Download 2012 Solution Landscape on Oxytocin and Misoprostol Quality

Postpartum Hemorrhage
2012 Solution Landscape on Oxytocin
and Misoprostol Quality Solutions for
Management of Postpartum Hemorrhage
Acknowledgments
Accelovate-a Partnership in Accelerated Global Health Innovation
Accelovate is a global program dedicated to increasing the availability and use of lifesaving innovations for low-resource settings.
Led by Jhpiego, the Accelovate program began in 2011 as a five-year, United States Agency for International Development
(USAID)-funded program under the Technologies for Health (T4H) grant.
Also available from Accelovate:
Postpartum
Hemorrhage
Rehabilitative
Medicine
Pre-eclampsia
& Eclampsia
Male
Circumcision
Design Challenges promote the development of innovative solutions where appropriate technology is lacking
Solution Landscapes assess what solutions exist
Value Propositions assess the benefits and drawbacks of an array of solutions for our context
Business Cases assess manufacturability and commercial potential
Market Readiness Assessments evaluate a selected technology/solution for market-level readiness factors
Briefs describe technology access and utilization challenges in a topical area and outline Accelovate’s approach
Excel Tools present raw data that implementers may develop for programming and advocacy purposes
Literature Reviews review secondary data, usually to understand a bottleneck
This report is made possible by the generous support of the American people through USAID, under the terms of the
Technologies for Health award AID-OAA-A-11-00050. The contents are the responsibility of the authors and do not
necessarily reflect the views of USAID or the United States Government.
Jhpiego is an international, nonprofit health organization affiliated with Johns Hopkins University. For more than 40 years,
Jhpiego has empowered frontline health workers by designing and implementing effective, low-cost, hands-on solutions to
strengthen the delivery of health care services for women and their families. By putting evidence-based health innovations
into everyday practice, Jhpiego works to break down barriers to high-quality health care for the world’s most vulnerable
populations.
This Solution Landscape was developed in 2012 and does not survey later innovations in the field of postpartum hemorrhage
management.
Suggested Citation: Tanuku, Deepti. 2015. 2012 Solution Landscape on Oxytocin and Misoprostol Quality Solutions for
Management of Postpartum Hemorrhage. Baltimore, MD: Jhpiego. Accessed at: www.jhpiego.org/accelovate.
Published by:
Jhpiego
Brown’s Wharf
1615 Thames Street
Baltimore, Maryland 21231-3492, USA
www.jhpiego.org
© Jhpiego Corporation, 2015. All rights reserved.
Table of Contents
List of Abreviations
iv
1.0 Introduction and Objectives of Solution Landscapes
1
2.0 Methodology
2
3.0 Solution Landscapes Research Findings
3
3.1 Five Main Barriers to Maintaining Uterotonic Drug Quality
3.2 Survey of Innovations Used to Overcome Challenges
4.0 Recommendations
4.1 Selecting Appropriate Solutions: Define Operating Contexts
3
7
9
9
5.0 Conclusions and Next Steps
11
Appendix One: Participants in the Solution Landscapes
12
Appendix Two: List of Interview Guide Questions
13
Appendix Three: Comparing Oxytocin and Misoprostol
17
Appendix Four: List of Innovations Surveyed
19
page iii
List of Abreviations
AMTSL Active Management of Third Stage of Labor
API
Active Pharmaceutical Ingredient
DTTU
Delivery Team Topping Up
MCHIP Maternal and Child Health Integrated Program
MIS Management information system
PPH
Postpartum Hemorrhage
USAID United States Agency for International Development
page iv
USP
United States Pharmacopeia
WHO
World Health Organization
1.0 Introduction and Objectives of Solution Landscape
According to the 2012 Millennium Development Goals Report
launched in New York by the Secretary-General on 2 July 2012,
decreases in maternal mortality are far from the 2015 target.
Meeting the remaining targets, while challenging, remain possible.
One way in which this can be achieved is in addressing one of
the largest contributing factors of maternal mortality: postpartum
hemorrhage (PPH).
Uterotonic drugs are critical for reducing high rates of maternal
mortality in the developing world. Although the two main
uterotonic drugs recommended—oxytocin and misoprostol—are
largely considered available at low-cost, these drugs are susceptible
to breakdowns in quality that render them either unavailable
when required or ineffective when used. This reduces the ability
of a health system to prevent PPH and save mothers’ lives.
Part of the solution lies in looking at innovative solutions to
overcome barriers to assuring the quality of uterotonics, as well
exploring solutions that can both boost and ensure the quality
of oxytocin and/or misoprostol, thereby boosting its efficacy and
impact for PPH prevention.
These drugs are
available at low cost
but susceptible to
breakdowns in
quality, reducing the
ability of a health
system to save
mothers’ lives.
This document is a solution landscape of innovations, including
devices, products, and processes that are in use or in development
to ensure the quality of two uterotonic drugs used to combat
PPH, a leading cause of maternal mortality worldwide. Desk
research, coupled with key informant interviews with Accelovate
program partners, uncovered the barriers and challenges to
quality faced by both oxytocin and misoprostol. Those barriers are
summarized here, in addition to a survey of innovations that aim
to tackle key challenges. The associated successes and challenges
for each innovation, and recommendations for Accelovate to
further prioritize the innovations that will be supported in the
coming years, are also included. The ultimate aim of the project
is to support innovation that assures the quality of oxytocin and
misoprostol throughout the supply chain and at the time of use.
