PV of Life Saving Commodities Contents
The United Nations Commission on Life-Saving Commodities (UNCoLSC) have identified 13 commodities that can improve reproductive, maternal, child and new-born health and are estimated to be able to save an estimated 6 million lives. The FINAL REPORT of the Commission is available here. These products are however not widely accessible nor available due to several reasons including regulatory barriers, lack of awareness of their existence and use and quality and safety issues.
The medical products listed on the UNCoLSC are all incorporated in the current version of the WHO Model List of Essential Medicines. Access the list here
The products available are generally considered to have very favourable benefit-risk profiles. However, the countries where these products will make the greatest impact are not known to have robust pharmacovigilance systems. As such, it is important to support the PV infrastructure in these and all other countries to ensure that the promotion of increased access to these life-saving commodities is accompanied by equally active promotion and improvement of the PV systems to provide continuous assurance of the safety of the products
The PV of Life Saving Commodities toolkit provides information on these products and gives guidance on the safety monitoring and development of risk management plans for some of these products.
Based on country demand, more generic risk management plans and guidance will be provided on these pages. For help and assistance, all interested stakeholders should contact firstname.lastname@example.org
The UN Commission on Life-Saving Commodities for Women and Children (UNCoLSC) is a high-level commission established by the UN Secretary General to examine approaches towards improving maternal and child health. In September 2012, the Commission produced its report which highlighted approaches towards attainment of its main which is the development of strategies and approaches to increase access to life-saving medicines and health supplies to save and improve the lives of millions of women and children worldwide. In its final report, the Commission produced concrete recommendations for improving access to 13 life-saving commodities.
The 13 life-saving commodities focus on reproductive, maternal, newborn and child health (RMNCH).
The UNCoLSC believes firmly that the lives of more than 6 million women and children can be saved if these somewhat “overlooked” products are made more widely accessible and used properly. The current 13 life-saving commodities are shown in the table below:
Table1: The 13 UN Life Saving Commodities of the UN Commission on Life Saving Commodities
|RMNCH Continuum of Care||Commodity||Usage|
|1. Female Condoms
3. Emergency Contraception
|1. Family planning/Contraception
2. Family planning/Contraception
3. Family planning/Contraception
6. Magnesium sulfate
|4. Post-Partum Haemorrhage
5. Post-Partum Haemorrhage
6. Eclampsia and Severe Pre-Eclampsia/Toxaemia of Pregnancy
|Newborn Health||7. Injectable antibiotics
8. Antenatal Corticosteroid (ANCS)
10. Resuscitation Equipment
|7. Newborn Sepsis
8. Respiratory Distress Syndrome for preterm babies
9. Newborn Cord Care
10. Newborn Asphyxia
|Child Health||11. Amoxicillin
12. Oral Rehydration Salts (ORS)
The Commission’s made the following 10 recommendations to achieve its by:
- Facilitating improved markets for life-saving commodities
- Improving national delivery of life-saving commodities
- Improving integration of private sector and consumer needs
The focus of the Commission in order to achieve rapid success is to concentrate action on countries with the highest burden of diseases including several countries in Africa who have been described as “Focus Countries” in view of the high burden of disease and the potential to achieve substantial disease reduction by improving access to these commodities.
A careful analysis of the UNCoLSC’ s final report indicates a commitment to improve access and rational use of these commodities but the issue of safety is given only scant mention, often in relation to the quality of products. This is perhaps understandable given the fact that the main mission of the Commission was to advice on approaches to improve access to and demand for these commodities which have been shown to beneficial in improving reproductive, maternal, newborn and child health (RMNCH).
In surveys carried by the World Health Organisation (WHO) on behalf of the Commission, about 23% of 204 samples failed quality tests with 47 failing one or more tests and 5 having extreme deviations “in content and/or dissolution which were likely to affect the therapeutic effect of the product”.
It is entirely conceivable that these products which did not meet quality specifications could have adverse effects on users which in turn can negatively impact the expected outcomes following the use of these commodities. This and several other considerations underline the importance of having a strong and robust pharmacovigilance component in the work of the UN Commission on Life Saving Commodities. Pharmacovigilance per se, was never mentioned in the report of the Commission though “safety” was mentioned under recommendation 4 “Quality strengthening” where it was mentioned among other things that “…. By 2015 the WHO and partners will support joint regulatory reviews to assess the safety of administration of life-saving commodities by lower-level health workers”.
