17
PPH Medicines - the case for access to safe, effective medicines EAC Regional Meeting on Life- Saving Medicines for PPH Nairobi 12-13 December 2019
PPH Medicines -the case for access to safe effective medicines
EAC Regional Meeting on Life-Saving Medicines for PPH
Nairobi 12-13 December 2019
bull ldquoOxytocin doesnrsquot prevent PPH
Quality oxytocin doesrdquo
bull Dr Patrick Lukulay United States
Pharmacopoeia
Background
bull PPH is the leading cause of maternal mortality worldwide
bull WHO has recommended oxytocin a temperature-sensitive medicine as the first-line choice for prevention and treatment of PPH
bull Over the next ten years universal access to oxytocin and similar medicines could avert an estimated 41 million PPH cases and save 14 million lives
bull Keeping oxytocin cool is a challenge particularly in countries where daytime temperatures often exceed 30degC (86degF) electricity is unavailable or unreliable and adequate cold-chain infrastructure is lacking
bull Maintaining cold chain conditions is always difficult but especially so LMICs While most countries have functioning cold rooms at the national level the ability to maintain 2degC to 8degC storage declines at lower levels of the chain Many health care centers lack reliable electricity or functioning equipment
WHO Recommendations for the Prevention and Treatment of Postpartum Haemorrhage Geneva WHO 2012 Seligman B Liu X Economic Assessment of Interventions for Reducing Postpartum Haemorrhage in
Developing Countries Bethesda MD Abt Associates Inc 2006 Taking advantage of the true heat stability of vaccines Fact Sheet PATH July 2012
httpwwwpathorgpublicationsfilesTS_opt_ths_ctcpdf
Why are we talking about Quality
bull High maternal mortality continues in many parts of the world
bull One of the causes is poor quality medicine
bull Consistently demonstrated that Maternal Health medicines in LMICs are often of poor quality
bull Maternal mortality causes severe financial economic and social impacts
bull Quality concerns are behind new recommendations on uterotonics
What is a GOOD Quality medicine
A medicine that containsbull Exactly the specified amount of active ingredient needed to
achieve the expected resultbull The results when used are predictable and expected
bull Only those additional compounds that are necessary to make the active ingredient usable safe and effectivebull The medicine works exactly the way it is supposed to and
does not cause unexpected side-effects
bull Nothing elsebull There are no additionalforeign substances that could
cause adverse reactions or prevent the medicine from working correctly
POOR Quality and itrsquos effects ndash an oxytocin example
Quality Problem Effect
Contains too much active ingredient needed to achieve the expected result
Too much oxytocin can cause additional side effects andor contractions that are too strong
Contains too little active ingredient need to achieve the expected result
Failure of the uterus to contract continued bleeding hemorrhage additional surgical interventions use of additional drugs potential death
Contains anything else Medicines containing anything other than they are supposed to can cause serious and sometimes fatal consequences
In the case of injectables is not sterile Unsterile injectable medicines can cause serious infections and sometimes death
What are the causes of POOR Quality
bull Sub-standard spurious falsified counterfeit
bull Poor manufacturing
bull Cost cutting
bull Use of low quality or substitute ingredients
bull Poor quality or inappropriate packaging labelling
bull Incorrect processes
bull skipping essential processes
bull Unsterileunclean environment
bull Poor management
bull Degradation
bull Heat
bull Moisture
bull Lightbull Time
Process to ensure that a woman receives a quality medicine
Procedure Purpose
Pharmacopoeia Sets the standard for how the medicine is manufactured
Trials Demonstrate that the medicine works (and the appropriate dose method of delivery etc)
Manufacturingbull APIbull FPP labelling and
packaging
Needs to be done properly
Assessmentcertification Confirms that the medicine is manufactured correctly
Registration Provides country level control over medicine quality and suitability
Supply Chain To get the product to the end user in the correct state
Controls Testing and policing to ensure quality
Correct use Training materials equipment supplies and resources for medicine to be properly used
Medicines for PPH
bull Oxytocinbull Misoprostolbull Ergometrinebull CarbetocinHeat Stable
Carbetocinbull TXA
What do we know - Oxytocin qualitybull Stanton India 20141
bull Oxytocin ampoules outside manufacturer specification
bull 40 in Karnataka
bull 50 in Uttar Pradesh
bull 96 in Bagalkot
bull 100 in Hassan
bull WHO Systematic Review 20152
bull 456 of oxytocin samples failed quality tests (median prevalence of failed
samples)
bull USP Ghana 20133
bull 5562 of the 169 Oxytocin samples failed assay
bull UNCOLSC 20154
bull 64 of oxytocin injection samples non-compliant
bull USP and NAFDAC Study Nigeria 20185
bull 742 oxytocin samples failed
bull Govt of India Nationwide Survey India 20176
bull 413 of oxytocin samples were out of specification
WHO Prequalified 4
Grindeks Latvia (2015 2019)
PT Sanbe Farma Indonesia
(2017)
Steril-Gene Life Sciences
India (2019)
What do we know - Misoprostol quality
Hall Bangladesh Egypt Cambodia Kenya India Mexico Nigeria
Pakistan Peru and Viet Nam Nepal Argentina Indonesia the
Philippines and Kazakhstan 2011 and 2014-15
bull 40 were below 90 of labelled content
bull 14 contained no misoprostol at all
bull 5 were between 110 and 121 of LC (due to manufacturersrsquo
concern of degradation over time) WHO Prequalified 3
Cipla (2014)
China Resources Zizhu
(2016)
Acme Formulation (2016)
What do we know - Ergometrine quality
bull Stanton India 20141
bull Methylergometrine ampoules outside manufacturer
specification
bull 54 in Agra
bull 44 in Gorakhpur
bull USP Ghana 20133
bull 7374 of the 99 Ergometrine injection samples failed
assay
WHO Prequalified 0
What do we know ndash Tranexamic Acid (TXA) quality
Almost no public information
WHO Prequalified 0
EOI released
Temperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC
bull Accelerated and temperature cycling stability studies were performed with oxytocin ampoules procured by the United Nations Population Fund (UNFPA) from four manufacturers
bull Results All ampoules evaluated exhibited similar stability profiles under accelerated degradation conditions with the exception of one product formulated for le25degC storage where the rate of degradation increased at 50degC relative to other formulations
bull Conclusion Oxytocin ampoules labelled for non-refrigerated storage are no more stable than those labelled for cold-storage
bull Furthermore these products should not be procured for use in territories with high ambient temperatures where all oxytocin injection products should be supplied and stored under refrigerated conditions
Nguyen T Lambert P Minhas RS et alTemperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC an observational assessment under controlled accelerated and temperature cycling conditionsBMJ Open 20199e029083 doi 101136bmjopen-2019-029083
Tools
Accelerated stability study
summarising percentage oxytocin
content versus time profiles of products
labelled for refrigerated storage
(white symbols) compared with those
formulated for storage outside the
cold chain (black symbols) when stored at 30degC (A) 40degC (B) and 50degC
(C)
Tools
bull Manual for Procurement amp Supply of Quality-Assured Maternal Newborn and Child Health Commodities GHSC PSM
bull Oxytocin Quality ndash Evidence for Action Concept Foundation
bull Buy Quality Oxytocin ndash Keep It Cold RHSC USAID PATH
bull Appropriate Storage and Management of Oxytocin ndash A Key Commodity for Maternal Health WHOUNFPAUNICEF Joint Statement
References
bull Family Care International A Price too High to Bear The costs of maternal mortality to families and communities ndash Summary of Research Findings March 2014 Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl1)S4 doi1011861742-4755-12-S1-S4
bull Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl 1)S4 doi1011861742-4755-12-S1-S4
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Anyakora C Oni Y Ezedinachi U et al 2018 ldquoQuality medicines in maternal health results of oxytocin misoprostol magnesium sulfate and calcium gluconate quality auditsrdquo BMC Pregnancy and Childbirth Accessed January 31 2018 doi httpsdoiorg101186s12884-018-1671-y
bull National Institute of Biologicals 2017 Survey of Extent of Problems of Spurious and Not of Standard Quality Drugs in the Country 2014-16 Noida Ministry of Health amp Family Welfare Government of India Accessed 2017
bull WHO Drug Information Vol 30 No 1 2016 Quality of Misoprostol Hall P Concept Foundation httpappswhointmedicinedocsenmabstractJs22361en
bull Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis An evaluation from multi-country surveys and stakeholder interviews Nurse-Findlay et al Published December 27 2017 httpsdoiorg101371journalpmed1002473
bull ldquoOxytocin doesnrsquot prevent PPH
Quality oxytocin doesrdquo
bull Dr Patrick Lukulay United States
Pharmacopoeia
Background
bull PPH is the leading cause of maternal mortality worldwide
bull WHO has recommended oxytocin a temperature-sensitive medicine as the first-line choice for prevention and treatment of PPH
bull Over the next ten years universal access to oxytocin and similar medicines could avert an estimated 41 million PPH cases and save 14 million lives
bull Keeping oxytocin cool is a challenge particularly in countries where daytime temperatures often exceed 30degC (86degF) electricity is unavailable or unreliable and adequate cold-chain infrastructure is lacking
bull Maintaining cold chain conditions is always difficult but especially so LMICs While most countries have functioning cold rooms at the national level the ability to maintain 2degC to 8degC storage declines at lower levels of the chain Many health care centers lack reliable electricity or functioning equipment
WHO Recommendations for the Prevention and Treatment of Postpartum Haemorrhage Geneva WHO 2012 Seligman B Liu X Economic Assessment of Interventions for Reducing Postpartum Haemorrhage in
Developing Countries Bethesda MD Abt Associates Inc 2006 Taking advantage of the true heat stability of vaccines Fact Sheet PATH July 2012
httpwwwpathorgpublicationsfilesTS_opt_ths_ctcpdf
Why are we talking about Quality
bull High maternal mortality continues in many parts of the world
bull One of the causes is poor quality medicine
bull Consistently demonstrated that Maternal Health medicines in LMICs are often of poor quality
bull Maternal mortality causes severe financial economic and social impacts
bull Quality concerns are behind new recommendations on uterotonics
What is a GOOD Quality medicine
