1. 7.1% Chlorhexidine Digulconate for Umbilical Cord Care
A summary of global introduction efforts, policy evidence, and product availability

2. What is chlorhexidine digluconate?
A broad-spectrum antiseptic
Commonly used worldwide for various applications
Excellent safety record with topical application on humans
Routinely practiced in many developed-country settings throughout the 1970s and 1980s without adverse health consequences

3. Evidence for chlorhexidine intervention

4. Evidence from randomized controlled trials on chlorhexidine for cord care
All trials had neonatal mortality and omphalitis as primary outcomes. All used dry cord care as their comparison group. All trials used water-based liquid formulation of 7.1% chlorhexidine digluconate.
Publication
Mullany Nepal
Arifeen Bangladesh
Soofi Pakistan
Sazawal Tanzania
Semrau Zambia
Total live births
15,123
29,790
9,741
36 ,911
37,856
Schedule of application
Days 1,2,3,4,6,8,10
Within 1st 24 hours,
then daily for 7 days
Daily for 14 days
Daily until 3 days after cord drops
Intervention provider
Project staff
Traditional birth attendant & mother/ caretaker
Mother or caretaker
First application within 24 hours of birth
63%
87%
100%
94%
90%
Application of other substances to the cord
~ ½
few
~90%
N/A
~10%
% infants with birthweight <2500g
30%
33% 5% 7%
% health facility births 8% 0%
54%
64%

5. Pooled analysis of the RCTs conducted in Bangladesh, Pakistan, and Nepal
Results showed:
A 23% reduction in all-cause neonatal mortality compared with the control.
Reduced risk of cord infection by 27%–56% depending upon severity of infection.
Cord separation time was increased by 1.7 days over dry cord care.
Washing of umbilical cord with soap and water was not advantageous compared with dry cord care in community settings.

6. Reduction in NMR in 5 chlorhexidine RCTs
Reduction in NMR in 5 chlorhexidine RCTs *Statistically significant at 95% CI

7. Evidence summary regarding use of 7
Evidence summary regarding use of 7.1% chlorhexidine to the umbilical cord
Use does reduce risk of omphalitis, even in low mortality settings where there is no evidence of impact on mortality risk.
Despite previously reported substantial reductions in South Asia, use did not significantly reduce NMR in study sites in Tanzania or Zambia.
This means that study results have shown an impact on mortality risk in populations with high NMR (35-40 deaths/1,000 live births) and have not shown an impact on mortality risk in populations with low NMR (≤18 deaths/1,000 live births).
In high-mortality settings, use reduced deaths regardless of whether infants were born at home or in a facility (Hodgins 2017; Mullany, et al. 2017).

8. WHO recommendation on postnatal care of the mother and newborn, 2014
RECOMMENDATION 6: Cord care daily chlorhexidine (7.1% chlorhexidine digluconate aqueous solution or gel, delivering 4% chlorhexidine) application to the umbilical cord stump during the first week of life is recommended for newborns who are born at home in settings with high neonatal mortality (30 or more neonatal deaths per 1,000 live births).
Clean, dry cord care is recommended for newborns born in health facilities and at home in low neonatal mortality settings. Use of chlorhexidine in these situations may be considered only to replace application of a harmful traditional substance, such as cow dung, to the cord stump.