PV of LSCs in Africa
In December 2014, the Pharmacovigilance Department under the Safety and Vigilance (SAV) sector of WHO provided support to the WHO Collaborating Centre for Advocacy and Training in Pharmacovigilance, University of Ghana to initiate activities to examine pharmacovigilance and regulatory issues related to dispersible amoxicillin when used for community-based treatment of childhood pneumonia and levonorgestrel when used in emergency hormonal contraception in African countries
This support was further increased in 2015 to include further expansion on the work on safety monitoring of the 2 products as well as the development of a web-based repository (toolkit) to provide information on the pharmacovigilance of amoxicillin and levonorgestrel in support of the work of the UNCoLSC.
The toolkit for Life-Saving Commodities is a growing resource and welcomes views and comments from all stakeholders. The aim is to provide adequate information and, where appropriate, technical resources to countries so that they can provide safety surveillance in all settings and for their entire populations. Since PV involves global collaboration, the experiences of one country goes a long way to support other countries.
Pneumonia is the single biggest cause of death in children, accounting annually for the deaths of approximately 1.4 million children under 5 years of age – nearly 20% of all deaths in that age category. In several countries, children affected with pneumonia do not get access to care depriving them of prompt effective treatment which have been shown to reduce mortality significantly. The importance of amoxicillin (especially dispersible amoxicillin) is underscored by the fact that the World Health Organisation has currently included it in its list of “Priority life‐saving medicines for children under five years of age for major causes of mortality and morbidity, palliative care and child survival” for the treatment of pneumonia in children. Whilst there are other antibiotics on the list for pneumonia, dispersible amoxicillin tablet is the only orally available product in view of evidence for its safety and efficacy as well as convenience for use in multiple settings. Despite the proven benefits and the potential of this product to save hundreds of thousands of lives annually, its uptake is very low especially in low and middle income countries. The reasons for this are many, including ignorance about its effectiveness; concerns about development of resistance; safety issues; regulatory barriers by national competent authorities and lack of training of several different cadres of health workers.
A survey undertaken by WHO of 50 countries shows that 10 of these countries account for more than 75% of all cases of pneumonia. Thus, whilst there were 96 million cases of pneumonia in the 50 countries – 71 million of which are untreated – the number of total and untreated cases in the 10 countries (focus countries) were respectively 74 million and 56 million. The focus countries, 7 of which are in Africa include India, Nigeria, Pakistan, Bangladesh, Democratic Republic of Congo, Ethiopia, Tanzania, Uganda, Kenya and Niger. Any intervention that reduces the number of cases in these target countries will reduce the overall incidence globally.
There is the need to ascertain the various barriers and challenges faced by these towards the provision of community-based care of pneumonia using dispersible amoxicillin tablets.
This toolkit provides highlights of assessments undertaken by the WHO Collaborating Centre for Advocacy and Training in Pharmacovigilance to understand the regulatory status as well as the PV of amoxicillin in some countries in Africa
Regulatory Status of Amoxicillin in Africa
Dispersible Amoxicillin was found to be a Prescription only Medicine (POM) in 7 out of 8 African countries surveyed including the 7 focus countries. Most respondents claimed however that despite this legal status, amoxicillin is available for purchase over-the-counter in nearly all outlets. There is an urgent need to explore options for this life-saving commodity legally available whilst taking cognisance of the wider imperative to prevent antibiotic resistance
Regulatory Barriers and Challenges
Though amoxicillin was found to be a POM in most countries, there appears to be no significant regulatory barriers or challenges confronting availability. The main issues that remain drawbacks are lack of knowledge on the diagnosis of childhood malaria as well as information on the proper use of amoxicillin to manage childhood malaria.
Amoxicillin use for pneumonia
Amoxicillin is specifically indicated for the treatment of pneumonia in 6 out of 8 countries surveyed. The dispersible form (amoxicillin tablets) have been approved for community-based care of pneumonia for children under five years in 3 of the 8 countries sampled. There is a need to increase advocacy for the rational and effective use of dispersible amoxicillin in the focus countries.
Pharmacovigilance of dispersible amoxicillin
All the countries surveyed have national PV centres who are members of the WHO Programme for International Drug Monitoring. However, the reporting of ADRs generally appear to be poor with very few reports of ADRs to amoxicillin. In view of long-term experience in use, formal risk management plans for amoxicillin when used in the community are not required from manufacturers or marketing authorisation holders. The normal “spontaneous adverse drug reporting system” is utilised for routine pharmacovigilance. The general indication from a search of the WHO individual case safety reports (ICSRs) database, VigiBase, and the expert opinion from stringent regulatory authorities including the US FDA and the European Medicines Agency is that amoxicillin is a product with a good safety profile. Nonetheless, it is important to collect more data from Africa to give assurance of its safety especially when used for community based care. Furthermore, the known side effects including anaphylaxis, penicillin-sensitivity, rashes and erythema multiforme, though rare should still be monitored to ensure that the benefit-risk profile of the product remains positive.
