2012 solution landscape on oxytocin and misoprostol...

2012 Solution Landscape on Oxytocin and Misoprostol Quality Solutions for Management of Postpartum Hemorrhage

2012 Solution Landscape on Oxytocin and Misoprostol Quality Solutions for Management of Postpartum Hemorrhage

Postpartum Hemorrhage

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:

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:JhpiegoBrown’s Wharf1615 Thames StreetBaltimore, Maryland 21231-3492, USAwww.jhpiego.org

© Jhpiego Corporation, 2015. All rights reserved.

Acknowledgments

Postpartum Hemorrhage

Pre-eclampsia & Eclampsia

RehabilitativeMedicine

Male Circumcision

page iii

List of Abreviations iv

1.0 Introduction and Objectives of Solution Landscapes 1

2.0 Methodology 2

3.0 Solution Landscapes Research Findings 33.1 Five Main Barriers to Maintaining Uterotonic Drug Quality 3

3.2 Survey of Innovations Used to Overcome Challenges 7

4.0 Recommendations 94.1 Selecting Appropriate Solutions: Define Operating Contexts 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

Table of Contents

page iv

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

USP United States Pharmacopeia

WHO World Health Organization

List of Abreviations

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.

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.

These drugs are available at low cost but susceptible to breakdowns in quality, reducing the ability of a health system to save mothers’ lives.

See Appendix One: Participants in the Solution Landscape.

See Appendix Two: The List of Interview Guide Questions.

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.

2.0 Methodologyi

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These issues are outlined inAppendix Three: Comparing Oxytocin and Misoprostol.

It is unknown whether improved cold storage alone improves oxytocin drug quality, thereby potentially saving lives.

3.1 Five Main Barriers to Maintaining Uterotonic Drug QualityTo 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.

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.”

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.

3.0 Solution Landscape Research Findings

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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

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

High drug quality

Controlled and regulated

production

Inconsistencies at point of use

Inadequate storage

conditions

Challengesin transport

anddistribution

Ineffecientprocurement

processes

Breakdowns to drug quality

Faultypackaging

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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 good-quality 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

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-maternal-health)

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 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.

nn 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.

nn 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.

nn 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.

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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.

nn 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 ChallengesThe literature review and key informant interviews provided some general methods of effective drug management to help assure the quality of uterotonic drugs:

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

nn Explore bulk purchasing mechanisms so that prices remain low while at the same time creating more attractive markets for manufacturers

nn Decrease the prevalence of substandard medicines

nn Support new product development and delivery innovations that encourage widespread usage of the drug

nn Strengthen management information systems to ensure medicine availability and avoid stock-outs, but not too far in advance to risk expiration

nn Improve knowledge and skills of health care providers and supply chain managers

These innovations are described in detail in Appendix Four: List of Innovations Surveyed.

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 Experimenting with new formulations and presentations of the drug

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Drug quality audits must test the breakdown of quality along the supply chain in order to pinpoint drop-offs in potency.

4.0 RecommendationsAs 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.

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

Innovation is needed to develop testing approaches that are inexpensive, robust, and easily administered in a decentralized manner.

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 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

Alongside a pipeline of innovation, we must develop the capability of health systems to absorb new innovations within appropriate timeframes.

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.

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.

Appendix One: Participants in the Solution Landscape

# Point of ContactName of Partner

Org/AgencyLocation

1 James BonTempo, Team Leader, Information Services and Technology Support

Jhpiego Baltimore, MD

2 ‘Dipo Otolorin, Country Director, Nigeria

Maternal and Child Health Integrated Program (MCHIP) Field Office

Lagos, Nigeria

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 QuestionsSection 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?

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?

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?

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?

Appendix Three: Comparing Oxytocin and MisoprostolOxytocin 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:

TemperatureStability of Oxytocin at Corresponding

Temperature, WHO Guidelines2°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 By and large, oxytocin is widely available and relatively

cheap, but stock-outs still remain because of inaccurate forecasting, hoarding of drug, etc.

nn Oxytocin is the first-line preferred drug and is on country Essential Medicines Lists

nn 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 IntroductionMisoprostol 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.

Challenges Specific to Misoprostolnn This drug has not been used for as long as oxytocin

nn Although it is a second-line drug, often other drugs are chosen in its stead

nn This is not on every country’s Essential Medicines List and may not be as readily available

nn Although this drug is more stable in tropical climates, it can still degrade in conditions of high sun and humidity

nn 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*

# InnovationIssue

AddressedProcess or Product

Local or National

DescriptionImplementation

Group and Status

Improving Clinic Level Quality1 Health worker

education on the importance of cold chain

Inconsistencies at point of use

Process Local Increase health care provider education—traditional birth attendants, community health workers, providers at the clinic and hospital levels—on appropriate oxytocin drug management practices (and AMTSL protocol).

Various

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 USAID-funded program, Securing Ugandans’ Right for Essential Medicines (Uganda SURE) working on ensuring adequate quantities of good-quality essential medicines and 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.

MSH, in progress (project 2009–present)

Visible Markers of Potency5 Vaccine vial monitors Uncertainty

regarding the potency of drug

Product 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.

WHO, product development complete

6 Cold-chain monitor Product National A cold-chain monitor is used to show exposure to temperatures above the safe range during transportation and storage. It has an indicator that responds to two 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).


* This Solution Landscape was developed in 2012 and does not survey later innovations in the field of postpartum hemorrhage management

# InnovationIssue


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Group and Status

8 Stop!Watch Product National This device combines the Monitor Mark™ indicator from the cold-chain monitor with Freeze Watch. It is used to monitor temperatures in a refrigerator over time.


9 DT and TT shipping indicator

Product National This device consists of a blue card with a temperature-sensitive 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.


Tools and Tests for Quality Assessment10 Diagnostics for All Uncertainty

regarding the potency of drug

Product Local Creating low-cost, easy-to-use, point-of-care diagnostics designed specifically for the 60% of the developing world that lives beyond the reach of urban hospitals and medical infrastructures.

DFA, private nonprofit enterprise

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

Portable, Off-Grid Cold Storage Solutions13 SureChill Inadequate

storage conditions

Product National Solar-powered compression refrigerators that run on a battery charged by photovoltaic cells, which convert sunlight to energy.


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 unit purposely designed to keep insulin cool within safe temperatures of 18–26°C (64.4–78.8°F) for 45 hours, even in a constant environmental temperature of 37.8°C (100°F).

FrioUK, product development completed

# InnovationIssue


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Group and Status

17 Paraffin- or gas- powered 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

Controlled Drug Distribution Systems22 Delivery Team

Topping Up (DTTU)Challenges in transport and distribution

Process National Zimbabwe’s DTTU distributes contraceptives, test kits, anti-malarial drugs, and other health products to each of the country’s 1,600 public health facilities.

JSI, Zimbabwe National Family Planning Council, and the UK Department for International Development operate and manage the DTTU system, in progress

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

# InnovationIssue


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Group and Status

25 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 micro-entrepreneurs 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, educate women on the use of misoprostol, and distribute the drug for use immediately following childbirth.

Various national governments

Systematic and e-Tracking of Quality and Demand28 Improved drug

management training

Inefficient procurement processes

Process National Improved management of uterotonic drugs through certain 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.

Various

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

# InnovationIssue


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Group and Status

Experimenting with New Formulations and Presentations of the Drug (Oxytocin-only) 34 Aerosol oxytocin Faulty or easily

degradable packaging

Product 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 large-scale production, of heat-stable oxytocin. This development includes the production of three batches of heat-stable product.

Oxytocin Consortium, product in development

2012 solution landscape on oxytocin and misoprostol...

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