprequalied products and details of QCLs meetingprequalication requirements were posted, as werenew or revised guidance documents, together withWHOPIRs, WHOPARs and workshop trainingmaterials.

A new and more user-friendly prequalication web-site was launched in November 2006.

Gae

A new and revised guidance on variations(changes) to a prequalied dossier wasadopted by the WHO Expert Committee onSpecications for Pharmaceutical Preparations.The guidance stipulates, among other things, thatif manufacturers have notied the Programme of

a variation or variations belonging to a certaincategory as dened in the guidance that theywish to make to a product, and are not contacted

by the Programme within three months, then theymay go ahead and implement those variations.

The EOI for reproductive health products waspublished on the Prequalication Programmeweb-site, as was a list of recommended comparatorproducts within the area of reproductive health.

The lists of recommended comparator products forHIV/AIDS, TB and malaria products were revisedand updated on an ongoing basis.

The following were adopted in October 2006 bythe WHO Expert Committee on Specications forPharmaceutical Preparations: Procedure for Assessing

the Acceptability, in Principle, of PharmaceuticalProducts for Purchase by United Nations Agencies(Annex 4) and Procedure for Assessing the

Acceptability, in Principle, of Quality ControlLaboratories for Use by United Nations Agencies


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National disease control programmes and global

health initiatives: Prequalifcation not only reduces

the risk o expenditure on poor-quality, ineective or

countereit medicines, but is also extending the range o

suppliers o good-quality medicines. Given extension o

treatment to unprecedented levels, this is critical. Access

to antiretroviral (ARV) therapy is set to expand ten-old

by 2010, based on the commitment made by the Group

o Eight in 2005, and current unding commitments or

treatment o malaria with artemisinin-based combination

treatment is driving a one hundred-old increase. Without

quality medicine supplies, these increases will be

impossible.

In due course, once medicines and commodities or

reproductive health start to be prequalifed, more

individuals will be able to access amily planning

services and more individuals requiring treatment or

sexually transmitted inections will be able to obtain

such treatment.

(Annex 5). The rst document is an update to thealready existing general procedure for prequalifyingmedicines, while the second document describesgeneral procedures for prequalifying QCLs. I.e.taken together, these documents describe the

general principles of prequalication.

tralao

The Technical Ofce for Studies on InternationalCooperation (Ofce Technique dEtudes deCoopration Internationales6 OTECI) completedtranslation of training material on GMP intoFrench. It will be a major contribution to trainingworkshops to be held in francophone Africa.

Translation into Chinese of the most importantparts of the prequalication web-site started in2006, in cooperation with the Chinese Ministry ofHealth.

inFORMAtiOn MAnAGEMEnt

A database to log and track dossier assessment,inspections and other activities is being developed.It will also incorporate all correspondence withmanufacturers, as well as assessment andinspection reports. The database is expected to

become fully operational in 2007.

AdvOcAcY And AWAREnEss

Prequalication team members took part in avariety of meetings in 2006, to present and explain

the Programmes activities. In so doing, they helpedto maintain awareness and understanding of theneed for and impact of prequalied medicines.

The most important meeting was that of the

International Conference of Drug RegulatoryAuthorities (ICDRA). ICDRAs have been heldevery two years since 1980. They provide regulatoryauthorities of WHO Member States with a forumfor discussing national and international prioritiesfor regulation of medicines, vaccines, biomedicinesand herbal medicines. They are key to efforts toharmonize regulation and to improve the safety,efcacy and quality of medicines globally.


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The 12th ICDRA, took place in 2006 in Seoul,Republic of Korea and was attended by regulatorsfrom nearly 100 countries. It included a session,

Access to medicines: new regulatory pathways forpublic health needs that included presentationson: procedures relating to access to medicinesunder Article 58 of European Union legislation; the

United States FDAs tentative approval procedurelinked to the Presidents Emergency Plan for AIDsRelief (PEPFAR); the Canadian access to medicinesregime; and the WHO Prequalication Programme.The following recommendations resulted from thissession:

1. In the assessment of products, particularly thosedeveloped for public health needs, countriesshould make use of new regulatory pathways

provided by highly-evolved regulatory agencies inorder to avoid duplication of effort. This wouldenable optimal use of limited resources.

2. In cooperation with well-resourced regulatoryagencies, WHO is urged to assist Member Statesto provide training on the best use of regulatoryinformation on product approvals available in thepublic domain.