A medicine that containsbull Exactly the specified amount of active ingredient needed to
achieve the expected resultbull The results when used are predictable and expected
bull Only those additional compounds that are necessary to make the active ingredient usable safe and effectivebull The medicine works exactly the way it is supposed to and
does not cause unexpected side-effects
bull Nothing elsebull There are no additionalforeign substances that could
cause adverse reactions or prevent the medicine from working correctly
POOR Quality and itrsquos effects ndash an oxytocin example
Quality Problem Effect
Contains too much active ingredient needed to achieve the expected result
Too much oxytocin can cause additional side effects andor contractions that are too strong
Contains too little active ingredient need to achieve the expected result
Failure of the uterus to contract continued bleeding hemorrhage additional surgical interventions use of additional drugs potential death
Contains anything else Medicines containing anything other than they are supposed to can cause serious and sometimes fatal consequences
In the case of injectables is not sterile Unsterile injectable medicines can cause serious infections and sometimes death
What are the causes of POOR Quality
bull Sub-standard spurious falsified counterfeit
bull Poor manufacturing
bull Cost cutting
bull Use of low quality or substitute ingredients
bull Poor quality or inappropriate packaging labelling
bull Incorrect processes
bull skipping essential processes
bull Unsterileunclean environment
bull Poor management
bull Degradation
bull Heat
bull Moisture
bull Lightbull Time
Process to ensure that a woman receives a quality medicine
Procedure Purpose
Pharmacopoeia Sets the standard for how the medicine is manufactured
Trials Demonstrate that the medicine works (and the appropriate dose method of delivery etc)
Manufacturingbull APIbull FPP labelling and
packaging
Needs to be done properly
Assessmentcertification Confirms that the medicine is manufactured correctly
Registration Provides country level control over medicine quality and suitability
Supply Chain To get the product to the end user in the correct state
Controls Testing and policing to ensure quality
Correct use Training materials equipment supplies and resources for medicine to be properly used
Medicines for PPH
bull Oxytocinbull Misoprostolbull Ergometrinebull CarbetocinHeat Stable
Carbetocinbull TXA
What do we know - Oxytocin qualitybull Stanton India 20141
bull Oxytocin ampoules outside manufacturer specification
bull 40 in Karnataka
bull 50 in Uttar Pradesh
bull 96 in Bagalkot
bull 100 in Hassan
bull WHO Systematic Review 20152
bull 456 of oxytocin samples failed quality tests (median prevalence of failed
samples)
bull USP Ghana 20133
bull 5562 of the 169 Oxytocin samples failed assay
bull UNCOLSC 20154
bull 64 of oxytocin injection samples non-compliant
bull USP and NAFDAC Study Nigeria 20185
bull 742 oxytocin samples failed
bull Govt of India Nationwide Survey India 20176
bull 413 of oxytocin samples were out of specification
WHO Prequalified 4
Grindeks Latvia (2015 2019)
PT Sanbe Farma Indonesia
(2017)
Steril-Gene Life Sciences
India (2019)
What do we know - Misoprostol quality
Hall Bangladesh Egypt Cambodia Kenya India Mexico Nigeria
Pakistan Peru and Viet Nam Nepal Argentina Indonesia the
Philippines and Kazakhstan 2011 and 2014-15
bull 40 were below 90 of labelled content
bull 14 contained no misoprostol at all
bull 5 were between 110 and 121 of LC (due to manufacturersrsquo
concern of degradation over time) WHO Prequalified 3
Cipla (2014)
China Resources Zizhu
(2016)
Acme Formulation (2016)
What do we know - Ergometrine quality
bull Stanton India 20141
bull Methylergometrine ampoules outside manufacturer
specification
bull 54 in Agra
bull 44 in Gorakhpur
bull USP Ghana 20133
bull 7374 of the 99 Ergometrine injection samples failed
assay
WHO Prequalified 0
What do we know ndash Tranexamic Acid (TXA) quality
Almost no public information
WHO Prequalified 0
EOI released
Temperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC
bull Accelerated and temperature cycling stability studies were performed with oxytocin ampoules procured by the United Nations Population Fund (UNFPA) from four manufacturers
bull Results All ampoules evaluated exhibited similar stability profiles under accelerated degradation conditions with the exception of one product formulated for le25degC storage where the rate of degradation increased at 50degC relative to other formulations
bull Conclusion Oxytocin ampoules labelled for non-refrigerated storage are no more stable than those labelled for cold-storage
bull Furthermore these products should not be procured for use in territories with high ambient temperatures where all oxytocin injection products should be supplied and stored under refrigerated conditions
Nguyen T Lambert P Minhas RS et alTemperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC an observational assessment under controlled accelerated and temperature cycling conditionsBMJ Open 20199e029083 doi 101136bmjopen-2019-029083
Tools
Accelerated stability study
summarising percentage oxytocin
content versus time profiles of products
labelled for refrigerated storage
(white symbols) compared with those
formulated for storage outside the
cold chain (black symbols) when stored at 30degC (A) 40degC (B) and 50degC
(C)
Tools
bull Manual for Procurement amp Supply of Quality-Assured Maternal Newborn and Child Health Commodities GHSC PSM
bull Oxytocin Quality ndash Evidence for Action Concept Foundation
bull Buy Quality Oxytocin ndash Keep It Cold RHSC USAID PATH
bull Appropriate Storage and Management of Oxytocin ndash A Key Commodity for Maternal Health WHOUNFPAUNICEF Joint Statement
References
bull Family Care International A Price too High to Bear The costs of maternal mortality to families and communities ndash Summary of Research Findings March 2014 Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl1)S4 doi1011861742-4755-12-S1-S4
bull Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl 1)S4 doi1011861742-4755-12-S1-S4
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Anyakora C Oni Y Ezedinachi U et al 2018 ldquoQuality medicines in maternal health results of oxytocin misoprostol magnesium sulfate and calcium gluconate quality auditsrdquo BMC Pregnancy and Childbirth Accessed January 31 2018 doi httpsdoiorg101186s12884-018-1671-y
bull National Institute of Biologicals 2017 Survey of Extent of Problems of Spurious and Not of Standard Quality Drugs in the Country 2014-16 Noida Ministry of Health amp Family Welfare Government of India Accessed 2017
bull WHO Drug Information Vol 30 No 1 2016 Quality of Misoprostol Hall P Concept Foundation httpappswhointmedicinedocsenmabstractJs22361en
bull Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis An evaluation from multi-country surveys and stakeholder interviews Nurse-Findlay et al Published December 27 2017 httpsdoiorg101371journalpmed1002473
Background
bull PPH is the leading cause of maternal mortality worldwide
bull WHO has recommended oxytocin a temperature-sensitive medicine as the first-line choice for prevention and treatment of PPH
bull Over the next ten years universal access to oxytocin and similar medicines could avert an estimated 41 million PPH cases and save 14 million lives
bull Keeping oxytocin cool is a challenge particularly in countries where daytime temperatures often exceed 30degC (86degF) electricity is unavailable or unreliable and adequate cold-chain infrastructure is lacking
bull Maintaining cold chain conditions is always difficult but especially so LMICs While most countries have functioning cold rooms at the national level the ability to maintain 2degC to 8degC storage declines at lower levels of the chain Many health care centers lack reliable electricity or functioning equipment
WHO Recommendations for the Prevention and Treatment of Postpartum Haemorrhage Geneva WHO 2012 Seligman B Liu X Economic Assessment of Interventions for Reducing Postpartum Haemorrhage in
Developing Countries Bethesda MD Abt Associates Inc 2006 Taking advantage of the true heat stability of vaccines Fact Sheet PATH July 2012
httpwwwpathorgpublicationsfilesTS_opt_ths_ctcpdf
Why are we talking about Quality
bull High maternal mortality continues in many parts of the world
bull One of the causes is poor quality medicine
bull Consistently demonstrated that Maternal Health medicines in LMICs are often of poor quality
bull Maternal mortality causes severe financial economic and social impacts
bull Quality concerns are behind new recommendations on uterotonics
What is a GOOD Quality medicine
A medicine that containsbull Exactly the specified amount of active ingredient needed to
achieve the expected resultbull The results when used are predictable and expected
bull Only those additional compounds that are necessary to make the active ingredient usable safe and effectivebull The medicine works exactly the way it is supposed to and
does not cause unexpected side-effects
bull Nothing elsebull There are no additionalforeign substances that could
cause adverse reactions or prevent the medicine from working correctly
POOR Quality and itrsquos effects ndash an oxytocin example
Quality Problem Effect
Contains too much active ingredient needed to achieve the expected result
Too much oxytocin can cause additional side effects andor contractions that are too strong
Contains too little active ingredient need to achieve the expected result
Failure of the uterus to contract continued bleeding hemorrhage additional surgical interventions use of additional drugs potential death
Contains anything else Medicines containing anything other than they are supposed to can cause serious and sometimes fatal consequences
In the case of injectables is not sterile Unsterile injectable medicines can cause serious infections and sometimes death
What are the causes of POOR Quality
bull Sub-standard spurious falsified counterfeit
bull Poor manufacturing
bull Cost cutting
bull Use of low quality or substitute ingredients
bull Poor quality or inappropriate packaging labelling
bull Incorrect processes
bull skipping essential processes
bull Unsterileunclean environment
bull Poor management
bull Degradation
bull Heat
bull Moisture
bull Lightbull Time
Process to ensure that a woman receives a quality medicine
Procedure Purpose
Pharmacopoeia Sets the standard for how the medicine is manufactured
Trials Demonstrate that the medicine works (and the appropriate dose method of delivery etc)
Manufacturingbull APIbull FPP labelling and
packaging
Needs to be done properly
Assessmentcertification Confirms that the medicine is manufactured correctly
Registration Provides country level control over medicine quality and suitability
Supply Chain To get the product to the end user in the correct state
Controls Testing and policing to ensure quality