This analysis was supported by Jhpiego’s Accelovate program, a
five-year USAID award for advancing global health innovations.
page 1
2.0 Methodology
This document is a compilation of 2012 desk research and key
informant interviews, reaching out to field staff and program
partners to collect information on quality assurance of oxytocin
and misoprostol at different points in the chain. The interviews
reached out to a wide range of stakeholders to gauge “what is out
there,” and included health care providers as well as representatives
of companies making products, nongovernmental organizations,
and facilities using different tools.
We restricted our Solution Landscape to the two uterotonic drugs
of oxytocin and misoprostol, but where it was appropriate we
also asked questions regarding ergometrine, since that was a drug
often mentioned and is often substituted as a second- or even
first-line drug in cases of oxytocin and misoprostol stock-out. In
one case, an interviewee mentioned using prostodin—a drug that
belongs to the class of prostaglandins and is used to minimize
blood loss from the placental site. Since it was only mentioned
in one interview and is not normally recommended in the course
of active management of third stage of labor (AMTSL), we did
not evaluate that drug extensively in this solution landscape. We
also did not explore non-uterotonic drug interventions used for
PPH treatment, including: uterine tamponades, blood products,
or anti-shock garments—an exploration of which is beyond the
scope of this analysis.
page 2
i
i
See Appendix One: Participants in
the Solution Landscape.
See Appendix Two: The List of
Interview Guide Questions.
3.0 Solution Landscape Research Findings
3.1 Five Main Barriers to Maintaining Uterotonic Drug Quality
To assess barriers to maintaining effective uterotonic drug quality
in low-resource settings, this Solution Landscape determined
breakdowns to drug quality in oxytocin and misoprostol, and also
explored how that drug potency erodes as drugs are packaged,
transported, stored, and used. While these drugs are frequently
mentioned together, there are certain issues and aspects that are
specific to each of the two drugs.
i
These issues are outlined in
Appendix Three: Comparing
Oxytocin and Misoprostol.
The most significant insight uncovered during desk research and
key informant interviews is that uncertainty regarding potency of the
drug is the most pervasive, frequently cited barrier to maintaining
uterotonic quality. While trying to assess the availability,
affordability, and quality of both oxytocin and misoprostol, key
informant interviews reported the widespread perception that
both drugs were relatively available and affordable—although
oxytocin is definitely seen as being more available and affordable
than misoprostol. However, it was more difficult to confirm that
these drugs were available at appropriate quality at point of use.
Beyond anecdotal evidence of women receiving two, three, or four
times the recommended dosage with little effect, drug quality studies
have largely focused on assessing quality in binary measurement
terms (yes/no availability or yes/no sufficient active ingredient at time
of purchase). However, in cases where drug potency erodes over time
as it travels from the factory to the point of use, providers have little
information regarding at what stage drugs are losing their potency.
This lack of information makes it difficult to assess whether, for
example, improved cold storage solutions alone could help improve
oxytocin drug quality—and, in turn, have an increased impact on
saving lives. Not knowing if the drugs reaching the clinic are in fact of
high quality or if that quality has already been compromised during
transportation renders a singular focus on improving cold storage
solutions ineffective. Put another way, as one interviewee mentioned,
“There can be no innovation without information and awareness.”
It is unknown
whether improved
cold storage alone
improves oxytocin
drug quality, thereby
potentially saving
lives.
Even a cursory review of the literature reveals several potential
barriers to uterotonic quality. In a report entitled, “Medicines for
Maternal Health,” prepared for the United Nations Commission
on Life-Saving Commodities for Women and Children, several
key barriers to uterotonic drug quality were mentioned.
page 3
Verifying desk research with key informant interviews, the
Solution Landscape was able to identify five main breakdowns
to drug quality, captured in Figure 1. The three top areas of
concern—as measured by frequency of citation by key
informant interviewees—were: 1) challenges in transport and
distribution, 2) inadequate storage conditions (for oxytocin), and
3) inconsistencies at point of use.
Faulty or Easily Degradable Packaging: Key informant issues suggest
that one major packaging error comes from inconsistent and
sometimes inaccurate product labels, specifically when it comes
to instructions regarding optimal storage conditions for the drug.
Several interviewees reported seeing the words “Does Not Require
Refrigeration” on packages of oxytocin, which run counter to
current World Health Organization (WHO) recommendations.
Interviewees suggested that this confusing instruction routinely
challenges the integrity of the drug as providers do not refrigerate
the drug. For misoprostol, many interviewees reported drugs
being available in vacuum-sealed, single-foil blister packs that
provide moderate protection from light and humidity. While
not as effective as double-foil packaging that can provide full
protection from excess light and humidity, there were few
complaints questioning the integrity of misoprostol packaging.
As indicated later in the survey of innovations, concerns in this
category can be addressed by developing heat-stable or alternateive
drug formulations that can withstand faulty or easily degradable
packaging. In addition, when it comes to misoprostol, often
drugs are packaged for alternative uses and providers are forced
to calculate appropriate dosage levels for their particular use.
Misoprostol packaging specific to PPH use—in either 600 mcg
or 800 mcg packages—is not always available and often leads to
inadequate dosing errors in the field.
Inefficient Procurement Processes: Several factors that contribute
to inefficient drug procurement were mentioned, including:
improper drug inventory management practices and protocols
at the clinic level that lead to inaccurate forecasts, improper
surveillance and tracking of deliveries that lead to unfulfilled or
delayed procurements, a centralized drug purchase and ordering
system that makes it difficult to place and approve orders for
replacement drugs, and a lack of available funds or a delay in
page 4
i
The full list has been included in
Appendix Four: List of Innovstions
Surveyed.
