7.

1% Chlorhexidine Digulconate
for Umbilical Cord Care
A summary of global introduction efforts, policy
evidence, and product availability
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
Evidence for chlorhexidine intervention
 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 2006 Arifeen 2012 Soofi 2012 Sazawal 2016 Semrau 2016
Nepal Bangladesh Pakistan Tanzania Zambia
Total live births 15,123 29,790 9,741 36 ,911 37,856
Schedule of
application Within 1st 24 hours, Daily until 3 days Daily until 3 days
Days 1,2,3,4,6,8,10 Daily for 14 days
then daily for 7 days after cord drops after cord drops

Intervention
Traditional birth
provider Mother or Mother or
Project staff Project staff attendant & mother/
caretaker caretaker
caretaker
First application
within 24 hours of 63% 87% 100% 94% 90%
birth
Application of other
substances to the ~½ few ~90% N/A ~10%
cord
% infants with
birthweight <2500g 30% 33% N/A 5% 7%
% health facility
births 8% 7% 0% 54% 64%
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.
Reduction in NMR in 5 chlorhexidine RCTs
*Statistically significant at 95% CI
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).
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.
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.
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.
Dosage form, regimen, and setting for use by
country
COUNTRY DOSAGE FORM REGIMEN LOCATION
BANGLADESH Liquid Single-day Community and Facility
DR CONGO Liquid & Gel Multiple-day Community and Facility
ETHIOPIA Gel Multiple-day Community and Facility
KENYA Gel Multiple-day Community and Facility
LIBERIA Liquid & Gel Multiple-day Community and Facility
MADAGASCAR Gel Single-day Community and Facility
MALAWI Gel Single-day Facility
MOZAMBIQUE Gel Single-day Facility and Community
NEPAL Gel Single-day Community and Facility
NIGERIA Gel Multiple-day Community and Facility
PAKISTAN Gel Multiple-day Community and Facility
Product availability and production
strategy
Three-pronged approach to enable access
to chlorhexidine products of high quality

Facilitate product Ensure approval

availability and procurement
through inclusion of appropriate
of chlorhexidine products through
in WHO Model development and
List of Essential Support dissemination of
Medicines. sustainable standardized
supply of high- information.
quality product
through
partnership with
manufacturers in
LMICs.
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?

YES NO

Local (or regional) production Import

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

Pre-purchase/sales inspections
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.
Manufacturers of 7.1% chlorhexidine
digluconate for umbilical cord care
(in alphabetical order).
Manufacturer Country of
Product Dosage form
(contact information) Origin
ACI Limited
Hexicord® Liquid Bangladesh
(http://www.aci-bd.com/)
Drugfield Pharmaceuticals Ltd.
Chlorxy-G® Gel Gel Nigeria
(http://www.drugfieldpharma.com/)
GSK United
Umbipro™ Gel
(http://www.gsk.com/) Kingdom*
Lomus Pharmaceutical Pvt. Ltd.
Kawach Gel Nepal
(http://www.lomus.com.np/)
Universal Corporation Ltd.
CHX Gel Gel Kenya
(http://ucl.co.ke/)
7.1% chlorhexidine digluconate for umbilical cord care can also be purchased from the UNICEF
Supply Division Catalogue (https://supply.unicef.org).
* 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.
 To accelerate global scale-up, CWG is
supporting local and regional manufacturing

GlaxoSmithKline
Brentford, England Lomus Pharmaceuticals
Received positive scientific Kathmandu, Nepal
opinion from European EMA 2010

ACI Limited
Drugfield Pharmaceuticals Dhaka, Bangladesh
Songo‐Atta, Nigeria 2015
2014 Assessment underway

Galentic Pharmaceuticals
Emzor Pharmaceutical Industries Ltd. Mumbai, India
Lagos, Nigeria Available through UNICEF
Addis Pharmaceutical Factory
Approved by NAFDAC. Manufacturing Supply
pending
Tuyil Pharmaceutical Industry Ltd.
Iloryn, Nigeria
Approved by NAFDAC. Manufacturing Universal Corporation
pending Kikuyu, Kenya, 2015