9. Inclusion of chlorhexidine in WHO Model List of Essential Medicines
In 2008, USAID and HealthTech jointly made the first application to list 7.1% chlorhexidine digluconate for umbilical cord care.
In 2013, 7.1% chlorhexidine digluconate was listed in the WHO Model List for Essential Medicines.
Facilitated the inclusion of chlorhexidine for umbilical cord care in national EMLs.
Eliminated confusion with chlorhexidine for other applications.
In 2008, USAID and HealthTech made the first application to the WHO to list 7.1% chlorhexidine digluconate for umbilical cord care. In 2010, USAID and HealthTech made a second application to the WHO to list this commodity. Due to lack of commercial availability of chlorhexidine products, the first two applications were not successful. In 2013, HealthTech submitted an amendment documents to show availability of commercial supply, and 7.1% chlorhexidine digluconate was included in the WHO model list of essential medicines for children as a medicine for umbilical cord care.
Including chlorhexidine into the WHO EML contributed to listing this product in national EMLs in countries. Additionally, listing the right strength, “7.1% chlorhexidine digluconate”, for the right indication for use, “for umbilical cord”, alleviated confusions, since different strengths of chlorhexidine digluconate are available for other applications. For example, 5% chlorhexidine digluconate is included in the same WHO EML as general antiseptic.

10. Programmatic decisions for context-appropriate CHX implementation
Settings for use
Home, facility, or both.
Distribution channels must align with intended setting of use.
ANC, private sector outlets (kiosk, pharmacy, etc.), TBA, and CHW.
Regimen: Single-day vs. multiple-day application
Begin application as early as possible (within first 24 hours).
Consider cultural practices around cord care.
Dosage form (gel vs. liquid)
Ensure proper use of product by selecting containers that are packaged differently from other newborn medicines commonly available in the country.
Avoid forms of primary packaging that could easily be mistaken for eye or ear care products.
Conduct formative research on preference as part of larger market research if possible.

11. Dosage form, regimen, and setting for use by country
Location
Bangladesh
Liquid
Single-day
Community and Facility
DR Congo
Liquid & Gel
Multiple-day
Ethiopia
Gel
Kenya
Liberia
Madagascar
Malawi
Facility
Mozambique
Facility and Community
Nepal
Nigeria
Pakistan

12. Product availability and production strategy

13. Three-pronged approach to enable access to chlorhexidine products of high quality
Facilitate product availability through inclusion of chlorhexidine in WHO Model List of Essential Medicines.
Support sustainable supply of high-quality product through partnership with manufacturers in LMICs.
Ensure approval and procurement of appropriate products through development and dissemination of standardized information.
Access to medicines or other medical products should be access to “quality” medicines and other medical products. Chlorhexidine for umbilical cord care is no exception. In order to increase access to quality 7.1% chlorhexidine digluconate for umbilical cord care, we took a three-pronged approach.
Many countries require a medicine to be listed in their national essential medicine/drug lists in order for them to procure the medicine. We facilitated this process by including 7.1% chlorhexidine digluconate for umbilical cord care in the WHO’s model list of essential medicines.
We partnered with select pharmaceutical manufacturers in low and middle income counties to support an uninterrupted supply of chlorhexidine.
Manufacturers, procurers, and regulators will need to have consistent information on the chlorhexidine product to ensure product quality. We therefore developed various standardized information for them so they will approve and procure appropriate chlorhexidine products.
Now I would like to talk about more about each of these approaches.

14. Assess Feasibility of Local Production
Capability and capacity of pharmaceutical companies:
Is there an interested pharmaceutical manufacturer that can produce a “quality” chlorhexidine product?
Affordability:
Can local production achieve affordable pricing?
Sustainability:
Can local production sustain supply of the product?
However, local production is not feasibly in every country, and feasibly of local product should be carefully assessed.
Is there an interested pharmaceutical manufacturer that can produce a quality of chlorhexidine product? Can infrastructure and regulatory mechanisms in your country support production, distribution and use of a quality product?
Can local production achieve affordable pricing? If large investment is required to produce and distribute a quality medicine, local production does not necessarily achieve affordable pricing.
Can local production sustain supply of the product given the potential market size of your country/
YES NO
Local (or regional) production
Import

