IMPROVING TB DRUG MANAGEMENT Accelerating DOTS …IMPROVING TB DRUG MANAGEMENT — ACCELERATING DOTS EXPANSION 4 1 Fixed-dose combination products contain two, three, or four TB drugs

IMPROVINGTB DRUG

MANAGEMENT

AcceleratingDOTS expansion

World HealthOrganization

Stop TBPartnership

ManagementSciences for Health

WHO/CDS/STB/2002.19

The Stop TB Partnership Secretariatis hosted by the World Health Organization

20, avenue Appia – CH-1211 Geneva 27www.stoptb.org – [email protected]

Fax (+41) 22 791 4886

IMPROVING TB DRUGMANAGEMENT

ACCELERATINGDOTS EXPANSION



STOP TBPartnership

IMPROVING TB DRUG MANAGEMENT — ACCELERATING DOTS EXPANSION

II

© World Health Organization, 2002

This document is not a formal publication of the World Health Organization (WHO) and all rightsare reserved by the Organization. The document may, however, be freely reviewed, abstracted,reproduced or translated, in part or in whole, but not for sale or for use in conjunction with commercialpurposes. The views expressed in documents by named authors are solely the responsibility ofthose authors.The mention of specific companies or of certain manufacturers’ products does not imply that theyare endorsed or recommended by WHO in preference to others of a similar nature that are notmentionned, Errors and omissions excepted, the names of proprietary products are distinguishedby initial capital letters.

III

TB DRUG SECTOR SURVEY IN TWO DEVELOPING COUNTRIES ................................. 1

Overview .......................................................................................................................... 2

Republic of Congo ............................................................................................................ 3

Uttar Pradesh, India ......................................................................................................... 8

HARMONIZATION OF TB DRUGS AND THEIR PRESENTATIONS ...............................13

Overview ........................................................................................................................ 14

Treatment for tuberculosis: the importanceof standardization and simplification ............................................................................... 16

Central needs and the GDF ............................................................................................ 20

The GDF......................................................................................................................... 21

New opportunities .......................................................................................................... 25

DRUG PROCUREMENT FOR TUBERCULOSIS ............................................................27

Overview ........................................................................................................................ 28

Components of TB drug procurement ............................................................................ 29

USING INDICATORS TO MONITOR TB DRUG SUPPLY ..............................................35

Overview ........................................................................................................................ 36

Choosing indicators for monitoring ................................................................................. 37

OPERATIONAL FRAMEWORK TO STRENGTHENTB DRUG MANAGEMENT .......................................................................................41

Overview ........................................................................................................................ 42

Operational framework to strengthen TB drug procurement and supply ...................... 43

Activities to strengthen management of TB drug procurement and supply ................... 47

TABLE OF CONTENTS


IV

The incidence of tuberculosis (TB) isincreasing in many parts of the world,and partner organizations of Stop TB

recognize the significant role drug managementplays in ensuring that safe, effective, qualitydrugs are available when and where patientsneed them. The workshop Improving TB DrugManagement: Accelerating DOTS Expansionwas held on 6-8 June 2002 in Washington, DC,sponsored by three organizations:• Stop TB Partnership Secretariat, World Health

Organization;• Management Sciences for Health, through

the Rational Pharmaceutical ManagementPlus Program (RPM Plus) and the Strategiesfor Enhancing Access to Medicines (SEAM)initiative;

• Royal Netherlands Tuberculosis Foundation,KNCV.

The outcome of the workshop was country-specific action plans, developed by national TBand essential drugs managers in collaborationwith TB partners and designed to improve drugmanagement in their countries. The planscontained a description of the activity, the

resources and technical assistance needed, thetimeline for implementation, responsibility forimplementation and completion of individualactivities, and monitoring indicators based onthe realities of the local situation.

A series of papers were prepared as back-ground information and self-analysis tools forworkshop participants. Contents of the paperswere presented during plenary sessions and usedby participants during group sessions. Thepapers were revised on the basis of feedbackreceived during the workshop and are includedin this report.

It is hoped that others will find these documentsuseful in analysing their TB drug managementsystems, identifying specific weaknesses, andselecting implementation activities that willimprove problem areas. Titles of the papers are:• TB drug sector survey in two developing

countries;• Harmonization of TB drugs and their

presentations;• Drug procurement for tuberculosis;• Using indicators to monitor TB drug supply;• Operational framework to strengthen TB

drug management.

INTRODUCTION

1

TB DRUG SECTOR SURVEY INTWO DEVELOPING COUNTRIES

Prepared byThomas Moore

Technical Officer for Stop TB/MSH

The Stop TB Partnership Secretariat and Management Sciences for Healthwish to acknowledge the following people who have contributed to the preparation

of this report: Michael Derosena, Anglade Malan-Kla, Marjorie Janvier,Paul Lalvani, Andy Marsden, Keith Johnson, Rena Eichler, Joseph M’Boussa


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The main objective of the survey discussedin this paper was to identify specific problemsin connection with drug management andavailability of drugs for treating tuberculosis(TB) at the central and peripheral levels in twodeveloping countries, Republic of Congo andIndia (the state of Uttar Pradesh).

The Rational Pharmaceutical ManagementPlus (RPM Plus) programme, funded by theUnited States Agency for InternationalDevelopment (USAID) under cooperativeagreement HRN-A-00-00-0016-00, providedsupport for the survey which used theassessment tool Drug management fortuberculosis (DMTB) developed byManagement Sciences for Health (MSH).Congo and Uttar Pradesh were chosen for thefollowing reasons:

• As an international TB partner, USAID isinterested in the TB situation in developingcountries.

OVERVIEW

• Congo was one of the first recipients of aTB drug grant from the Global TB DrugFacility (GDF) of the Stop TB Partnership.

• India bears one-third of the global TB burden.

• Uttar Pradesh is one of the states in Indiacurrently receiving little support from theGovernment.

Between 10 April and 8 May 2002, RPMPlus consultants and local personnel conducteda qualitative and quantitative survey in the twocountries. The assessment focused on TB drugmanagement aspects of the national TBprogrammes. The country teams collected dataon the selection, procurement, distribution, anduse of TB drugs based on a set of indicatorsdescribed in the DMTB.

The reports on Congo and Uttar Pradesh arepresented in separate sections of this paper. Atthe end of each section is a list of recom-mendations based on the survey findings.

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TB DRUG SECTOR SURVEY IN TWO DEVELOPING COUNTRIES

Background

TB in Congo

In the past few years, TB has evolved from aserious public health problem to a public healthcatastrophe in this country of 3.15 millioninhabitants. TB is the third most common illnessin Congo, behind only malaria and acuterespiratory infection. At the end of the civil warin 1997, there were 3417 cases of TB; 9880cases were reported in 2001—nearly a three-fold increase.

As of 1999, Congo indicated that it had a TBcase-detection rate of 75% and a cure rate of70%. In order to meet the Stop TB targets, thecountry needs to improve its case-detection rateto at least 85% by 2005.

The French Cooperation for developingcountries provided support for TB drug supplyto Congo before the civil war and up to andincluding 1997. The Belgian Governmentprovided timely assistance in the amount of US$222 222 for 1998, and the French Cooperationprovided support again from 1999 to 2002, inthe amount of US$ 453 636, for TB drug supply,laboratory products, and equipment. In 2002GDF procured drugs worth US$ 133 500 andgranted them to the Congolese Government.An annual budget of US$ 66 712 was proposedfor TB drugs for several years by the CongoleseGovernment, but the funds have never beenreleased.

Data collected during the survey indicatedthat the average percentage of unexpired TBdrugs and products available in facilities visited(n = 20) was only 57%. Although health facilitieswere out of stock of TB drugs only 4% of thetime, according to local experts, there are fearsthat the country will run out of TB drugs in thenear future if immediate action is not taken. Itis hoped that donors will be able to continue tosupport the national TB programme (NTP)because the Government has not procured TBdrugs in many years.

REPUBLIC OF CONGO

TB health facilities consist of Centres forDiagnosis and Treatment (CDTs) and Centresfor Directly Observed Treatment (CDOTs). TBcan be diagnosed only at the CDTs but,depending on where they live, patients may betreated at either a CDT or a CDOT during the2-month intensive phase. CDOTs do notprovide a continuous-treatment phase, and theirpatients are therefore referred to the closestCDT for sputum (bacilloscopy) follow-up duringthe 6-month continuation phase. Congocurrently maintains 23 CDTs and 127 CDOTs,which also function as integrated health centresfor other diseases.

Survey method

The survey sample consisted of 18 randomlyselected CDTs and CDOTs in the regions ofBrazzaville (10), Pointe Noire (6), and Dolisie(1), and in the city of Gamboma (1). Two centralmedical stores, one in Brazzaville and the otherin Pointe Noire, were also surveyed. Some ofthe sites originally proposed were eliminatedbecause they lacked security. More centresfrom Brazzaville and Ponte Noire were chosenfor the survey for two reasons: (1) the politicalsituation in the country has left large areasinsecure in the aftermath of the civil war, and(2) 90% of the TB patients in Congo arediagnosed and treated in Brazzaville and PointeNoire. Approximately half of the survey wastherefore carried out in the Brazzaville regionand Pointe Noire.

The quantitative portion of the survey wasconducted by 12 data collectors and supervisorswho received practical training before visitinghealth facilities to begin their work. The trainingsessions were conducted by RPM Plusconsultant Dr Michael Derosena, who wasassisted by Professor Joseph M’Boussa,Director of the NTP, and Dr Daniel Yokolo,Medical Director of the Anti-TuberculosisCentre in Brazzaville. Forms used by the datacollectors for the quantitative part of the survey


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1 Fixed-dose combination products contain two, three,or four TB drugs in one tablet or capsule.

2 HRZE = isoniazid (H)/300 mg + rifampicin (R)/450mg + pyrazinamide (Z)/750 mg + ethambutol (E)/600mg.

3 HR = isoniazid (H)/300 mg + rifampicin (R)/450 mg.4 HRZES = HRZE same as Category I + (S)

streptomycin 1 g administered twice weekly.5 HRE = isoniazid (H)/300 mg + rifampicin (R)/450 mg

+ ethambutol (E)/600 mg.6 HRZ = isoniazid (H)/300 mg + rifampicin (R)/450

mg + pyrizinamide (Z)/750 mg.

were adapted for use in Congo from those inthe DMTB. RPM Plus technical assistant Ms.Marjorie Janvier modified the data collectionforms as required and developed the data-entrysoftware used to calculate indicators for thesurvey.

The qualitative portion of the survey wasconducted by RPM Plus consultant ProfessorAnglade Malan-Kla using structured question-naires. WHO country representatives assistedProfessor Anglade in setting up interviews withlocal experts in drug selection, procurement,distribution, use, quality assurance, and nationalpolicy.

The TB drug tracer list used by the datacollectors was developed in collaboration withNTP and includes the first-line TB drugscurrently in use, as well as syringes and needlesfor injection of streptomycin (see Annex 1).

Survey results

Drug policy

A national drug policy for Congo was developedin 2000, but has not yet been signed or published.Among other things, it proposes a drug controland administration programme, drug registration,and licensing of pharmaceutical laboratories.

The country has published an essential drugslist that contain all drugs provided by the NTP,most of which are fixed-dose combinationproducts.1

Receipt of TB drugs is covered by a drugdonation policy of the NTP and requires priorconsent from the Government or an initialrequest for the donation by the Government.

Supervision of drug management and of theTB programme in general is difficult becauseof lack of motor vehicles or other means oftransport.

Drug selection and use

The NTP implements the Directly ObservedTreatment, Short-course (DOTS) strategy andtreatment regimens are comparable to thoseproposed in DOTS literature. The treatmentregimens for the different types of TB are:

• Category I. New smear-positive/negativepulmonary TB (85% of all cases), treatedwith an intensive phase of EHRZ,2 1–4tablets (according to the body weight of thepatient) taken daily for 2 months. Thetreatment is followed by a continuous phaseof EH3 1–4 tablets (also according to bodyweight) taken daily for 6 months.

• Category II. Smear-positive pulmonaryrelapse/failure TB (10% of all cases), treatedwith an intensive phase of SEHRZ,4 takendaily for 2 months under direct supervision,and a continuous phase of EHRZ for 6months.

• Children. TB in children (5% of cases) istreated with an intensive drug regimen ofRHZ5 for 2 months, and a continuation phaseof RH.6 The number of tablets to be takenis adjusted according to the body weight ofthe patient.

Treatment regimens are monitored by the CDT,which keeps a file on each patient. Compliancewith the national programme and treatmentregimens is documented, and drugs that are notincluded in the standard regimens are not used.

Indicators were calculated from the datacollected in the health facilities and revealedthat 69% of new patients with pulmonary TB(n = 626) were prescribed correct drugs anddosages in accordance with standard treatment

5


regimens for the intensive phase of treatment.This indicator increased to 80% (n = 435patients) for the continuous phase. Possiblereasons for these low numbers may be lack ofappropriate training for prescribers andinsufficient monitoring by supervisors.

As the patients left the health facility theywere asked whether they had been observed bythe TB provider during treatment; 69% had beenobserved (n = 161). The observed patients werethen asked about their treatment schedule andwhat could happen if they did not return for ascheduled dose; 84% (n = 110) knew about theirtreatment schedule and the outcome if drugswere not taken. Patients who had not beenobserved were asked questions on more specifictopics, such as drug names, dosage frequency,and consequences of not continuing to take theprescribed drugs; 59% (n = 51) provided correctresponses to the questions.

The absence of copies of the officialtreatment guidelines in treatment facilities couldcontribute to prescriber non-adherence toestablished treatment protocols. The surveyindicated that an average of only 22% of visitedfacilities (n = 20) could show a copy of thetreatment guidelines.

Drug procurementand distribution

The NTP calculates the quantities of TB drugsneeded using the information sent from districts,consisting of drugs distributed and dispensed topatients, numbers of patients in preceding years,and incidence of new cases. The drug estimatesinclude a buffer (reserve stocks), which is a 1-month supply in Brazzaville and Pointe Noireand a 6-month supply in regional centres in theinterior of the country.

Even with this buffer system, data collectorsfound that an average of only 57% of unexpiredTB drugs were available on the day the healthfacilities were visited (n = 20), with a range of13–88%. The survey also found that drugs wereout of stock an average of 4% of the time duringthe previous 12 months, with a range of 0–13%in the visited facilities (n = 20).

Theoretically, the Centrale Nationale d’Achaten Médicaments Essentiels (CENAMES),which is in charge of the import of all essentialdrugs for the Ministry of Health, should procureTB drugs. However, no budget to allowCENAMES to issue a tender has been releasedin years. Normal tender procedures would beto contact three or four suppliers of genericdrugs appearing on the essential drugs list.Under present conditions, there is noprequalification of suppliers, a situation thatgreatly benefits the former suppliers, especiallythose with an acceptable record.

When essential drugs are tendered byCENAMES, they are distributed to public andprivate health centres on the basis of direct cashpurchase. However, TB drugs received atCENAMES from GDF and the French Co-operation are free. These drugs are sent to theNTP, which supplies TB health facilities wheretreatment is also free. The treatment centresof Brazzaville and Pointe Noire are suppliedmonthly, and the centres in the interior of thecountry every 3 months. Drugs are distributedaccording to the real needs in the health centres,as expressed in monthly or trimestrial reportssent to the NTP in Brazzaville. Roads, and thustransport vehicles, are practically non-existentso directors of the treatment centres travel tothe distribution points to collect their drugs. Atbest, this system is problematic.

The inventory control system in healthfacilities is simple, consisting only of the use ofstock cards or registers; no other informationmanagement system is used. The need forbetter stock management training is apparent,since the NTP estimates a 20% loss of drugsfrom expiry, theft, and inaccurate inventorymanagement. This loss estimate was alsosupported by data collected during the survey,which showed that only 79% of stock records(n = 152) corresponded to actual counts.

Nongovernmental organizations (NGOs)such as CARITAS (Catholic missionaryhospital) exist in faith-based or public health careinstitutions but do not participate in the fightagainst TB. No NGOs are known to purchasetheir own TB drugs and supplies.


6

The much-needed TB drug gift-in-kind fromthe GDF in 2001 was shipped in bottles of 1000tablets, which created the problem of findingcontainers for drug dispensing. In the end, paperenvelopes were used for drug quantities for lessthan 7 days’ treatment, and plastic bags fordrugs for a 1-month treatment. Also, no syringeswere provided with the streptomycin drugs,which placed an undue burden on the NTP tofind another source of these supplies.

