On January 3rd, 2014 IAPHL launched a moderated discussion for members to discuss the integration of Oxytocin into vaccine cold chains. Topics included Oxytocin potency loss, implementation and cold chain capacity risks with country-specific examples. This discussion was facilitated by members of the World Health Organization (WHO), United Nations International Children’s Emergency Fund (UNICEF), and the GAVI Alliance. A summary of the discussion is below:
Original message: “We are going to start of the New Year with a discussion regarding integrating Oxytocin in our cold chains. This is an important issue and deserves careful consideration. We hope you’ll share your thoughts and relevant experiences with us on this topic.
This discussion will be led by Patrick Lydon of WHO, Benjamin Schreiber of UNICEF and Daniel Thornton of the GAVI Alliance. Patrick Lydon has been working for the World Health Organization within the Expanded Programme on Immunization (EPI) team for nearly 14 years. Between 2008-2012 Patrick was key member of project Optimize – a WHO and PATH collaboration on rethinking the vaccine supply chain for the future were he focused on supply chain optimization including supply chain network redesign in countries; supply chain integration; and private sector engagement. With the close of project Optimize, Patrick’s work shifted to establish a joint, WHO and UNICEF supply chain hub for technical knowledge and expertise.
Benjamin Schreiber works with UNICEF as a Senior Immunization Specialist with a focus on vaccine and immunization supply chain management. Before joining UNICEF, Benjamin worked as the Chief Operating Officer of the Agence de Médicine Préventive (AMP) where he oversaw overall project operations, and was part of the senior management team. Before that, Benjamin worked in different positions in the private sector.
Daniel Thornton is Director of Strategic Initiatives at the GAVI Alliance Secretariat. In this role he is jointly leading the development of an immunisation supply chain strategy for the GAVI Alliance. He has previously worked at the Secretariat as Chief of Staff, and before that in a variety of roles over nearly 20 years in the UK civil service, including at the Foreign Office, the Treasury and No10 Downing Street.”
With the launch by the UN of the “Every Women, Every Child” initiative (http://everywomaneverychild.org), and the ambitions to scale up the use of oxytocin to prevent and treat postpartum haemorrhage in women, questions are re-surfacing as to whether the vaccine cold chain could be leveraged to store oxytocin at service delivery levels.
Oxytocin is a time and temperature sensitive product whose efficacy and shelf life can increase significantly when stored in a 2-8 degree celsius temperature controlled chain. Studies have demonstrated that significant loss of potency occurs from exposure to high temperatures during transport or storage, and by the time it reaches the women who need it most. The opportunity to store oxytocin in the vaccine cold chain would have far reaching benefits to achieving maternal mortality reduction goals. But how can this be done in practise? What are the risks? And what is the current thinking from those working on immunization in WHO, UNICEF and GAVI?
The WHO, UNICEF and GAVI are discussing the possibilities of moving to a more integrated vaccine supply chain as a way to achieve both child and maternal mortality reduction objective that are key goals of the Global Vaccine Action Plan 2011-2020 (GVAP). Perhaps Oxytocin is the pathfinder product for segmented integration if it could be stored in the vaccine cold chain. Before we can get to a point where specific policy recommendations and strategies can be made, the first step is to gather all the necessary evidence available.
Anecdotal evidence highlights that several countries are storing Oxytocin in the vaccine cold chain. That said:
• What are the risks and benefits of a strategy to include oxytocin in the vaccine cold chain?
• What kind of experiences have countries encountered when they have stored oxytocin in their supply chains?
These are just some of the questions we would like to pose to the IAPHL community. (Patrick Lydon, Switzerland- host of Moderated Discussion)
““I believe that there will be some benefit in adding oxytocin to the vaccine supply chain. This is because in the private sector especially, most suppliers fail to adhere to the 2-8 degrees Celsius temperature condition either in their warehouses or during transport. This results in reduction in potency causing our midwives to inject more than usual just to make the uterus contract.Since the public sector cold chain practice is more reliable, I believe integrating the two will be of benefit.The challenge I for see is the management or administration of the supply chain. Vaccines are managed by the public health department while oxytocin is managed by the medical stores.” (Christian Ayin, Ghana)
“In my experience in the private sector in Nigeria, Oxytocin was and is still stored as cold chain product. It is highly temperature sensitive and its clinical benefits enormous and practically life saving. Its cold chain storage should be encouraged or even enforced.
However, care must be taken as regards the inclusion of Oxytocin in the Vaccine cold chain. This is basically due to the potential toxicity, misuse and ethical issues surrounding the use of oxytocin. The oxytocin/Vaccines combined cold chain would be a good way forward but a very strategic technical training must cascade down to the service delivery points to ensure safety and overall positive outcomes.” (Timi Omole, Nigeria)
“I think this would need to be taken on a case by case or country by country basis. There are some settings where integrating oxytocin in the vaccine cold chain would not be a problem as the health workers are well trained to handle vaccines. I work in a setting where human resource capacity is a major constraint, and this integration would be a recipe for disaster. We worry that oxytocin will be confused with diluents and used to reconstitute vaccines. I have experience from another country where oxytocin was used to reconstitute BCG with fatal results.” (Ms. Ranganai Matema, South Sudan)
“I imagine that there will be significant logistics, administrative, and health staff mobilization issues along the path to integrating Oxytocin into the vaccine cold chain, not the least of which will be, of course, that it will then strictly cease to be called a “Vaccine” cold chain. But before we progress, I think it could be useful to have a reasonably general understanding on the stability profile and hence assigned shelf life for this important product. From my experience procuring this item over many years, I recall that the assigned shelf life has usually been between 2-3 years. However, I must say that the supporting stability study data presented with bids has often left much to be desired. It will therefore be also useful to look into the issue of qualified sources of oxytocin, globally, if possible.” (Murtada Sesay, Sierra Leone)
“It’s important to know the specifics of the brand and presentation of the pharmaceutical as well as the volume/probable through put before committing the cold chain resources. It would not necessarily be correct to say that every program in every location necessarily has excess capacity for this distribution in their refrigerators for storage and in their cold boxes for transportation.” (John Durgavich, USA)
On the topic of potency loss, an interesting study from the New England Journal of Medicine was shared on the effects of freezing (http://www.nejm.org/doi/full/10.1056/NEJMc1209761). The results show that the potency of Oxytocin is largely unaffected after being exposed to either (a) continuous freezing temperatures of −5°C, −20°C, on ice, and on dry ice for a period of 7 days, or (b) multiple cycles of freezing and thawing during a period of 5 days. The study concludes that health workers can be reassured that Oxytocin can be safely used in the event of accidently freezing in the cold chain either during storage or transportation.