15. Ensure Product Quality
Acquisition of raw materials from quality sources
Production of the finished product by good manufacturing practices (GMP)-compliant manufacturers and validation of the production process
No matter where the product is produced, quality of the product is critical. Product should be assured in three layers:
Acquisition of raw materials from quality sources:
The API and excipients must be purchased from well-established sources, i.e., manufacturers with cGMP or WHO GMP certificates or approved by stringent regulatory authorities (SRAs), or those from USFDA Drug Master File (DMF).
Production of the finished product by GMP-compliant manufacturers and validation of the production process
Manufactured by pharmaceutical companies that comply with applicable industry regulations and manufacturing quality standards, such as GMPs.
Conforms to United States Pharmacopeia or other pharmacopeial standards.
Released only after applicable quality control.
Registered for sale according to in-country regulations.
Pre-purchase/sale inspections
Make sure that the product was manufactured, tested, and approved for sale according to applicable regulations and standards.
Product quality should be ensured through evaluation by third-party laboratories as required.
Pre-purchase/sales inspections

16. Assuring product quality
Manufacturers should be certified with WHO cGMP. Desirable to be audited by credible international agencies.
Manufacturers must register chlorhexidine for umbilical cord care in country of sales by conforming to national drug regulatory authority standards.
Make sure that the product are tested according to proper protocols before release.
Topical solution monograph included in USP-NF.
Gel monograph to be included in the new global health section of USP-NF.
Suppliers should be able to provide validation methods and a certificate of analysis (COA) together with the product.
Government tender documents should be clear about which dosage form they are requested (gel or liquid).
Make sure the product does not contain alcohol.

17. Manufacturers of 7.1% chlorhexidine digluconate for umbilical cord care
(in alphabetical order).
Product
Dosage form
Manufacturer
(contact information)
Country of Origin
Hexicord®
Liquid
ACI Limited (
Bangladesh
Chlorxy-G® Gel
Gel
Drugfield Pharmaceuticals Ltd. (
Nigeria
Umbipro™
GSK (
United Kingdom*
Kawach
Lomus Pharmaceutical Pvt. Ltd. (
Nepal
CHX Gel
Universal Corporation Ltd. (
Kenya
7.1% chlorhexidine digluconate for umbilical cord care can also be purchased from the UNICEF Supply Division Catalogue (
* Umbipro™ received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for the prevention of omphalitis (infection of the umbilical cord) in newborn infants. This application was submitted and reviewed under Article 58 of Regulation (EC) No. 726/2004, a pathway offered by EMA in co‐operation with the World Health Organization (WHO) for products exclusively intended for markets outside the European Union.

18. To accelerate global scale-up, CWG is supporting local and regional manufacturing
GlaxoSmithKline Brentford, England
Received positive scientific opinion from European EMA
Lomus Pharmaceuticals Kathmandu, Nepal 2010
ACI Limited
Dhaka, Bangladesh
2015
Drugfield Pharmaceuticals Songo‐Atta, Nigeria
Assessment underway
Galentic Pharmaceuticals Mumbai, India Available through UNICEF Supply
Emzor Pharmaceutical Industries Ltd.
Lagos, Nigeria
Approved by NAFDAC. Manufacturing pending
Addis Pharmaceutical Factory
Five years later, the number of chlorhexidine manufacturing partners has grown significantly as you can see here.
6 pharmaceutical manufacturing partners in 4 counties (Bangladesh, Nepal, Kenya and Nigeria) were identified jointly by HealthTech and PQM/USP. PQM/USP has provided technical assistance to them. Their products were approved by national regulatory authorities in respective counties, and they are now supplying their chlorhexidine products to the domestic and exporting markets. In addition, 2 other manufacturers in Nigeria have received product registration, and will be soon manufacturing their chlorhexidine products. PQM/USP is providing TA to one pharmaceutical manufacturer in Ethiopia and assessing four manufacturers in Pakistan. Therefore, a few more manufacturers will be supplying chlorhexidine products in the near future.
GSK’s product has recently received positive scientific opinion under EMA Article 58, which is an approval given by European Medicine Authority to medicines which will be sold outside EU. GSK is willing to be a back-up supplier and supply their product to counties where pharmaceutical manufacturing partners in low and middle income counties are not easily supply their products.
Finally, UNICEF Supply Division Catalog lists topical solution of 7.1% chlorhexidine digluconate for umbilical cord care, and they will soon add gel chlorhexidine in tube and sachet.
As more counties are introducing and scaling their newborn care programs using 7.1% chlorhexidine digluconate for umbilical cord care, these manufacturing partners will be ready to support their implementation efforts.
Tuyil Pharmaceutical Industry Ltd.
Iloryn, Nigeria
Approved by NAFDAC. Manufacturing pending
Universal Corporation
Kikuyu, Kenya, 2015
Countries which have local production
Countries which decided to import the product