Quality assurance

The Ministry of Health has a functioning butweak quality assurance system for drugs andno laboratory testing programme. There are nocompetent laboratories in the country for qualitycontrol of drugs. The Ministry does have alaboratory, but its three laboratory-trainedpersonnel have been assigned to anotherdepartment.

There is no formal system for reporting drugproblems or for recalling substandard drugs.Local experts indicated that, when a drug recallis necessary, users are notified to awaitprocedures from the manufacturer beforereturning the drugs. No drug has been recalledin the past 3 years.

The only control exercised by the NTP onthe quality of the drugs it receives is physicalverification of drug characteristics (colour,shape, size), strength and dosage form, expirydates, and certificates of laboratory analysissupplied by the manufacturer (which are notalways supplied). If drugs are donated, thedonor should ensure that certificates oflaboratory analysis will also be sent to the NTP;otherwise there is no guarantee that the drugscontain the expected dose of the TB drug.

Private sector

The private sector is not usually involved in TBdrug treatment because the free service in thepublic sector includes drugs. There is littlechance of finding a private pharmacy or retailoutlet with all TB drugs present because suchoutlets are not interested in investing money inproducts that are given free to patients. Looking

at the average percentage of unexpired TBdrugs available in health facilities (57%) andhealth facilities out of stock of drugs (4%), itappears that patients may find themselves insituations where the treatment must beinterrupted, this adds to the burden of TB andto the difficulty of treating the disease whenthe public sector is unable to provide sustainablesupport.

Private retail outlets were surveyed to deter-mine whether rifampicin and streptomycin couldbe purchased without a prescription. Asimulated purchase technique was used for thisactivity, with a data collector posing as a relativeof a TB patient. In 32% of the outlets visited(n = 25), rifampicin was sold without aprescription, which is particularly worrisomebecause TB is known to rapidly developresistance to rifampicin taken as a single drug.Rifampicin should always be taken inconjunction with other drugs and always withan order from the prescriber. In 32% of theoutlets visited (n = 25), streptomycin was alsosold without a prescription. Streptomycin is aninjectable drug that can have long-term side-effects and should therefore be available topatients only on the order of a physician.

Weaknesses of the TBdrug managementprogramme

Data collected during the survey revealed thefollowing weaknesses, many of which may beattributed to lack of Government commitmentto fighting TB effectively:

• Absence of roads and lack of vehicles toensure supervision and regular supply ofdrugs.

• Poor stock management within storage andtreatment centres for the already scarcedrugs.

• High unavailability of drugs that is expectedto worsen without consistent donor support.

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Annex 1

Republic of Congo tracer drug list

1. Pyrazinamide, 400 mg tablets

2. Streptomycin, 1 g injection

3. Streptomycin, 0.75 g injection

4. Isoniazid + ethambutol, 150 mg/400 mg tablets

5. Rifampicin + isoniazid, 150 mg/100 mg tablets

6. Rifampicin + isoniazid + pyrazinamide + ethambutol, 150 mg/75 mg/400 mg/275 mgtablets

7. Distilled water (water for injection), 5 ml

8. Syringe

7

• No Government-supplied funds to purchaseTB drugs.

• Prescriber compliance with national TBtreatment guidelines in need of improvement.

• Very basic quality assurance programme;donors must be informed of the need toconsistently require suppliers to providecertificates of analysis for shipped drugs.

• Private-sector practices that may haveadverse consequences for development ofresistance to TB drugs.

• Patients’ poor knowledge patients with regardto the treatment of TB during the continuationphase.



8

Background

TB in Uttar Pradesh

The state of Uttar Pradesh (UP) has a populationof 166 052 859 and contains 70 administrativedistricts. The national TB programme has revisedits strategy for treating TB patients and institutedthe Revised National Tuberculosis ControlProgramme (RNTCP). The RNTCP fullysubscribes to the DOTS strategy and is currentlyimplementing it in eight districts of UP; extensionto another 31 districts by the end of 2002 isplanned. The Government of India fully fundsthe RNTCP.

At the request of the Government, the RPMPlus survey was carried out only in the eightdistricts—population 20.6 million—where theRNTCP is already functional. In 2000–2001the annual TB case-detection rate was 133per 100 000 habitants, with a smear-positivecase-detection rate of 56 per 100 000. Thetotal number of treated cases was 14 994.

Under the RNTCP, four types of centres cantreat TB. In decreasing order of servicesdelivered, these are: diagnosis and treatmentcentre (DTC); TB unit (TBU); microscopy unit(MU); DOTS centre. The RNTCP system isorganized so that one DTC has severalassociated TBUs, MUs, and DOTS centres.

All other districts in the state are functioningunder the older scheme, called NationalTuberculosis Control Programme (NTCP),which does not subscribe to DOTS and is only50% funded by the Government. In thosedistricts without RNTCP, it is likely that patientsand their families are covering the remainingcosts, which may account for the estimate bylocal experts that 40–50% of TB patients receivetreatment in the private sector.

The cost of a 6-month course of treatmentin the private sector is US$ 102 for the drugsused with a standard DOTS regimen in the

UTTAR PRADESH, INDIA

public sector. A worker earning the minimumannual salary of US$ 1 225 (position of TBhealth visitor) would therefore spend onemonth’s income on treatment. This vivdlyunderscores the financial burden TB places onthe population if TB treatment is not free.

In the public sector there is one treatmentfacility for every 100 000 persons, but this figureimproves dramatically to one per 5 000 personswhen DOTS centres and sub-centres areincluded.

Survey methods

Background information was collected and anoverview of TB drug management operationswas prepared for use in the training of the datacollectors. The Centre for Symbiosis ofTechnology, Environment and Management(STEM) was contracted by RPM Plus toconduct the survey.

The following sampling plan was establishedto capture a more comprehensive view of TBdrug delivery in health facilities:

• One DTC, one TBU, two MUs, and twoDOTS centres were selected in each district.

• As far as possible, TBUs, MUs, and DOTScentres were chosen at random, but medicaldirectors sometimes decided which sitesshould be visited.

• The nearest retail drug outlet to each of theTB facilities was visited to determine whetherstreptomycin and rifampicin would be soldwithout a prescription.

Using this scheme, 48 TB treatment centresand 48 retail outlets were selected for surveyin the following districts: Bagpat, Barabanki,GB Nagar, Ghaziabad, Lucknow, Meerut,Raibareily, and Unnao. STEM identified a teamof 16 data collectors and a local coordinatorfamiliar with drug management to assist andoversee application of the DMTB process. Thequalitative survey was also coordinated by

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STEM, using the RPM Plus-approved local TBdrug and medical expertise of Professor Joe S.Bapna and Dr. Pagnioli Dwivedi.

Training was conducted by RPM Plusconsultants Andy Marsden and Paul Lalvani,who were able to identify skills, competence,and participant understanding of the purposeof the survey. Paul Lalvani was the overallcoordinator for the survey in India.

The TB tracer drug list used by the datacollectors was developed jointly with the stateTB programme director and MSH consultants(see Annex 2).

WHO/India supported the team with localadministrative logistics as needed.

Survey results

Drug policy

The drug policy of India was developed in 1986and approved in 1994. It encourages Indianpharmaceutical companies to produce drugs atreasonable prices and emphasizes the strength-ening of quality control. The policy is supportedby the Identification and Recruitment Act onindustrial licensing aspects, the EssentialCommodities Act on drug price controls, andthe Drugs and Cosmetics Act on quality andstandards of medicines.

Drugs approved for TB treatment regimensare published in Technical guidelines fortuberculosis (New Delhi, May 1997) by theRevised National Tuberculosis ControlProgramme of the Central TB Division,Directorate General of Health Services.

When new drugs are introduced for the firsttime the are registered centrally with the DrugController General of India. No TB drug hasbeen registered since 1997. To register a newdrug, a supplier must pay a fee of US$ 1 021;the fee for re-registration is US$ 306.

TB drug selection and use

The TB drug treatment regimens used in UPunder the RNTCP programme are comparableto those promoted by the DOTS strategy. Forall categories of patients during the intensivephase, oral drugs are administered three timesa week under the direct observation of healthstaff. In the continuation phase, patients arerequired to take the prescribed drugs threetimes weekly and receive the drugs in weeklyblister packs, one pack at a time; drug-takingis not supervised.

Drugs are not provided as fixed-dose combi-nation products (all drugs in one tablet) but areuniquely arranged in blister packs according tothe treatment category, which facilitates under-standing by both prescriber and patient of thedrugs and dosages to be taken. The followingtreatment categories are used.

• Category I: New smear-positive pulmonaryand smear-negative serious (e.g. meningitis)TB cases are given the regimen HRZE1 for2 months during the intensive phase, followedby HR2 for 4 months.

• Category II: Smear-positive relapses, smear-positive failure cases, and smear-positivepatients being treated after default are giventhe drugs HRZES3 for 2 months during theintensive phase, followed by HRZE for 1month and HRE4 for an additional 5 monthsduring the continuation phase. This categoryincludes patients who have received TBtreatment for more than 1 month in the pastand who are at increased risk of havingmultidrug-resistant TB.

1 HRZE = isoniazid (H)/300 mg + rifampicin (R)/450 mg+ pyrazinamide (Z)/750 mg + ethambutol (E)/600 mg.

2 HR = isoniazid (H)/300 mg + rifampicin (R)/450 mg.3 HRZES = HRZE same as Category I + (S)

streptomycin 1 g administered twice weekly.4 HRE = isoniazid (H)/300 mg + rifampicin (R)/450 mg +

ethambutol (E)/600 mg.5 HRZ = isoniazid (H)/300 mg + rifampicin (R)/450 mg +

pyrizinamide (Z)/750 mg.



10

• Category III: New cases of smear-negativepulmonary and extra-pulmonary TB that isnot very serious are given RHZ5 for 2 monthsduring the intensive phase, and HR for 4months during the continuation phase.

Table 1 compares the public-sector procure-ment prices by each treatment category withthose of the GDF published at the following Website: http://www.stoptb.org/GDF/whatis/docs/FactsheetGDF011205.pdf. The dosages of thefixed-dose combination tablets procured by theGDF from international sources cannot bematched exactly since the India TB pro-grammes use the intermittent dose schedulerequiring higher strengths of each drug to betaken at one time. Calculating prices for a fullcourse of treatment for one patient makes theprice comparison more meaningful. Such acomparison shows that the Government of India(GOI) procures drugs at prices as good as orslightly better than those of the GDF when thetotal treatment regimen is considered.

Table 1. GDF/GOI treatment pricecomparisons

Treatment category Prices in US$

India GDF

Category I 8 10

Category II 12 12

Category III 7 7

The GOI prices also compare very favourablywith the price of a similar treatment regimenfor Category I in the private sector, estimatedby local experts to be about US$ 102 for 6months of treatment.

An individual card for each patientundergoing TB treatment is maintained at thehealth unit where treatment is administered. Allinformation related to the patient’s treatment isrecorded on the card.

Data collected during the survey indicated that100% of new smear-positive patients (n = 1375)with pulmonary TB were prescribed the correctdrugs in the correct dosages in accordance with

approved treatment protocols. Of the TB facilitiesvisited, 58% (n = 47) had an official manual oftreatment guidelines for TB. Apparently,prescribers have been well trained (100% correctprescribing), but the availability of treatmentguidelines would help to support their training,especially in facilities where there is only oneprescriber and no one else with whom to consult.

Data collectors observed patients in theintensive phase of treatment to determinewhether they were directly observed by thehealth worker when taking their TB drugs.Direct observation took place 98% of the timein visited facilities (n = 212). Although this resultis good, the DOTS strategy promotes directlyobserved therapy 100% of the time.

Patients were interviewed as they left thetreatment facilities and asked whether theyunderstood how to take their prescribed drugs;76% (n = 484) could correctly describe how theirdrugs should be taken. Improving this percentagemay be an appropriate focus during DOTSexpansion activities as the NTP strives to improveits cure rate. Perhaps prescribers could spendmore time explaining how patients should be takingtheir drugs.

Drug procurement

The Central TB Division (CTBD) of the GOIquantifies drug needs on the basis of the numberof TB cases detected (and reported), plus abuffer stock. The CTBD finalizes the technicalspecifications and delivery schedules for TBdrugs.

The procurement process is in the form of atender, which takes 7–8 months to complete;the process of drug quantification is thereforestarted 12–14 months before the drugs will beneeded by the TB programme. The supply lineof CTBD is well maintained, and there wereno shortages of TB drugs in the RNTCPfacilities visited. For the survey, no stock-outdays were reported and 100% of the tracerdrugs were available in all facilities visited.

As for all drugs, the Metallurgical andConstruction Engineers Ltd (MECON) is theprocurement agency for the Government of India.MECON prepares the draft bid document, which

11


is approved by the World Bank (a World Bankloan is used to procure the drugs). MECONadvertises the tender in newspapers in India andsells tender documents to interested suppliers.Manufacturers and suppliers submit bids that areevaluated jointly by MECON and the Ministry ofHealth. A bid evaluation report is approved by thepurchase advisory committee of the CTBD andthe World Bank. The bid is awarded and thecontract is signed, after which the drugs aredelivered and payments made in according withcontract terms. MECON handles all contractdisputes with suppliers.

Distribution and stockmanagement

The transport of drugs to RNTCP facilities isby trucks and is separate from that of theessential drugs programme. Distribution movesfrom the central stores to states and districtswith a normal frequency of 3 months. Motor-cycles are used to transport TB drugs fromdistrict centres to the periphery. Personnel withinthe supply system in UP indicated that there is ashortage of warehousing space, although addi-tional warehouses are now under construction.

Stocks in UP are managed by a compu-terized information system at all six regionalwarehouses. In treatment facilities stocks ofTB drugs are managed through computers andledgers. Information on expiration dates and lotnumbers is available only down to the level ofregional warehouses. Data collected during thesurvey indicated that stock records in the visitedfacilities differed from actual counts 83% of thetime on average; this indicates a need for furthertraining in good stock management procedures.

The CTBD receives quarterly reports by e-mail from most of the RNTCP centres for casestreated, but these reports are sometimes incor-rect and have to be verified. After verification,the reports are forwarded to MECON for drugquantification purposes.

Quality assurance

Suppliers of TB drugs have every batch ofdrugs tested by an approved laboratory accord-

ing to contract specifications. The batch analysisreports are provided to MECON for approvalbefore shipment. After drugs are distributedwithin the public sector, random samples arecollected periodically from warehouses andhealth centres. In UP the number of samplescollected for testing in 1999 was 3 144 but only29.7% (n = 936) were actually tested becauseof a lack of resources. Of the drug batchesprocured, 21% were tested; no failures due topoor quality were reported in any of the testsperformed.

There is no reporting system for drugproblems in UP, and no information aboutsubstandard or counterfeit TB drugs, or aboutpoor-quality packaging was available to datacollectors. However, local experts estimatedthat 1% of the TB drugs procured by the GOIwere substandard.

Private pharmacies and manufacturingcompanies are required to be inspected at leasttwice a year, but there are no inspectionrequirements for warehouse and governmentpharmacies. Although data were not availablefor UP, an adjoining similar state has 52inspectors who undertook inspection of 786manufacturing companies and 11 360 privatepharmacies in 1999.

Strengths of the TB drugmanagement programme

The data collected during the survey revealedthe following strengths:

• Tracer TB drugs in the RNTCP facilitieswere always available in the facilities visited,and no stock-out days were recorded for thetracer drugs over the past 12 months.

• Prescriber adherence to treatment guidelinesfor new smear-positive cases was 100% inthe RNTCP facilities visited.

• The Government of India favourablyprocures TB drugs at a competitive price.


