An Analysis of the Upstream Supply Chain for Second-Line Drugs for Multidrug-Resistant ...

346 Pages·2017·8.3 MB·English

An Analysis of the Upstream Supply
Chain for Second-Line Drugs for
Multidrug-Resistant Tuberculosis
by
Deon Lingervelder
Thesis presented in fulfilment of the requirements for the degree
of Master of Engineering (Industrial Engineering) in the Faculty of
Engineering at Stellenbosch University
Department of Industrial Engineering,
University of Stellenbosch,
Private Bag X1, Matieland 7602, South Africa.
Supervisor: Louzanne Bam
March 2017
Stellenbosch University https://scholar.sun.ac.za
Declaration
By submitting this thesis electronically, I declare that the entirety of the work contained
therein is my own, original work; that I am the sole author thereof (save to the extent
explicitly otherwise stated); that reproduction and publication thereof by Stellenbosch
University will not infringe any third-party rights, and that I have not previously in its
entirety or in part submitted it for obtaining any qualification.
Date: March 2017
Copyright © 2017 Stellenbosch University
All rights reserved
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Abstract
Systematic problems in the supply chain of second-line anti-TB drugs (SLDs) for multi-
drug-resistant tuberculosis (MDR-TB) are well documented and contribute significantly
to the comprehension of the difficulties preventing successful control of the disease.
Though literature contains a wealth of proposed changes to global SLD supply chain
policies, there is a significant research gap related to quantitative modelling of the SLD
supply chain to accurately predict the expected impact of these proposed changes on
the availability of SLDs.
The global SLD supply chain consists of two components: (i) the ‘upstream’ component
which includes all activities from the manufacturing of the active pharmaceutical
ingredient through to the warehousing of drugs prior to shipment; and (ii) the
‘downstream’ component which includes in-country warehousing and delivery of drugs
to various healthcare facilities. A prominent problem in the supply chain, is the erratic
demand patterns, since these prohibit accurate forecasting and effective planning.
Consequently, manufacturers are forced to produce drugs in inefficient batch sizes,
causing higher prices and longer, inconsistent lead times. A possible solution to address
this problem, is the implementation of a large buffer stockpile directed at (i) preventing
stock-outs and treatment interruptions, and (ii) combining and timing orders to permit
current manufacturers to produce medicines more efficiently.
The aim of this study is to model a part of the upstream supply chain of MDR-TB SLDs
and to evaluate the impact of implementing such a buffer stockpile. The supply chain is
modelled using system dynamics and the model is used to evaluate the likely impact
of a range of alternative inventory management policies on the supply chain
performance. Three different SLD formulations are included in the model to ensure that
the recommendations based on this research are robust. These formulations, namely
capreomycin, kanamycin and cycloserine, account for approximately 58% of the total
procurement costs of the current supply chain.
The modelling results indicate that the inventory policies that will most likely lead to the
most significant improvement in the supply chain performance, are the policies that
implement a reorder quantity based on an exponential smoothing forecast of previous
demand, specifically when a smoothing factor of either 0.1 or 0.5 and a high reorder
point are implemented.
This research contributes to the current academic literature by increasing the
understanding of the upstream SLD supply chain, by providing a quantitative evaluation
of the expected impact of suggested changes to the supply chain, and by presenting
an example of an application of the system dynamics modelling approach that is not
common in literature.
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Opsomming
Sistematiese probleme in die voorsieningsketting van tweede lyn anti-TB-middels
(SLDs) vir multi-weerstandbiedende tuberkulose (MDR-TB) is goed gedokumenteer en
maak ‘n aansienlike bydrae om die probleme wat die suksesvolle beheer van die siekte
voorkom, te verstaan. Alhoewel literatuur 'n rykdom van voorgestelde wysigings aan
die globale SLD voorsieningsketting bevat, is daar 'n beduidende navorsing gaping wat
verband hou met die kwantitatiewe modellering van die SLD voorsieningsketting om
die verwagte impak wat hierdie voorgestelde wysigings aan die beskikbaarheid van
SLDs sal hê, akkuraat te voorspel.
Die globale SLD voorsieningsketting bestaan uit twee komponente: (i) die 'stroomop’
komponent wat alle aktiwiteite van die vervaardiging van die aktiewe farmaseutiese
bestanddeel, tot die verpakking van die teenmiddels vir distribusie, insluit; en (ii) die
‘stroomaf’ komponent wat die binnelandse (nasionale) pakhuise en die aflewering van
teenmiddels na verskeie gesondheidsorg fasiliteite insluit. 'n Prominente probleem in
die voorsieningsketting is die dinamiese en wisselvallige aanvraag patrone vir die
teenmiddels, aangesien dit akkurate vooruitskatting en effektiewe beplanning verhoed.