Figure 1: Five Main Breakdowns to
Uterotonic Drug Quality in Low-Resource
Settings
High drug quality
Controlled
and regulated
production
Breakdowns to drug quality
Faulty
packaging
Ineffecient
procurement
processes
Challenges
in transport
and
distribution
Inadequate
storage
conditions
Inconsistencies
at point
of use
releasing funds so that drug purchases can occur in a timely
manner. All of these challenges lead to persistent stock-outs or
delivery of expired stocks of both oxytocin and misoprostol.
Challenges in Transport and Distribution: Both oxytocin and misoprostol
are routinely distributed in unrefrigerated trucks or placed
directly in the sun when transported by informal means of public
transportation. For oxytocin, transportation without refrigeration
serves as the first major breakdown in quality. While oxytocin can
survive for short periods without refrigeration, these periods are
not regulated or noted by the health clinics upon receipt of the
drug, complicating any understanding of how much potency is
lost during transportation. For misoprostol, the drugs are often
kept in direct sunlight, which threatens to degrade the active
pharmaceutical ingredient (API), making it an equally relevant
challenge for both drugs.
Inadequate Storage Conditions: Cited the most frequently, key informant
interviewees highlighted the lack of cold storage solutions at the
clinic level, due equally to a lack of refrigerators and a lack of
electricity to power those refrigerators. When refrigerators are
available, space limitations mean that oxytocin competes for
shelf space with vaccines and blood. Frequently, interviewees
mentioned the failure of previously used cold storage facilities—
namely, solar-powered refrigerators that stopped working after the
initial battery wore out, or paraffin- or gas-powered refrigerators
that required frequent refills that became too costly and were
eventually abandoned. Either way, it is clear that few interviewees
could identify robust, low-maintenance cold storage solutions
that can withstand conditions in peripheral health centers.
Inconsistencies in Point of Use: Few quality protocols are in place to
monitor or check for quality upon the receipt of a drug at the
district and sub-district level, and this issue is compounded by a
lack of training and provider awareness on what constitutes goodquality drugs, how to maintain appropriate storage conditions,
and the inability of health care professionals to test for drug
potency beyond checking for expiration dates. There are also
several inconsistencies in use and dosage of drugs that persist
because adequate time and resources have not been invested to
update guidelines for drug use or provide continuin education and
page 5
training updates—for both pre-service and in-service training.
These variations in provider quality mean that even if two doses of
the same drug arrive at a clinic with similar potency levels, there
is room for variation in quality depending on varying practices
adopted by the providers.
Additional issues that came up are the following:
nn
nn
nn
nn
page 6
Replacing first-line uterotonics with ergometrine: Stock-outs of
oxytocin and misoprostol necessitate their substitution
by another drug—namely, ergometrine, whose use is
contraindicated in some patients and therefore is not the
preferred uterotonic agent used during AMTSL.
Inter-manufacturer variability leading to inaccurate dosage instructions:
When certain manufacturers produce misoprostol for the
alternate application of medical abortion, the provided
dosing instructions become invalid for the context of PPH.
Health care providers believe they can simply recalculate the
new dosage, but this can lead to incorrect and harmful doses
administered to mothers in labor.
Hoarding drugs: Non-use of oxytocin and/or misoprostol
at clinics even when oxytocin stocks are available at the
medical facility is fueled by uncertain and inconsistent drug
procurements, leading to providers “keeping the drug until
we really need it” and not administering it as a standard
part of AMTSL.
Counterfeit drugs: The availability of counterfeit drugs is
estimated to be up to 10% in some areas. Generally
speaking, oxytocin procurement is more controlled and has
less demand on the black market, so it is not as lucrative
a target for counterfeit drugs. However, misoprostol
procurement is often not as controlled, and it has more
demand because of its use in medical abortion. As a result,
the threat of counterfeit drugs is greater for misoprostol
than oxytocin.
i
For an analysis of barriers to
medicine quality, see “Medicines
for Maternal Health: Key Data
and Findings,” prepared for the
UN Commission on Life-Saving
Commodities for Women and
Children. (www.unfpa.org/
publications/medicines-maternalhealth)
nn
nn
Infrastructure and security issues in transportation: These issues
include the difficulty of getting drugs out to peripheral
clinics without motorable roads or bandits who routinely
pilfer vehicles passing through the area.
Use of oxytocin other than for AMTSL: Oxytocin can be used for
stimulating milk production in cows, transforming its
use from health assurance to livelihood generation, and
potentially threatening stocks in peripheral health clinics.
In addition, traditional birth attendants use the drug to
expedite labor. Misuse of oxytocin in these two ways can be
mitigated by adequate supervision, but health personnel are
not always able to prevent such instances of oxytocin misuse.