Countries which have local production

Countries which decided to import the product
Global collaboration for country
introduction and scale
 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] • Ministry of Health, Ethiopia (Maternal & Child Health)
• ayzh • Ministry of Health, Kenya (Child & Adolescent Health)
• Bill & Melinda Gates Foundation • Ministry of Health, Liberia (Family Health)
• Boston University • Ministry of Health, Malawi (Reproductive Health)
• Burnet Institute • Ministry of Health, Mozambique (Child Health)
• Centre for Infectious Disease Research in Zambia • PSI
• Clinton Health Access Initiative • Promoting the Quality of Medicines/ United States
• Drugfield Pharmaceuticals Ltd. (Nigeria) Pharmacopeia
• Duke University • Save the Children/Saving Newborn Lives
• GSK (UK) • SHOPS Plus/Abt Associates
• Global Health Action • Systems for Improved Access to Pharmaceuticals and
• Jhpiego Services/Management Sciences for Health
• John Snow, Inc. • United Nations Children’s Fund
• Johns Hopkins Bloomberg School of Public Health • United States Agency for International Development
• Johnson & Johnson (USA) • Universal Corporation Ltd. (Kenya)
• Lomus Pharmaceuticals Pvt. Ltd. (Nepal) • University of Illinois at Chicago School of Nursing
• Maternal and Child Survival Program • University Research Co., LLC | Center for Human Services
• Ministry of Health, DRC (Reproductive Health) • World Health Organization
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.

 Implementation/scale-up
Pilot introduction and/or policy alignment
Expressed interest

2011 CWG provided TA to local manufacturers

 Implementation/scale-up
Pilot introduction and/or policy alignment
Expressed interest

CWG provided TA to local manufacturers

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

Page 25 25
 Nigeria - Roadmap to Introduction

Launch of national
Market research scale-up strategy
to inform strategy (2016)
Inclusion of
chlorhexidine on for national scale-
national Essential up and effort to
Ministry of Health Medicines List establish local
prioritizes (2013) production is
chlorhexidine as a complete (2013-
Introduction of key newborn 2014)
chlorhexidine gel health commodity
in Sokoto state (2013)
(2013)
Policymakers and key
stakeholders hold technical
meeting to introduce
chlorhexidine (2012)
Formative research in
Sokoto and Bauchi
states. (2012)

Page 26 26
 Madagascar - Roadmap to Introduction

Scale-up of
Chlorhexidine for
umbilical cord care
Pilot introduction (2014- present)
of chlorhexidine
Manufacturing gel in Mahabo
landscape region (2013)
assessment
conducted (2013)

Formative research
on cord care
practices and user
preference (2012-
MoH visit to 2013)
Nepal to
observe
chlorhexidine
intervention
(2012)

Page 27 27
 Liberia - Roadmap to Introduction

Efforts to
Due to Ebola introduce and
outbreak all scale up
chlorhexidine chlorhexidine for
Completion of activities were put on umbilical cord
user study hold (2014)
preference study care are ongoing
Supply strategy (2013) (2015- present)
assessment
completed (2013)

Chlorhexidine policy
approved to allow
for home and facility
births (2013)
Key stakeholder/
policymaker
technical
meeting (2013)

Page 28 28
 Kenya - Roadmap to Introduction

Implementation
Managed Access research in 5 counties
Program in (2015-16)
Bugoma County
Pilot introduction of (2014-15)
chlorhexidine gel in
Mahabo region
Manufacturing (2013)
established at
Universal
Corporation, Nairobi
Market research (2014)
conducted to
determine
distribution strategy
(2014)
MoH policy aligned
to include
chlorhexidine for
umbilical cord care
(gel and liquid)
(2013)

Page 29 29
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.
CWG resource page on Healthy Newborn
Network (HNN) website
http://www.healthynewbornnetwork.org/issue/chlorhexidine-
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
For additional information,
please visit the chlorhexidine
resource page on the healthy
newborn network site.