12

Annex 2

Uttar Pradesh tracer drug list

1. Isoniazid, 100 mg tablets2. Isoniazid, 300 mg tablets3. Rifampicin, 150 mg capsules4. Rifampicin, 450 mg capsules5. Pyrazinamide, 500 mg tablets6. Ethambutol, 600 mg tablets7. Ethambutol, 800 mg tablets8. Streptomycin, 750 mg injection vial9. Streptomycin, 1000 mg injection vial10.Thiacetazone, 50 mg tablets11.Isoniazid + rifampicin, 600 mg/450 mg tablets and capsules12.Isoniazid + rifampicin, 50 mg/100 mg kit13. Isoniazid + rifampicin + pyrazinamide, 600 mg/450 mg/1500 mg tablets and capsules14.Isoniazid + rifampicin + pyrazinamide, 300 mg/450 mg/750 mg blister pack, kit15.Isoniazid + rifampicin + pyrazinamide + ethambutol, 300 mg/450 mg/1500 mg/800 mg

tablets16.Isoniazid + rifampicin + pyrazinamide + ethambutol, 600 mg/450 mg/1500 mg/1200 mg

blister pack: tablets, capsules17.Isoniazid + rifampicin + ethambutol, 600 mg/450 mg/1200 mg blister pack: tablets,

capsules18.Isoniazid + ethambutol, 300 mg/800 mg tablets19.Isoniazid + thiacetazone + pyridoxine HCl, 75 mg/37.5 mg/75 mg tablets20.Ethionamide, 250 mg tablets21.Cycloserine, 250 mg capsules, tablets

12

Weaknesses of the TBdrug managementprogramme

The data collected during the survey revealedthe following weaknesses:

• Many patients were unable to describe howthey should take their medications after theyleave the health facility.

• Stock records were sometimes different fromactual counts in all facilities visited, indicatingthe need to strengthen stock managementtraining.

13

HARMONIZATION OF TB DRUGSAND THEIR PRESENTATIONS

Prepared byPeter Evans


of this paper: Virginia Arnold, Robert Matiru, Ian Smith, Thomas Moore


14

Current guidelines of the International UnionAgainst TB and Lung Diseases (IUATLD) andWHO allow for a wide range of acceptableways to treat TB, all of which are consideredvalid under the umbrella of DOTS. Thisflexibility may work well for countries withstrong infrastructure and sufficient financialresources but proves an unnecessary burdenon the poorer countries.

Individual countries have interpreted theseguidelines and in many cases undertakenoperational research. Several have found

different ways to improve programme perform-ance through the choice of drug or presentation:

• Choosing fixed-dose combinations (FDCs)overcomes the problem of the excessivenumber of tablets that a patient must take.Use of FDCs also reduces the number ofdrugs that have to be stocked, selected,dispensed, and observed.

• Choosing drugs presented in packagesdesigned to contain the entire treatmentwhen the patient first arrives overcomes theproblem of failed treatment due to stock

TB treatmentcategory

I

II

III d

TB patients

New smear-positive patients;new smear-negative pulmonaryTB with extensive parenchymalinvolvement; severe concomitantHIV disease or severe forms ofextra-pulmonary TB

Previously treated sputumsmear-positive pulmonary TB:— relapse;— treatment after interruption;— treatment failure c

New smear-negative pulmonaryTB (other than in Category 1)and less severe forms ofextra-pulmonary TB

TB treatment

Initial phase 1

Daily(28 doses/month)

2 (RHZE) b

= 56 doses of RHZE

2 (RHZE)S/1 (RHZE)= 84 doses of RHZEplus 56 doses of S

2 (RH) Z= 56 doses of RHZ

3 times per week(12 doses/month)

2 H3R3Z3E 3 b

= 24 doses of RHZE

2 H3R3Z3E3S3 / 1H3R3Z3E3

= 36 doses of RHZEplus 24 doses of S

2 R3H3Z3

= 24 doses of RHZ

OVERVIEW

15

HARMONIZATION OF TB DRUGS AND THEIR PRESENTATIONS

shortages. Forecasting and stock controlcan be simplified.

• Choosing drugs packed as daily treatments,usually in blister packs, reduces the possibilityof dispensing error. Use of blister packs alsoprovides an additional record for the healthworker and supervisor of what has beendispensed.

• Choosing formulations designed to providepatients with the same number of tablets ateach visit, no matter where they are in thetreatment schedule, reduces the possibilityof error. The 4-drug fixed dose combination

a Direct observation of treatment intake is alwaysrequired for treatments including rifampicin

b In meningitis ethambutol should be replaced bystreptomycin

c Failures of Regimen I that include rifampicin in thecontinuation phase are more likely resistant to H andR and have a lower chance of cure with regimen II,which includes only one new drug. Alternatives toRegimen II are strengthening the regimen by adding1-2 reserve drugs or using regimen IV in failurepatients with proven MDR, according to theresources and capacity to keep patients on treatment

d Countries may choose to use regimen I also forCategory III patients, to simplify training anddrug supply. This however results in unnecessarymedication and may reduce the priority thatshould be given to infectious cases

regimens

Continuation phase a

Daily(28 doses/month)

4 (RH)= 112 doses of RH

or6 (HE)

= 168 doses of HE

5 (RH) E= 140 doses of RHE

4 (RH)= 112 doses of RH

or6 (HE)

= 168 doses of HE

3 times per week(12 doses/month)

4 (RH) 3

= 48 doses of RH

5 (RHE)3

= 60 doses of RHE

4 (RH)3

= 48 doses of RH

(4FDC) tablet makes it easier to adjust doseto the patient’s body weight.

• Colour-coding products to match trainingmaterials provides an additional visualindication to the health worker that thecorrect drug is being dispensed.

The Global Drug Facility should make easilyand rapidly available to all national DOTSexpansion programmes TB drug formulationsand package designs, of known good quality, ataffordable prices, which provide the maximumpossibility of enhancing TB drug management.


16

Introduction

Current IUATLD/WHO guidelines allow for awide range of acceptable ways to treat TB, allof which are considered valid under the umbrellaof DOTS. The variations in interpretation allowflexibility of choice at the national programmelevel. However, little guidance is available onpackaging of drugs.

This flexibility may work well for countries withstrong infrastructure, capable of independentlydetermining the best drugs and treatmentregimens, preparing training materials,evaluating manufacturers, conducting qualityassurance, and tendering internationally to obtainbest prices. However, it works poorly forcountries that lack the infrastructure or fundsto make such independent determinations.

Even for strong programmes, the cost ofindependence is high. TB drugs are moreexpensive than necessary (2–4), trainingprogrammes have to be established independ-ently, programmes are unable to build upon theexperience of, or compare their performancewith, other programmes, and there isconsiderable duplication of effort in findingsuitable suppliers.

TREATMENT FOR TUBERCULOSIS:THE IMPORTANCE OF STANDARDIZATION AND SIMPLIFICATION

All countries should choose drugs andtreatment regimens that meet the needs of theirprogrammes. The choice of regimens, drugs,and drug package presentations has a significantimpact on programme management.

The Global Drug Facility (GDF) of the StopTB Partnership acts as an international supplymechanism and assists in providing suitablepresentations. Standardization and thecombining of orders for similar drugs havemany benefits for TB control.

This paper illustrates the impacts of drugchoice on management issues at all levels.Situations from the health centre level, thecentral level, and the GDF are provided.

The programme

Crucially, the achievement of a curative TBprogramme within a public health systemdepends on the successful interaction betweenthe health worker and the patient. Theprogramme and the drugs must therefore bedesigned to that ensure this relationship is assuccessful as possible.

Diversity in TB Treatment

• 19 TB products for 6 drugs on the WHOModel list of essential drugs (and manyother products in use by nationalprogrammes) (1)

• 11 regimens approved by WHO in3 treatment categories

• 2 recommended dosages—daily andintermittent

• 3 weight categories (not always consistent)• Variety of packaging: blisters, foil-wrapped,

loose tablets

17


1.Some programmes have introduced fixed-dose combinations, so that fewer tabletshave to be taken (5).

2.Some programmes concentrate onintermittent therapy to reduce the numberof visits to the health centre. Some havechosen the fixed combination productisoniazid/rifampicin (RH) in thecontinuation phase to reduce the totalduration of treatment.

3.Some programmes reserve the entiretreatment when the patient first registers,thus ensuring availability of the drugswhenever that patient comes in. Reservingdrugs under a patient’s name at registrationtransfers ownership of the drugs from thehealth centre to the patient; that is, thedrugs become the patient’s drugs. Patientsare more likely to continue treatment sothat they may receive all of their drugs.

4.Some programmes use tablets in blisterpacks, which are seen by many patients asbeing of higher quality than foil-wrappedor loose tablets; this enhances patients’perception of the treatment.

The patient

For patients to come to a health centre fortreatment, they must know that they are sick,know that there are drugs that are safe,effective, and able to cure them, and know thatthese drugs will always be available whenneeded. A patient is more likely to complete acourse of treatment if it is short-lasting, if thedrugs are easy to take, and if the treatment isaffordable.

If drugs are not available when patientsattend the health centre, the likelihood of theirreturning for every appointment and their beliefthat treatment must be completed to beeffective will diminish.

The health workerThe health worker must ensure that the correctdrugs are available, dispensed, and taken—onschedule—in the correct dosages. Directobservation by the health worker or otherdesignated individual remains paramount. Forthese apparently simple tasks to be achieved,many things must be in place. The followingdiscussion indicates for which tasks the healthworker must bear the responsibility, althoughsometimes they may need to rely on other experts.

Know the patient’s status

The health worker must know the needs of thepatient and whether the patient has beenfollowing the necessary treatment schedule. Heor she must also know the patient’s TBtreatment category and body weight and thestage of the treatment regimen reached. It isequally important to know when patients havefailed to come for scheduled treatment; suchpatients must be identified within a day or twoand encouraged to continue treatment to avoidrelapse which can promote development ofmultidrug-resistant TB (MDR-TB). Theseprocesses are normally controlled through arecord-keeping system.

1.Some programmes use patient boxes tohelp health workers with these tasks; the“patient pack” used in India is an example.One pack is reserved for the patient at thebeginning of treatment and is identifiedwith the patient’s name. Thereafter thehealth worker need only match patientwith pack to identify needs and status.Once the patient has been matched withhis or her pack, the next blister pack ofdrugs is opened and the contents given tothe patient. The packs are stacked in onedesignated place at the beginning of theday and moved to a second place when TBdrugs have been administered. Any packsthat do not move during the day serve toidentify missing patients so that follow-upcan be initiated (6).

2.Some programmes use tablets packed inblisters as an indicator of each patient’streatment status: used blisters are retainedas a record of what drugs have been taken.


18

Dispense correctly

Some regimens require that different quantitiesof up to five drugs are counted out and given toeach patient on each occasion. The number oftablets to be counted out, vary according to thepatient’s body weight. Some treatmentrecommendations require tablets to be brokenin half.

While counting out two, three, or four tabletsof each of three or four drugs may seem asimple task for trained health workers, errorsdo occur. It is relatively easy to select the wrongdrug from the shelf when there are many tochoose from, or to mistakenly select two tabletsof one drug and three of a second instead ofthree of the first and two of the second. If oneor two drugs of a four-drug combined treatmentare unavailable, there may be a temptation togive the patient only partial treatment rather thanexplain why drugs are being withheld. Partialtreatment is unacceptable when simultaneousadministration of multiple drugs is the norm forsuccessful treatment and for reducing thelikelihood of MDR-TB.

1.Some programmes have standardized oncombination products to reduce thepossibility of dispensing errors. The numberof products available to the health workeris reduced and fewer tablets have to becounted out (5).

2.Some programmes chose formulations thatallow the patients to take the same numberof tablets at every visit, regardless of whatstage of the treatment schedule has beenreached.

3.Some programmes colour-code theproducts to provide extra visualreassurance to the health worker that theright drugs have been chosen.

4.Some programmes have standardized onpatient boxes, which separate the treatmentinto periodic requirements. Health workersneed only identify each patient and locatehis or her box. They can then dispense thenext treatment by taking out the tablets forthat day—no need to identify drugs, noneed to count tablets (6).

Replenishment of stocks

The health worker has a responsibility to ensurethat drugs are available when needed. He orshe must therefore have some backgroundknowledge of drugs used and patients treated,and must know whether and how future drugneeds will change, what stocks are on hand andon order, and when the delivery after next willarrive. Because forecasting future TB cases isnotoriously difficult, many programmes requirehealth workers to hold reserve drug stocksequal to the quantity used during one orderperiod, so as to avoid stock shortages.

Determining whether the stocks on hand aresufficient and in the right proportions for futurepatients is difficult. Estimating how manypatients can be treated from a partially full bulkcontainer of tablets requires good documen-tation of the receipt and dispensing of drugs.Stock shortages of one or more drugs in thepast are a sign of weakness, possible inforecasting, at some level within the system;no matter the origin of the error, subsequentforecasting at the health centre becomesespecially difficult.

In countries that have standardized onpatient packs, knowledge of stock used byhealth workers becomes a matter of knowingthe number of patients treated in eachcategory. Disease burden and treatment databecome synonymous. Stock in hand can bedetermined by counting packs. Countingstock in terms of patient treatments ratherthan assessing it from bulk containers oftablets makes stock control simpler at alllevels but especially at the health centre (6).

19

National TB programmemanager

The manager of the national TB programme(NTP) is responsible for the programme’ssuccess. The manager must both establish theobjectives of the NTP and ensure that thoseobjectives are being achieved

In a standardized programme the NTPmanager can take lessons learned from thesuccessful aspects of the programme and applythem to the less successful aspects. On a globalscale, lessons learned in one country may beapplied to another—but only if the same regimenand the same drugs are being used in both.

Some programmes forecast, order, anddispense drugs in terms of numbers ofpatients rather than numbers of tablets.Thus the register of patients and the registerof drugs used can be matched and can beself-correcting. It then becomes much easierfor the manager to have an overview oftreatments needed and treatments provided.


A key indicator of success is the smooth anduninterrupted flow of TB drugs from the centralreceiving area to patient treatment centres. Formany programmes it is difficult to oversee thisflow, and part of the problem lies in the wayinformation is handled. Patients treated arecounted and recorded in one set of registers,and containers of tablets received and dispensedare recorded in another. Reconciling the tworecords is further complicated by the need toadjusting drug quantities according to patients’body weights. However, while it is not alwayseasy, or even possible, to achieve thisreconciliation, this need not be the case.


20

Finance office andregulatory authority

The range of TB drugs acceptable to thecountry and the standards that apply are theresponsibility of the national regulatory authority(RA) and controlled through the process ofregistration. Every drug that is used within thecountry should be officially registered. Changingdrugs and producers frequently overburdens theRA: when drugs are changed, supportingdocumentation from the manufacturers of allchosen drugs must be made available forexamination.

The health system’s finance office needs toknow the cost of the approved quantity of drugs;its job is complicated by unexpected increasesin drug costs due either to price changes or toincreased demand. While the finance officemay focus on affordability, it is usually unpre-dictability that causes the greatest problems.

CENTRAL NEEDS AND THE GDF

1.The GDF assists registration by requiringthat approved manufactures keep available,for rapid transmittal on demand, a file ofdocuments designed for registration ofstandard items,. This registration file,together with data of the registration anduse of the same drugs in other countries,will facilitate registration.

2.The GDF has published prices of a selectionof standard TB drugs (4) to provide abenchmark for programmes and financeoffices. Prices may vary but should becomparable to the benchmark. If theprogramme finds costs are significantlyhigher than GDF prices, the GDF may berequested to assist in the supply process.

Manufacturer

The manufacturer aims to produce drugs at thelowest possible cost and sell at the highestpossible price. For most generic drugs in thepublic sector, the manufacturer must offer betterprices than anyone else to obtain orders but muststill be able to make a reasonable profit.Lowering production costs is in the best interestsof both buyer and seller—and is the key toallowing the manufacturer to sell at the lowestpossible price.

Manufacturers can obtain lower prices onraw materials if they commit to large orders,even if the materials will be delivered over anextended period. Production costs can belowered: by manufacturing a small number oflarge batches rather than a large number of smallbatches; if drugs are produced, tested, andpacked to the same standards and specifications;if production takes place when there is sparecapacity rather than having to interrupt themanufacture of another item; if uncertaintyabout future orders can be removed.

1.To assist the manufacturer in lowering hiscosts, the GDF makes long-term forecastsfor a specified number of TB drugs, withcontinual new advice as new informationon the size of the market is received.

2.The ability to provide accurate forecasts isdependent on having a large client baseand a limited list of standard TB drugs.

21

The nature of the market place is suchthat, the fewer suppliers and the morecustomers there are, the stronger is the positionof the seller. Many marketing approaches arethus designed to result in segmentation of themarket and increased market share in each ofthe segments. The opposite is true for the buyer.Buyers benefit when there are more sellers andfewer buyers; they are empowered by standard-izing specifications and consolidating orders.These two opposites will be in constant tension,with either the buyer or the seller sharing poweraccording to the market split.