3.2 Survey of Innovations Used to Overcome Challenges
The literature review and key informant interviews provided some
general methods of effective drug management to help assure the
quality of uterotonic drugs:
nn
nn
nn
nn
nn
nn
Quantify the unmet need for maternal health medicines
so that manufacturers can adequately scale up to meet
that need and calculate cost estimates to achieve universal
coverage
Explore bulk purchasing mechanisms so that prices remain
low while at the same time creating more attractive markets
for manufacturers
Decrease the prevalence of substandard medicines
Support new product development and delivery innovations
that encourage widespread usage of the drug
Strengthen management information systems to ensure
medicine availability and avoid stock-outs, but not too far
in advance to risk expiration
Improve knowledge and skills of health care providers and
supply chain managers
page 7
In terms of specific solutions, we found several organizations
working on solutions either directly related to improving
oxytocin and/or misoprostol quality or working on comparable
technologies that could potentially be adapted to improving
uterotonic drug quality. We have organized those solutions into
the following categories:
nn
Improving clinic-level quality
nn
Visible markers of potency
nn
Tools and tests for quality assessment
nn
Portable, off-grid cold storage solutions
nn
Controlled drug distribution systems
nn
Systematic and e-tracking of quality and demand
nn
page 8
Experimenting with new formulations and presentations of
the drug
i
These innovations are described
in detail in Appendix Four: List of
Innovations Surveyed.
4.0 Recommendations
As mentioned earlier in this report, the three top areas of concern
were: insufficient cold storage, inconsistencies at the point of use,
and inefficient transport and distribution systems, as measured
by frequency of citation by key informant interviews. However,
preceding these concerns was the generalized observation that
information is still lacking about the point at which the quality
of uterotonics erodes. As we move toward recommended solutions
to enhance oxytocin and misoprostol quality, it is critical to first
address this issue through data quality audits that test the breakdown of
quality along the supply chain, pinpointing the point(s) in the chain
where the biggest drop-offs in drug potency occur.
In order to perform these data quality audits consistently, as
well as to enhance drug quality in general at the point of use,
the ability to test the quality of drugs at various points along the
chain—from production to point of use—is critical. To be able
to offer affordable tools and tests for quality assessment, cheap testing
that is robust and easily administered in a decentralized manner
is one extremely effective innovation being explored. In the
context of this Solution Analysis, United States Pharmacopeia
(USP) was interviewed regarding the MiniLabs technology,
which is a method of measuring the quality and potency of drugs.
Currently being used for anti-retrovirals and anti-malarials, this is
a technology that could be adapted into a simplified, point-of-use
testing mechanism for maternal health drugs as well.
Drug quality
audits must test
the breakdown of
quality along the
supply chain in
order to pinpoint
drop-offs in
potency.
4.1 Selecting Appropriate Solutions: Define Operating Contexts
Identifying the appropriate level of implementation—whether
national or local—is critical in selecting the appropriate solution.
So is understanding whether process or product innovations are
the most appropriate for the environment and the context in
which they will be implemented. To support this statement, each
of the innovations listed has been categorized according to two
parameters:
nn
Process versus product innovation
nn
National versus local implementation
page 9
It is the recommendation of this Solution Analysis to define unique
operating contexts to assess which combination of those parameters
make the most sense. In some contexts, a national-level product
innovation is the best strategy and could be considered in places
where widespread drug quality is of great concern and there
needs to be a centralized mechanism to ensure that drugs are not
counterfeit. In other contexts, where purchasing of drugs is more
decentralized, it may make more sense to adopt a localized process
innovation that can fortify quality controls and quality-check
protocols to ensure that peripheral health clinic staff are doing the
best they can to evaluate and maintain the quality of the drug at
the local level. Before entering each country to scale innovations,
assessing countries in this way will help select the most effective
and appropriate solution. Figure 2 summarizes the innovations
surveyed based on these two parameters.
Figure 2: Classification of Innovations that Address Oxytocin and Misoprostol
Quality
Process Innovation
page 10
Product Innovation
National-Level
Implementation
SURE Essential Medicines
Program, community distribution
of misoprostol, improved drug
management training systematic,
MIS for better demand forecasts,
JSI Delivery team topping up, text
message reminders for malaria
treatment
Vaccine vial monitors, cold
chain monitor, Freeze Watch,
Stop!Watch, DT and TT shipping
indicator, Sproxil, PharmaCheck,
PharmaSecure, mPedigree, aerosol
oxytocin, oxytocin in Uniject, health
stable oxytocin, SureChill, paraffin/
gas-powered refrigeration, ice lined
refrigerators, Chotukool, mini-labs
Local-Level
Implementation
Health worker education on
importance of cold chain, quality
control protocols at the clinical level,
village reach, Cola Life, Riders for
Health, Living Goods
Diagnostics for All, Blood Safety
Microchip, CoolComply, human/
kinetic-powered refrigeration,
FrioUK, Zeer Pots, VacTrax, vaccine
delivery kits
Innovation is
needed to develop
testing approaches
that are inexpensive,
robust, and easily
administered in
a decentralized
manner.
5.0 Conclusions and Next Steps
Whatever solutions are found, it will be necessary to develop and
scale devices, products, and processes that meet the needs of target
populations.
However, the challenge is not just one of developing a pipeline
of innovation, but also concurrently developing the capability of
the health systems to absorb new innovations within appropriate
timeframes.
Other factors are equally important. Getting buy-in from country
governments from the very beginning is critical to introducing
a successful project or product that will eventually be sustained
in the country without donor/outside assistance or influence.
This means building relationships between different units of the
ministry of health to create effective linkages in complicated,
nuanced environments.
Alongside a pipeline
of innovation, we
must develop the
capability of health
systems to absorb
new innovations
within appropriate
timeframes.