Gevolglik word vervaardigers gedwing om die teenmiddels in onekonomiese
hoeveelhede te vervaardig wat hoër pryse en langer wagtye tot gevolg het. 'n
Moontlike oplossing om hierdie probleem aan te spreek, is die implementering van 'n
groot buffer voorraad wat gerig is op: (i) die voorkoming van onderbrekings in die
behandeling van MDR-TB, deur te verseker dat daar altyd teenmiddels op voorraad is;
asook (ii) om beter tydsberekening toe te laat om die verskeie bestellings te kombineer,
sodat huidige vervaardigers die teenmiddels meer doeltreffend kan produseer.
Die doel van hierdie navorsing is om 'n deel van die ‘stroomop’ voorsieningsketting van
MDR-TB SLDs te modelleer en om die impak wat 'n buffer voorraad op die
voorsieningsketting kan hê, te evalueer. Die model is ontwikkel deur ‘n Stelsel Dinamika
Modellering benadering en word gebruik om die moontlike impak van 'n
verskeidenheid alternatiewe voorraadbestuur beleide op die voorsieningsketting te
evalueer. Drie verskillende SLD formulerings is ingesluit in die model om te verseker
dat die aanbevelings, op grond van hierdie navorsing, robuus is. Hierdie formulerings,
naamlik capreomycin, kanamycin en cycloserine, is verantwoordelik vir ongeveer 58%
van die totale aankoopkoste van die huidige voorsieningsketting.
Die resultate van die modellering dui daarop dat die voorraadbestuur beleid wat meer
waarskynlik sal lei tot die mees beduidende verbetering in die voorsieningsketting, is
die beleide waar die herbestel hoeveelheid bepaal word op grond van 'n
eksponensiële ‘gladstryking’ voorspelling van vorige aanvraag, spesifiek wanneer ‘n
‘gladstryking’ faktor van óf 0.1 of 0.5 en 'n hoë herbestelvlak geïmplementeer word.
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Hierdie navorsing dra by tot die huidige akademiese literatuur deur die begrip van die
stroomop SLD voorsieningsketting te verbeter, deur 'n kwantitatiewe evaluering van die
verwagte impak van voorgestelde wysigings aan die voorsieningsketting te verskaf en
deur 'n voorbeeld van ‘n Stelsel Dinamika Modellering te verskaf, wat nie algemeen in
die literatuur is nie.
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Acknowledgments
I am immeasurably grateful to my study leader, Louzanne Bam. Without her dedication,
guidance, direction and support this research would not have been possible.
I give a special note of thanks to Prashant Yadav for steering us in the right direction,
with regard to data as well as our understanding of the supply chain.
To Adam de Beer, who supported me throughout this thesis more than anyone could
realise, I give very special thanks for the constant encouragement and support in the
preparation of this final report.
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Table of contents Page | ix
Table of contents
Declaration .................................................................................................................................................. i
Abstract ....................................................................................................................................................... iii
Opsomming ................................................................................................................................................ v
Acknowledgments .................................................................................................................................. vii
Table of contents ..................................................................................................................................... ix
List of figures .......................................................................................................................................... xvii
List of tables ............................................................................................................................................ xxi
Nomenclature ....................................................................................................................................... xxv
Chapter 1: Introduction ............................................................................................................................. 1
1.1 Background information ................................................................................................................ 1
1.2 Problem statement ....................................................................................................................... 3
1.3 Aim and objectives ....................................................................................................................... 3
1.4 Boundaries and limitations ........................................................................................................ 4
1.5 Expected contributions ............................................................................................................... 5
1.6 Research design ........................................................................................................................... 5
1.6.1 Research category ................................................................................................................ 6
1.6.2 Research purpose ................................................................................................................ 6
1.6.3 Data acquisition ..................................................................................................................... 6
1.6.4 Data analysis .......................................................................................................................... 7
1.7 Research methodology ................................................................................................................ 7
1.8 Structure of the report ................................................................................................................. 9
1.9 Conclusion: Introduction ............................................................................................................ 10
Chapter 2: Overview of MDR-TB ........................................................................................................ 11
2.1 An introduction to TB and MDR-TB ......................................................................................... 11
2.2 Advancement of MDR-TB ........................................................................................................ 12
2.3 Diagnosis of TB and MDR-TB ................................................................................................. 14
2.4 Treatment of TB and MDR-TB ................................................................................................ 14
2.4.1 Directly Observed Therapy Short Course ................................................................... 18
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