For the GDF to maximize its impact it shouldstandardize TB drugs to the greatest extentpossible and consolidate orders from as manysmaller buyers as possible. It should also ensurethat there is a pool of quality producers competingfor the business. In this way, power will shiftfrom seller to buyer and the GDF will be able todo more for Stop TB. As the buyer’s powerincreases, it becomes possible to stabilize pricesand to design products that more closely meetprogramme needs rather than simply acceptwhat is available.

THE GDF

GDF philosophyand purpose

The GDF is a drug supply mechanism,established to ensure that TB drugs would beavailable for DOTS expansion. It ensures theavailability of drugs when needed, of known goodquality, and at prices that are an efficient use ofdonor funds—in all respects meeting the needsof a TB programme. Whenever the GDF has acomparative advantage, it encourages TBprogrammes to use the services it offers, whichfall into three areas:

• Grants of drugs

• Procurement services

• A “white list” of suppliers of drugs of knowngood quality.

It is expected that each country will only usethe supply services it needs.

Because the GDF suppliers and prices havebeen published, countries with sound financesand good infrastructure for procurement andquality assurance can approach their preferredcompanies directly and, using the GDF pricesas a benchmark, should be able to purchasedrugs at similar prices. If they cannot prices asfavourable as those available to the GDF theymay choose to use the GDF services.

Countries that are financially sound and havegood procurement mechanisms but that lack arobust quality assurance system may chooseto purchase only from companies used by theGDF, knowing they will receive drugs of knowngood quality.

Countries that are financially sound but thatlack both good procurement and qualityassurance systems may use the procurementservices of the GDF, knowing that they willreceive drugs of known good quality at low cost.

Finally, countries that are dependent ondonors for some or all of their drug supply and


BUYERSTRONG

NO ONEINFLUENCES

SELLERSTRONGPARTNERS

POWER

MORE BUYERS

MONOPOLY

MO

RE

SELL

ERS

MO

NO

PS

ON

Y


22

Category2 months 4 monthsintensive continuation

(daily) (daily)

I 2 (RHZE) 4 (RH)

II 2 (RHZE) + 5(RH) + ES/1 (RHZE)

III 2 (RH) + Z 4 (RH)

that wish to expand their DOTS programmesmay apply for grants and receive drugs free ofcharge (7)

For each of these situations the GDF aimsto adopt standards of excellence so that it willat least match any other option that a countryprogramme may choose. However, the GDF isnot a national procurement agent but aninternational agent. Where the national agentserves the priority needs of a single country,the GDF is an international agent and balancesneeds and benefits for all countries.

Areas of standardization

There are several components of TB drugtreatment where standardization will beeffective.

1. Regimens: drugs, dosage, duration oftreatment and patient weight ranges

2. Products: drugs, strengths, combinations,packaging presentations, standards, andtesting.

3. Calculations of quantities of drugs to .

It is not necessary for a programme to redefinepolicy, but merely to show that within existingpolicy, standardization has operationaladvantages, making DOTS expansion easier.

Example regimen (daily)one tablet a day

two tablets a day

three tablets a day

four tablets a day

five tablets a day

While many possibilities for drugs and regimensexist with the WHO/IUATLD guidelines, eachcountry will choose one regimen, set of drugs,and presentation style. The more countriesmake the same choices, the more the GDF cando to influence manufacturers to meet theneeds of the programme.

Example of recommended drugs

• RHZE, combination tablets, supplied as H75 mg + E 275 mg + R 150 mg + Z 400 mg inblisters of 28 tablets and boxes of 12 blisters.

• RH, combination tablets, supplied as H 75mg + R 150 mg in blisters of 28 tablets andboxes of 24 blisters.

• Z, tablets, supplied as Z 400 mg in blisters of28 tablets and boxes of 12 blisters.

• E, tablets, supplied as E 275 mg in blisters of28 tablets and boxes of 30 blisters.

• S, injectable, supplied as vials of 750 mgtogether with 3 ml of diluent, syringe. anddisposal box in boxes of 112 treatments.

With just five drugs, all adult patients, of allweights, in all categories can receive indivi-dualized treatment that fully meets IUATLD/WHO recommendations.

Recommended weight bands

For all drugs and all treatment categories

Patients of very low

body weight, < 25 kg

Patients of low body

weight, weight 25–39 kg

Patients of average body

weight, 40–55 kg

Patients of high body

weight, 56–70 kg

Patient of very high body

weight, > 70 kg

Streptomycin is provided to patients of averageweight as 750 mg, diluted in 3 ml. This may beconsidered equivalent to 3 doses of 250 mg/ml.If necessary, the dose may be adjusted—in

23

accordance with a patient’s weight—to actuallybe equivalent to the number of tablets. Thus apatient of lower weight, requiring only twotablets a day, would also require only 2 ml ofthe diluted streptomycin.

Recommended standards

While many standards are acceptable, the GDFrecommends that drugs are manufactured toUnited States Pharmacopoeia standards andtested according to USP protocols, when theyexist. This makes production and testing of drugsconsistent. For the GDF, tablets are subjected tobioavailability testing of the active ingredient ata laboratory recommended by WHO; producersand drugs will be examined according to new WHOstandards for TB drugs supplied internationally.

GDF has adopted standards for blister design,including layout, materials, markings, identity byunique colouring, and package inserts.

Recommended calculation:patients not bottles or tablets

Because of the risk of drug resistance it isrecommended that a patient does not start on acourse of treatment with assurance thatsufficient drugs will be available to completethe course without interruption. The healthworker must therefore view stock levels asnumbers of complete treatments rather thannumbers of bottles or tablets, and drugs shouldbe supplied in formats that lend themselves tothis kind of calculation. One approach is todistribute drugs in patient boxes, each containingsufficient drugs for a full course of treatment.Once the box has been selected for the patient,the drugs are reserved for that patient and onlythat patient. The advantages of this approachare obvious, but it does require either thatpatients of all weights receive the sametreatment or that drug packages suitable for allweights are kept in stock. Trying to ensure thatthe right balance of treatments for differentweights is always available can be complex.

Another approach has been devised,designed to meet the needs of both healthworkers and patients. Drugs are provided in

Weight 2 (RHZE) Blisters 4(RH) Blisters tablets tablets

Very light 1 1 x 2 1 1 x 4

Light 2 2 x 2 2 2 x 4

Average 3 3 x 2 3 3 x 4

Heavy 4 4 x 2 4 4 x 4

Very heavy 5 5 x 2 5 5 x 4


Blisters for individual patients

Points to note

• The number of tablets to be taken is the samefor both (all) drugs.

• Calculation for blisters needed is tablets perday x months of treatment.

• If there are insufficient blisters available thepatient’s treatment is not started.

Inventory control systems, tendering, ordering,and stock on hand should be based on orcalculated as patient treatments.

While these drugs may be used in the samemanner as other TB drugs, including bulksupplies, the GDF design allows for pro-grammes to introduce and use a simplifiedforecasting and ordering system. Thus:

• 50 boxes of RHZE combination blisters couldbe counted as 50 patient treatments (category1 intensive)

• 50 boxes of HE combination blisters couldbe counted as 50 patient treatments (category1 continuation), etc.

master boxes, which—when needed—areconverted at the health centre to individualpatient boxes to meet individual patient require-ments. Blisters of 28 tablets, for example, aretaken from the master box and placed in apatient box, which is then reserved for aparticular patient.


24

Delivery

The GDF standard is to make drugs availableto countries through the grant mechanism within60 days from the date of application to receiptof goods or 30 days from order placement todelivery of drugs to the consignee. In addition,it is intended that every step of the deliveryprocess be transparent. The shipment deliverydate will be confirmed at the time of orderplacement; the country will be able to track theprogress of the order at any time using web-based information or weekly from status reportsprovided by fax or email.

Guaranteeing such rapid delivery necessitatesthe stockpiling of drugs in advance of firmrequests. In turn, this requires a focus on alimited number of items with an expected highturnover, and means that programmes mustwant the drugs that are stockpiled. Drugs notstockpiled may still be made available but willhave to be produced and undergo independentquality assurance testing—a process that willtake 4–5 months.

Quality

The GDF standard demands the best availableindependent quality assurance system. The GDFhas arranged for the newly initiated WHOscheme to be the main focus of the qualityassurance system. Using the system recom-

mended by the “Expert Committee on theSelection and Use of Essential Medicines”selection, products and producers will beexamined by a WHO-appointed team and thefindings published. Samples selected randomlyfrom finished goods will still be sent forindependent laboratory analysis, and allshipments will be inspected to ensure that theymatch both the purchase order and countryneeds. Countries receiving goods through theGDF will be assured that the drugs are of knowngood quality.

Prices

The GDF standard is to have TB drugs ofknown good quality always available, at a priceequal to or lower than that charged by any othermechanism providing TB drugs internationally.The GDF seeks out as many producers of goodquality drugs as possible. It also consolidatesthe requests for TB drugs from several countriesto make an interesting quantity for themanufacturer; this has ensured significantcompetition for GDF business and resulted inprice reductions.

Low prices are dependent on high volumesof standard drugs, manufactured as efficientlyas possible. The GDF reduces risk to theproducer by a precise and advantageouspayment system and by a constant informationflow on both short-term and long-term demand.

25


Fixed-dose combinations

The availability of fixed-dose combinations(FDCs), particularly the 4FDC, at prices—evenfor drugs provided in blisters—that are the sameas or lower than those of other TB drugs is arecent and welcome development. It offers arare opportunity for national programmes toswitch to FDCs, making DOTS easier in manyrespects:

• Easier to finance—the per-treatment cost islower than previous costs.

• Easier to dispense—fewer drugs are neededto be selected and counted. This will help inavoiding the development of drug resistance.Drugs for individual patients are counted in asimilar manner across different weightcategories.

• Easier for the patient—fewer tablets aretaken.

• Easier to buy—drugs are available at lowcost from a limited number of suppliers whohave been closely examined.

• Easier to stock at all levels—just five drugsmay be suitable for all categories and allpatient weights.

• Easier to assure quality—the few supplierswill be examined according to WHOstandards and centrally monitored.

• Easier to adjust dosage by weight.

Because of the operational advantages to theprogramme, the GDF is focusing on FDCs.

Blisters

GDF has received numerous requests for drugsto be supplied in blisters. However, there wasno consistency in what was being requestedand no internationally accepted standards forblister designs. Although still supplying tabletsin bulk, the GDF wished to meet this demandfor blisters for a variety of reasons:

NEW OPPORTUNITIES

• Many patients and health workers perceiveblister-packed drugs as being of higher qualitythan foil-wrapped or loose tablets.

• Blisters provide better protection for thetablets once the main container has beenopened.

• Blisters have the same shelf-life as foil-wrapped and loose drugs, at very similar cost.

• Blisters packed face to face occupy aboutthe same space as tablets packed in bulk.

• Blisters help the health worker to identify thedrugs needed and to count the tablets to bedispensed.

• Keeping empty blisters can provide apermanent record for the health worker ofwhat each patient has taken.

• Keeping empty blisters can provide apermanent record for the supervisor of whatthe health worker has been doing.

Blister-packed drugs can be used in allsituations in which foil-wrapped and loose drugsare used. Because of their operational advan-tages to the programme, the GDF is focusingon blister packs.

Blister pack design

The design of the blister pack opens up otheropportunities. Drugs may be provided incontinuous strips, enabling any number of tabletsto be extracted when required. However, it is pos-sible to design the pack into blister cards to assistthe health worker in counting and dispense drugs.

Each card contains 28 tablets—enough for onetablet a day for 4 weeks. If the patient is of averageweight, and therefore receives 3 tablets a day ofRHZE combination for 2 months, 3 x 2 cards areselected; 6 cards provide complete treatmentfor the average patient in the intensive phase.

For the continuation phase, the same patientneeds 3 tablets a day of RH combination for4 months, and 3 x 4 cards are selected; 12 cards


26

provide complete treatment for the averagepatient in the continuation phase.

If the patient is of lighter weight and needsonly 2 tablets a day, 2 x 2 cards of RHZEcombination will be needed for the intensivephase, and 2 x 4 cards of RH combination forthe continuation phase.

In general, number of tablets per day xmonths of treatment = number of cards needed.

Once the first daily dose is extracted fromthe blisters, the empty shells provide the healthworker with an extra check on the number oftablets to be provided and a permanent recordof what was dispensed.

The same principle also applies to strepto-mycin. The dose for a patient of average weightis 0.75 g and the dilution volume varies between2 and 5 ml. If the diluent volume is standardizedas 3 ml, a patient who would require 3 tabletswill require 3 ml of diluted streptomycin. A lighterpatient who would require only 2 tablets dailyshould receive 2 ml of streptomycin diluted inthe standard manner.

As the DOTS programme expands the useof community-based treatment supportersincreases. Blister packs and blister cards are aconvenient way of providing drugs to the com-munity-based treatment supporter, helping boththe responsible health worker and the communityobserver to count and dispense the correctdosage. Returning the empty blisters to the healthworker provides a record of treatment given.

Because of the operational advantages to theprogramme, the GDF focuses on blister cardscontaining 28 tablets.

Patient boxes

TB differs from many public health problemsin that, if the patient is not treated properly ordoes not complete treatment, the result—froma public health perspective—is worse than notreatment at all. The partially treated patientmay have no symptoms but remain infectious,infecting first his or her family, then friends, andthen the community at large with TB organ-isms that may be drug-resistant. A contributingfactor to incomplete treatment is the frequentstock shortages of TB drugs in some pro-grammes. A patient’s treatment should not bestarted without assurance that sufficient drugswill be available for completion of the course.

Reserving the full treatment as soon as a newpatient present is quite easy when blister cardsare used. The drugs are put into a box markedwith the patient’s details (at least name, date,and number of tablets). The patient is told thatthese are his or her drugs and that they will notbe given to anyone else. The patient now hasall the drugs needed to complete the course oftreatment and will be unaffected by changes indrugs, regimens, or stock shortages.

The GDF provides FDCs in adjustable patientboxes. These can be used only with blistered prod-ucts with all product information included on theblister sheet. Each box holds a complete averagetreatment. Adding or removing blisters, accord-ing to the number of tablets needed, allows thehealth worker to create a patient box for patientsof higher or lower body weight. It allows eachdrug to be dispensed according to the patient’sweight but still requires stocking only one prepack-aged patient box per category. Because of theoperational advantages to the programme, theGDF focuses on drug presentations that can beeffectively managed as patient boxes.

References

1. Essential drugs and medicines policy. Geneva, World Health Organization, 2001 (available at www.who.int/medicines/).2. International drug price indicator guide. Boston, MA, Management Sciences for Health (in collaboration with the

World Health Organization; updated annually).3. Laing RO, McGoldrick KM. Tuberculosis drug issues: prices, fixed-dose combination products and second-line drugs.

International Journal of Tuberculosis and Lung Disease, 2000, 4(Suppl. 2):S194–S207.4. First-line tuberculosis drugs & formulations currently supplied/to be supplied by the global TB drug facility. Geneva,

World Health Organization, 2002(available at www.stoptb.org/gdf/drugsupplydrugs.available.html).5. Fixed-dose combination tablets for the treatment of tuberculosis: report of an informal meeting held in Geneva,

Tuesday, 27 April 1999. Geneva, World Health Organization, 1999 (WHO/CDS/CPC/TB/99.267; also available atwww.who.int/gtb/publications/fdc/PDF/fdc.pdf ).

6. 5th Round application notice. Geneva, World Health Organization, 2002 (available at www.stoptb.org/GDF/applying/application.materials.html).

27

DRUG PROCUREMENTFOR TUBERCULOSIS


Technical Officer, Stop TB/MSH


of this paper: Malcolm Clark, Peter Evans, Keith Johnson, Richard Laing,Souly Phanouvong, Ian Smith, Robert Staley, Hugo Vrakking, Andrey Zagorskiy


28

This paper aims to explain procurementpractices specific to tuberculosis (TB) drugs.The information it contains is meant to providea basic understanding of the components ofprocuring good-quality TB drugs in globalmarkets. The process of procurement is oftencomplicated by lack of experience amongpersonnel, the unpredictability of drugavailability from many global manufacturers,weak quality assurance systems among somemanufacturers, and the poor management ofsome national quality assurance programmes.Although not specific to TB, the interagencyguidelines, Operational principles for goodpharmaceutical procurement (1) served as thebasis for this paper.