Amoxicillin is widely available in all the focus countries. Regulatory and safety considerations do not appear to be hindrances towards its use. Rather, education of health workers and the community and widespread availability through multiple channels (public sector; private sector) holds the key towards more widespread use. Active promotion on the benefits of amoxicillin in childhood pneumonia through appropriate channels may also be needed. The risk mitigation strategy for amoxicillin when used for community based treatment should include education by healthcare workers to parents/carers at the time of product administration or supply and the promotion and use of simplified methods for spontaneous reporting of any adverse events.
Emergency Hormonal Contraceptives (EHC) are considered one of the UN’s life-saving commodities in view of their potential impact on health and the aversion of unwanted pregnancies as well as preventing unwanted abortions and saving lives.
The availability of EHC in low and middle income countries (LMICs) appear to be low and several reasons have been adduced for the low uptake of EHC in LMICs.
Emergency hormonal contraception (EHC) specifically the use of levonorgestrel 1.5 mg or 2 x 75mg is widely accepted as an important public health intervention especially as it greatly reduces the need for unwanted pregnancies as well as unsafe abortions as well as the mortality associated with the latter. The WHO Fact Sheet (WHO_RHR_HRP_10.06) on the on the safety of levonorgestrel-alone emergency contraceptive pills (LNG ECPs) highlights the benefits of LNG ECPs in preventing pregnancies when taken after inter-course whether as back-up in case of unprotected intercourse, contraceptive failure or after rape or coerced sex.
The WHO Model Formulary 2008 recommends levonorgestrel for emergency contraception. It states that “1.5 mg should be taken as a single dose within 120 hours of unprotected intercourse; alternatively, levonorgestrel, 750 micrograms, can be taken within 72 hours of unprotected intercourse followed 12 hours later by another dose of 750 micrograms. Side effects include nausea, vomiting, headache, dizziness, breast discomfort, and menstrual irregularities. If vomiting occurs within 2–3 hours of taking the tablets, replacement tablets can be given with an antiemetic”.
Whilst there are several legitimate concerns relating to the use of LNG ECPs, the available evidence (see WHO Factsheet) shows it to be safe and effective when used appropriately. Furthermore, the concerns that the availability of emergency contraception either increase sexual activity or lead to sexually-risky behaviour have been shown to be unfounded.
In spite of the benefits of EHC with LNG ECPs, their uptake is very low due mainly to regulatory barriers as well as cultural considerations. The availability of EHC with LNG without the need for a prescription from a physician will greatly enhance access and eventually improve maternal care. It has been shown to be safe and effective when used appropriately with a controlled trial clearly demonstrating both effectiveness and responsible use in women who had access to them.
Regulatory status of LNG in Africa
A survey of 18 countries in Africa showed that LNG is available as an Over-The-Counter product in 9 countries, Pharmacy Medicine in 1 country and as a Prescription-Only-Medicine in 8 countries. These results are fully in line with the findings of the International Consortium for Emergency contraception and its published information on Emergency Contraceptive Pill Registration Status by Country. In that report, 22 countries have no emergency contraceptive (EC) pill brands registered and these also appear not to import EC whilst 26 countries have no registered product but import ECs and 146 countries have at least one EC pill brand registered.
Regulatory and safety considerations do not appear to be barriers restricting availability of LNG ECPs in LMICs. Key informant interviews to explore the regulatory barriers and attitudes restricting the supply of LNG ECPs revealed sensitivities (with possible socio-cultural and religious foundations) around usage. Only 3 out of 18 countries surveyed permitted advertisement of LNG for EHC
Information provided by key informants/respondents include the following statements: “People have been misusing it”; “They prefer to sell it to ladies instead of males” (Restricted to ladies); “Although it is supposed to be P.O.M, anybody at all can get it OTC”; “It is OTC now and it is currently being over-used”. “They are available in all public hospitals, in maternal and child health services and private healthcare facilities as POM”. These findings are in line with those of a review of global access to emergency contraception which showed that despite the widespread availability of ECs, majority of women in low-income countries have not heard of them and that providers have negative attitudes towards providing ECs to women who need them.
Safety of LNG
A search conducted from the WHO ICSR database (VigiBase) for data on individual case safety reports to levonorgestrel globally revealed gross under-reporting of ICSRs from Africa with only about 0.4% of the 100k+ reports coming from Africa. The adverse events reported were mainly related to reproductive system with gastrointestinal and neurological disorders reported though to much smaller extents. Generally, LNG is considered to have a very favourable safety profile.
LNG for ECP appears to be safe and well tolerated. It is widely available in countries across the world but very poorly used. The focus on improving usage should therefore be on both provider and patient education on its availability and track record of safety though such education should continue to stress the need to report any suspected adverse events to the relevant national authorities.