Ultimately, adopting a systems-based, contextual approach is
crucial for creating and scaling low-resource innovations that
make the most sense in each operating context.
page 11
Appendix One: Participants in the Solution Landscape
#
page 12
Point of Contact
Name of Partner
Org/Agency
Location
1
James BonTempo, Team
Leader, Information Services and
Technology Support
Jhpiego
Baltimore, MD
2
‘Dipo Otolorin, Country Director,
Nigeria
Maternal and Child Health Lagos, Nigeria
Integrated Program
(MCHIP) Field Office
3
Bulbul Sood, Country Director,
India
Jhpiego
Delhi, India
4
Soumyadipta Acharya,
Accelovate Co-Research Technical
Director
Engineering/Innovation
Institutions
Baltimore, MD
5
Sheena Currie, Senior Maternal
Health Advisor, Global Program
Operations
Jhpiego/MCHIP
Washington, DC
6
Somesh Kumar
Jhpiego
Delhi, India
7
Shabana Zaeem, Country
Director, Pakistan
Jhpiego
Islamabad, Pakistan
8
Rosemary Kamunya
Jhpiego
Nairobi, Kenya
9
Usha Kiran Tarigopula
Bill & Melinda Gates
Foundation
Delhi, India
10
N. Taylor Thompson
PharmaSecure
Cambridge, MA
11
Shawn Sarwar
Vax Trac
Washington, DC
12
Nancy Kidula
Jhpiego
Nairobi, Kenya
13
Carmen Sheehan,
Program Officer, MCHIP
MCHIP
Washington, DC (and
field experience in
Pakistan, Afghanistan,
South Sudan, and
Ethiopia)
14
Beth Yeager
MSH/SIAPS
Washington, DC
15
Kusum Thapa, Maternal Health
Technical Advisor
MCHIP
Kathmandu, Nepal
16
Aditya Dev Sood and Divya
Datta
Center for Knowledge
Societies
Bihar, India
17
Tricia Morente
Institute for Healthcare
Improvement
New York, NY
18
Pam Lynam, East and Southern
Africa, Global Program Operations
Jhpiego
Nairobi, Kenya
19
Leah Thayer, Country Director,
Uganda
Jhpiego
Kampala, Uganda
20
Emmanuel Byaruhanga
Jhpiego
Kampala, Uganda
21
Patrick Lukalay, Souly
Phanouvong, Victor Pribluda
USP - US Pharmacopia
Convention
Washington, DC
Appendix Two: List of Interview Guide Questions
Section 1: Current Oxytocin and Misoprostol Practices
1. What is your definition of postpartum hemorrhage (PPH)?
By this definition, how many cases of PPH do you or your
program staff see in a given year?
2. Do clinical protocols currently in place for the prevention
and treatment of PPH include active management of PPH
using oxytocin and/or misoprostol?
If Yes, Skip to Question 3.
If No, a) What are the reasons you do not use these two drugs?
b) What other drugs/alternative methods you use?
3. Please describe your experience using oxytocin and/or
misoprostol, specifically:
Packaging
• What packaging does the drug come in?
• What challenges have you noticed related to their packaging?
• Does misoprostol generally come in a single or double aluminum foil?
Procurement
• How are these drugs procured by the clinic?
• What procurement protocols are in place for ordering each drug,
including prescriptions for choice of manufacturer?
Transport
• How are these drugs delivered to your clinic?
• What quality checks does your clinic do upon receipt of the drugs?
Storage
• How are these drugs stored in a clinic or other health facility setting?
• What protocols exist for their storage?
Patient Demand
• Is the patient demand for this drug?
• Do patients purchase this drug on their own?
• Have you noticed any resistance or patient aversion to using either of
these two drugs?
Section 3: Barriers and Challenges in Drug Quality Assurance
4. What are your general impressions of oxytocin and/or
misoprostol as it is used in the field, with regard to:
Availability
• Are these drugs considered widely or easily available?
Affordability
• What is the per-unit cost of oxytocin and/or misoprostol for patients? For
a hospital?
• Is it common for these drugs to not be used because of being high-cost?
Quality
• What is the perceived quality or effectiveness of these drugs when you use
them?
• Have you noticed instances of altering administered dosage (higher/lower)
because the recommended dose does not have the requisite effect?
• What quality checks does your clinic do upon receipt of the drugs?
page 13
5. In your opinion, what are the main challenges to maintaining
drug quality at different points in the supply chain?
(For Interviewer: if the interviewee struggles to enumerate issues,
probe for the following reasons for drug quality breakdown)
Unclear demand: drug stock-outs and expiration stemming
from poor quantification of need, unclear demand,
inadequate forecasting tools
Lack of data systems: to monitor and programs unable to plan
for purchase and use
Inefficient transport and distribution infrastructure: leading to breaks
in cold chain, poor storage conditions
Counterfeit drugs: prevalence of fake drugs, basic access to
safe, high-quality medicines hindered by complicated drug
registration processes
Poorly defined protocols: lack of quality assurance protocols
upon receipt of drug to clinic
Need to train providers: inadequate knowledge and skills of
health care providers and supply chain managers
Gaps in funding and financing: gaps in funding at the national
level impacting purchase and availability of drugs, lack of
interest to include supplies in budgets, slow release of funds
to central stores
Weak national policies and implementation: failure of ministry to
disseminate policy information to facilities, medicines not on
the national WHO Essential Medicines List
Politics of abortion: in the case of oxytocin and misoprostol only
If unaddressed, also ask:
6. Could you comment on issues in measuring quality at
different points in the supply chain?
7. What tools or protocols have you seen in place to maintain
an effective cold chain, particularly in rural areas?
page 14
Section 4: Status of Current Solutions and Future Opportunities
8. Are you aware of existing and emerging technologies that
address the challenges in achieving quality, widespread
distribution, and sustained use of oxytocin and misoprostol?