Complexity of TB drugprocurement

In national health systems the infrastructure forprocuring TB drugs varies considerably. Insome countries TB drug procurement is apurely vertical programme in which staff select,procure, and distribute only TB drugs andsupplies—and do so quite separately fromselection, procurement, and distribution of otheressential drugs. In contrast, procurement of TBdrugs in other countries is managed jointly withprocurement of other drugs. Between these twoscenarios are various other drug managementoptions, such as those in which the national TBprogramme selects TB drugs and quantifiesdrug needs, but the essential drugs programmecarries out procurement and distribution, orthose in which procurement is the responsibilityof an agency nominated by the donor payingfor the drugs.

Regardless of the method, TB drugprocurement is a complicated process and caninvolve many different agencies within acountry as well as outside (in the case ofinternational procurements). Procurement takesfrom 12 to 24 months on average and requiresspecific knowledge if it is to be successful.

Objectives of TB drugprocurement

Regardless of the structure of the health systemwithin a country, the objective of TB drugprocurement remains the same — to purchasequality drugs from reliable suppliers at the bestpossible prices. To promote this objective, a TBprogramme manager should be aware of howsuccessful procurement is accomplished andshould, where appropriate, facilitate specificprocurement activities.

Checklist of procurementactivities for good TB drugmanagement

The following checklist summarizes the commoncomponents of a comprehensive TB drugprocurement system. The TB programmemanager can use this list and the subsequentdiscussion of each component to understand andpromote improved procurement activities.

• Management support through politicalcommitment and a viable managementinformation system.

• A drug selection mechanism for establishingand approving Directly Observed Treatment,Short-course (DOTS) drug treatmentregimens, ideally using fixed-dose combi-nation drugs (FDCs), and updating thenational essential drugs list with the TB drugsincluded in the treatment regimens.

• Drug quantification methods that accuratelyestimate TB drug needs for all categories ofTB patients.

• Competitive procurement practices that notonly use appropriate tender methods to fostercompetition but also assure the quality of TBdrugs and supplies (for example, by providingsuppliers with product quality and packagingspecifications required for TB drugs).

• Supplier selection and qualification proce-dures that allow assessment of suppliers’

OVERVIEW

29

capacities for providing quality drugs in atimely manner.

• A quality assurance system that definesrequirements and requires documentation ofquality assurance procedures used by themanufacturer to ensure provision of good-quality TB drugs. The Ministry of Health(MOH) can use a quality assurance systemto monitor the quality of drugs received fromthe suppliers and during storage in MOHfacilities until drugs are dispensed to thepatient. A good system will also allowtracking of drugs within the MOH supplysystem in the event that a manufacturerrecalls a drug product. Optimally, a national

quality assurance programme would alsohave the resources to inspect suppliers forgood manufacturing practices (GMPs).

• A supervision and monitoring mechanism thatuses validated indicators to measure theperformance of the TB drug procurementsystem.

• A strategy allowing facilitated procurementthrough the Global TB Drug Facility (GDF),and other non-profit suppliers, or other donororganizations to fill TB drug availability gapsfor those TB programmes that haveinsufficient resources to procure on their owngood-quality TB drugs in a timely manner.

DRUG PROCUREMENT FOR TUBERCULOSIS

COMPONENTS of TB DRUG PROCUREMENT

A well-functioning TB drug procurement systemwill have adequate management support to guidethe various components of the system. Ideally,such guidance is sustained by a responsivemanagement system within the programme, withvisible support from political and administrativesuperiors. In typical procurement systems,activities are ideally divided among differentoffices, committees, and individuals, each withappropriate expertise and resources to allow theeffective execution of the following procurementactivities:

• Drug selection: Selecting the most appro-priate drug treatment regimens and productsfor the TB programme, based on DOTS.

• Drug quantification: Estimating drugrequirements based on epidemiological data,and using a systematic method such asmorbidity-based (the approach recommendedby the World Health Organization) orconsumption-based quantification.

• Competitive procurement methods:Establishing a restricted procurementprocess with pre-qualification of suppliers.

• Supplier selection and qualification:Identifying and qualifying local andinternational suppliers.

• Quality assurance: Ensuring acceptabledrug product quality and packaging for TBdrugs.

• Monitoring and supervision: Monitoringsupplier quality and performance, andsupervising and monitoring the procurementsystem with regular evaluation

Procurement activities should be transparent,and personnel should follow written guidelinesbased on established, proven procedures toavoid being perceived as corrupt and losing theconfidence of the public, donors, and otherpotential suppliers in the TB control programme.Development of an efficient procurementservice requires planning and monitoringactivities throughout the procurement cycle.


30

Drug selection

Following the selection and implementation ofworkable treatment regimens such as DOTS,drug products for a national TB programme(NTP) need to be selected by an expert committee,ideally composed of a TB medical specialist, apharmacologist, a TB programme manager, anepidemiologist, a pharmacist, and a nurse. Drugselection encompasses identification oftreatment regimens, strengths of drugs, anddosage schedules to be used in the programme.It also includes choosing the appropriatepackaging configuration for the TB drugs (suchas loose tablets, patient boxes, or blister packs)and the FDC drugs that will be made available.

Experts generally recommend that FDCtablets be used wherever possible for treatmentof both children and adults. Many experts feelthat FDCs contribute directly to the likelihoodof rational prescribing of anti-TB regimensbecause all the required drugs are included inone tablet. In addition, FDCs should makedispensing easier because there are fewertablets or capsules to handle, which in turnshould improve adherence by patients who takefewer numbers of tablets or capsules at anyone time. FDCs come in two-, three-, and four-drug combinations and are appropriatetreatment regimens to consider if their selectionis based on the morbidity profile of a givenpopulation. Because fewer tablets need to bestocked, FDCs occupy less storage space inwarehouses and dispensing areas and facilitatestock rotation to keep the drugs fresh.

Standardizing—and thereby harmonizing—treatment regimens within a TB controlprogramme offers the added advantage oflimiting the products that need to be procured.In decentralized health systems, where districtmanagers have the authority to procure theirown TB drugs, inappropriate and potentiallyincorrect drugs and dosages could be procured.Whether drugs are procured centrally or atlower levels, TB drugs should always beincluded in the national essential drugs list oncethey have been approved by the health system.Because of the complicated treatment regimensnecessary for breaking the transmission of TB,having the right drugs in the right quantities

Management support for DOTS,quantification, and managementinformation system

It is important that the government adopt theDOTS strategy recommended by WHO inorder to support a well-functioning TB drugprocurement service. Five components areinvolved:

• Government commitment to sustained TBcontrol activities.

• Case-detection by sputum-smear microscopyamong symptomatic patients self-reportingto health services.

• A standardized treatment regimen of 6–8months for at least all sputum smear-positivecases, with directly observed therapy for atleast the first 2 months.

• A regular, uninterrupted supply of allessential TB drugs.

• A standardized recording and reportingsystem that allows assessment of treatmentresults for each patient and of the overallperformance of the TB control programme.

An uninterrupted supply of essential TB drugsrequires accurate data on numbers of expectedcases of the different categories of TB in thenext procurement cycle, consumption data fromthe previous cycle, financial commitment forresources and drugs needed by the TB controlprogramme, and diligence in seeking appro-priate resources from donors and globalinitiatives to fill the resource gaps.

The backbone for obtaining appropriate datafor procurement activities is a managementinformation system (MIS) that provides datafor accurately quantifying drug needs and formonitoring procurement activities. Withoutaccurate data, TB drug estimates will becompromised, leading to stock-outs of drugs thatare needed by patients. Drug availability iscrucial in the treatment of TB: four or five drugshave to be taken simultaneously, on a daily basis,for 6–8 months without interruption to effect asuccessful cure and prevent development ofdrug resistance and consequent relapse.

31

available when the patient needs them is ofutmost importance.

Drug quantification

Drug quantification means estimating the numberof expected cases of all categories of TB to betreated in the upcoming year and multiplying theprojected number of cases in each category bythe number of single-drug or fixed-dosecombination tablets required for that category.Inaccurate quantification is one of the biggestobstacles to good procurement, and the NTPmanager must understand where to obtain thedata and how to calculate drug needs accurately.

The two methods best suited to estimatingTB drug needs are morbidity-based andconsumption-based. Using both methods is agood idea, especially in countries where druginformation systems are inadequate. Regardlessof the quantification method used, however, thegeneral approach is to calculate enough of eachdrug for 12 months. The quantities to beprocured can be adjusted up or down accordingto the availability of funds.

TB drug treatment regimens comprise fouror five drugs that are taken for the first 2 months(the intensive phase of treatment), followed bytwo to four drugs taken over the next 4–6months (the continuous phase). Use of themorbidity-based method to estimate needs,requires the NTP manager to know thepopulation of the country, the overall incidenceof TB, the ability of the health system to detectTB cases, and the number of expected casesof TB for all categories. Although the numberof expected cases can be based in part on thenumber of patients treated in the past, managersmay need to pay attention to special circum-stances within the country, such as rapidlyincreasing TB incidence due to HIV, or knownmigratory populations moving into the country.The morbidity-based method is defined byWHO in the Tuberculosis handbook (2) andis suited to countries with inadequate drug MISfor providing data on drug distribution,dispensing, stock-out, and expiry.

A well-functioning MIS is imperative for theconsumption-based method, which relies on


accurate data from storerooms and pharmacyoutlets for drugs distributed and dispensed;number of days out of stock; and number ofdrugs lost through expiry, diversion, and poorstock management. Few countries have a well-functioning MIS, but when these data areavailable, drug quantification is usually moreaccurate since numbers are based on realhistorical data rather than on expected numbersof patients as with the morbidity method. Somecountries use data on number of drugs issuedduring the previous procurement cycle, but thisis not quite as good as actual consumption datadescribed above. The consumption-basedmethod is described in the Drug managementfor tuberculosis tool developed by ManagementSciences for Health.

When quantifying TB drug requirements, theNTP manager should also determine thepreferred packaging (e.g., blister-packed drugs,patient boxes, loose tablets) and the exactformulations (e.g. which FDC tablets) neededto help ensure greater drug availability andadherence to treatment regimens. In the caseof blister packs, the drugs for a full day or fullweek of treatment can be packaged in oneblister. An example is the multidrug blister packdeveloped by India’s TB control programme,which uses blister packing for a daily dose andfor patient boxes. This packaging makesprescribing, dispensing, and securing patientadherence to therapy much easier.

Patient boxes, which have been tries by anumber of countries on a pilot basis, may beuseful in TB control programmes that havetrouble maintaining an adequate supply of theTB drugs needed by patients under treatment.All of the drugs needed for both intensive andcontinuous phases of treatment of a specificpatient, usually 6–8 months’ supply dependingon the category of TB patient, are placed in abox that is labelled with that patient’s name.The drugs in the box are used only for thatpatient, and the supply of medicines needed tocomplete therapy for that patient is ensured.This approach works well if patients do notmove around during treatment.

After a reliable quantification has beencompleted, it may still be necessary to adjust


32

the quantities that can be procured to conformto available funding. Having fewer drugs thanneeded for full treatment of an individual patientmay promote the development of multidrug-resistant TB (MDR-TB); before the treatmentof a given patient begins, therefore, all drugsmust be available for both the intensive andcontinuous phases of treatment. Should drugquantities need to be reduced for a particularprocurement cycle, they should be adjusted ona per-patient basis.

Competitive procurement methods

Competition is the best way for a TB pro-gramme to obtain the most cost-effective,quality TB drugs possible. The task is not easysince TB drugs are all off patent and there aremany suppliers worldwide, with unit prices thatvary wildly. The recommended method forprocuring TB drugs is through restricted tenderwith pre-qualification and performancemonitoring of suppliers.

At the outset, the TB drug procurementdepartment must determine government policyon international procurement and to what extentlocal TB drug manufacturers must be used.Moreover, if funding for the purchase of theTB drugs is through a World Bank loan, Bankprocurement procedures must be followed;these explicitly support international competitivebidding, with supplier prequalification, and asmall percentage of the loan being allowed forlocal procurement.

Potential suppliers must be qualified forservice reliability and product quality before thedrug tender is prepared and the procurementservice can invite bids only from such suppliers.

Once the contract is signed, performancemonitoring of the supplier can begin, based onthe quality and delivery terms of the contract.

Countries that do not have fully functionalprocurement systems may also acquire TBdrugs by facilitated procurement from theGlobal Drug Facility (GDF) and non-profitsuppliers. The GDF programme is describedlater in this paper. Advantages of this methodare competitive prices, products of good quality,

timely deliveries, and procurement by experi-enced professionals.

Supplier selection and qualification

Although restricted tender with prequalificationis recommended for procuring TB drugs, aprocurement service may choose to qualifysuppliers after tendering. This “post-qualifi-cation” must be planned and carried out wellin advance of actual tenders to avoid delaysin receiving drugs. Even so, pre-qualificationof suppliers tends to reduce the complexity ofthe tender process. Whichever method ischosen, buyers should:

• require certificates from manufacturers andregulatory agencies indicating that themanufacturers are licensed and inspected bylocal authorities;

• obtain financial reports showing that thesuppliers are established and able to fulfil thedrug order;

• gather information on suppliers’ reliability andthe quality of their products based on pastperformance;

• inspect samples of products; and

• if necessary, conduct laboratory tests of drugsthat may be unstable or have low bio-availability.

To gather much of the information neededto determine suppliers’ qualifications, buyerscan use both the “Quality of a Product Movingin International Commerce” certificate, devel-oped by WHO, and drug batch analysiscertificates. More information is available onthe following web site: http://www.who.int/medicines/library/theme/theme_qual.shtml.

To avoid confusion in tender documents topre-qualify suppliers of TB drugs, the procurementdepartment should use criteria established bythe NTP and the national regulatory authorityand include in the terms and conditions the exactstrengths of the single-dose and FDC drugs, aswell as quality specifications for each drugproduct. Appropriate standards for packagingmust also be specified to indicate appropriatelabelling and to protect drug products during

33

shipment and storage. Reference should bemade in the terms and conditions to the pharma-copoeias that manufacturers are required to useto test their products (e.g. US Pharmacopoeia(USP), British Pharmacopoeia (BP), andInternational Pharmacopoeia (IP)). Packagingof TB drugs can also be complicated whenspecial blister packs are requested for improvingpatient and prescriber compliance. Qualityissues with rifampicin-only tablets andrifampicin in FDCs have been noted by bothWHO and the International Union Against TBand Lung Disease (IUATLD), and are discussedbelow, in the “Quality assurance” section.

In the absence of prequalification, supplierreliability may be determined only afterpurchase, that is, when the supplier delivers therequired quantities of drugs according to thespecifications and dates in the contract.Procurement departments in neighbouringcountries may prove to be a valuable resourceif they are able to provide information abouttheir experiences with certain suppliers. However,whether pre- or post-qualification of suppliersis effected, appropriate monitoring of perform-ance will help to eliminate undesirable suppliers.

Quality assurance

Quality assurance involves many areaswithin the national TB control programme, butdiscussion here is limited to those areas specificto drug registration and procurement.

Like other drugs, TB drugs should beregistered in the country where they are to beused to ensure that they are safe and effective.The national drug regulatory authority usuallyconducts registration. Most countries have suchan authority, but where none exists the MOHshould establish an agency to be responsiblefor registration. The registration criteria specificto TB drugs have been published in theInternational Journal of Tuberculosis andLung Disease (3) and include evidence thatFDCs are tested as required by WHO andIUATLD. Other quality assurance issuesspecific to TB drugs are the criteria that shouldbe stated in tender documents, that is, a signedstatement from the manufacturer containing thefollowing information:

• Comparative bioavailability results forrifampicin in single-drug and FDC productsnot older than 3 years, and the laboratoriesat which the tests were performed.Laboratory tests must be equivalent torifampicin single-drug standard methods inorder to comply with recognized pharma-copoeial standards.

• Comparative dissolution tests for allcomponents of FDC products.

• A declaration of consistency between thestarting and subsequent batches.

• A correlation over time between dissolutiontests of different batches.

• A statement that the raw materials are inaccordance with reference specifications.