Correct use Training materials equipment supplies and resources for medicine to be properly used
Medicines for PPH
bull Oxytocinbull Misoprostolbull Ergometrinebull CarbetocinHeat Stable
Carbetocinbull TXA
What do we know - Oxytocin qualitybull Stanton India 20141
bull Oxytocin ampoules outside manufacturer specification
bull 40 in Karnataka
bull 50 in Uttar Pradesh
bull 96 in Bagalkot
bull 100 in Hassan
bull WHO Systematic Review 20152
bull 456 of oxytocin samples failed quality tests (median prevalence of failed
samples)
bull USP Ghana 20133
bull 5562 of the 169 Oxytocin samples failed assay
bull UNCOLSC 20154
bull 64 of oxytocin injection samples non-compliant
bull USP and NAFDAC Study Nigeria 20185
bull 742 oxytocin samples failed
bull Govt of India Nationwide Survey India 20176
bull 413 of oxytocin samples were out of specification
WHO Prequalified 4
Grindeks Latvia (2015 2019)
PT Sanbe Farma Indonesia
(2017)
Steril-Gene Life Sciences
India (2019)
What do we know - Misoprostol quality
Hall Bangladesh Egypt Cambodia Kenya India Mexico Nigeria
Pakistan Peru and Viet Nam Nepal Argentina Indonesia the
Philippines and Kazakhstan 2011 and 2014-15
bull 40 were below 90 of labelled content
bull 14 contained no misoprostol at all
bull 5 were between 110 and 121 of LC (due to manufacturersrsquo
concern of degradation over time) WHO Prequalified 3
Cipla (2014)
China Resources Zizhu
(2016)
Acme Formulation (2016)
What do we know - Ergometrine quality
bull Stanton India 20141
bull Methylergometrine ampoules outside manufacturer
specification
bull 54 in Agra
bull 44 in Gorakhpur
bull USP Ghana 20133
bull 7374 of the 99 Ergometrine injection samples failed
assay
WHO Prequalified 0
What do we know ndash Tranexamic Acid (TXA) quality
Almost no public information
WHO Prequalified 0
EOI released
Temperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC
bull Accelerated and temperature cycling stability studies were performed with oxytocin ampoules procured by the United Nations Population Fund (UNFPA) from four manufacturers
bull Results All ampoules evaluated exhibited similar stability profiles under accelerated degradation conditions with the exception of one product formulated for le25degC storage where the rate of degradation increased at 50degC relative to other formulations
bull Conclusion Oxytocin ampoules labelled for non-refrigerated storage are no more stable than those labelled for cold-storage
bull Furthermore these products should not be procured for use in territories with high ambient temperatures where all oxytocin injection products should be supplied and stored under refrigerated conditions
Nguyen T Lambert P Minhas RS et alTemperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC an observational assessment under controlled accelerated and temperature cycling conditionsBMJ Open 20199e029083 doi 101136bmjopen-2019-029083
Tools
Accelerated stability study
summarising percentage oxytocin
content versus time profiles of products
labelled for refrigerated storage
(white symbols) compared with those
formulated for storage outside the
cold chain (black symbols) when stored at 30degC (A) 40degC (B) and 50degC
(C)
Tools
bull Manual for Procurement amp Supply of Quality-Assured Maternal Newborn and Child Health Commodities GHSC PSM
bull Oxytocin Quality ndash Evidence for Action Concept Foundation
bull Buy Quality Oxytocin ndash Keep It Cold RHSC USAID PATH
bull Appropriate Storage and Management of Oxytocin ndash A Key Commodity for Maternal Health WHOUNFPAUNICEF Joint Statement
References
bull Family Care International A Price too High to Bear The costs of maternal mortality to families and communities ndash Summary of Research Findings March 2014 Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl1)S4 doi1011861742-4755-12-S1-S4
bull Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl 1)S4 doi1011861742-4755-12-S1-S4
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Anyakora C Oni Y Ezedinachi U et al 2018 ldquoQuality medicines in maternal health results of oxytocin misoprostol magnesium sulfate and calcium gluconate quality auditsrdquo BMC Pregnancy and Childbirth Accessed January 31 2018 doi httpsdoiorg101186s12884-018-1671-y
bull National Institute of Biologicals 2017 Survey of Extent of Problems of Spurious and Not of Standard Quality Drugs in the Country 2014-16 Noida Ministry of Health amp Family Welfare Government of India Accessed 2017
bull WHO Drug Information Vol 30 No 1 2016 Quality of Misoprostol Hall P Concept Foundation httpappswhointmedicinedocsenmabstractJs22361en
bull Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis An evaluation from multi-country surveys and stakeholder interviews Nurse-Findlay et al Published December 27 2017 httpsdoiorg101371journalpmed1002473
Why are we talking about Quality
bull High maternal mortality continues in many parts of the world
bull One of the causes is poor quality medicine
bull Consistently demonstrated that Maternal Health medicines in LMICs are often of poor quality
bull Maternal mortality causes severe financial economic and social impacts
bull Quality concerns are behind new recommendations on uterotonics
What is a GOOD Quality medicine
A medicine that containsbull Exactly the specified amount of active ingredient needed to
achieve the expected resultbull The results when used are predictable and expected
bull Only those additional compounds that are necessary to make the active ingredient usable safe and effectivebull The medicine works exactly the way it is supposed to and
does not cause unexpected side-effects
bull Nothing elsebull There are no additionalforeign substances that could
cause adverse reactions or prevent the medicine from working correctly
POOR Quality and itrsquos effects ndash an oxytocin example
Quality Problem Effect
Contains too much active ingredient needed to achieve the expected result
Too much oxytocin can cause additional side effects andor contractions that are too strong
Contains too little active ingredient need to achieve the expected result
Failure of the uterus to contract continued bleeding hemorrhage additional surgical interventions use of additional drugs potential death
Contains anything else Medicines containing anything other than they are supposed to can cause serious and sometimes fatal consequences
In the case of injectables is not sterile Unsterile injectable medicines can cause serious infections and sometimes death
What are the causes of POOR Quality
bull Sub-standard spurious falsified counterfeit
bull Poor manufacturing
bull Cost cutting
bull Use of low quality or substitute ingredients
bull Poor quality or inappropriate packaging labelling
bull Incorrect processes
bull skipping essential processes
bull Unsterileunclean environment
bull Poor management
bull Degradation
bull Heat
bull Moisture
bull Lightbull Time
Process to ensure that a woman receives a quality medicine
Procedure Purpose
Pharmacopoeia Sets the standard for how the medicine is manufactured
Trials Demonstrate that the medicine works (and the appropriate dose method of delivery etc)
Manufacturingbull APIbull FPP labelling and
packaging
Needs to be done properly
Assessmentcertification Confirms that the medicine is manufactured correctly
Registration Provides country level control over medicine quality and suitability
Supply Chain To get the product to the end user in the correct state
Controls Testing and policing to ensure quality
Correct use Training materials equipment supplies and resources for medicine to be properly used
Medicines for PPH
bull Oxytocinbull Misoprostolbull Ergometrinebull CarbetocinHeat Stable
Carbetocinbull TXA
What do we know - Oxytocin qualitybull Stanton India 20141
bull Oxytocin ampoules outside manufacturer specification
bull 40 in Karnataka
bull 50 in Uttar Pradesh
bull 96 in Bagalkot
bull 100 in Hassan
bull WHO Systematic Review 20152
bull 456 of oxytocin samples failed quality tests (median prevalence of failed
samples)
bull USP Ghana 20133
bull 5562 of the 169 Oxytocin samples failed assay
bull UNCOLSC 20154
bull 64 of oxytocin injection samples non-compliant
bull USP and NAFDAC Study Nigeria 20185
bull 742 oxytocin samples failed
bull Govt of India Nationwide Survey India 20176
bull 413 of oxytocin samples were out of specification
WHO Prequalified 4
Grindeks Latvia (2015 2019)
PT Sanbe Farma Indonesia
(2017)
Steril-Gene Life Sciences
India (2019)
What do we know - Misoprostol quality
Hall Bangladesh Egypt Cambodia Kenya India Mexico Nigeria
Pakistan Peru and Viet Nam Nepal Argentina Indonesia the
Philippines and Kazakhstan 2011 and 2014-15
bull 40 were below 90 of labelled content
bull 14 contained no misoprostol at all
bull 5 were between 110 and 121 of LC (due to manufacturersrsquo
concern of degradation over time) WHO Prequalified 3
Cipla (2014)
China Resources Zizhu
(2016)
Acme Formulation (2016)
What do we know - Ergometrine quality
bull Stanton India 20141
bull Methylergometrine ampoules outside manufacturer
specification
bull 54 in Agra
bull 44 in Gorakhpur
bull USP Ghana 20133
bull 7374 of the 99 Ergometrine injection samples failed
assay
WHO Prequalified 0
What do we know ndash Tranexamic Acid (TXA) quality
Almost no public information
WHO Prequalified 0
EOI released
Temperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC
bull Accelerated and temperature cycling stability studies were performed with oxytocin ampoules procured by the United Nations Population Fund (UNFPA) from four manufacturers
bull Results All ampoules evaluated exhibited similar stability profiles under accelerated degradation conditions with the exception of one product formulated for le25degC storage where the rate of degradation increased at 50degC relative to other formulations
bull Conclusion Oxytocin ampoules labelled for non-refrigerated storage are no more stable than those labelled for cold-storage
bull Furthermore these products should not be procured for use in territories with high ambient temperatures where all oxytocin injection products should be supplied and stored under refrigerated conditions
Nguyen T Lambert P Minhas RS et alTemperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC an observational assessment under controlled accelerated and temperature cycling conditionsBMJ Open 20199e029083 doi 101136bmjopen-2019-029083
Tools
Accelerated stability study
summarising percentage oxytocin
content versus time profiles of products
labelled for refrigerated storage
(white symbols) compared with those
formulated for storage outside the
cold chain (black symbols) when stored at 30degC (A) 40degC (B) and 50degC
(C)
Tools
bull Manual for Procurement amp Supply of Quality-Assured Maternal Newborn and Child Health Commodities GHSC PSM
bull Oxytocin Quality ndash Evidence for Action Concept Foundation
bull Buy Quality Oxytocin ndash Keep It Cold RHSC USAID PATH