3. WHO should continue its efforts to prequalify

APIs for priority diseases, including HIV/AIDS, malaria and TB. Information concerningprequalied products and approved sites shouldcontinue to be made public in the form of

WHOPIRs.

4. WHO should assist national regulatory agenciesto develop innovative approaches to improveaccess to safe and effective essential medicines ofquality which address public health needs.

The proceedings of the 12th ICDRA, together withall power point presentations, are available on theWHO medicines web-site: http://www.who.int/medicines/icdra/en/

vALuE FOR MOnEY

The Prequalifcation Programme is helping to ensure

that donor unds are spent on good-quality medicines

and achieve maximum impact. Indeed, the Global Fund

to Fight AIDS, TB and Malaria (GFATM) stipulates that

any single- or limited-source pharmaceuticals procured

with GFATM unds must have been prequalifed by WHO.

Prequalifcation o products in turn puts pressure on

manuacturers to bring prices down, which also serves to

optimize use o national and donor resources.


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Other meetings attended by Programme staff in2006 included:

2nd Seminar on National Policy on Medicines,So Paulo, Brazil, in April.

Meeting on artemisinin-based combination

therapies organized by Drugs for NeglectedDiseases Initiative and held in June, in Geneva,Switzerland.

42nd meeting on improving access to quality-assured TB drugs, organized by the Campaignfor Access to Essential Medicines, of MdecinsSans Frontires (MSF), in Geneva, Switzerland,in June.

Rencontre dt (summer meeting) on paediatricmedicines for treatment of HIV/AIDS, TB

and malaria, organized by ReMed (Rseau deMdicaments et Dveloppement), a Frenchnongovernmental organization (NGO) in Paris,in July.

The annual Technical Brieng Seminar onEssential Medicines Policies, in September, inGeneva, for a selected group of 35 core nationalsrepresenting ministries of health, regulatory

agencies, professional pharmaceutical associationsand NGOs, as well as WHO eld staff.

The African Medicines Regulatory AuthoritiesConference, in Addis Ababa, Ethiopia, inOctober/November.

The annual meeting organized by AFSSAPS, inParis, in November, on public health problems(especially those related to HIV/AIDS) faced bysub-Saharan francophone African countries.

Interagency Pharmaceuticals CoordinationGroup meeting at the Pan American HealthOrganization, in Washington, DC, in November.

Interagency meeting on medicines issues

organized by MSF in Paris in Novemberfor pharmacists working with NGOs orinternational organizations.

World Trade Organization workshop on theTRIPS Agreement and public health, held inGeneva, in November.

The expansion o ARV therapy in Arica provides ample

illustration o the health impact resulting rom the fnancial

savings generated by the Programme. Between June

2004 and June 2005, coverage increased by 350,000

people, to hal a million people living with HIV. Most were

enrolled to one o WHOs recommended frst-line regimens.

On average, these regimens are available or US$ 560

per patient per year when purchased rom innovator

companies. Generic companies, whose products have been

widely available only as a result o WHO prequalifcation

(and whose availability accords with national law and

donor policy), provide these regimens or less than

US$ 190 per patient per year. Assuming that 80% o

those enrolled in Arica in the last year began treatment

with these regimens, the value o using prequalifed

generic products can be quantifed as more than US$ 100

million. (This is the dierence in total cost o using these

medicines rather than comparable innovator products

or 280,000 patient-years.) This sum, when reinvested,

provides an additional560,000 patients with access to one

year o treatment.

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Additionally, Programme staff briefed nationaland international journalists on medicines qualityissues, helping to maintain public awareness ofthe need not only to increase access to essentialmedicines but also to improve medicines quality

globally.

tEcHnicAL AssistAncE

seleo of epee exper for proo of

ehal aae

Since its inception, the Programme has beenworking hard to build the capacity of bothregulators and manufacturers. Additionally, in thelatter half of 2006, it started to coordinate effortsto provide customized technical assistance aimedat resolving the specic technical problems ofindividual NMRAs, manufacturers or laboratories.

MiLLEnniuM dEvELOPMEnt GOALs

Each o the impacts described above is contributing to

achieving the ollowing targets set under the Millennium

Development Goals:

Target 7: to have halted by 2015 and begun to reverse

the spread o HIV/AIDS

Target 8: to have halted by 2015 and begun to reverse

the incidence o malaria and other major diseases

Target 17: in cooperation with pharmaceutical

companies, provide access to aordable, essential

drugs in developing countries.