Even after drug registration, and withappropriate documentation in hand showingthat manufacturers have followed good manu-facturing practices, the appropriate MOHdepartments should verify the quality ofshipped drugs and supplies using physical andlaboratory tests. If laboratory services areunavailable or inadequate, random samplingwith testing by a WHO reference laboratoryis suggested. A quality assurance departmentmay also want to consider laboratory screeningby thin-layer chromatography, which requiresfewer resources and provides quick identi-fication and measures content uniformity of adrug. At a minimum, a physical inspection shouldbe made to ensure that drugs appear adequate(not crushed or discoloured, for example) andare labelled and packaged according to specifi-cations (e.g. blisters or requested configurationof FDCs in the blister).

In summary, with an appropriate qualityassurance system in place, the TB programmewill receive drugs with the correct ingredients,with the potency specified on the label, in therequired dosage form and in the packagingconfiguration ordered, and with active ingre-dients that are bio-available.

Monitoring and supervision

The need for continual planning and monitoringthroughout the procurement process is not



34

Personnel supervision is one method ofmonitoring, but the collection of standardizeddata to measure specific indicators is also anappropriate way of quantitatively assessingperformance of the procurement system. Thoseindicators are presented in another paper in thisdocument, Using indicators to monitor TBdrug supply.

Facilitated procurementfrom the Global DrugFacility

National TB control programmes may be usinga variety of mechanisms to procure TB drugs,including working with suppliers who participatein national tenders, those who participate ininternational tenders, and international not-for-profit suppliers. While NTPs should alwaysstrive to be as self-sufficient as possible, thosecountries without available resources andexperience may find it advantageous to purchase

References

1. Operational principles for good pharmaceutical procurement. Geneva, World Health Organization, 1999(Interagency Guidelines) (document WHO/EDM/PAR/99.5; available at http://whqlibdoc.who.int/hq/1999/WHO_EDM_PAR_99.5.pdf’).

2. Tuberculosis handbook. Geneva, World Health Organization, 1998 (document WHO/TB/98.253; available at http://whqlibdoc.who.int/hq/1998/WHO_TB_98.253.pdf).

3. Assuring bioavailability of fixed-dose combinations of anti-tuberculosis medications. A joint statement of theInternational Union Against Tuberculosis and Lung Diseases and the World Health Organization. InternationalJournal of Tuberculosis and Lung Disease, 1999, 3(Suppl. 3):S282–S283.

TB drugs through global initiatives like the GDF.The GDF is an initiative of the Stop TBPartnership that provides a mechanism forincreasing access to, and availability of, high-quality TB drugs to facilitate global DOTSexpansion. The advantages of using the GDFinclude the following:

• Competitive prices can be expected.

• Procurement is done by others.

• Quality products are assured.

• Timely deliveries are made.

• Ongoing development of packages such asFDCs and blisters promotes patientcompliance.

• Linkage exists with the DOTS expansionprogrammes of WHO Member Statesproviding the greatest benefit of drug usewithin the country.

The GDF has a grants-in-kind mechanism tofill the gap in TB resources of countries usingthe DOTS scheme, and in 2002 established thedirect procurement mechanism to meet yetanother demand. To use this direct procurementmechanism, countries must meet specificcriteria: details are available on the Stop TBweb site at http://www.stoptb.org/GDF/drugsupply/Direct_procurement_process.doc,which specifies the sale of drugs only to thoseorganizations and countries that follow DOTSguidelines and are committed to using TB drugsprocured through the GDF only in DOTS pro-grammes. To continue purchasing from the GDF,countries must submit routine annual DOTSprogramme performance reports to WHO.

unique to TB drug procurement but is worthyof mention here. The procurement process iscyclical: when the NTP has received one orderof TB drugs, the next cycle of procurementmust be started by collecting quantification dataand pre-qualifying additional suppliers. Inaddition, supplier performance must be monitoredto determine reliability of delivery and qualityspecifications agreed upon in the contract.

35

USING INDICATORSTO MONITOR TB DRUG SUPPLY


Technical Officer, Stop TB/MSH

The Stop TB Partnership Secretariat and Management Sciences for Health wish toacknowledge the following people who have contributed to the preparation of this paper:

Virginia Arnold, David Lee, Peter Evans, Keith Johnson, Richard Laing, SoulyPhanouvong, Ian Smith, Andrey Zagorskiy


36

To ensure a reliable supply of TB drugs,managers must pay attention to four keycomponents of the drug supply system—selection, procurement, distribution, and usewithin their countries—which need to besupported by appropriate financing and amanagement information system to feedbackstrategic information. The activities covered byeach of these components are described inanother of the papers in this document,Operational framework to strengthen TBdrug management.

Why monitor?

Monitoring is an integral part of TB drug supply;it should be performance-based and involve anongoing review of activities to determine theextent to which established targets are beingmet. Indicators will help policy-makers to makemore informed decisions relative to their nationalprogrammes. Moreover, with a monitoring systemin place, action can be taken immediately torectify any problems that occur (1).

Although the indicators suggested in thispaper are intended for in-country monitoring ofdrug supply, some can also be used for reportingto partners and global TB initiatives such asthe Global Drug Facility (GDF) and the GlobalFund to Fight AIDS, Tuberculosis and Malaria(GFATM).

Using indicators

There are several methods for monitoring a TBdrug supply system—direct supervision ofpersonnel is one of them. Direct supervision,or even periodic supervisory visits, can beproblematic in some developing countriesbecause of lack of resources. A supplementalmethod is the use of indicators, which isdescribed in this paper.

To calculate indicators, data about theprogramme are needed. These data should beavailable within the TB information system for

vertically managed TB programmes, and withinthe drug information system of the essentialdrugs programme in countries where TB drugsupply is integrated with other health programmes.If all the drug supply and use data are not readilyavailable in the country’s TB drug informationsystem, the programme manager may want toseek technical assistance from TB partners insetting us a viable system.

When selecting which monitoring indicatorsto use for the first time, managers commonlychoose too many. Some of the indicators maythen not be used, or prompt feedback may notbe given to those involved, causing personnelto lose faith in the monitoring system andperhaps rendering it ineffective. It may be bestto identify all the indicators that would useful,and then select one or two core indicators foreach component of the TB drug supply system(selection, procurement, distribution, use,financing, quality assurance, and national drugpolicy). Once the monitoring system is fullyestablished, more indicators can be added, asfeasible, or some of the core indicators can bereplaced with others.

Taking action

If indicators are to be used effectively, the TBdrug supply manager should take actionappropriate to the nature of any problemidentified: this may take the form of positivefeedback or corrective feedback. It may alsoinvolve reassigning staff, adjusting TB drugsupply targets, or requesting additional infor-mation to provide a better understanding of theproblem. With a good monitoring system in place,managers make optimal use of scarce resources.

The next section discusses in more detail theuse of monitoring indicators in TB drug supply.The last section, “Illustrative TB drugmanagement indicators”, provides a list ofindicators to consider for use in monitoring aTB drug programme.

OVERVIEW

37

USING INDICATORS TO MONITOR DRUG SUPPLY

Introduction

All countries have national drug policies whichare published in laws, regulations or procedures.These may vary from country to country butgenerally have the same objectives: makingeffective, safe, low-cost, essential drugs avail-able and affordable, meeting the needs of theentire population, and ensuring that the drugsare of good quality and used rationally. With agood drug monitoring system in place, a TBdrug management programme can promote theaccomplishment of the national drug policies.

In some countries the TB drug supply systemis vertically managed by the national TBprogramme, while in others it is part of theessential drugs programme. In countries withdecentralized health systems, it is managed atthe district level. Regardless of the type of TBdrug supply system, effective monitoring canhelp managers to achieve the goals of thenational drug policy and the TB controlprogramme. Monitoring is also important as ameans of reporting progress to partners andglobal initiatives such as the World HealthOrganization, the Stop TB Partnership, andGFATM.

Several types of monitoring system aredescribed in the publication Managing drugsupply (1), but it is not the intention to discussthem all here. The purpose of this paper is todiscuss drug management indicators in thecontext of TB drug supply.

The four main components of the drugmanagement cycle—selection, procurement,distribution, and use—can be used to breakdown TB drug management into more discreetactivities to provide a better understanding ofwhat should be monitored.1 For example, thefollowing core indicators might be chosen foreach of the components:

• Selection—proportion of TB drugs used thatare in the standard treatment guidelines.

• Procurement—supplier contract deliverytimes.

• Distribution—number of stock-outs in TBdrug storerooms.

• Use—percentage of patients given their TBdrugs in directly observed therapy.

Indicators are a viable choice for monitoringdrug management activities, having been aroundsince the early 1990s (1). Drug managementindicators specific to TB are the same as thoseused by essential drugs programmes butadapted to the specifics of TB drugs. Somedrug management indicators have been testedin various countries and others have been adapt-ed for specific national or global programmes.

TB drug management indicators take severalforms: some are merely data that can besummed, such as “numbers of TB drugs thatfailed quality tests”, while others are averages,percentages, or proportions and requirecalculation, such as “percentage of stock-outsof TB drugs in health facilities”. Indicatorsmeasured at only one point in time are less usefulthan those that are measured on a regular basisand allow trends to be monitored over time.More comprehensive information on drugmanagement indicators is available inIndicators for monitoring national drugpolicies (2).

Selecting TB drug managementindicators

Setting up a monitoring system without clearconnection to the drug management programme,as often happen, can lead to the selection oftoo many or inappropriate indicators. At theoutset, using many indicators may mean thecollection of useful data, but if time cannot befound to analyse those data and providefeedback for appropriate action, the monitoring1 See also the final paper in this document, Operational

framework to strengthen TB drug supply.

CHOOSING INDICATORS FOR MONITORING


38

programme is likely to fail. To avoid this, TBdrug programmes may want to start small andexpand the number of indicators only when thesystem is well established. It may be a goodapproach to start by selecting just one or twocore indicators at each level of TB drug supply—central, district, treatment centre—and thenexpand to include more or different indicatorsonce the monitoring system is well established.

When selecting indicators for TB drugmanagement, it is important to ensure both thatthey are meaningful and understandable by thosewhose activities are being measured and thatthe data are readily available or retrievable. Datacollection for monitoring indicators must becomepart of regular monthly or quarterly activities.However, if the TB drug information system isnot functioning well, the first step is to improveits performance so that indicator data will bereliable. Even with a sub-optimal informationsystem, indicators should be chosen for the datathat are currently available, and an annual surveyshould be undertaken to fill the gap for datathat are unavailable. One useful way to set upan indicator monitoring system is to selectstrategic sentinel sites or a smaller set of healthfacilities for reporting. However, if a sentinelsystem is used, there is still the possibility ofproblematic sites remaining undetected.

Collecting datato calculate indicators

The number of drug products needed for TBprogrammes is small when compared with thehundreds of products involved in essential drugsprogrammes. For that reason, the TB drugmonitoring system may include all drugs usedin the national TB programme. However, if themonitoring system needs to start small, a tracerlist of TB drugs—which should be those drugsthat are available at all levels of the healthsystem—can be selected. In this case the tracerlist may consist of all drugs used to treat patientsin Categories I, II, III of the WHO/DOTSstrategy (3), since all drugs must be availableat all times for successful treatment andprevention of drug-resistant TB.

In countries where the private sector isimportant in TB drug supply, the nationalprogramme may want to include retailpharmacies or private clinics in the routinemonitoring—but certainly in periodic surveys.

There are other reasons governing theselection of drugs to monitor. Perhaps the TBprogramme is expanding its use of fixed-dosecombination products or of blisters packagedespecially for patient boxes. In this case, theproducts to monitor at the central warehouse,local storerooms, and treatment centres maybe the different drug combinations or packagingconfigurations. Other choices may be drugs thathave caused difficulties in the past, because ofquality problems with the active ingredients ofthe tablets themselves or with the productpackaging.

Information neededto calculate indicators

Depending on whether the indicators areprepared as summed data or need to becalculated, the following information must begiven to determine the feasibility of theiradoption within a TB drug system.

• Name of the indicator or monitoring point

• Rationale for the indicator

• Definition of the indicator

• Data that constitute the numerator anddenominator (for summed data only thenumerator data are given)

• Where to go to get the data

• Whom to ask for the data

• What data must be collected and reported

• How data are to be analysed.

In the data collection tool Drug managementfor tuberculosis (DMTB) developed byManagement Sciences for Heath (MSH),several drug management indicators have beenadapted for monitoring TB drug supply. The toolis still in draft form, however, and the indicatorsare currently being field-tested in two countries;test results should be available by the end of

39

2002. In the interim, the DMTB tool may serveas a guide to understanding the components ofa drug management indicator.

In the MSH training guide Drugprocurement for tuberculosis (4), indicatorsfor the procurement of drugs for a national TBprogramme have been suggested. These arealso being field-tested, but results may not beavailable for some time because of the need totrack long procurement periods.

Illustrative TB drug managementindicators

Several TB drug indicators are listed below forconsideration by national TB programmes. Theyare purely illustrative, although some have beentested through a general essential drugsprogramme. For better understanding they aregrouped under the appropriate components ofthe drug management cycle. To assist inidentifying what data must be collected andwhere, and how the indicator should becalculated, reference can be made to thedocuments cited above and also to Indicatorsfor monitoring national drug policies (2).TB partners may be able to provide technicalassistance to national programmes in setting upa TB drug monitoring system based on localrequirements.

Indicators marked with an asterisk (*) arecore indicators established by the GDF formonitoring countries with which it hasagreements.

Drug legislation, regulation,and policy related indicators

• Percentage of a set of TB drugs that areregistered in the country as compared withthe contract delivery dates.

• Average number of days to register TBdrugs.

• Percentage of TB treatment facilities visitedthat have the latest official manual oftreatment guidelines for TB.

Selection-related indicators

• Percentage of first-line TB drugs on theWHO Model list of essential drugs (5)included on the national essential drugs list.

Procurement-related indicators

• *Costs of drugs procured as a percentageof costs if GDF drugs were used.

• Dates the different shipments of TB drugsarrived in country.

• Average time required to clear shipments ofTB drugs from the port of entry.

• Percentage of mean international price paid,CIF1 /ex-factory, for a set of TB drugs thatwas part of the last regular Ministry of Health(MOH) procurement.

• Percentage of drugs purchased by inter-national tender over the past 3 years.

Distribution and storage related indicators

• *Average percentage of time out of stockfor a set of TB drugs in MOH storage andtreatment facilities at different levels of thehealth system.

• Average percentage of a set of unexpiredTB drugs available in MOH storage andtreatment facilities on the day of inspection.

• Average percentage of stock records thatcorrespond with physical counts for a set ofTB drugs in MOH storage and TB facilitieson the day of inspection.

• Number of drugs beyond expiry date out oftotal of number of TB drugs surveyed on theday of inspection.

Drug use related indicators

• *Percentage of new smear-positive patientswith pulmonary TB who were prescribedcorrect drugs in correct dosages in accordancewith treatment standards adopted by the country.

• Percentage of TB patients who could cor-rectly describe how the prescribed medica-tion should be used (for the continuationphase of treatment).

1 CIF: cost, insurance, freight.

USING INDICATORS TO MONITOR DRUG SUPPLY


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References

1.Quick JD et al., eds. Managing drug supply: the selection, procurement, distribution and use ofpharmaceuticals, 2nd ed. Hartford, CT, Kumarian Press, 1997 (Chapter 5).

2.Brudon P, Rainhorn J-D, Reich MR. Indicators for monitoring national drug policies, 2nd ed. Geneva,World Health Organization, 1999 (document WHO/EDM/PAR/99.3).

3.Tuberculosis handbook. Geneva, World Health Organization, 1998 (document WHO/TB/98.253):73.4.Drug procurement in tuberculosis: trainer’s guide and participant’s notes. Boston, MA, Management

Sciences for Health, 2000.5.WHO Model List of Essential Drugs, 12th edition, 2002, (available at http://www.who.int/medicines/

organization/par/edl/eml.shtml)

• Percentage of prescribed TB drugs actuallydispensed.

• Percentage of private drug retail outletswhere rifampicin and streptomycin wereavailable without a prescription.

• Percentage of private retail outlets whereTB drugs are sold.

• Cost (CIF/ex-factory) of drugs prescribedas a percentage of costs if DOTS norms fortreatment were followed.

Quality control related indicators

• *Number of TB drug samples that failedquality control testing out of the total numberof TB drug samples tested.