bull Appropriate Storage and Management of Oxytocin ndash A Key Commodity for Maternal Health WHOUNFPAUNICEF Joint Statement
References
bull Family Care International A Price too High to Bear The costs of maternal mortality to families and communities ndash Summary of Research Findings March 2014 Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl1)S4 doi1011861742-4755-12-S1-S4
bull Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl 1)S4 doi1011861742-4755-12-S1-S4
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Anyakora C Oni Y Ezedinachi U et al 2018 ldquoQuality medicines in maternal health results of oxytocin misoprostol magnesium sulfate and calcium gluconate quality auditsrdquo BMC Pregnancy and Childbirth Accessed January 31 2018 doi httpsdoiorg101186s12884-018-1671-y
bull National Institute of Biologicals 2017 Survey of Extent of Problems of Spurious and Not of Standard Quality Drugs in the Country 2014-16 Noida Ministry of Health amp Family Welfare Government of India Accessed 2017
bull WHO Drug Information Vol 30 No 1 2016 Quality of Misoprostol Hall P Concept Foundation httpappswhointmedicinedocsenmabstractJs22361en
bull Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis An evaluation from multi-country surveys and stakeholder interviews Nurse-Findlay et al Published December 27 2017 httpsdoiorg101371journalpmed1002473
What is a GOOD Quality medicine
A medicine that containsbull Exactly the specified amount of active ingredient needed to
achieve the expected resultbull The results when used are predictable and expected
bull Only those additional compounds that are necessary to make the active ingredient usable safe and effectivebull The medicine works exactly the way it is supposed to and
does not cause unexpected side-effects
bull Nothing elsebull There are no additionalforeign substances that could
cause adverse reactions or prevent the medicine from working correctly
POOR Quality and itrsquos effects ndash an oxytocin example
Quality Problem Effect
Contains too much active ingredient needed to achieve the expected result
Too much oxytocin can cause additional side effects andor contractions that are too strong
Contains too little active ingredient need to achieve the expected result
Failure of the uterus to contract continued bleeding hemorrhage additional surgical interventions use of additional drugs potential death
Contains anything else Medicines containing anything other than they are supposed to can cause serious and sometimes fatal consequences
In the case of injectables is not sterile Unsterile injectable medicines can cause serious infections and sometimes death
What are the causes of POOR Quality
bull Sub-standard spurious falsified counterfeit
bull Poor manufacturing
bull Cost cutting
bull Use of low quality or substitute ingredients
bull Poor quality or inappropriate packaging labelling
bull Incorrect processes
bull skipping essential processes
bull Unsterileunclean environment
bull Poor management
bull Degradation
bull Heat
bull Moisture
bull Lightbull Time
Process to ensure that a woman receives a quality medicine
Procedure Purpose
Pharmacopoeia Sets the standard for how the medicine is manufactured
Trials Demonstrate that the medicine works (and the appropriate dose method of delivery etc)
Manufacturingbull APIbull FPP labelling and
packaging
Needs to be done properly
Assessmentcertification Confirms that the medicine is manufactured correctly
Registration Provides country level control over medicine quality and suitability
Supply Chain To get the product to the end user in the correct state
Controls Testing and policing to ensure quality
Correct use Training materials equipment supplies and resources for medicine to be properly used
Medicines for PPH
bull Oxytocinbull Misoprostolbull Ergometrinebull CarbetocinHeat Stable
Carbetocinbull TXA
What do we know - Oxytocin qualitybull Stanton India 20141
bull Oxytocin ampoules outside manufacturer specification
bull 40 in Karnataka
bull 50 in Uttar Pradesh
bull 96 in Bagalkot
bull 100 in Hassan
bull WHO Systematic Review 20152
bull 456 of oxytocin samples failed quality tests (median prevalence of failed
samples)
bull USP Ghana 20133
bull 5562 of the 169 Oxytocin samples failed assay
bull UNCOLSC 20154
bull 64 of oxytocin injection samples non-compliant
bull USP and NAFDAC Study Nigeria 20185
bull 742 oxytocin samples failed
bull Govt of India Nationwide Survey India 20176
bull 413 of oxytocin samples were out of specification
WHO Prequalified 4
Grindeks Latvia (2015 2019)
PT Sanbe Farma Indonesia
(2017)
Steril-Gene Life Sciences
India (2019)
What do we know - Misoprostol quality
Hall Bangladesh Egypt Cambodia Kenya India Mexico Nigeria
Pakistan Peru and Viet Nam Nepal Argentina Indonesia the
Philippines and Kazakhstan 2011 and 2014-15
bull 40 were below 90 of labelled content
bull 14 contained no misoprostol at all
bull 5 were between 110 and 121 of LC (due to manufacturersrsquo
concern of degradation over time) WHO Prequalified 3
Cipla (2014)
China Resources Zizhu
(2016)
Acme Formulation (2016)
What do we know - Ergometrine quality
bull Stanton India 20141
bull Methylergometrine ampoules outside manufacturer
specification
bull 54 in Agra
bull 44 in Gorakhpur
bull USP Ghana 20133
bull 7374 of the 99 Ergometrine injection samples failed
assay
WHO Prequalified 0
What do we know ndash Tranexamic Acid (TXA) quality
Almost no public information
WHO Prequalified 0
EOI released
Temperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC
bull Accelerated and temperature cycling stability studies were performed with oxytocin ampoules procured by the United Nations Population Fund (UNFPA) from four manufacturers
bull Results All ampoules evaluated exhibited similar stability profiles under accelerated degradation conditions with the exception of one product formulated for le25degC storage where the rate of degradation increased at 50degC relative to other formulations
bull Conclusion Oxytocin ampoules labelled for non-refrigerated storage are no more stable than those labelled for cold-storage
bull Furthermore these products should not be procured for use in territories with high ambient temperatures where all oxytocin injection products should be supplied and stored under refrigerated conditions
Nguyen T Lambert P Minhas RS et alTemperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC an observational assessment under controlled accelerated and temperature cycling conditionsBMJ Open 20199e029083 doi 101136bmjopen-2019-029083
Tools
Accelerated stability study
summarising percentage oxytocin
content versus time profiles of products
labelled for refrigerated storage
(white symbols) compared with those
formulated for storage outside the
cold chain (black symbols) when stored at 30degC (A) 40degC (B) and 50degC
(C)
Tools
bull Manual for Procurement amp Supply of Quality-Assured Maternal Newborn and Child Health Commodities GHSC PSM
bull Oxytocin Quality ndash Evidence for Action Concept Foundation
bull Buy Quality Oxytocin ndash Keep It Cold RHSC USAID PATH
bull Appropriate Storage and Management of Oxytocin ndash A Key Commodity for Maternal Health WHOUNFPAUNICEF Joint Statement
References
bull Family Care International A Price too High to Bear The costs of maternal mortality to families and communities ndash Summary of Research Findings March 2014 Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl1)S4 doi1011861742-4755-12-S1-S4
bull Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl 1)S4 doi1011861742-4755-12-S1-S4
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Anyakora C Oni Y Ezedinachi U et al 2018 ldquoQuality medicines in maternal health results of oxytocin misoprostol magnesium sulfate and calcium gluconate quality auditsrdquo BMC Pregnancy and Childbirth Accessed January 31 2018 doi httpsdoiorg101186s12884-018-1671-y
bull National Institute of Biologicals 2017 Survey of Extent of Problems of Spurious and Not of Standard Quality Drugs in the Country 2014-16 Noida Ministry of Health amp Family Welfare Government of India Accessed 2017
bull WHO Drug Information Vol 30 No 1 2016 Quality of Misoprostol Hall P Concept Foundation httpappswhointmedicinedocsenmabstractJs22361en
bull Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis An evaluation from multi-country surveys and stakeholder interviews Nurse-Findlay et al Published December 27 2017 httpsdoiorg101371journalpmed1002473
POOR Quality and itrsquos effects ndash an oxytocin example
Quality Problem Effect
Contains too much active ingredient needed to achieve the expected result
Too much oxytocin can cause additional side effects andor contractions that are too strong
Contains too little active ingredient need to achieve the expected result
Failure of the uterus to contract continued bleeding hemorrhage additional surgical interventions use of additional drugs potential death
Contains anything else Medicines containing anything other than they are supposed to can cause serious and sometimes fatal consequences
In the case of injectables is not sterile Unsterile injectable medicines can cause serious infections and sometimes death
What are the causes of POOR Quality
bull Sub-standard spurious falsified counterfeit
bull Poor manufacturing
bull Cost cutting
bull Use of low quality or substitute ingredients
bull Poor quality or inappropriate packaging labelling
bull Incorrect processes
bull skipping essential processes
bull Unsterileunclean environment
bull Poor management
bull Degradation
bull Heat
bull Moisture
bull Lightbull Time
Process to ensure that a woman receives a quality medicine
Procedure Purpose
Pharmacopoeia Sets the standard for how the medicine is manufactured
Trials Demonstrate that the medicine works (and the appropriate dose method of delivery etc)
Manufacturingbull APIbull FPP labelling and
packaging
Needs to be done properly
Assessmentcertification Confirms that the medicine is manufactured correctly
Registration Provides country level control over medicine quality and suitability
Supply Chain To get the product to the end user in the correct state
Controls Testing and policing to ensure quality
Correct use Training materials equipment supplies and resources for medicine to be properly used
Medicines for PPH
bull Oxytocinbull Misoprostolbull Ergometrinebull CarbetocinHeat Stable
Carbetocinbull TXA
What do we know - Oxytocin qualitybull Stanton India 20141
bull Oxytocin ampoules outside manufacturer specification
bull 40 in Karnataka
bull 50 in Uttar Pradesh
bull 96 in Bagalkot
bull 100 in Hassan
bull WHO Systematic Review 20152
bull 456 of oxytocin samples failed quality tests (median prevalence of failed
samples)
bull USP Ghana 20133
bull 5562 of the 169 Oxytocin samples failed assay
bull UNCOLSC 20154
bull 64 of oxytocin injection samples non-compliant
bull USP and NAFDAC Study Nigeria 20185
bull 742 oxytocin samples failed
bull Govt of India Nationwide Survey India 20176
bull 413 of oxytocin samples were out of specification