19. Global collaboration for country introduction and scale

20. Chlorhexidine Working Group (CWG)
An international collaboration of organizations dedicated to advancing the use of 7.1% chlorhexidine digluconate (delivering 4% chlorhexidine) for umbilical cord care through advocacy and technical assistance.
PATH [CWG Secretariat]
ayzh
Bill & Melinda Gates Foundation
Boston University
Burnet Institute
Centre for Infectious Disease Research in Zambia
Clinton Health Access Initiative
Drugfield Pharmaceuticals Ltd. (Nigeria)
Duke University
GSK (UK)
Global Health Action
Jhpiego
John Snow, Inc.
Johns Hopkins Bloomberg School of Public Health
Johnson & Johnson (USA)
Lomus Pharmaceuticals Pvt. Ltd. (Nepal)
Maternal and Child Survival Program
Ministry of Health, DRC (Reproductive Health)
Ministry of Health, Ethiopia (Maternal & Child Health)
Ministry of Health, Kenya (Child & Adolescent Health)
Ministry of Health, Liberia (Family Health)
Ministry of Health, Malawi (Reproductive Health)
Ministry of Health, Mozambique (Child Health)
PSI
Promoting the Quality of Medicines/ United States Pharmacopeia
Save the Children/Saving Newborn Lives
SHOPS Plus/Abt Associates
Systems for Improved Access to Pharmaceuticals and Services/Management Sciences for Health
United Nations Children’s Fund
United States Agency for International Development
Universal Corporation Ltd. (Kenya)
University of Illinois at Chicago School of Nursing
University Research Co., LLC | Center for Human Services
World Health Organization

21. Coordinating global uptake
The Chlorhexidine Working Group accelerates introduction and scale up of chlorhexidine for umbilical cord care by:
Coordinating efforts for global policy development (e.g., WHO, EML, and WHO cord care recommendation).
Managing clinical, technical, and program knowledge.
Ensuring rational decision making for resource allocation and priority setting.
Identifying and troubleshooting issues that arise.
Aligning demand with high-quality supply.

22. 2011 Implementation/scale-up
Pilot introduction and/or policy alignment
Expressed interest
CWG provided TA to local manufacturers
2011

23. Implementation/scale-up
Pilot introduction and/or policy alignment
Expressed interest
CWG provided TA to local manufacturers
[Expressed interest - blue] 5 countries have expressed interest (Angola, Burkina Faso, Côte d’Ivoire, Lesotho, Papua New Guinea)
[Pilot introduction/policy alignment - orange] 14 countries have reached pilot/policy alignment (Afghanistan, Benin, Cameroon, Ghana, Haiti, Mali, Myanmar, Niger, Senegal, Timor-Leste, Uganda, Yemen, Zambia, Zimbabwe)
[Implementation/scale-up - green] 12 countries have reached introduction/scale-up (Bangladesh, DRC, Ethiopia, Kenya, Liberia, Madagascar, Malawi, Mozambique, Nepal, Nigeria, Pakistan, Sierra Leone)
2017

24. Twelve countries have added 7
Twelve countries have added 7.1% CHX to national Essential Medicines List (nEML)
Country
Year added
Nepal
2011
DRC
2014
Ethiopia
Mozambique
Madagascar
Myanmar
Mali
2015
Kenya
2016
Nigeria
Pakistan
Afghanistan
2017
Ghana

