Updates on ID needs: AMR and vaccines
Dr. Anton アンㇳン Villanueva, Dept. of International Trials
Focus: Quality & Risk and the Philippines
© 2018 National Center for Global Health and Medicine 2
Disclaimer
These Power Point slides are the intellectual property of NCGM under the copyright laws.Used by permission. All rights reserved. NCGM and the NCGM logo are registeredtrademarks of the National Center for Global Health and Medicine.
©2018 NCGM | CCS | Department of International Trial
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© 2018 National Center for Global Health and Medicine
Targets
• 1. Intro to ASEAN
• 2. Infectious disease trends
• 3. AMR and Vaccines
Intramuros
© 2018 National Center for Global Health and Medicine
ASEAN health market
Country-specific:
• Application:
• GCP: IRB LTO Risk Sites Pilipino (Informed Consent)
• IB: CPR PCIU Import Permit
• (MOU) MOA MTA
• Fees: FDA Php 2500, IRB Php 15-60k or %
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ACTD=ASEAN Common Technical DossierGCP=Good Clinical PracticeIB=Investigator’s Brochure
IRB=Institutional Review Board (Ethics)LTO=License to OperateCPR=Certificate of Product RegistrationPCIU=Permit for Clinical Investigational Use
Contracts: MOU=Memorandum of UnderstandingMOA=Memorandum of AgreementMTA=Material Transport/Transfer Agreement
Pacific Bridge Medical (2014)
harmonization
©2018 NCGM | CCS | Department of International Trial
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© 2018 National Center for Global Health and Medicine
Targets
• 1. Intro to ASEAN
• 2. Infectious disease trends
• 3. AMR and Vaccines
Department of Health
© 2018 National Center for Global Health and Medicine
‘Pilipinas’‘Maharlika’Health Burden
• Emerging economy with triple burden of diseases• Infectious Diseases
(tropical)
• Non-communicable
• Mental health
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© 2018 National Center for Global Health and Medicine 8
http://www.wpro.who.int/philippines/areas/communicable_diseases/ continuation_communicable_diseases/en/https://www.cdc.gov/globalhealth/countries/Philippines/https://www.doh.gov.ph/populationhttps://www.doh.gov.ph/mortalityhttps://www.doh.gov.ph/morbidityhttps://pharmaboardroom.com/country_reports/philippines-pharma-report/Philippine health research registry
Clinical trials on drugsPhilippine General Healthcare Market Gap:
- High morbidity due to infections, therefore need improved screening, diagnosis, and prevention including vaccines
- Already much on diabetes; cardiovascular lacking
©2018 NCGM | CCS | Department of International Trial
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© 2018 National Center for Global Health and Medicine
Targets
• 1. Intro to ASEAN
• 2. Infectious disease trends
• 3. AMR and Vaccines
Global City
© 2018 National Center for Global Health and Medicine 10
Need new regimen and more vaccineshttp://www.wpro.who.int/philippines/areas/communicable_diseases/continuation_communicable_diseases/en/https://www.cdc.gov/globalhealth/countries/Philippines/Research Institute of Tropical Medicine (2016). Antimicrobial Resistance Surveillance Program Data Summary Report. Available at: http://arsp.com.ph/wp-content/uploads/2017/06/2016_annual_report_summary.pdf
AMR
Japanese Encephalitis
© 2018 National Center for Global Health and Medicine 11
Philippine Infectious Diseases Market Gap:
- Highly endemic to many seasonal, epidemic-prone, as well as neglected tropical diseases, including recurring global infections like measles and chicken pox
- AMR: also Sexually-Transmitted Infections
MDR-TB/HIV
Emerging/Re-emerging
© 2018 National Center for Global Health and Medicine
Required Vaccines
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© 2018 National Center for Global Health and Medicine
Recommended Vaccines Gap
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© 2018 National Center for Global Health and Medicine 14
Arigatǭ gozaimasu!ありがとうございます!
Maraming salamat po
VIET NAM
Nguyen Tam
© 2018 National Center for Global Health and Medicine
Table of content
Recent need of infectious diseases in Vietnam
Vaccine manufacturing in Vietnam
Recent updates on Vietnam Pharmaceutical Sectors
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© 2018 National Center for Global Health and Medicine
Recently needs of infectious diseases in Vietnam
Emergence of infectious diseases
• Un-controlled Antimicrobial Resistance based on current controlling program
• Difficult of differential diagnosis and technology of diagnosis
• Meningococcal infection and Encephalitis, except for Encephalitis by Herpes and Japanese Encephalitis
Expectation from Pharmaceuticals
• Evidence-based for usage of antibiotic combination of
• ceftazidim/avibactam
• meropenem/vaborbactam
• Anti-fungal medicine
• Echinocandins: The product (Caspofungin) is licensed in Vietnam. However, the safety and efficacy data are not sufficient for medical needs.