WHO Prequalified 4
Grindeks Latvia (2015 2019)
PT Sanbe Farma Indonesia
(2017)
Steril-Gene Life Sciences
India (2019)
What do we know - Misoprostol quality
Hall Bangladesh Egypt Cambodia Kenya India Mexico Nigeria
Pakistan Peru and Viet Nam Nepal Argentina Indonesia the
Philippines and Kazakhstan 2011 and 2014-15
bull 40 were below 90 of labelled content
bull 14 contained no misoprostol at all
bull 5 were between 110 and 121 of LC (due to manufacturersrsquo
concern of degradation over time) WHO Prequalified 3
Cipla (2014)
China Resources Zizhu
(2016)
Acme Formulation (2016)
What do we know - Ergometrine quality
bull Stanton India 20141
bull Methylergometrine ampoules outside manufacturer
specification
bull 54 in Agra
bull 44 in Gorakhpur
bull USP Ghana 20133
bull 7374 of the 99 Ergometrine injection samples failed
assay
WHO Prequalified 0
What do we know ndash Tranexamic Acid (TXA) quality
Almost no public information
WHO Prequalified 0
EOI released
Temperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC
bull Accelerated and temperature cycling stability studies were performed with oxytocin ampoules procured by the United Nations Population Fund (UNFPA) from four manufacturers
bull Results All ampoules evaluated exhibited similar stability profiles under accelerated degradation conditions with the exception of one product formulated for le25degC storage where the rate of degradation increased at 50degC relative to other formulations
bull Conclusion Oxytocin ampoules labelled for non-refrigerated storage are no more stable than those labelled for cold-storage
bull Furthermore these products should not be procured for use in territories with high ambient temperatures where all oxytocin injection products should be supplied and stored under refrigerated conditions
Nguyen T Lambert P Minhas RS et alTemperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC an observational assessment under controlled accelerated and temperature cycling conditionsBMJ Open 20199e029083 doi 101136bmjopen-2019-029083
Tools
Accelerated stability study
summarising percentage oxytocin
content versus time profiles of products
labelled for refrigerated storage
(white symbols) compared with those
formulated for storage outside the
cold chain (black symbols) when stored at 30degC (A) 40degC (B) and 50degC
(C)
Tools
bull Manual for Procurement amp Supply of Quality-Assured Maternal Newborn and Child Health Commodities GHSC PSM
bull Oxytocin Quality ndash Evidence for Action Concept Foundation
bull Buy Quality Oxytocin ndash Keep It Cold RHSC USAID PATH
bull Appropriate Storage and Management of Oxytocin ndash A Key Commodity for Maternal Health WHOUNFPAUNICEF Joint Statement
References
bull Family Care International A Price too High to Bear The costs of maternal mortality to families and communities ndash Summary of Research Findings March 2014 Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl1)S4 doi1011861742-4755-12-S1-S4
bull Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl 1)S4 doi1011861742-4755-12-S1-S4
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Anyakora C Oni Y Ezedinachi U et al 2018 ldquoQuality medicines in maternal health results of oxytocin misoprostol magnesium sulfate and calcium gluconate quality auditsrdquo BMC Pregnancy and Childbirth Accessed January 31 2018 doi httpsdoiorg101186s12884-018-1671-y
bull National Institute of Biologicals 2017 Survey of Extent of Problems of Spurious and Not of Standard Quality Drugs in the Country 2014-16 Noida Ministry of Health amp Family Welfare Government of India Accessed 2017
bull WHO Drug Information Vol 30 No 1 2016 Quality of Misoprostol Hall P Concept Foundation httpappswhointmedicinedocsenmabstractJs22361en
bull Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis An evaluation from multi-country surveys and stakeholder interviews Nurse-Findlay et al Published December 27 2017 httpsdoiorg101371journalpmed1002473
What are the causes of POOR Quality
bull Sub-standard spurious falsified counterfeit
bull Poor manufacturing
bull Cost cutting
bull Use of low quality or substitute ingredients
bull Poor quality or inappropriate packaging labelling
bull Incorrect processes
bull skipping essential processes
bull Unsterileunclean environment
bull Poor management
bull Degradation
bull Heat
bull Moisture
bull Lightbull Time
Process to ensure that a woman receives a quality medicine
Procedure Purpose
Pharmacopoeia Sets the standard for how the medicine is manufactured
Trials Demonstrate that the medicine works (and the appropriate dose method of delivery etc)
Manufacturingbull APIbull FPP labelling and
packaging
Needs to be done properly
Assessmentcertification Confirms that the medicine is manufactured correctly
Registration Provides country level control over medicine quality and suitability
Supply Chain To get the product to the end user in the correct state
Controls Testing and policing to ensure quality
Correct use Training materials equipment supplies and resources for medicine to be properly used
Medicines for PPH
bull Oxytocinbull Misoprostolbull Ergometrinebull CarbetocinHeat Stable
Carbetocinbull TXA
What do we know - Oxytocin qualitybull Stanton India 20141
bull Oxytocin ampoules outside manufacturer specification
bull 40 in Karnataka
bull 50 in Uttar Pradesh
bull 96 in Bagalkot
bull 100 in Hassan
bull WHO Systematic Review 20152
bull 456 of oxytocin samples failed quality tests (median prevalence of failed
samples)
bull USP Ghana 20133
bull 5562 of the 169 Oxytocin samples failed assay
bull UNCOLSC 20154
bull 64 of oxytocin injection samples non-compliant
bull USP and NAFDAC Study Nigeria 20185
bull 742 oxytocin samples failed
bull Govt of India Nationwide Survey India 20176
bull 413 of oxytocin samples were out of specification
WHO Prequalified 4
Grindeks Latvia (2015 2019)
PT Sanbe Farma Indonesia
(2017)
Steril-Gene Life Sciences
India (2019)
What do we know - Misoprostol quality
Hall Bangladesh Egypt Cambodia Kenya India Mexico Nigeria
Pakistan Peru and Viet Nam Nepal Argentina Indonesia the
Philippines and Kazakhstan 2011 and 2014-15
bull 40 were below 90 of labelled content
bull 14 contained no misoprostol at all
bull 5 were between 110 and 121 of LC (due to manufacturersrsquo
concern of degradation over time) WHO Prequalified 3
Cipla (2014)
China Resources Zizhu
(2016)
Acme Formulation (2016)
What do we know - Ergometrine quality
bull Stanton India 20141
bull Methylergometrine ampoules outside manufacturer
specification
bull 54 in Agra
bull 44 in Gorakhpur
bull USP Ghana 20133
bull 7374 of the 99 Ergometrine injection samples failed
assay
WHO Prequalified 0
What do we know ndash Tranexamic Acid (TXA) quality
Almost no public information
WHO Prequalified 0
EOI released
Temperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC
bull Accelerated and temperature cycling stability studies were performed with oxytocin ampoules procured by the United Nations Population Fund (UNFPA) from four manufacturers
bull Results All ampoules evaluated exhibited similar stability profiles under accelerated degradation conditions with the exception of one product formulated for le25degC storage where the rate of degradation increased at 50degC relative to other formulations
bull Conclusion Oxytocin ampoules labelled for non-refrigerated storage are no more stable than those labelled for cold-storage
bull Furthermore these products should not be procured for use in territories with high ambient temperatures where all oxytocin injection products should be supplied and stored under refrigerated conditions
Nguyen T Lambert P Minhas RS et alTemperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC an observational assessment under controlled accelerated and temperature cycling conditionsBMJ Open 20199e029083 doi 101136bmjopen-2019-029083
Tools
Accelerated stability study
summarising percentage oxytocin
content versus time profiles of products
labelled for refrigerated storage
(white symbols) compared with those
formulated for storage outside the
cold chain (black symbols) when stored at 30degC (A) 40degC (B) and 50degC
(C)
Tools
bull Manual for Procurement amp Supply of Quality-Assured Maternal Newborn and Child Health Commodities GHSC PSM
bull Oxytocin Quality ndash Evidence for Action Concept Foundation
bull Buy Quality Oxytocin ndash Keep It Cold RHSC USAID PATH
bull Appropriate Storage and Management of Oxytocin ndash A Key Commodity for Maternal Health WHOUNFPAUNICEF Joint Statement
References
bull Family Care International A Price too High to Bear The costs of maternal mortality to families and communities ndash Summary of Research Findings March 2014 Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl1)S4 doi1011861742-4755-12-S1-S4
bull Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl 1)S4 doi1011861742-4755-12-S1-S4
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Anyakora C Oni Y Ezedinachi U et al 2018 ldquoQuality medicines in maternal health results of oxytocin misoprostol magnesium sulfate and calcium gluconate quality auditsrdquo BMC Pregnancy and Childbirth Accessed January 31 2018 doi httpsdoiorg101186s12884-018-1671-y
bull National Institute of Biologicals 2017 Survey of Extent of Problems of Spurious and Not of Standard Quality Drugs in the Country 2014-16 Noida Ministry of Health amp Family Welfare Government of India Accessed 2017
bull WHO Drug Information Vol 30 No 1 2016 Quality of Misoprostol Hall P Concept Foundation httpappswhointmedicinedocsenmabstractJs22361en
bull Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis An evaluation from multi-country surveys and stakeholder interviews Nurse-Findlay et al Published December 27 2017 httpsdoiorg101371journalpmed1002473
Process to ensure that a woman receives a quality medicine
Procedure Purpose
Pharmacopoeia Sets the standard for how the medicine is manufactured
Trials Demonstrate that the medicine works (and the appropriate dose method of delivery etc)
Manufacturingbull APIbull FPP labelling and
packaging
Needs to be done properly
Assessmentcertification Confirms that the medicine is manufactured correctly
Registration Provides country level control over medicine quality and suitability
Supply Chain To get the product to the end user in the correct state
Controls Testing and policing to ensure quality
Correct use Training materials equipment supplies and resources for medicine to be properly used
Medicines for PPH
bull Oxytocinbull Misoprostolbull Ergometrinebull CarbetocinHeat Stable
Carbetocinbull TXA
What do we know - Oxytocin qualitybull Stanton India 20141
bull Oxytocin ampoules outside manufacturer specification
bull 40 in Karnataka
bull 50 in Uttar Pradesh
bull 96 in Bagalkot
bull 100 in Hassan
bull WHO Systematic Review 20152
bull 456 of oxytocin samples failed quality tests (median prevalence of failed
samples)
bull USP Ghana 20133
bull 5562 of the 169 Oxytocin samples failed assay
bull UNCOLSC 20154