25. Nepal- Roadmap to Introduction
Page 25

26. Nigeria - Roadmap to Introduction
Formative research in Sokoto and Bauchi states. (2012)
Policymakers and key stakeholders hold technical meeting to introduce chlorhexidine (2012)
Introduction of chlorhexidine gel in Sokoto state (2013)
Inclusion of chlorhexidine on national Essential Medicines List (2013)
Launch of national scale-up strategy (2016)
Market research to inform strategy for national scale-up and effort to establish local production is complete ( )
Ministry of Health prioritizes chlorhexidine as a key newborn health commodity (2013)
Page 26

27. Madagascar - Roadmap to Introduction
MoH visit to Nepal to observe chlorhexidine intervention (2012)
Formative research on cord care practices and user preference ( )
Manufacturing landscape assessment conducted (2013)
Scale-up of Chlorhexidine for umbilical cord care (2014- present)
Pilot introduction of chlorhexidine gel in Mahabo region (2013)
Page 27

28. Liberia - Roadmap to Introduction
Key stakeholder/ policymaker technical meeting (2013)
Chlorhexidine policy approved to allow for home and facility births (2013)
Completion of user study preference study (2013)
Efforts to introduce and scale up chlorhexidine for umbilical cord care are ongoing (2015- present)
Due to Ebola outbreak all chlorhexidine activities were put on hold (2014)
Supply strategy assessment completed (2013)
Page 28

29. Kenya - Roadmap to Introduction
MoH policy aligned to include chlorhexidine for umbilical cord care (gel and liquid) (2013)
Market research conducted to determine distribution strategy (2014)
Manufacturing established at Universal Corporation, Nairobi (2014)
Managed Access Program in Bugoma County ( )
Implementation research in 5 counties ( )
Pilot introduction of chlorhexidine gel in Mahabo region (2013)
Page 29

30. Key Chlorhexidine Successes
Inclusion of CHX in WHO EMLc, WHO postnatal care guidelines, LiST, MANDATE, and the DHS Newborn Module. CHX available from 1 global and 7 local manufacturers. 17 countries approved market registration of a CHX product (Bangladesh, Benin, Cameroon, Cote d’Ivoire, DRC, Ethiopia, Ghana, Kenya, Liberia, Madagascar, Mozambique, Nepal, Niger, Nigeria, Tanzania/Zanzibar, Uganda, Zambia) 12 country and regional stakeholder meetings (Afghanistan, DRC, Kenya, Liberia, Madagascar, Malawi, Mozambique, Niger, Nigeria, Pakistan, Uganda, and regional meeting of Burkina Faso, Côte d’Ivoire, Niger, Senegal). 12 countries added CHX to their national EML (Afghanistan, DRC, Ethiopia, Ghana, Kenya, Madagascar, Mali, Myanmar, Mozambique, Nepal, Nigeria, Pakistan) 12 countries implementing /scaling-up (Bangladesh, DRC, Ethiopia, Kenya, Liberia, Madagascar, Malawi, Mozambique, Nepal, Nigeria, Pakistan, Sierra Leone). 14 countries aligning policy/piloting the intervention (Afghanistan, Benin, Cameroon, Ghana, Haiti, Mali, Myanmar, Niger, Senegal, Timor-Leste, Uganda, Yemen, Zambia, Zimbabwe). 5 countries have expressed interest (Angola, Burkina Faso, Côte d’Ivoire, Lesotho, Papua New Guinea). 36 journal articles.

31. CWG resource page on Healthy Newborn Network (HNN) website
for-umbilical-cord-care/
Materials for:
Consensus building
Building evidence for implementation
Aligning policies and guidelines
Demand generation and training
Manufacturing and distribution
Monitoring and evaluation

32. For additional information, please visit the chlorhexidine resource page on the healthy newborn network site.