• Total number of quality problems reportedduring the year by storeroom, prescriber, anddispensing personnel and patients.

• Percentage of shipments received over thepast 3 years that were physically inspectedfor quality defects.

Financing related indicators

• Average number of days to pay suppliersafter receipt of TB drugs for the last threeprocurements.

• Average percentage of expenditures for allTB drugs paid for by the government.

41

OPERATIONAL FRAMEWORKTO STRENGTHEN

TB DRUG MANAGEMENT


Technical Officer Stop TB/MSH

The Stop TB Partnership Secretariat and Management Sciences for Health wishto acknowledge the following people who have contributed to the preparation of

this paper: Malcolm Clark, Peter Evans, David Lee, Keith Johnson, Richard Laing,Souly Phanouvong, Ian Smith


42

Once managers have a full understanding ofthe cycle they can more easily identify existinggaps and shortcomings in their own programmesand recommend specific improvements forensuring the uninterrupted procurement andsupply of TB drugs.

Introduction

This paper provides a strategic framework thatcan be used by TB programme managers,Ministry of Health (MOH) TB drug managersand local TB partner organizations to developa comprehensive action plan for improvingweaknesses in drug procurement and supplyfor the national TB programme (NTP). For bestuse of the framework, the first step is to identifyspecific weaknesses in the programme.Identifying drug management problems can bedone in several ways:

• Using personal knowledge and experiencefrom working within the national programme.

• Through a special workshop or committee bring-ing together both individuals familiar with theNTP and experts in TB drug management.

• Formally, through an assessment such as thatprovided by data collection tool Drugmanagement for tuberculosis (DMTB),developed by Management Sciences forHeath (MSH), which quantifies the extentof the problems.

Each of the methods will produce a differentlevel of understanding of TB programmeweaknesses. Once it has good knowledge ofspecific problems, the TB programme can usethe framework provided in this paper and selectappropriate activities to implement forstrengthening drug management capacity.

This framework was developed for the StopTB/MSH drug management meeting inWashington, DC, in June 2002. Using theframework, participants of the meeting willselect specific activities, establish a realistictimeline, person(s) responsible for carrying outeach activity, and the resources needed. Usingthis methodology resource gaps will bedocumented so that partners understand howthey can best provide specific assistance to theTB programme.

Objectives of drug management

TB drug management activities must be designedto support the NTP; providing drugs fromapproved standard treatment regimens for TBpatients of Categories I, II and III when neededshould be the primary objectives. It is no simpletask to procure and supply drugs since thereare many suppliers in local and internationalmarkets, prices and quality vary tremendously,and drug procurement and supply personnel maynot have the necessary training, experience,financial resources, or appropriate establishedprocedures. In addition, TB treatment regimensare complicated and it is difficult for patients tocontinue taking the 4–5 drugs requiredthroughout the 6–8-month treatment period.

Operational framework andactivities for strengthening TBdrug procurement and supply

The procurement and supply of TB drugs is arecurring process, and using the drug manage-ment cycle illustrated below is a good way tounderstand the various components of the processand their interrelationships. Those components areselection, procurement, distribution, use, andmanagement Support, all of which are supportedby a “Policy and legal framework”:

OVERVIEW

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OPERATIONAL FRAMEWORK TO STRENGTHEN DRUG MANAGEMENT

The next section in this paper outlines thestrategic framework for strengthening TB drugprocurement and supply, and the final sectiondescribes specific activities that managers can

Components of drugmanagement

To address TB drug management appropriately,managers need to know the specific roles ofeach component of the drug management cycle,since any flaw that interrupts the patients’ timelyuse of TB drugs may lead to treatment failureand promote the spread of multidrug-resistantTB (MDR-TB). There are four majorcomponents of the cycle:

• Selection of essential TB drugs

• Procurement of selected drugs

• Distribution of procured drugs

• Use of distributed drugs.

Each component of the cycle is supported by apolicy and legal framework and a managementsupport system.

Management support

Management support is an integral part of eachof the components of the cycle, and managerresponsibilities will be spread throughout severaldepartments of the MOH in a typical NTP. Forexample, the NTP control manager may bedirectly involved in the selection of drugs andregimens, estimation of quantities of each drugneeded, and distribution of drugs to treatmentfacilities.

The essential drugs manager may also beinvolved in the selection of drugs and regimens,and may—instead of the NTP manager—be

responsible for receipt of TB drugs and theirdistribution to treatment facilities. The procure-ment manager is usually involved in selectingand qualifying of local and internationalsuppliers, tendering for good-quality, cost-effective drugs, and monitoring supplier contractperformance. The receipt and clearance of TBdrugs from the port of entry could be theresponsibility of any of these managers.

Prescribers and patients are responsible forusing the TB drugs. It is the prescriber whomust first diagnose that the patient has TB, thenprescribe the drugs and treatment periodsaccording to treatment guidelines, and thendirectly observe the patient taking the drugs,especially during the first 2 months of treatment.The patient is also responsible for rational druguse and must comply with the complicatedtreatment regimen necessary to combat TB.

Verifying the quality of TB products is theresponsibility of the national drug regulatoryauthority. This involves carrying out registrationof suppliers’ drug products, ensuring that suppliersuse good manufacturing practices, and monitoringthe quality of received products through physicalinspection and laboratory analysis.

A viable drug management informationsystem (MIS) must be in place to provide thespecific programme data needed to manageeach component of the cycle. To monitoreffectiveness of treatment and provide feedbackinformation for ongoing TB programme needs,prescribers must record all case data usingstandardized patient care and reporting forms.The programme will need patient case data to

choose to overcome the weaknesses they identifyin their TB programmes. For each implemen-tation activity, the expected outcome or benefitis also provided.

OPERATIONAL FRAMEWORKTO STRENGTHEN TB DRUG PROCUREMENT AND SUPPLY


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determine needed resources for the programme,to quantify TB drug needs for the nextprocurement cycle, and to report to local andglobal partners such as the WHO Stop TBPartnership.

Finally, the NTP should have in placestrategies to monitor the effectiveness of theTB drug management programme. Monitoringcan take the form of supervision of employeesand use of indicators to track trends in drugprocurement and supply. Indicators are espe-cially useful for demonstrating to stakeholdersand TB partners alike the status of drugmanagement within the programme. With suchdata a programme may be able to obtain moreassistance—technical expertise, and human andfinancial resources—to improve TB drugprocurement and supply.

Policy and legal framework

The success of a TB control programmedepends largely on political commitment fromthe government and from doctors and otherhealth professionals to support a DOTSprogramme. Government commitment takesthe form of drug policy activities for allocatingbudgets, promoting education initiatives, definingthe role of the public and private sectors, andresponding to global initiatives for procurement,supply, and use of TB drugs. Commitment ofthe health provider consists in diagnosing,prescribing, and administering approvedtreatment regimens for Categories I, II, and IIIpatients, directly observing drug-taking by thepatient, patient education, and documentationof TB drug use and compliance. The DOTSstrategy promoted by WHO outlines thecommitment needed by an NTP:

• Government commitment to sustain TBcontrol activities.

• Case detection by sputum-smear microscopyamong symptomatic patients who report tohealth facilities voluntarily.

• Standardized treatment regimen of 6–8months for all patients with positive sputumsmears and directly observed therapy for atleast the initial 2 months.

• A regular, uninterrupted supply of all essentialTB drugs.

• A standardized recording and reportingsystem that allows assessment of treatmentresults for each patient and of the overallperformance of the TB control programme.

With both management support and a policy andlegal framework in place, the four componentsof the drug management cycle are easier tomanage. Activities specific to each of the fourcomponents (selection, procurement, distri-bution, and use) are discussed in the followingsections.

Selecting TB drugs

Selecting drugs for TB programmes usuallyinvolves a team of people with differentbackgrounds—the NTP manager, a medicalspecialist in TB treatment, a pharmacologist, aprocurement specialist, a pharmacist, and anurse, for example. The team reviews patternsof TB morbidity and resistance and, using theDOTS regimens as a basis, identifies treatmentsof choice, and selects the drugs and dosageforms that will be available in TB treatmentfacilities.

In selecting specific drugs and drug combi-nations, the team must also consider thestructure of the health system, the ratio ofproviders to TB patients, and the accessibilityof health facilities to patients. WHO recom-mends that the TB patient should be directlyobserved while taking the TB drugs during thefirst 2 months of treatment: this is greatlyfacilitated by the use of fixed-dose combination(FDC) products, which WHO and its partnershave supported for several years. In additionto 2- and 3-drug combination products, a 4-drugproduct (4FDC) has recently become available,which contains all the drugs needed by theCategory I patient during the initial phase oftreatment. Based on the patient’s weight, oneor more 4FDC tablets are taken daily, makingdrug calculations easier for the prescriber anddrug-taking easier for the patient. The 4FDC isalso useful for the Category II patient to whomit can be jointly administered with the fifth drugneeded for treatment— injectable streptomycin.

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Another consideration for the selection teamis the packaging of drugs. Until quite recently,blister-packed drugs were much more costlythan loose tablets in multi-dose bottles of 100or 1 000 tablets; now, however, with improvedtechnology and greater competition, the pricedifference is practically negligible. Blister packagingis thus a viable alternative for TB programmes,helping prescribers to give patients a better under-stand of their treatment regimens. For example,the blister pack may contain all TB drugs orFDCs needed for 1 day, 1 week, or longer.

Some TB programmes have experimentedwith patient boxes—containers, marked witheach patient’s name, into which all the drugsfor at least the first 2 months of treatment areplaced. This system was developed to avoidthe problem of starting a patient on the intensivephase of treatment and then having to interrupttreatment (and risk the development of MDR-TB) because of stock-outs.

Once the drugs are selected, they should beincluded on the national essential drugs list. Thishelps to enforce the procurement of onlyapproved drugs, especially in decentralizedhealth systems where drugs can be purchasedat local levels.

Procuring TB drugs

Procurement of TB drugs involves obtaining aregular supply of adequate quantities of high-quality drugs at the lowest possible cost. Asmentioned in the previous section, stock-outscause the interruption of patients’ treatment andcan lead to the development of MDR-TB. Theneed for timely procurement to promoteavailability of drugs in the health system is thusobvious. Details of the following procurementactivities are described in another paper in thisdocument, Drug procurement for tuberculosis:

• Drug selection: Serving as a member of theteam that selects the most appropriate drugtreatment regimens and products for the TBprogramme, the procurement manager canprovide background information on suchmatters as expected costs, availability in themarket place, and which drugs are alreadyregistered in the country.

• Drug quantification: Estimating drugrequirements on the basis of epidemiologicaldata, and using a systematic method such asmorbidity-based (recommended by WHO)or consumption-based quantification.Depending on the programme, responsibilityfor quantification may rest with the NTP orwith procurement personnel. Estimating thequantities of each needed drug is critical forensuring that drugs are available when andwhere needed by the patient.

• Competitive procurement methods: Under-standing the advantages of the restrictedprocurement method with pre-qualificationof suppliers. There are several procurementmethods, but only this method isrecommended for TB drugs; it involves aformal process of collecting data aboutpotential suppliers before tendering for thedrugs themselves. With a limited list ofsuppliers with known potential for producingdrugs of good quality, the procurementdepartment has fewer tender bids to review,reducing lead time for receiving the drugs.

• Supplier selection and qualification:Identifying and qualifying local andinternational suppliers. TB drugs have beenon the market for more than 30 years, areavailable as generic formulations from manyproducers worldwide, and have shown qualityproblems with the drug rifampicin in FDCproducts. Through pre-qualification, aprocurement manager must be able to identifythe best suppliers for the TB programmebased on their ability to produce and deliverthe drugs when needed, using acceptablequality standards, at an optimum price. Pre-qualification allows a procurement managerto prevent undesirable suppliers frombidding, thereby saving time and resources.

• Quality assurance: Understanding qualityaspects of drug and packaging specificationsfor TB drugs. Many things can go wrong inthe attempt to provide drugs of good quality,and all those involved in the procurementprocess must contribute to overcoming thesepotential problems. Manufacturers must followvalidated processes, using the same ingre-dients and the same equipment, with trained



46

personnel. The drug packaging must be testedto ensure that it will preserve the quality ofthe drugs at least until the expiry date specifiedon the labelling. The national regulatoryauthority can verify this through on-siteinspections or through the use of the WHOcertification scheme on the quality ofpharmaceutical products moving ininternational commerce (1).

Shippers must use procedures that maintainproduct quality until delivery to the TB pro-gramme, such as meeting the manufacturer’sspecified conditions for temperature extremesand humidity. The TB programme must thenmaintain product quality during distributionto the facilities and storage within healthfacilities until drugs are given to the patient.

Despite prequalification of suppliers, the TBprogramme must still inspect and test theproducts for quality assurance purposes. Itshould establish receiving procedures forsampling of the shipment for physicalinspection to determine whether the drugshave deteriorated, been crushed, or changedcolour and whether they are labelled appro-priately, and laboratory testing to establishthat drugs contain the correct activeingredient(s) in the dosages specified.

· Monitoring and supervision: Monitoringsupplier quality and performance, monitoringand supervising the procurement system.Supervising personnel is one method ofmonitoring, but can be time-consuming andsubjective. A supplemental method ismonitoring through the use of indicators toquantitatively demonstrate performance ofthe procurement system. Depending on theindicators chosen, they can measure theprocurement lead time, contract deliverytimes by suppliers, number of qualityproblems found by the system, percentageof drugs out of stock in TB drug facilities,and percentage of drugs past their expirydates. Potential indicators are described indetail in another paper in this document,Using indicators to monitor TB drug supply.

Distributing TB drugs

Distribution comes into play once drugs areappropriately selected and the drug quantitiescalculated and procured. The process beginswith rapid clearance through customs to avoiddeterioration of drugs waiting at the port ofentry in inappropriate storage conditions. Oncedrugs have passed quality inspections they canbe delivered to warehouses and treatment facilities.

Timely provision of TB drugs relies oninformation from local warehouses and healthfacilities on quantities of existing stocks and thenumber of additional drugs needed. To deliverorders promptly, the distribution manager mustestablish a transportation schedule that takesaccount of the geography of the country, theavailability of vehicles, and the condition of theroads. Provision should be made for emergencyorders with a safeguard to prevent overuse ofthe emergency system as a result of poorinventory control.

Good inventory control procedures must beused at all levels in the programme to avoidstock-outs and to supply reliable data forestimation of drug needs for the next procure-ment. The following procedures for good stockmanagement should be followed to promote theavailability of TB drugs when they are neededby the patients and in the prescribed quantities:

• The receiving warehouse should documentreceipts and deliveries of all drug shipmentsto TB depots and health facilities when theyoccur.

• Local warehouses and treatment centresshould document receipts of all drug deliverieswhen they occur.

• Treatment centres should document quan-tities of each drug dispensed or administeredto patients every day.

• Warehouses and treatment centres shouldstore drugs in an appropriate way so theyare easy to find, protected from pilferage,and protected from deterioration fromsunlight and moisture.

• Warehouses and treatment centres shouldrotate stocks, putting drugs that will expirefirst at the front; this avoids exceeding the

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shelf life and therefore loss of drugs(FEFO—first to expire, first out).

Using TB drugs

To promote rational drug use, health careproviders must prescribe the appropriate TBdrugs in the right doses and patients must adhereto the drug regimens prescribed. The rationaluse of drugs is facilitated by other componentsof the drug management cycle, as describedabove, with drugs being selected from approvedtreatment regimens and made available attreatment centres in the quantities and at thetimes needed by patients. It is also facilitatedby the development work of WHO and itspartners, who continue to study ways ofimproving TB treatment regimens. Oneoutcome of such work, the use of FDCs, hasalready been (see “Selection” above).

With the lengthy and complex treatmentregimens necessary to fight TB, use of FDCsgreatly facilitates the job of the prescriber andenhances patient compliance. For the prescriber,FDCs simplify the calculation of doses, makingthe task of matching numbers of tablets to thepatient’s body weight much easier. For the

In order to identify weakness in drugmanagement, TB programmes can comparetheir organizational structure and procedureswith the model provided by the operationalframework described above. Appropriatesolutions can then be selected. This sectioncontains a variety of problems and activities forovercoming drug management weaknesses. Tobetter use the information, programmemanagers should create a table to organize theoutcome of their drug management analysis.For each problem and activity selected they canindicate the resources needed, resources


patient treated with FDCs, fewer tablets haveto be taken at one time.