bull 64 of oxytocin injection samples non-compliant
bull USP and NAFDAC Study Nigeria 20185
bull 742 oxytocin samples failed
bull Govt of India Nationwide Survey India 20176
bull 413 of oxytocin samples were out of specification
WHO Prequalified 4
Grindeks Latvia (2015 2019)
PT Sanbe Farma Indonesia
(2017)
Steril-Gene Life Sciences
India (2019)
What do we know - Misoprostol quality
Hall Bangladesh Egypt Cambodia Kenya India Mexico Nigeria
Pakistan Peru and Viet Nam Nepal Argentina Indonesia the
Philippines and Kazakhstan 2011 and 2014-15
bull 40 were below 90 of labelled content
bull 14 contained no misoprostol at all
bull 5 were between 110 and 121 of LC (due to manufacturersrsquo
concern of degradation over time) WHO Prequalified 3
Cipla (2014)
China Resources Zizhu
(2016)
Acme Formulation (2016)
What do we know - Ergometrine quality
bull Stanton India 20141
bull Methylergometrine ampoules outside manufacturer
specification
bull 54 in Agra
bull 44 in Gorakhpur
bull USP Ghana 20133
bull 7374 of the 99 Ergometrine injection samples failed
assay
WHO Prequalified 0
What do we know ndash Tranexamic Acid (TXA) quality
Almost no public information
WHO Prequalified 0
EOI released
Temperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC
bull Accelerated and temperature cycling stability studies were performed with oxytocin ampoules procured by the United Nations Population Fund (UNFPA) from four manufacturers
bull Results All ampoules evaluated exhibited similar stability profiles under accelerated degradation conditions with the exception of one product formulated for le25degC storage where the rate of degradation increased at 50degC relative to other formulations
bull Conclusion Oxytocin ampoules labelled for non-refrigerated storage are no more stable than those labelled for cold-storage
bull Furthermore these products should not be procured for use in territories with high ambient temperatures where all oxytocin injection products should be supplied and stored under refrigerated conditions
Nguyen T Lambert P Minhas RS et alTemperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC an observational assessment under controlled accelerated and temperature cycling conditionsBMJ Open 20199e029083 doi 101136bmjopen-2019-029083
Tools
Accelerated stability study
summarising percentage oxytocin
content versus time profiles of products
labelled for refrigerated storage
(white symbols) compared with those
formulated for storage outside the
cold chain (black symbols) when stored at 30degC (A) 40degC (B) and 50degC
(C)
Tools
bull Manual for Procurement amp Supply of Quality-Assured Maternal Newborn and Child Health Commodities GHSC PSM
bull Oxytocin Quality ndash Evidence for Action Concept Foundation
bull Buy Quality Oxytocin ndash Keep It Cold RHSC USAID PATH
bull Appropriate Storage and Management of Oxytocin ndash A Key Commodity for Maternal Health WHOUNFPAUNICEF Joint Statement
References
bull Family Care International A Price too High to Bear The costs of maternal mortality to families and communities ndash Summary of Research Findings March 2014 Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl1)S4 doi1011861742-4755-12-S1-S4
bull Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl 1)S4 doi1011861742-4755-12-S1-S4
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Anyakora C Oni Y Ezedinachi U et al 2018 ldquoQuality medicines in maternal health results of oxytocin misoprostol magnesium sulfate and calcium gluconate quality auditsrdquo BMC Pregnancy and Childbirth Accessed January 31 2018 doi httpsdoiorg101186s12884-018-1671-y
bull National Institute of Biologicals 2017 Survey of Extent of Problems of Spurious and Not of Standard Quality Drugs in the Country 2014-16 Noida Ministry of Health amp Family Welfare Government of India Accessed 2017
bull WHO Drug Information Vol 30 No 1 2016 Quality of Misoprostol Hall P Concept Foundation httpappswhointmedicinedocsenmabstractJs22361en
bull Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis An evaluation from multi-country surveys and stakeholder interviews Nurse-Findlay et al Published December 27 2017 httpsdoiorg101371journalpmed1002473
Medicines for PPH
bull Oxytocinbull Misoprostolbull Ergometrinebull CarbetocinHeat Stable
Carbetocinbull TXA
What do we know - Oxytocin qualitybull Stanton India 20141
bull Oxytocin ampoules outside manufacturer specification
bull 40 in Karnataka
bull 50 in Uttar Pradesh
bull 96 in Bagalkot
bull 100 in Hassan
bull WHO Systematic Review 20152
bull 456 of oxytocin samples failed quality tests (median prevalence of failed
samples)
bull USP Ghana 20133
bull 5562 of the 169 Oxytocin samples failed assay
bull UNCOLSC 20154
bull 64 of oxytocin injection samples non-compliant
bull USP and NAFDAC Study Nigeria 20185
bull 742 oxytocin samples failed
bull Govt of India Nationwide Survey India 20176
bull 413 of oxytocin samples were out of specification
WHO Prequalified 4
Grindeks Latvia (2015 2019)
PT Sanbe Farma Indonesia
(2017)
Steril-Gene Life Sciences
India (2019)
What do we know - Misoprostol quality
Hall Bangladesh Egypt Cambodia Kenya India Mexico Nigeria
Pakistan Peru and Viet Nam Nepal Argentina Indonesia the
Philippines and Kazakhstan 2011 and 2014-15
bull 40 were below 90 of labelled content
bull 14 contained no misoprostol at all
bull 5 were between 110 and 121 of LC (due to manufacturersrsquo
concern of degradation over time) WHO Prequalified 3
Cipla (2014)
China Resources Zizhu
(2016)
Acme Formulation (2016)
What do we know - Ergometrine quality
bull Stanton India 20141
bull Methylergometrine ampoules outside manufacturer
specification
bull 54 in Agra
bull 44 in Gorakhpur
bull USP Ghana 20133
bull 7374 of the 99 Ergometrine injection samples failed
assay
WHO Prequalified 0
What do we know ndash Tranexamic Acid (TXA) quality
Almost no public information
WHO Prequalified 0
EOI released
Temperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC
bull Accelerated and temperature cycling stability studies were performed with oxytocin ampoules procured by the United Nations Population Fund (UNFPA) from four manufacturers
bull Results All ampoules evaluated exhibited similar stability profiles under accelerated degradation conditions with the exception of one product formulated for le25degC storage where the rate of degradation increased at 50degC relative to other formulations
bull Conclusion Oxytocin ampoules labelled for non-refrigerated storage are no more stable than those labelled for cold-storage
bull Furthermore these products should not be procured for use in territories with high ambient temperatures where all oxytocin injection products should be supplied and stored under refrigerated conditions
Nguyen T Lambert P Minhas RS et alTemperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC an observational assessment under controlled accelerated and temperature cycling conditionsBMJ Open 20199e029083 doi 101136bmjopen-2019-029083
Tools
Accelerated stability study
summarising percentage oxytocin
content versus time profiles of products
labelled for refrigerated storage
(white symbols) compared with those
formulated for storage outside the
cold chain (black symbols) when stored at 30degC (A) 40degC (B) and 50degC
(C)
Tools
bull Manual for Procurement amp Supply of Quality-Assured Maternal Newborn and Child Health Commodities GHSC PSM
bull Oxytocin Quality ndash Evidence for Action Concept Foundation
bull Buy Quality Oxytocin ndash Keep It Cold RHSC USAID PATH
bull Appropriate Storage and Management of Oxytocin ndash A Key Commodity for Maternal Health WHOUNFPAUNICEF Joint Statement
References
bull Family Care International A Price too High to Bear The costs of maternal mortality to families and communities ndash Summary of Research Findings March 2014 Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl1)S4 doi1011861742-4755-12-S1-S4
bull Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl 1)S4 doi1011861742-4755-12-S1-S4
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Anyakora C Oni Y Ezedinachi U et al 2018 ldquoQuality medicines in maternal health results of oxytocin misoprostol magnesium sulfate and calcium gluconate quality auditsrdquo BMC Pregnancy and Childbirth Accessed January 31 2018 doi httpsdoiorg101186s12884-018-1671-y
bull National Institute of Biologicals 2017 Survey of Extent of Problems of Spurious and Not of Standard Quality Drugs in the Country 2014-16 Noida Ministry of Health amp Family Welfare Government of India Accessed 2017
bull WHO Drug Information Vol 30 No 1 2016 Quality of Misoprostol Hall P Concept Foundation httpappswhointmedicinedocsenmabstractJs22361en
bull Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis An evaluation from multi-country surveys and stakeholder interviews Nurse-Findlay et al Published December 27 2017 httpsdoiorg101371journalpmed1002473
What do we know - Oxytocin qualitybull Stanton India 20141
bull Oxytocin ampoules outside manufacturer specification
bull 40 in Karnataka
bull 50 in Uttar Pradesh
bull 96 in Bagalkot
bull 100 in Hassan
bull WHO Systematic Review 20152
bull 456 of oxytocin samples failed quality tests (median prevalence of failed
samples)
bull USP Ghana 20133
bull 5562 of the 169 Oxytocin samples failed assay
bull UNCOLSC 20154
bull 64 of oxytocin injection samples non-compliant
bull USP and NAFDAC Study Nigeria 20185
bull 742 oxytocin samples failed
bull Govt of India Nationwide Survey India 20176
bull 413 of oxytocin samples were out of specification
WHO Prequalified 4
Grindeks Latvia (2015 2019)
PT Sanbe Farma Indonesia
(2017)
Steril-Gene Life Sciences
India (2019)
What do we know - Misoprostol quality
Hall Bangladesh Egypt Cambodia Kenya India Mexico Nigeria
Pakistan Peru and Viet Nam Nepal Argentina Indonesia the
Philippines and Kazakhstan 2011 and 2014-15
bull 40 were below 90 of labelled content
bull 14 contained no misoprostol at all
bull 5 were between 110 and 121 of LC (due to manufacturersrsquo
concern of degradation over time) WHO Prequalified 3
Cipla (2014)
China Resources Zizhu
(2016)
Acme Formulation (2016)
What do we know - Ergometrine quality
bull Stanton India 20141
bull Methylergometrine ampoules outside manufacturer
specification
bull 54 in Agra
bull 44 in Gorakhpur
bull USP Ghana 20133
bull 7374 of the 99 Ergometrine injection samples failed
assay
WHO Prequalified 0
What do we know ndash Tranexamic Acid (TXA) quality
Almost no public information
WHO Prequalified 0
EOI released
Temperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC
bull Accelerated and temperature cycling stability studies were performed with oxytocin ampoules procured by the United Nations Population Fund (UNFPA) from four manufacturers
bull Results All ampoules evaluated exhibited similar stability profiles under accelerated degradation conditions with the exception of one product formulated for le25degC storage where the rate of degradation increased at 50degC relative to other formulations