This is a great advantage of Oxytocin over many of the new vaccines being used in EPI. Temperature monitoring studies have shown that 35% of EPI vaccines are exposed to extended periods of freezing in the cold chain. This is a real concern. Vaccines that lose potency from freezing represent about 70% of the value of vaccines procured through UNICEF (the main procuring agency for vaccines in the world). The more traditional EPI vaccines like Polio, need to be kept in freezing temperatures, and others like BCG and Measles can be frozen without loss of potency given that they come in a lyophilized (freeze-dried) presentation. Does this mean that Oxytocin should be kept with the EPI vaccines that are not freeze sensitive like Polio? Perhaps not. But it may mitigate the risk of confusing the products in the cold chain between only Polio and Oxytocin. It is something to think about? I could help justify where in the supply chain integration could happen.
• Cold chain capacity risk
On the topic of cold chain capacity, I didn’t pick up on any new insights on this. Instead, I would like to share some that relate to the Effective Vaccine Management (EVM) assessments that have been conducted by WHO and UNICEF in approximately 70 countries since 2010. The EVM assessment is essentially a continuous quality improvement process that is recommended to countries to ensure their vaccine supply chains meet minimum standards at all levels of the in-country system (national, sub-national and service levels) and according to 9 criteria (vaccine arrival, temperature control, storage capacity, quality of the infrastructure and it’s maintenance, vaccine management, distribution, stock management, LMIS…). A recent WHO analysis of the data from 65 low and lower-middle income countries revealed that only 1 country met all recommended standards at all levels of their supply chain. This is a key concern in EPI given that for vaccines, the state of the supply chain has numerous shortcomings. When considering Oxytocin in the vaccine cold chain, the state of the vaccine supply chain is something that needs to be considered very carefully.
• Implementation risks
While the first few weeks of discussion had a strong focus on the risks of potency loss from not having Oxytocin in the cold chain, and the risk that the vaccine cold chain isn’t planning necessarily for the capacity needs for such time and temperature health products, the past few weeks has seen more inputs on the implementation risks.
The main take home message is that there isn’t a one-size-fits-all solution. Implementing a strategy to include Oxytocin in the vaccine cold chain is not one that may be advisable in all setting and countries. A tailored approach will be needed and on a country by country basis. For the majority of countries that are not already implementing such a strategy, certain pre-conditions prior to implementation ought to be required and monitored to gauge country-readiness for such a policy change. In those countries that are implementing, additional tools and methods are most certainly required. And particularly to avoid any risk of confusion of products in the cold chain. The case of were the diluent for a lyophilized vaccine (BCG) was accidently used was cited as an example that led to a fatal outcome.
Ideas for next steps:
So where does this leave us in moving forward? As we begin to close down this discussion, it would be good to reflect on where to go next, and to ensure that all the great inputs from the IAPHL community can be brought forward to those working on Oxytocin in the cold chain as part of the UN Commission on Life Saving Commodities. Although I know for a fact that many are tuned into this discussion even if they’ve been shy to join in.
Picking up on the ideas of many of you, I’ve bulleted below what can constitute the beginnings of a list of next steps forward. These are listed in no particular order:
1. Document the specific experiences in countries that have already integrated Oxytocin in the vaccine cold chain (in settings where it has worked well and where it has not worked so well) to understand the reasons for doing so and understand what worked and what didn’t work. The ultimate idea is to draw lessons learned from selected countries that are already implementing a practise of Oxytocin in the vaccine cold chain
2. Document the specific reported incidents where Oxytocin in the cold chain led to a bad outcome, and undertake the root-cause analysis.
3. Conduct one or two pilot projects in countries to implement Oxytocin in the cold chain and fully evaluate the good, the bad and the ugly.
4. Define the segments of the supply chain that could benefit from integration. In other words, should integration occur at national level and then vaccines/Oxytocin get split out into separate distribution chains between sub-national and service levels. Or should integration occur only at the last mile and not at national level? A mixed between the two? The idea is to understand what model of integration would be advisable in what setting.
5. Forecast the combined needs for EPI vaccines and Oxytocin for the next 5 years (or up to 2020 for example) against the available and planned capacity in the vaccine cold chain.
6. Develop a framework for assessing country readiness to include Oxytocin in the cold chain.
7. Develop a list of issues, risks and mitigation strategies of including Oxytocin in the cold chain.
8. Work at global level on product presentation and packaging that can mitigate risk of confusion with vaccines.
9. Develop global guidance and recommendations and work with normative agencies and partners at regional/country level to support policy change.
10. Conduct training and capacity building activities to ensure a smooth change management for health workers in implementing a practise of Oxytocin in the cold chain.
(Patrick Lydon, Switzerland- host of Moderated Discussion)