If Yes, Proceed to Question 9
If No, Skip to Question 10
9. Please describe your knowledge of this technology/
innovation with regard to:
Status of
Technology
• Is this technology existing or emerging?
• Where is it in the development pipeline?
Manufacturing
and Intellectual
Property
• Is there a manufacturer? Who? Where?
• Is there appropriate capacity for production (e.g., production
capabilities, quality product, and appropriate production output)?
• Who owns the license/patent for the product?
• What barriers exist in the production and distribution of the technology?
• Is the technology difficult to manufacture?
• Does it require a new systems framework?
• Are manufacturing incentives used?
Cost and Cost
Drivers
• What is the unit cost?
• Describe important issues (e.g., barriers) that influence the cost of the
technology.
• Is it considered affordable by those purchasing it? And/or cost-effective
for health systems?
Delivery Channels
• How does/can the technology reach the consumer? What are the
bottlenecks in the supply?
• How does the distribution of the technology involve the private and
public sectors?
• Who are the buyers of the technology (e.g., end user, donors, host
governments)?
• In what setting (i.e., hospital, clinic, or home) is the technology
acquired and used by the consumer?
• How does the end-user acquire the technology (e.g., public/private
sector program)?
• Are there alternatives for the supply of the technology (e.g., sources of
necessary materials)? Is there an existing system for the distribution of
the technology?
Business Models
• How can this technology be sustainable and commercially viable in the
long term?
• Are there ways in which this product/intervention could become
independent of long-term donor support?
• Are there social entrepreneurship models/public-private partnership
models that could sustain this in the long term? Have there been
previous attempts along those lines?
• Are there existing models of social entrepreneurship that could be
applicable to this context?
page 15
Regulatory
Barriers
• Describe any factors that prevent the technology from entering the
market and prevent uptake.
• Are there any policies that conflict with the uptake of the technology?
• Has the product received necessary approvals (e.g., Food and Drug
Administration, WHO lists, UNICEF approval)?
• Does the technology require training?
Training Barriers
• Does the technology require an investment in human resources?
User Demand
• What is the current interest in and use of the technology and by whom?
• What is the product attractiveness from user perspective?
• What is the market penetration/coverage of categories and the
individual technologies?
• Is adaptation of the technology needed?
• What are the barriers or disincentives to use?
• Is market shaping required?
• Is there a need for social/behavior change marketing)?
• Are there existing financing mechanisms for technology uptake (e.g.,
micro-grants for small business, vouchers)?
10.Are you aware of any of the following technologies and
solutions being used?
Labels that indicate drug potency/quality, such as: vaccine vial monitors
Low-cost cold chain maintenance solutions, such as: FrioUK,
Chotukool
New distribution models, such as: Village Reach, Cola Life
Tracking of counterfeit drugs, such as: PharmaCheck, PharmaSecure,
mPedigree, Sproxil
Drug delivery, such as: PATH’s pilot program for Oxytocin in
Uniject
Use of Radio-Frequency Identification or m-Health
technologies to track product demand, distribution, and
use, and to inform supply chain forecasts
11.In your opinion, what is still needed in the way of innovation,
tools, and processes to address the barriers named earlier in
this interview?
12.When thinking about rural settings and the barriers to
quality uterotonics in the field as discussed earlier, what
do you think is the most effective way to combat PPH?
Is it through the use of uterotonic drugs like oxytocin/
misoprostol, or are other options (balloon intrauterine
tamponades, anti-shock garments, etc.) better fits?
page 16
Appendix Three: Comparing Oxytocin and Misoprostol
Oxytocin Introduction
Oxytocin is the first-line drug of choice recommended during
active management of the third stage of labor (AMTSL) for
prevention of postpartum hemorrhage (PPH). It also serves
to assist the uterus in clotting the placental attachment point
postpartum. It requires refrigeration to remain stable at the
following temperatures:
Temperature
Stability of Oxytocin at Corresponding
Temperature, WHO Guidelines
2°C–8°C
3 years
Below 21°C
2 years
25°C
1 year
30°C
6–12 months
40°C
1–2 weeks
Challenges Specific to Oxytocin
nn
nn
nn
By and large, oxytocin is widely available and relatively
cheap, but stock-outs still remain because of inaccurate
forecasting, hoarding of drug, etc.
Oxytocin is the first-line preferred drug and is on country
Essential Medicines Lists
The big problem remains the stability of uterotonics in
tropical climates
nn
Storage under refrigeration is between 2°C–8°C
nn
Effects of temperature on corresponding shelf life
nn
Packaging and storage requirements
nn
How it is used in the field—prefilled in syringes
Misoprostol Introduction
Misoprostol is a low-cost, off-patent drug that is now being used
in some settings to prevent PPH. Its other core features are that it
does not require refrigeration (it is an evidence-based alternative
to oxytocin and ergometrine, which both require cold chain) and
that it is taken orally and so can be administered by all kinds of
providers.
page 17
Challenges Specific to Misoprostol
nn
nn
nn
nn
nn
page 18
This drug has not been used for as long as oxytocin
Although it is a second-line drug, often other drugs are
chosen in its stead
This is not on every country’s Essential Medicines List and
may not be as readily available
Although this drug is more stable in tropical climates, it can
still degrade in conditions of high sun and humidity
Packaging and storage requirements—requires foil because
of degradation with light and humidity
nn
How it is used in the field—tablets or rectally
nn
Adoption of community distribution of misoprostol
Appendix Four: List of Innovations Surveyed*
#
Innovation
Issue
Addressed
Process or
Product
Local or
National
Inconsistencies
at point of use
Process
Local
Description
Implementation
Group and
Status
Improving Clinic Level Quality
1
Health worker
education on the
importance of cold
chain
Increase health care provider education—traditional
Various
birth attendants, community health workers, providers at
the clinic and hospital levels—on appropriate oxytocin
drug management practices (and AMTSL protocol).