bull Conclusion Oxytocin ampoules labelled for non-refrigerated storage are no more stable than those labelled for cold-storage
bull Furthermore these products should not be procured for use in territories with high ambient temperatures where all oxytocin injection products should be supplied and stored under refrigerated conditions
Nguyen T Lambert P Minhas RS et alTemperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC an observational assessment under controlled accelerated and temperature cycling conditionsBMJ Open 20199e029083 doi 101136bmjopen-2019-029083
Tools
Accelerated stability study
summarising percentage oxytocin
content versus time profiles of products
labelled for refrigerated storage
(white symbols) compared with those
formulated for storage outside the
cold chain (black symbols) when stored at 30degC (A) 40degC (B) and 50degC
(C)
Tools
bull Manual for Procurement amp Supply of Quality-Assured Maternal Newborn and Child Health Commodities GHSC PSM
bull Oxytocin Quality ndash Evidence for Action Concept Foundation
bull Buy Quality Oxytocin ndash Keep It Cold RHSC USAID PATH
bull Appropriate Storage and Management of Oxytocin ndash A Key Commodity for Maternal Health WHOUNFPAUNICEF Joint Statement
References
bull Family Care International A Price too High to Bear The costs of maternal mortality to families and communities ndash Summary of Research Findings March 2014 Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl1)S4 doi1011861742-4755-12-S1-S4
bull Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl 1)S4 doi1011861742-4755-12-S1-S4
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Anyakora C Oni Y Ezedinachi U et al 2018 ldquoQuality medicines in maternal health results of oxytocin misoprostol magnesium sulfate and calcium gluconate quality auditsrdquo BMC Pregnancy and Childbirth Accessed January 31 2018 doi httpsdoiorg101186s12884-018-1671-y
bull National Institute of Biologicals 2017 Survey of Extent of Problems of Spurious and Not of Standard Quality Drugs in the Country 2014-16 Noida Ministry of Health amp Family Welfare Government of India Accessed 2017
bull WHO Drug Information Vol 30 No 1 2016 Quality of Misoprostol Hall P Concept Foundation httpappswhointmedicinedocsenmabstractJs22361en
bull Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis An evaluation from multi-country surveys and stakeholder interviews Nurse-Findlay et al Published December 27 2017 httpsdoiorg101371journalpmed1002473
What do we know - Misoprostol quality
Hall Bangladesh Egypt Cambodia Kenya India Mexico Nigeria
Pakistan Peru and Viet Nam Nepal Argentina Indonesia the
Philippines and Kazakhstan 2011 and 2014-15
bull 40 were below 90 of labelled content
bull 14 contained no misoprostol at all
bull 5 were between 110 and 121 of LC (due to manufacturersrsquo
concern of degradation over time) WHO Prequalified 3
Cipla (2014)
China Resources Zizhu
(2016)
Acme Formulation (2016)
What do we know - Ergometrine quality
bull Stanton India 20141
bull Methylergometrine ampoules outside manufacturer
specification
bull 54 in Agra
bull 44 in Gorakhpur
bull USP Ghana 20133
bull 7374 of the 99 Ergometrine injection samples failed
assay
WHO Prequalified 0
What do we know ndash Tranexamic Acid (TXA) quality
Almost no public information
WHO Prequalified 0
EOI released
Temperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC
bull Accelerated and temperature cycling stability studies were performed with oxytocin ampoules procured by the United Nations Population Fund (UNFPA) from four manufacturers
bull Results All ampoules evaluated exhibited similar stability profiles under accelerated degradation conditions with the exception of one product formulated for le25degC storage where the rate of degradation increased at 50degC relative to other formulations
bull Conclusion Oxytocin ampoules labelled for non-refrigerated storage are no more stable than those labelled for cold-storage
bull Furthermore these products should not be procured for use in territories with high ambient temperatures where all oxytocin injection products should be supplied and stored under refrigerated conditions
Nguyen T Lambert P Minhas RS et alTemperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC an observational assessment under controlled accelerated and temperature cycling conditionsBMJ Open 20199e029083 doi 101136bmjopen-2019-029083
Tools
Accelerated stability study
summarising percentage oxytocin
content versus time profiles of products
labelled for refrigerated storage
(white symbols) compared with those
formulated for storage outside the
cold chain (black symbols) when stored at 30degC (A) 40degC (B) and 50degC
(C)
Tools
bull Manual for Procurement amp Supply of Quality-Assured Maternal Newborn and Child Health Commodities GHSC PSM
bull Oxytocin Quality ndash Evidence for Action Concept Foundation
bull Buy Quality Oxytocin ndash Keep It Cold RHSC USAID PATH
bull Appropriate Storage and Management of Oxytocin ndash A Key Commodity for Maternal Health WHOUNFPAUNICEF Joint Statement
References
bull Family Care International A Price too High to Bear The costs of maternal mortality to families and communities ndash Summary of Research Findings March 2014 Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl1)S4 doi1011861742-4755-12-S1-S4
bull Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl 1)S4 doi1011861742-4755-12-S1-S4
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Anyakora C Oni Y Ezedinachi U et al 2018 ldquoQuality medicines in maternal health results of oxytocin misoprostol magnesium sulfate and calcium gluconate quality auditsrdquo BMC Pregnancy and Childbirth Accessed January 31 2018 doi httpsdoiorg101186s12884-018-1671-y
bull National Institute of Biologicals 2017 Survey of Extent of Problems of Spurious and Not of Standard Quality Drugs in the Country 2014-16 Noida Ministry of Health amp Family Welfare Government of India Accessed 2017
bull WHO Drug Information Vol 30 No 1 2016 Quality of Misoprostol Hall P Concept Foundation httpappswhointmedicinedocsenmabstractJs22361en
bull Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis An evaluation from multi-country surveys and stakeholder interviews Nurse-Findlay et al Published December 27 2017 httpsdoiorg101371journalpmed1002473
What do we know - Ergometrine quality
bull Stanton India 20141
bull Methylergometrine ampoules outside manufacturer
specification
bull 54 in Agra
bull 44 in Gorakhpur
bull USP Ghana 20133
bull 7374 of the 99 Ergometrine injection samples failed
assay
WHO Prequalified 0
What do we know ndash Tranexamic Acid (TXA) quality
Almost no public information
WHO Prequalified 0
EOI released
Temperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC
bull Accelerated and temperature cycling stability studies were performed with oxytocin ampoules procured by the United Nations Population Fund (UNFPA) from four manufacturers
bull Results All ampoules evaluated exhibited similar stability profiles under accelerated degradation conditions with the exception of one product formulated for le25degC storage where the rate of degradation increased at 50degC relative to other formulations
bull Conclusion Oxytocin ampoules labelled for non-refrigerated storage are no more stable than those labelled for cold-storage
bull Furthermore these products should not be procured for use in territories with high ambient temperatures where all oxytocin injection products should be supplied and stored under refrigerated conditions
Nguyen T Lambert P Minhas RS et alTemperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC an observational assessment under controlled accelerated and temperature cycling conditionsBMJ Open 20199e029083 doi 101136bmjopen-2019-029083
Tools
Accelerated stability study
summarising percentage oxytocin
content versus time profiles of products
labelled for refrigerated storage
(white symbols) compared with those
formulated for storage outside the
cold chain (black symbols) when stored at 30degC (A) 40degC (B) and 50degC
(C)
Tools
bull Manual for Procurement amp Supply of Quality-Assured Maternal Newborn and Child Health Commodities GHSC PSM
bull Oxytocin Quality ndash Evidence for Action Concept Foundation
bull Buy Quality Oxytocin ndash Keep It Cold RHSC USAID PATH
bull Appropriate Storage and Management of Oxytocin ndash A Key Commodity for Maternal Health WHOUNFPAUNICEF Joint Statement
References
bull Family Care International A Price too High to Bear The costs of maternal mortality to families and communities ndash Summary of Research Findings March 2014 Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl1)S4 doi1011861742-4755-12-S1-S4
bull Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl 1)S4 doi1011861742-4755-12-S1-S4
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Anyakora C Oni Y Ezedinachi U et al 2018 ldquoQuality medicines in maternal health results of oxytocin misoprostol magnesium sulfate and calcium gluconate quality auditsrdquo BMC Pregnancy and Childbirth Accessed January 31 2018 doi httpsdoiorg101186s12884-018-1671-y
bull National Institute of Biologicals 2017 Survey of Extent of Problems of Spurious and Not of Standard Quality Drugs in the Country 2014-16 Noida Ministry of Health amp Family Welfare Government of India Accessed 2017
bull WHO Drug Information Vol 30 No 1 2016 Quality of Misoprostol Hall P Concept Foundation httpappswhointmedicinedocsenmabstractJs22361en
bull Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis An evaluation from multi-country surveys and stakeholder interviews Nurse-Findlay et al Published December 27 2017 httpsdoiorg101371journalpmed1002473
What do we know ndash Tranexamic Acid (TXA) quality
Almost no public information
WHO Prequalified 0
EOI released
Temperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC
bull Accelerated and temperature cycling stability studies were performed with oxytocin ampoules procured by the United Nations Population Fund (UNFPA) from four manufacturers
bull Results All ampoules evaluated exhibited similar stability profiles under accelerated degradation conditions with the exception of one product formulated for le25degC storage where the rate of degradation increased at 50degC relative to other formulations
bull Conclusion Oxytocin ampoules labelled for non-refrigerated storage are no more stable than those labelled for cold-storage
bull Furthermore these products should not be procured for use in territories with high ambient temperatures where all oxytocin injection products should be supplied and stored under refrigerated conditions
Nguyen T Lambert P Minhas RS et alTemperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC an observational assessment under controlled accelerated and temperature cycling conditionsBMJ Open 20199e029083 doi 101136bmjopen-2019-029083
Tools
Accelerated stability study
summarising percentage oxytocin