At a later stage, prequalifcation o reproductive health

medicines and commodities will contribute not only to

Targets 7 and 17, but also to an additional target:

Target 6: to reduce by three-quarters, between 1990

and 2015 the maternal mortality ratio.

Distinguishing between capacity building

and technical assistance

Within the Prequalifcation Programme, capacity building ocuseson strengthening the capacity o regulatory authorities, pharma-ceutical manuacturers and national QCLs to ollow proceduresor guaranteeing the quality and saety o medicines. Technicalassistance is defned as customized assistance provided to asingle regulatory authority, manuacturer or laboratory. In terms

o manuacture, it addresses bottlenecks in the development andmanuacture o good-quality products. As such, it ocuses on spe-cifc products and specifc problems relating to their production.Similarly, technical assistance to national QCLs ocuses on specifcproblems that a laboratory must tackle i it is to comply with theProgrammes requirements or QCL prequalifcation.

Twenty experts working either or nonproft organizations suchas OTECI, or acting as highly specialized technical, private consul-tants can be called upon to provide technical assistance andsupport to regulators, manuacturers or laboratories. Whenever anexpert visits a country, the NMRA is consulted and also given theopportunity to organize a general training workshop on quality andsaety issues with the experts participation.

The activities o these experts are strictly independent o anyPrequalifcation Programme assessment or inspection activities.In other words, involvement in technical assistance automaticallyexcludes an expert rom participation in any prequalifcationassessment or inspection activity.


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In 2006, technical assistance was organized asfollows:

tehal aae for mafarer a

reglaor

tehal aae: tazaa

October/November (13 days)

Subject: Good practices for QCLs, and analyticalmethod validation and verication.

tehal aae: Ehopa

October (5 days) and November/December (10 days)Subject: Good practices for national QCLs, andanalytical method validation and verication.

tehal aae a omze rag for

mafarer

trag: cha

June 2006 (2 days)Subject: Pre-audit inspection of CROs and GCP.7

trag: thala

August/September 2006 (5 days)Subject: Requirements relating to quality section ofdossiers.

trag: urae

October 2006 (3 days)Subject: Requirements relating to quality section of

dossiers.

trag: cha

October 2006 (5 days)Subject: GMP compliance for aseptic preparation ofinjectable artesunate.8

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WHO Preqalao Programme we-e: hp://www.who./preqal/WHO Preqalao Programme emal: preqal@who.

1 ThePharmaceuticalInspectionConventionandPharmaceuticalInspectionCooperationScheme(jointlyreferredtoasPIC/S)aremechanismsforpromotingcooperation,amongparticipatingnationalinspectorates,intheareaofGMP.

2 Acomparatorproductisusedtotestthequalityofbothinnovator

productsandtheirgenericalternatives,andtoensurethattwosubstancesunderinvestigationarechemicallyidentical.3 TheGlobalDrugFacilityisamechanismaimedatexpandingaccess

toandavailabilityofexistinghigh-qualityTBdrugstofacilitateglobalexpansionofDOTS,apublichealthstrategytocontrolTB,whichiscurrentlyavailableforonly27%ofallTBpatients.

4 Guidelines for the Treatment of Malaria.Geneva,WorldHealthOrganization,2006.

5 Pre-auditinspectionsareofferedtonationallaboratories,butnottocommerciallaboratories.

6 OTECIisaFrenchnongovernmentalorganization.Itenablesretiredprofessionalswithexperiencein,forexample,thehealth,agriculturalortextilesectors,tocontributetheirexpertisetodevelopmentprogrammes.

7 CustomizedtrainingandassistancewasprovidedtotwoCROs(oneofwhichfocusesonclinicalstudiesandtheotheronbioanalyticalstudies),whichwereresponsibleforperformingabioequivalencestudyforaco-blisteredformulationofartesunateandamodiquine.TheCROsreceivedtrainingoncompliancewithGCPandGLP.

8 CustomizedtrainingandsupportonensuringGMPcompliancewasgiventoaChinesemanufacturerofartesunatepowder.However,inspectionofthemanufacturingsitethereafterfoundthatitstilldidnotcomplywithcurrentGMPrequirementsforsterileproduction.Anindependentexpertwasengagedtoworkwiththemanufacturerforoneweektoremedyobservedproblems.

World Health Organization 2007

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who - who prequalification of medicines programme update for 2006

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