2
Text message
reminders for
malaria treatment/
incentivizing through
providing cell phone
airtime
Process
National
Individuals enrolled in program with reminders to take
artemisinin-based combination therapies for malaria in
Uganda, Kenya, and Zambia.
Innovations for
Poverty Action and
Clinton Health
Access Initiative, in
progress (selected
country studies)
3
Quality control
protocols at the clinic
level
Process
Local
Increase clinic-level training protocols upon receipt
of drug so that those using the drug (traditional birth
attendants, community health workers, providers at the
clinic and hospital levels) check for drug expiration in a
systematic way.
Various
4
SURE Essential
Medicines Program
Process
National
MSH, in progress
USAID-funded program, Securing Ugandans’ Right for
(project 2009–
Essential Medicines (Uganda SURE) working on ensuring
adequate quantities of good-quality essential medicines and present)
health supplies by strengthening the national pharmaceutical
supply system—includes improving Uganda’s regulatory
framework and supporting supply chain management at
national, district, and sub-district levels.
Visible Markers of Potency
5
Vaccine vial monitors Uncertainty
Product
regarding the
potency of drug
National
Vaccine vial monitors are thermochromic labels put on
vials containing vaccines that give a visual indication
of whether the vaccine has been kept at a temperature
which preserves its potency.
6
Cold-chain monitor
Product
National
A cold-chain monitor is used to show exposure to
WHO, product
temperatures above the safe range during transportation development
and storage. It has an indicator that responds to two
complete
different temperatures: the first part (marked ABC)
responds to temperatures above +10ºC; the second part
(marked D) responds to temperatures above +34ºC.
The indicator is mounted on a card.
7
Freeze Watch™
Product
National
Freeze Watch is an irreversible temperature indicator.
It consists of a white backing card and a small vial
of red liquid, both enclosed in plastic casing, with an
adhesive strip on the back. If Freeze Watch is exposed to
temperatures below 0ºC for more than one hour the vial
bursts and the red liquid is released, staining the backing
card. Freeze Watch is used to warn of freezing and is
packed with DTP, TT and DT vaccines (freezing point
-6.5ºC), and hepatitis B vaccine (freezing point -0.5ºC).
WHO, product
development
complete
WHO, product
development
complete
* This Solution Landscape was developed in 2012 and does not survey later innovations in the field of postpartum hemorrhage management
page 19
#
Innovation
Issue
Addressed
Process or
Product
Local or
National
Description
Implementation
Group and
Status
8
Stop!Watch
Product
National
This device combines the Monitor Mark™ indicator from WHO, product
the cold-chain monitor with Freeze Watch. It is used to development
monitor temperatures in a refrigerator over time.
complete
9
DT and TT shipping
indicator
Product
National
This device consists of a blue card with a temperaturesensitive dot in the center. It does not require activation and
the dot turns from silver-grey to black instantaneously at
temperatures above +48ºC. The change is irreversible.
Local
Creating low-cost, easy-to-use, point-of-care diagnostics DFA, private
nonprofit enterprise
designed specifically for the 60% of the developing
world that lives beyond the reach of urban hospitals and
medical infrastructures.
WHO, product
development
complete
Tools and Tests for Quality Assessment
10
Diagnostics for All
Uncertainty
Product
regarding the
potency of drug
11
GPHF-MiniLabs
Product
Local/
national
A mobile mini-laboratory for rapid drug quality
verification and counterfeit medicines detection
protecting the health of millions of people anywhere in
developing countries.
Global Pharma
Health Fund
(GPHF), a charitable
organization funded
by Merck
12
Blood Safety
Microchip
Product
Local
A blood safety microchip that assesses the safety
of donated blood used for transfusions. The chip is
a miniature, quick, point-of-care device that tests
for blood-borne infections using enzyme-linked
immunoassay and nucleic acid test kits.
The Regents of
the University of
California, product
still in development
Product
National
Solar-powered compression refrigerators that run on
a battery charged by photovoltaic cells, which convert
sunlight to energy.
WHO, product
development
complete
Portable, Off-Grid Cold Storage Solutions
page 20
13
SureChill
Inadequate
storage
conditions
14
CoolComply
Product
Local
CoolComply is a solar-powered wireless detection
system that monitors the doses and temperature of the
medication, relaying readings via wireless to local health
care workers to track treatment and intervene when
necessary.
Innovations in
International Health
at MIT, partnered
with the Global
Health Committee
and Massachusetts
General Hospital,
product in
development
15
Human-powered
refrigeration
Product
Local
Human-powered refrigeration (including those powered
by pedaling, and kinetic energy captured while walking)
are in various forms of development.
Various, products in
development
16
FRIO® insulin
cooling case
Product
Local
The FRÍO insulin mini wallet is an evaporative cooling
FrioUK, product
unit purposely designed to keep insulin cool within safe development
temperatures of 18–26°C (64.4–78.8°F) for 45 hours, completed
even in a constant environmental temperature of 37.8°C
(100°F).