content versus time profiles of products
labelled for refrigerated storage
(white symbols) compared with those
formulated for storage outside the
cold chain (black symbols) when stored at 30degC (A) 40degC (B) and 50degC
(C)
Tools
bull Manual for Procurement amp Supply of Quality-Assured Maternal Newborn and Child Health Commodities GHSC PSM
bull Oxytocin Quality ndash Evidence for Action Concept Foundation
bull Buy Quality Oxytocin ndash Keep It Cold RHSC USAID PATH
bull Appropriate Storage and Management of Oxytocin ndash A Key Commodity for Maternal Health WHOUNFPAUNICEF Joint Statement
References
bull Family Care International A Price too High to Bear The costs of maternal mortality to families and communities ndash Summary of Research Findings March 2014 Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl1)S4 doi1011861742-4755-12-S1-S4
bull Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl 1)S4 doi1011861742-4755-12-S1-S4
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Anyakora C Oni Y Ezedinachi U et al 2018 ldquoQuality medicines in maternal health results of oxytocin misoprostol magnesium sulfate and calcium gluconate quality auditsrdquo BMC Pregnancy and Childbirth Accessed January 31 2018 doi httpsdoiorg101186s12884-018-1671-y
bull National Institute of Biologicals 2017 Survey of Extent of Problems of Spurious and Not of Standard Quality Drugs in the Country 2014-16 Noida Ministry of Health amp Family Welfare Government of India Accessed 2017
bull WHO Drug Information Vol 30 No 1 2016 Quality of Misoprostol Hall P Concept Foundation httpappswhointmedicinedocsenmabstractJs22361en
bull Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis An evaluation from multi-country surveys and stakeholder interviews Nurse-Findlay et al Published December 27 2017 httpsdoiorg101371journalpmed1002473
Temperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC
bull Accelerated and temperature cycling stability studies were performed with oxytocin ampoules procured by the United Nations Population Fund (UNFPA) from four manufacturers
bull Results All ampoules evaluated exhibited similar stability profiles under accelerated degradation conditions with the exception of one product formulated for le25degC storage where the rate of degradation increased at 50degC relative to other formulations
bull Conclusion Oxytocin ampoules labelled for non-refrigerated storage are no more stable than those labelled for cold-storage
bull Furthermore these products should not be procured for use in territories with high ambient temperatures where all oxytocin injection products should be supplied and stored under refrigerated conditions
Nguyen T Lambert P Minhas RS et alTemperature stability of oxytocin ampoules labelled for storage at 2degCndash8degC and below 25degC an observational assessment under controlled accelerated and temperature cycling conditionsBMJ Open 20199e029083 doi 101136bmjopen-2019-029083
Tools
Accelerated stability study
summarising percentage oxytocin
content versus time profiles of products
labelled for refrigerated storage
(white symbols) compared with those
formulated for storage outside the
cold chain (black symbols) when stored at 30degC (A) 40degC (B) and 50degC
(C)
Tools
bull Manual for Procurement amp Supply of Quality-Assured Maternal Newborn and Child Health Commodities GHSC PSM
bull Oxytocin Quality ndash Evidence for Action Concept Foundation
bull Buy Quality Oxytocin ndash Keep It Cold RHSC USAID PATH
bull Appropriate Storage and Management of Oxytocin ndash A Key Commodity for Maternal Health WHOUNFPAUNICEF Joint Statement
References
bull Family Care International A Price too High to Bear The costs of maternal mortality to families and communities ndash Summary of Research Findings March 2014 Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl1)S4 doi1011861742-4755-12-S1-S4
bull Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl 1)S4 doi1011861742-4755-12-S1-S4
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Anyakora C Oni Y Ezedinachi U et al 2018 ldquoQuality medicines in maternal health results of oxytocin misoprostol magnesium sulfate and calcium gluconate quality auditsrdquo BMC Pregnancy and Childbirth Accessed January 31 2018 doi httpsdoiorg101186s12884-018-1671-y
bull National Institute of Biologicals 2017 Survey of Extent of Problems of Spurious and Not of Standard Quality Drugs in the Country 2014-16 Noida Ministry of Health amp Family Welfare Government of India Accessed 2017
bull WHO Drug Information Vol 30 No 1 2016 Quality of Misoprostol Hall P Concept Foundation httpappswhointmedicinedocsenmabstractJs22361en
bull Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis An evaluation from multi-country surveys and stakeholder interviews Nurse-Findlay et al Published December 27 2017 httpsdoiorg101371journalpmed1002473
Tools
Accelerated stability study
summarising percentage oxytocin
content versus time profiles of products
labelled for refrigerated storage
(white symbols) compared with those
formulated for storage outside the
cold chain (black symbols) when stored at 30degC (A) 40degC (B) and 50degC
(C)
Tools
bull Manual for Procurement amp Supply of Quality-Assured Maternal Newborn and Child Health Commodities GHSC PSM
bull Oxytocin Quality ndash Evidence for Action Concept Foundation
bull Buy Quality Oxytocin ndash Keep It Cold RHSC USAID PATH
bull Appropriate Storage and Management of Oxytocin ndash A Key Commodity for Maternal Health WHOUNFPAUNICEF Joint Statement
References
bull Family Care International A Price too High to Bear The costs of maternal mortality to families and communities ndash Summary of Research Findings March 2014 Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl1)S4 doi1011861742-4755-12-S1-S4
bull Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl 1)S4 doi1011861742-4755-12-S1-S4
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Anyakora C Oni Y Ezedinachi U et al 2018 ldquoQuality medicines in maternal health results of oxytocin misoprostol magnesium sulfate and calcium gluconate quality auditsrdquo BMC Pregnancy and Childbirth Accessed January 31 2018 doi httpsdoiorg101186s12884-018-1671-y
bull National Institute of Biologicals 2017 Survey of Extent of Problems of Spurious and Not of Standard Quality Drugs in the Country 2014-16 Noida Ministry of Health amp Family Welfare Government of India Accessed 2017
bull WHO Drug Information Vol 30 No 1 2016 Quality of Misoprostol Hall P Concept Foundation httpappswhointmedicinedocsenmabstractJs22361en
bull Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis An evaluation from multi-country surveys and stakeholder interviews Nurse-Findlay et al Published December 27 2017 httpsdoiorg101371journalpmed1002473
Tools
bull Manual for Procurement amp Supply of Quality-Assured Maternal Newborn and Child Health Commodities GHSC PSM
bull Oxytocin Quality ndash Evidence for Action Concept Foundation
bull Buy Quality Oxytocin ndash Keep It Cold RHSC USAID PATH
bull Appropriate Storage and Management of Oxytocin ndash A Key Commodity for Maternal Health WHOUNFPAUNICEF Joint Statement
References
bull Family Care International A Price too High to Bear The costs of maternal mortality to families and communities ndash Summary of Research Findings March 2014 Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl1)S4 doi1011861742-4755-12-S1-S4
bull Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl 1)S4 doi1011861742-4755-12-S1-S4
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Anyakora C Oni Y Ezedinachi U et al 2018 ldquoQuality medicines in maternal health results of oxytocin misoprostol magnesium sulfate and calcium gluconate quality auditsrdquo BMC Pregnancy and Childbirth Accessed January 31 2018 doi httpsdoiorg101186s12884-018-1671-y
bull National Institute of Biologicals 2017 Survey of Extent of Problems of Spurious and Not of Standard Quality Drugs in the Country 2014-16 Noida Ministry of Health amp Family Welfare Government of India Accessed 2017
bull WHO Drug Information Vol 30 No 1 2016 Quality of Misoprostol Hall P Concept Foundation httpappswhointmedicinedocsenmabstractJs22361en
bull Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis An evaluation from multi-country surveys and stakeholder interviews Nurse-Findlay et al Published December 27 2017 httpsdoiorg101371journalpmed1002473
References
bull Family Care International A Price too High to Bear The costs of maternal mortality to families and communities ndash Summary of Research Findings March 2014 Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl1)S4 doi1011861742-4755-12-S1-S4
bull Moucheraud C Worku A Molla M Finlay JE Leaning J Yamin AE Consequences of maternal mortality on infant and child survival a 25-year longitudinal analysis in Butajira Ethiopia (1987-2011) Reproductive Health 201512(Suppl 1)S4 doi1011861742-4755-12-S1-S4
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India Cynthia Stanton Deepak Nitya Nand Alissa Koski Ellie Mirzabagi Steve Brooke Breanne Grady and Luke C Mullany BMC Pregnancy and Childbirth 2014 14386 httpwwwbiomedcentralcom1471-239314386
bull BJOG 2016 Mar 22 doi 1011111471-052813998 Quality of oxytocin available in low- and middle-income countries a systematic review of the literature Torloni MR Gomes Freitas C KartogluUH Metin Guumllmezoglu A Widmer M
bull Post-market quality surveillance report ndash Maternal healthcare products (oxytocin and ergometrine) on the Ghanian market Report of first round Joint Project of Ghana Food and Drugs Authority (FDA) Laboratory Services Department and The Promoting the Quality of Medicines Program February 2013
bull Survey of the quality of medicines identified by the United Nations Commission on Life-Saving Commodities for Women and Children WHO 2015
bull Anyakora C Oni Y Ezedinachi U et al 2018 ldquoQuality medicines in maternal health results of oxytocin misoprostol magnesium sulfate and calcium gluconate quality auditsrdquo BMC Pregnancy and Childbirth Accessed January 31 2018 doi httpsdoiorg101186s12884-018-1671-y
bull National Institute of Biologicals 2017 Survey of Extent of Problems of Spurious and Not of Standard Quality Drugs in the Country 2014-16 Noida Ministry of Health amp Family Welfare Government of India Accessed 2017
bull WHO Drug Information Vol 30 No 1 2016 Quality of Misoprostol Hall P Concept Foundation httpappswhointmedicinedocsenmabstractJs22361en
bull Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis An evaluation from multi-country surveys and stakeholder interviews Nurse-Findlay et al Published December 27 2017 httpsdoiorg101371journalpmed1002473
![Modeling patient access to therapeutic oxytocin in ......PPH [2, 3]. In 2014, it was reported there were still 410 maternal deaths per 100,000 live births in Tanzania (compared to](https://static.documents.pub/doc/80x56/6089f07b8305b1577a687d43/modeling-patient-access-to-therapeutic-oxytocin-in-pph-2-3-in-2014.jpg)
