©2016. ALL RIGHTS RESERVED.

USP role in strengthening local pharmaceutical

production to improve and sustain access to

quality-assured medicines

Midrand, Johannesburg, South Africa 27 - 29 March 2018

PharmaConnect Africa Conference 2018 Panel – Local Pharmaceutical Production

Paul Nkansah, Ph.D. Deputy Director – Technical United States Pharmacopeia Promoting the Quality of Medicines Program

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Promoting the quality

of medicines Program

The PQM program is funded by USAID

and implemented by USP. The USP PQM

program provides technical assistance to

strengthen medicines quality assurance

systems in countries and support

manufacturers to be able to produce

quality-assured priority medicines.

©2016. ALL RIGHTS RESERVED.

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USP-PQM role in enabling local pharma production

through capacity building

Chlorhexidine case study

Barriers to local pharmaceutical production and the

place of technology transfer

Concluding remarks

Outline

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USP-PQM Technical Assistance to Manufacturers

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Provide hands-on training and consultation to manufacturers

on process/product development and manufacturing

Provide guidance on API process and scale-up

Provide guidance on FPP development and scale-up

Support for product dossier

Hands-on trainings on dossier compilation according to CTD format

Consult on critical research to fulfill dossier requirements Support for facility cGMP compliance

Manufacturers – Facility GMP compliance Support for BE /GCP Compliance

Manufacturers/CROs – BE protocol design and review

Contract research organizations(CROs) – BE GCP compliance

Technical Assistance to Manufacturers

R

T

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Manufacturers supported 2009 - Present

102 manufacturers across 24 countries

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Products Approved With PQM Technical Assistance Product Manufacturer Approval Status Approval date Disease Area

1 Zinc Sulfate FPP Lab Pharma Rodael WHO PQ 2012 MNCH

2 Cycloserine FPP Dong-A Pharma WHO PQ 2012 TB

3 Streptomycin API Shengxue Pharma Spanish RA 2013 TB

4 Isoniazid API Second Pharma WHO PQ 2013 TB

5 Capreomycin API NCPC Pharma WHO PQ 2014 TB

6 Capreomycin API Hisun Pharma WHO PQ 2014 TB

7 Levofloxacin API Langhua Pharma WHO PQ 2014 TB

8 Mebendazole API Yabang Phama CEP 2014 NTD

9 Azithromycin FPP HEC Pharma WHO PQ 2014 TB

10 Capreomycin FPP Hisun Pharma WHO PQ 2014 TB

11 Moxifloxacin API Hisun Pharma WHO PQ 2015 TB

12,13 Kanamycin API ( non-sterile) Fuzhou Fuxin USFDA, WHO PQ 2015 TB

14 Zinc Sulfate FPP Chi Pharma UNICEF 2015 MNCH

15 Moxifloxacin API HEC Pharma CEP 2015 TB

16 Kanamycin FPP Interpharma/SHP Global Fund ERP 2015 TB

17 Kanamycin API (Sterile) Fuzhou Fuxin Pharm WHO PQ 2016 TB

18 Mebendazole API Changzhou Yabang Pharma WHO PQ 2016 NTD

19 Cycloserine API Dong-A Pharma WHO PQ 2016 TB

20 Streptomycin API NCPC Huasheng Pharma WHO PQ 2016 TB

21 Rifampicin API Shenyang Antibiotic Manufacturer WHO PQ 2016 TB

22 Levofloxacin API Shangyu Jingxin Pharma WHO PQ 2016 TB

23 Praziqauntel API Shanghai Jiayi Pharma CEP 2016 NTD

24 Cycloserine API Hisun Pharma WHO PQ 2016 TB

25 Streptomycin 1g power for injection, FPP NCPC WHO PQ 2017 TB

26 Oxytocin, FPP PT Sanbe Farma WHO PQ 2017 MNCH

27 Amoxicillin FPP Sanbe Pharma UNICEF ERP 2017 MNCH

28 Praziquantel API Hisun Pharmaceuticals WHO PQ 2017 NTD

29 Capreomycin FPP NCPC China WHO PQ 2017 TB

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Chlorhexidine case study

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Evidence for application CHX for prevention of umbilical cord infection and neonatal mortality

4. Soofi S, Cousens S, Imdad A, Bhutto N, Ali N, Bhutta ZA. Topical application of chlorhexidine to neonatal umbilical cords for prevention of omphalitis and neonatal

mortality in a rural district of Pakistan: a community-based, cluster-randomised trial. Lancet. 2012;379(9820):1029-1036. doi:10.1016/S0140-6736(11)61877-1.

5. Mullany LC, Darmstadt GL, Khatry SK, et al. Topical applications of chlorhexidine to the umbilical cord for prevention of omphalitis and neonatal mortality in

southern Nepal: A community-based, cluster-randomised trial. Lancet. 2006;367(9514):910-918. doi:10.1016/S0140-6736(06)68381-5.

6. Arifeen S El, Mullany LC, Shah R, et al. The effect of cord cleansing with chlorhexidine on neonatal mortality in rural Bangladesh: a community-based,

cluster-randomised trial. Lancet. 2012;379(9820):1022-1028. doi:10.1016/S0140-6736(11)61848-5.