Local or
National
Paraffin- or gaspowered refrigerators
Product
National
Paraffin- or gas-powered absorption refrigerators with a
heating unit in the back.
Various, product
development
completed
18
Zeer Pots
Product
Local
Locally produced clay pots used as an off-grid, portable
cooling device; two pots are nested within each other
with wet sand packed in between, which extracts heat
from the inner chamber when wet. This keeps the
chamber at 25ºC.
Local groups and
Practical Actions,
product development
completed
19
Chotukool
Product
National
Cheap, economical, portable cooling device that can
work off-grid (without electricity) for hours.
Godrej, a private
for-profit company
(India), Product
development
completed
20
Vaccine delivery kits
Product
Local
A portable kit transported by community health workers
(auxiliary nurse midwives in the Indian context) to help
efficient and higher-quality delivery of immunization
services.
Center for Knowledge
Societies (CKS),
product prototype
completed and in
testing
21
Ice-lined
refrigeration
Product
National
Ice-lined refrigerators are used to maintain vaccine
storage temperature for up to five days.
Various
Process
National
Zimbabwe’s DTTU distributes contraceptives, test kits,
JSI, Zimbabwe
anti-malarial drugs, and other health products to each of National Family
the country’s 1,600 public health facilities.
Planning Council, and
the UK Department
for International
Development operate
and manage the
DTTU system, in
progress
Innovation
17
Issue
Addressed
Implementation
Group and
Status
Process or
Product
#
Description
Controlled Drug Distribution Systems
22
Delivery Team
Topping Up (DTTU)
Challenges in
transport and
distribution
23
VillageReach
Process
Local
In 2001, VillageReach launched an initiative to ensure
prompt and universal access to vaccines and related
medical supplies in Mozambique. The VillageReach
model is currently being implemented in 251 health
centers covering a population of over 5.2 million.
Village Reach,
a private social
enterprise, in
progress
24
ColaLife
Process
Local
ColaLife is working in developing countries to bring
Coca-Cola, its bottlers, and others together to open up
Coca-Cola’s distribution channels to carry social products
such as oral rehydration salts and zinc supplements to
save children’s lives.
Cola Life, a private
not-for-profit, in
progress
page 21
Local or
National
Riders for Health
Process
Local
Riders for Health boost transport infrastructure by
providing preventive maintenance for vehicles with the
understanding that it is cheaper to keep a vehicle running
efficiently than to repair it when it breaks down. This
means that health workers don’t waste valuable time
and resources bringing their vehicles into a garage for
servicing, and can spend more time in their communities.
Riders for Health,
a private social
enterprise, in
progress
26
Living Goods
Process
Local
A sustainable social enterprise empowering microentrepreneurs to deliver lifesaving and life-changing
products to the doorsteps of the poor.
Living Goods,
a private social
enterprise, in progress
27
Community
distribution of
misoprostol
Process
Local
Community health workers identify pregnant women,
Various national
educate women on the use of misoprostol, and distribute governments
the drug for use immediately following childbirth.
Process
National
Improved management of uterotonic drugs through certain Various
tools for keeping track of drug inventory, including: order
books, stock cards, daily log of uterotonic use, delivery
register, and oxytocin logbook in delivery room.
Innovation
25
Issue
Addressed
Implementation
Group and
Status
Process or
Product
#
Description
Systematic and e-Tracking of Quality and Demand
page 22
28
Improved drug
management
training
Inefficient
procurement
processes
29
Systematic logistics
management and
information system
for better demand
and forecasting
Process
National
Logistics management and information system is a
systematic, systematized method for keeping track of
drugs at national and sub-national levels.
Various
30
VacTrax
Product
Local
A vaccination registry that is operated and managed
by organizations in the field administering vaccines.
Patients are identified in the registry by their fingerprints.
When patients return after initial treatment, the health
worker who sees them is provided with an accurate
vaccination history.
VacTrax, a private
social enterprise,
product development
completed
31
Sproxil
Product
National
Sproxil is a venture-backed social enterprise that
provides brand protection in emerging markets by
leveraging mobile phones and scratch-off labels.
Sproxil, a private
social enterprise,
product development
completed
32
PharmaCheck
Product
National
A drug verification device that scans pills with
fluorescence and imaging to measure such properties as
their concentration to determine the potency of drugs.
Boston University
33
PharmaSecure
Product
National
Drug authentication technologies and software, creating
effective solutions to ensure consumers receive authentic
medications from trusted pharmaceutical manufacturers
in emerging markets.
PharmaSecure,
a private social
enterprise
#
Innovation
Issue
Addressed
Process or
Product
Local or
National
Description
Implementation
Group and
Status
Experimenting with New Formulations and Presentations of the Drug (Oxytocin-only)
34
Aerosol oxytocin
Faulty or easily Product
degradable
packaging
National
Development of an aerosol delivery system for oxytocin
that can be inhaled by patients from a simple,
disposable device immediately after childbirth.
Monash University,
product in
development
35
Oxytocin in Uniject
Product
National
A pre-filled, single-use injection device filled with
oxytocin that allows the drug to be delivered by
community health workers in remote villages.
PATH produced by
Becton Dickinson,
product development
complete and ready
for commercial
scale-up
36
Heat-stable oxytocin
Product
National
Pharmaceutical technological development, and eventual Oxytocin Consortium,
large-scale production, of heat-stable oxytocin. This
product in
development includes the production of three batches of development
heat-stable product.
page 23