The direct observation of patients that isinvolved in the DOTS (directly observedtreatment, short course) scheme also promotesthe rational use of TB drugs. Patients areobserved while taking their drugs, at least duringthe first 2 months of treatment, and this helpsin avoiding relapse or failure. Any relapse ortreatment failures that occur put affectedpatients in danger of developing MDR-TB,leading to both the necessity of using morecostly antibiotics and, sometimes, death.

Some TB programmes have experimentedwith the use of incentives for both prescribersand patients. For prescribers, incentives haveincluded bonuses for every patient treatedsuccessfully or recognition in the communityas a successful TB practitioner. For patients, incen-tives have taken the form of food supplementsor of stipends for successfully treated patientswho become spokespersons in theircommunities promoting good TB control (2).

It is crucial to make private sector—becoming more involved in TB treatment—prescribers and dispensers as aware as possibleof government TB treatment programmes.

available, resource gaps, person responsible tocarry out the activity, and potential TB partnerswho could provide financial and technicalassistance.

Activities to advocatefor needed changes in thenational drug policy

• Problem: There is no policy for promotingrational drug use or for updating personneltraining to promote rational drug use.

ACTIVITIESTO STRENGTHEN MANAGEMENT OF TB DRUG

PROCUREMENT AND SUPPLY


48

– Activity: Hold strategic meeting withpolicy-makers and demonstrate both the needand the positive outcomes if drug policy wereto include human resource capacity buildingand the rational use of TB drugs.

– Expected outcome: Drug policy will beupdated to affirm government support forrational TB drug use, including training for goodprocurement practices, good stockmanagement and inventory control, andappropriate use by prescribers. The TBprogramme budget will cover regular trainingfor appropriate staff that includes supervisoryactivities.

• Problem: Current drug registration proceduresare too lengthy and affect the availability ofTB drugs in the national programme.

– Activity: Hold strategic meetings with thenational drug regulatory authority (NDRA)and discuss acceptable ways to coordinateTB drug registration dossiers.

– Expected outcome: The NDRA will adoptprocedures such as fast-track registration1

and agreement on a model drug registrationdossier. The NDRA will share registrationprocedures with authorities of other countrieswithin the region when registering TB drugsfrom the same suppliers.

Activities that can promoteoverall drug management support

• Problem: The programme wishes to changefrom using single drugs to FDC products.

– Activity: Justify the change to FDCs withdecision-makers, then provide technicalassistance in establishing and implementinga changeover plan. The plan should includeannouncement of the changeover decisionto TB programme personnel; training for allpersonnel who will select, procure, distribute,and use the new TB products; ensuring that

only products of good quality will be procuredand used; updating the documentation systemto accommodate the FDCs; and a mechanismto monitor implementation (for example,procurement personnel will need tounderstand specifics of FDCs related toquality and packaging of 2-, 3-, and 4-drugFDCs and potential blister-pack configurations).The plan must also cover the phasing-out ofremaining single-drug products.

– Expected outcome: The changeover toFDCs will be smooth and avoid interruptingappropriate treatment of TB patients.

• Problem: The management informationsystem (MIS) is weak and unable consist-ently to feedback the number of treated casesand therefore the quantities of drugs neededfor the next procurement cycle.

– Activity: Seek and provide technicalassistance in developing an MIS that hasappropriate reporting forms and a computerizedor manual tracking system; assistance shouldinclude training for appropriate personnel inanalysis and interpretation of the data. Trainpersonnel on TB drug quantification using boththe morbidity- and consumption-based methods.Quantities from the two methods can then becompared to improve estimates of real drugneeds.

– Expected outcome: Programme data willbe available in a timely manner for nationalprogramme reviews by TB partners,reporting to global initiatives such as Stop TBand DOTS expansion, and identification ofproblem areas by the TB drug procurementand supply managers

• Problem: The NTP does not have anoptimum system for monitoring its drugmanagement activities.

– Activity: Seek and provide technicalassistance in establishing a system that combinesthe drug supply reporting mechanisms withsupervisory checklists, selecting appropriatedrug management programme indicators, andtraining programme personnel to calculateindicators as well as interpret the data. Thesystem may include the use of sentinel sitesfor surveillance and indicator monitoring.

1 Fast track drug registration involves the issuance ofconditional permission for a supplier to market a drugin-country. Prequalification of the supplier has usuallytaken place, the drug is used, and the supplier’s productis monitored for quality by the NDRA during theconditional period, often 6–12 months.

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– Expected outcome: The NTP will be ableto monitor critical activities and take actionwhen problems occur.

Activities that can improveselection of appropriate TB drugs

• Problem: The TB drug selection committeehas little experience in, or needs updating on,currently accepted therapies such as FDCs(the committee may be the same as theessential drugs committee).

– Activity: Provide specialized training forthe TB drug selection committee in currentlyaccepted therapy including, for example,FDC use, packaging, and function within theDOTS strategy.

– Expected outcome: Standard treatmentguidelines (STGs) are updated with appro-priate therapies for Categories I, II, and IIIpatients.

• Problem: TB or essential drugs selectioncommittee has not updated the STGs for TB inseveral years, and there have been recentchanges in national demographics and TBincidence, or newer therapies have been in-troduced.

– Activity: The selection committee issupported by partners to update the STGsand establishes a regular system for keepingthe STGs current, such as ad hoc meetingsheld at least yearly to evaluate whether anyconditions have changed.

– Expected outcome: STGs are updatedwith appropriate therapies for Categories I,II, and III patients.

• Problem: There is no TB drug selectioncommittee in the country and STGs need tobe established, approved, and adopted.

– Activity: Provide technical assistance toestablish and implement the use of STGs.Where an essential drugs committee exists,use it for this activity.

– Expected outcome: STGs are developed andapproved by the NTP for Categories I, II andIII patients; these may be country-specificSTGs or STGs for the WHO DOTS strategy.

• Problem: Drugs listed in the currentlyapproved STGs are not all on the nationalessential drugs list (EDL).

– Activity: Essential drugs committee issupported by partners to update the EDL withall currently approved TB drugs based onnational STGs.

– Expected outcome: In both vertical anddecentralized TB programmes, having anEDL limits the drugs that can be procuredfor TB and promotes cost-efficiency, efficacyof treatment, and quality assurance activities.

Activities that can improvequantification (estimation)of drug needs

• Problem: Quantification personnel are newto the TB programme and do not understandhow to estimate drug needs using morbiditydata, which is the method supported by WHOand many of its partners.

– Activity: Provide training for the newquantification personnel in both morbidity-and consumption-based methods. Trainingwill include comparison of quantities calculatedby the two methods to improve estimates ofdrug needs.

– Expected outcome: Estimates of TB drugneeds calculated by the new quantification per-sonnel will be more accurate and will minimizestock-outs of TB drugs in the programme.

• Problem: Quantification activities for theNTP were recently decentralized to thedistrict level; personnel are new to TB anddo not understand how to use morbidity data.

– Activity: Provide district personnel withtraining in estimating drug needs using themorbidity- and consumption-based methods,and in other TB programme policies andprocedures that affect them. Establish asupervisory monitoring programme to followtheir progress.

– Expected outcome: The estimates of TBdrug needs calculated by the district personnelwill be more accurate and minimize stock-outsof drugs in treatment facilities in their districts.



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• Problem: Quantification personnel atnational, district, or facility levels areproviding poor estimates of drug needs forprocurement.

– Activity: Provide all appropriate personnelwith technical assistance and practicaltraining in the morbidity- and consumption-based methods.

– Expected outcome: Estimates of TB drugneeds will be more accurate and stock-outsattributable to quantification weaknesses willbe reduced.

Activities that can improveprocurement of TB drugs

• Problem: The procurement department hasnever purchased TB drugs or has littleexperience in purchasing TB drugs on theinternational market, but is responsible fordrug acquisition for the NTP.

– Activity: Seek assistance from TB partnersfor training in purchasing TB drugs, includingidentification and qualification of internationalsuppliers, tendering and contracting, qualityassurance of TB drugs procured from localand international sources, and use ofrestricted tender with supplier prequalifi-cation (reference the DMTB data collectiontool). TB partners will provide technicalassistance during the first few procurements.

– Expected outcome: Personnel will be ableto locate and select appropriate TB drugsuppliers, conduct an international tender,establish a viable contract, and monitorsupplier performance; appropriate TB drugswill be procured.

• Problem: The procurement department hassome experience in purchasing TB drugs onthe international market but needs assistancein selected areas such as locating andprequalifying TB suppliers, assuring qualityof TB drugs, preparing tender documents,conducting and adjudicating tenders,contracting, or monitoring suppliers.

– Activity: From TB partners seek technicalassistance for procurement personnel inspecified areas of procurement; this may

involve training and hands-on assistance.

– Expected outcome: Procurement personnelwill become more proficient in procuring TBdrugs and will be able to reduce drug man-agement problems related to procurement.

• Problem: The TB programme consistentlyorders more drugs than available funds canprocure at any one time; suppliers havegrown weary of this and unit prices have risenon successive tenders to compensate for latepayments.

– Activity: Provide technical assistance forquantification and procurement personnel toimprove their understanding of methods ofreconciling TB drug estimates with availablefunds (estimating on a per-patient basis isbest for TB, for example), and of establishingmechanisms (for example, letter of credit orescrow accounts) to assure suppliers ofpayment.

– Expected outcome: Quantities of drugsordered each time will be only what theprogramme can afford, suppliers will beassured of timely payment, and TB drug unitprices will probably decrease.

• Problem: The country recently received aWorld Bank (WB) loan and the NTP needsto procure TB drugs using a part of the loan;procurement personnel have neverpurchased drugs using a WB loan.

– Activity: Provide technical assistance toprocurement department in following WBprocurement requirements for health sectorgoods, using restricted tender with prequali-fication of suppliers.

– Expected outcome: WB approval will beobtained more rapidly and may prevent stock-outs of TB drugs.

• Problem: The NTP was recently givenfunding by TB partners but does not have thehuman resources necessary to procure thedrugs.

– Activity: Provide information and technicalassistance on using the facilitated procurementactivity of the GDF of the Stop TB partner-ship or procure directly from non-profitsuppliers.

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– Expected outcome: The TB programmewill be able to purchase quality drugs andreceive them in a timely manner so as toprevent stock-outs and promote DOTSexpansion in their country.

Activities that can improvedistribution and stockmanagement within the country

• Problem: There is no established system fordistributing TB drugs to local treatmentfacilities; either the NTP relies on vehiclesfrom other health services or has vehiclesbut seems unable to catch up with deliveryneeds.

– Activity: Provide technical assistance tothe NTP in developing an appropriatetransportation system and delivery schedule,including potential need for capital equipmentsuch as more vehicles.

– Expected outcome: TB drugs will beavailable in appropriate dosage forms andquantities when needed for patient treatment.

• Problem: Local warehouse personnel seemunable to manage stocks so that correct ofdrugs are always available for delivery totreatment facilities when needed.

– Activity: Provide training and technicalassistance in good stock managementprocedures, including documentation of allquantities of drugs moving into the warehouseand from the warehouse to treatment facilities,and calculation of buffer stocks and minimumquantity levels to trigger an order, for example.

– Expected outcome: Stock levels will bemaintained so that needed quantities willalways be available for delivery to treatmentfacilities

• Problem: There has been a significant lossof drugs due to pilferage, expiry, anddeterioration over the previous 2 years.

– Activity: Provide training and technicalassistance in good storage practices such asavoidance of excessive moisture and directsunlight, exclusion of pests, provision ofsecure storage areas, and prevention of drug

expiry using the FEFO (first to expire, firstout) method of stock rotation.

– Expected outcome: Drug losses willdiminish, relieving this expensive burden onthe NTP.

• Problem: The receiving warehouse and thelocal warehouses do not have a managementinformation system (MIS) that will track drugrequirements, drug orders, and existing stocklevels in health facilities; there have beenmany drug stock-outs as a result.

– Activity: Provide technical assistance inestablishing an MIS.

– Expected outcome: Warehouse personnelwill be able to more accurately control themovement of TB drugs from receivingwarehouse to local warehouses and fromlocal warehouses to treatment facilities whenneeded.

Activities that can improveuse of TB drugs

• Problem: Not all prescribers are followingthe STGs approved by the NTP or notconsistently documenting that they usedirectly observed therapy.

– Activity: Provide technical assistance toestablish a prescriber monitoring system(may include periodic documentationreviews, use of indicators, comparison ofdrug quantities consumed versus number ofpatients who should have been treated).

– Expected outcome: Prescribers willunderstand the need to follow STGs asestablished by the programme; number ofpatients treated will be reported; and patientswill be treated more appropriately, leading tofewer relapses and treatment failures.

• Problem: Many patients are not followingthe prescribed treatment regimens and aredeveloping MDR-TB.

– Activity: Provide technical assistance indeveloping and implementing an incentiveplan for all patients to encourage adherenceto the prescribed treatment (may includetraining, recognition in a TB programme



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ceremony as a “successfully treated patient”,or financial reward for successful completionof therapy (2)).

– Expected outcome: Number of relapsesand treatment failures will decrease.

Activities that can improvequality assurance of TB drugs

• Problem: Drug-testing laboratories have fewresources for random testing of TB drugsreceived from local and international suppliers.

– Activity: Provide technical assistance inestablishing the optimum use of resources, suchas use of thin-layer chromatography testmethods, and limiting laboratory testing to themost problematic drugs (e.g. rifampcin in FDCs,or those drugs with quality problems foundduring physical inspection at port of entry).

– Expected outcome: Laboratory testingconcentrates on the most problematic products,offering the best possible quality assuranceprogramme for the NTP with the limitedresources available.

• Problem: Storeroom personnel, patients, andprescribers alike are complaining about thequality of the products they receive, such astoo many crushed tablets, discoloration, orempty blisters (i.e. containing no tablets).

– Activity: Provide technical assistance inestablishing a two-tier TB drug samplingsystem, first to physically inspect productsfor approval of shipments from suppliers, andsecond to collect samples from healthfacilities. Samples collected from the fieldwould be physically inspected and tested inthe laboratory as appropriate. Problematicsuppliers would be identified and then,depending on the nature of the qualityproblems, notified that they may be removedfrom the approved list of suppliers.

– Expected outcome: The number of qualityproblems would diminish.

• Problem: The NDRA has limited resourcesfor registering drugs from new suppliers andmonitoring the quality of drugs in the marketplace.

– Activity: Provide technical assistance tothe NDRA in establishing a targeted pro-gramme of activities such as using fast-trackdrug registration, establishing a model dossierto register drug products from local andinternational sources, or targeting local manu-facturers, distributors, and retail pharmaciesthat have been problematic in the past.

– Expected outcome: Drug registration willbe well controlled and timely and will not delayprocurement decisions, and inspection per-sonnel will use their time more wisely byinspecting known offenders against drug laws.

Activities for conductinga comprehensive assessmentof the TB drug sector

• Problem/situation: There are manyproblems in the private and public TB drugsectors, and previous assessments haveconsisted of only partial reviews; both theNTP and TB partners are interested inidentifying weaknesses of drug selection,procurement, distribution, and use.

– Activity: Use the DMTB tool to compre-hensively quantify and document actualweaknesses in the TB drug sectors (publicand private).

– Expected outcome: The NTP and partnersunderstand specific weaknesses in drug manage-ment and can discuss the appropriate levelsof support and technical assistance needed.

References

1. WHO certification scheme on the quality of pharmaceutical products moving in international commerce: with an updatedlist of participating countries. Geneva, World Health Organization, 1997 (document WHP/PHARM/82.4 Rev. 5).

2. Enablers and incentives in TB control programs. World Bank and Management Sciences for Health, 2001 (draft)

IMPROVINGTB DRUG

MANAGEMENT

AcceleratingDOTS expansion


Stop TBPartnership


WHO/CDS/STB/2002.19

The Stop TB Partnership Secretariatis hosted by the World Health Organization

20, avenue Appia – CH-1211 Geneva 27www.stoptb.org – [email protected]

Fax (+41) 22 791 4886

IMPROVING TB DRUG MANAGEMENT Accelerating DOTS …IMPROVING TB DRUG MANAGEMENT — ACCELERATING DOTS EXPANSION 4 1 Fixed-dose combination products contain two, three, or four TB drugs

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