7. Imdad A, Mullany LC, Baqui AH, et al. The effect of umbilical cord cleansing with chlorhexidine on omphalitis and neonatal mortality in community settings

in developing countries: a meta-analysis. BMC Public Health. 2013;13(Suppl 3):S15. doi:10.1186/1471-2458-13-S3-S15.

Region Reduction In Risk of

Newborn Umbilical

Infection

Reduction in Risk of

Neonatal Mortality

Community settings in

developing countries7 27-56% 23%

Nepal5 75% 24%

Bangladesh6 65% 20%

Pakistan4 42% 38%

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Chlorhexidine Experience in SSA

Nigeria 11 11 6 3

DRC 10 3 7 0

Kenya 7 7 5 2

Uganda 8 5 5 0

Ethiopia -- -- -- 8

EOI Completed

Questionnaires Rapid

Assessments GMP

Assessments

• 42%(13/31) of manufacturers that underwent GMP audit received technical assistance • Product development based on work done and published by USP/PATH/Lomus Pharma on

chlorhexidine digloconate 7.1% gel

• USP-PQM partnered with PATH, Chlorhexidine, Working Group(CWG), and the UN

Commission

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Baseline GMP rating from Ethiopia Roadmap

0 50 100

Mfg 1

Mfg 3

Mfg 5

Mfg 7

GMP Score (%)

Areas of Highest Noncompliance

Utilities*

Production

Premises*

QC laboratory*

Document management

QMS

Material handling*

> 80%: GMP compliance

*Findings from Kenya GMP Roadmap assessment

Inclusion of chlorhexidine in WHO model list of essential medicines • In 2013, based on application by USAID and HealthTech 7.1%

chlorhexidine digluconate was finally included in the WHO Model List for Essential Medicines.

• Facilitated the inclusion of chlorhexidine in national EMLs.

• Eliminated confusion with chlorhexidine for other applications.

4/4/2018 Page 12

Improved access through development and dissemination of standardized information • Monographs

• Topical solution monograph included in USP-NF.

• Gel monograph in new global health section of USP-NF (in 2016)

• Standardized patient information leaflet.

• Key consideration for procurers.

4/4/2018 Page 13

Status in 2011(beginning) Lomus Pharmaceuticals Kathmandu, Nepal 2010

Countries which have local production

Countries which decided to import the product

USP PQM history of chlorhexidine support

4/4/2018 Page 14

Status in 2017

Drugfield Pharmaceuticals Songo‐Atta, Nigeria 2014

Lomus Pharmaceuticals Kathmandu, Nepal 2010

Galentic Pharmaceuticals Mumbai, India

GlaxoSmithKline Brentford, England Received positive scientific opinion from European EMA

ACI Limited Dhaka, Bangladesh 2015

Pakistan ATCO Laboratories Ltd. Aspin Pharma Ltd., Akhai Pharmaceuticals Zafa Pharmaceuticals,

Universal Corporation Kikuyu, Kenya, 2015

Countries which have local production

Countries which decided to import the product

The Promoting the Quality of Medicines (PQM) program implemented by the US Pharmacopeia Convention (USP) and PATH are working to establish local and regional manufacturing hubs for chlorhexidine in Asia and Africa

Emzor Pharmaceutical Industries Ltd. Lagos, Nigeria

Tyil Pharmaceutical Industry Ltd. Iloryn, Nigeria

Addis Pharmaceutical Factory Addis Ababa, Ethiopia

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2017

Barriers to local pharmaceutical production

Human resource constraints and limited technical capacity

Poor quality systems and infrastructure (e.g., utilities, HVAC)

High production cost due to lack of auxiliary industries – e.g. for raw and

packaging materials, equipment repairs and calibration

Lack of economy of scale due to unfavorable market dynamics – unfair

competition, S/F medicines, donation programs

Lack of access to capital markets and high cost of financing

Lack of strong regulatory capacity and existing regulatory barriers

Lack of sound trade, economic and financial policies with linkage to countries

development priorities (e.g. UHC)

Lack of policy coherence across health, trade, finance, and science and

technology sectors 16

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Technology transfer as an enabler of local pharma production and medicines access • Tech Transfer can enable low- and middle-income countries to accelerate the

acquisition of knowledge, experience and equipment related to

pharmaceutical products and processes

• Tech transfer can increase reliability of supply and decrease reliance on

imports, raise competence of local workforce, and reverse “brain drain” from

low- and middle-income countries

• Technology transfer can create positive spillover effects into associated

industries and support public sector research and manufacturing infrastructure

• Transfer of technology is a key component of socio-economic development

• WHA resolution 61.21(2018) on Global Strategy and Plan of Action on Public

Health, Innovation and Intellectual Property focuses on local pharma production

and tech transfer as a means of promoting innovation, building capacity, and

improving medicines access

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+ Economic and public health benefits of a local pharma sector necessitates

deliberate interventions to address challenges with local production

+ More needs to be done in the areas of policies, upgrade of quality systems,

and capacity building, to enable local production

+ Governments must have clear health strategies that prioritize the enabling

of local manufacturing as a key element

+ Tech transfer can accelerate acquisition of knowledge, experience and equipment

necessary to build a strong local pharma sector

+ USP-PQM through its capacity building of manufacturers and NRAs, enables

medicines quality and access

+ GSK is partnering with USP to make available the formulation, process and other

technical data of their chlorhexidine gel (Umbipro) to local manufacturers

Concluding Remarks

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