• Flucytosine is not available in Vietnam although it is available in current guidelines
• New drug development on anti-biotic and anti-fungal
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© 2018 National Center for Global Health and Medicine 18
Vaccine manufacturing in VietnamVietnamese vaccine companies seek new collaborations to expand new technology and market by allowing higher percentage of foreigner-own
1960 (tOPV)
1990s (DTP and VAT Vaccine in 1990;BCG Vaccine in 1992; Cholera vaccine in 1993; JEV in 1997)
2000s (Hep B-2001; Td Vaccine in 2002; Hep A in 2003; Measles in 2009)
2010s (Rotavirus in 2012; bOPV in 2017; Measles and Rubella in Mar 2017; 2018 phase III Trial for seasonal influenza vaccine, H5N1; completed phase II for IPV Vaccine)
2020: projected to manufacture 5 in 1 Vaccine
❖ Manufactured 11 out of 12 vaccines for Expanded Program on Immunization
❖ Manufacturing volumes enough for the country’s need and exported to countries under WHO’s program
• Vietnamese vaccine companies IVAC
• POLYVAC
• VABIOTECH
• DAVAC
• Supporting from other international organization (WHO, Pasteur Paris, NIH Japan, JICA Japan, BARDA, etc.)
© 2018 National Center for Global Health and Medicine
Recent updates on Regulation in Vietnam in pharmaceutical sectors
Opening foreign –owners for
pharmaceutical companies and
public companies
• No limitation on percentage of owners
• M&A (Taisho Japan-DHG VN)
CPTPP
• Reducing tariff on pharmaceutical products
• Reduce the timeframe for New Drug Registration
New Circular on
Clinical Trials
• GCP Inspection to promote standard of clinical trials
• Shorten the review timeline
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© 2018 National Center for Global Health and Medicine 20
ありがとうございます。Cảm ơn
A wink on R&D targets for DRCongo:
“from vaccines to Cure”
Muchanga Sifa MJ, MD, PhD
© 2018 National Center for Global Health and Medicine
Population Trends
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UN estimates on November 5, 2018 Population: 84,874,826 (1.1% world population)Growth rate: 3.28%Population density: 37per km240.5% of the population is urban.Median age is 16.8 years
The data are in thousands or millions and represent the population in each age group.https://population.un.org/wpp/DataQuery/
79.3678.4376.63
74.8773.15
69.868.2
2010201120122013201420162017
Dea
ths/
1,0
00
live
bir
ths
Year
< 5y Mortality rate
© 2018 National Center for Global Health and Medicine 23
Vaccination Coverage and Infant Mortality Rate
10 Most common causes of infant
mortality (2016)
1. Malaria
2. Tuberculosis
3. Lower respiratory infection
4. Diarrheal diseases
5. Cerebrovascular diseases
6. Ischemic heart disease
7. Protein-energy malnutrition
8. HIV/AIDS
9. Neonatal preterm birth
10. Neonatal encephalopathy
All cannot be preventable by the current available vaccines.
Need new molecules!!!!!
Needs
© 2018 National Center for Global Health and Medicine 24
All-Causes Mortality
No death 2016
Malaria
Lower respiratory infection
Tuberculosis
Diarrheal diseases
Protein-energy
malnutrition
Neonatal preterm birth
Neonatal encephalopathy
Congenital defects
HIV/AIDS
Neonatal sepsis
Malaria has replaced diarrheal diseases as first. Tuberculosis is shifting, maybe due to resistance. All causes are mainly infectious.
Malaria Burden
Percentage of estimated malaria deaths attributable to the 18 countries with nearly 80% of global malaria deaths in 2017
© 2018 National Center for Global Health and Medicine 25
% MDR/RR-TB in previously treated TB
cases
Tuberculosis Burden
© 2018 National Center for Global Health and Medicine 26
Yellow feverJune 2016
700 cases
63 deaths
CholeraFeb 2018
83 cases 43 deaths
Vaccine derived
PolioJuly 2017
4 cases
Measles28506 suspects
386 deaths
Monkey Pox
Jan 2017-May 2018
2585 cases 42 deaths
Ebola
10th
August 2018
…cases…deaths
Outbreaks
Dec 19thTotal :542Deaths: 329Cured: 192Suspects: 86
EBOLA( Aug.2018)
Dec 17thTotal :531Deaths: 313Cured: 184Suspects: 86
© 2018 National Center for Global Health and Medicine 27
Referenceshttps://www.analyticsvidhya.com/blog/2016/06/bayesian-statistics-beginners-simple-english/https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)00115-4/fulltexthttps://reliefweb.int/report/democratic-republic-congo/democratic-republic-congo-epidemics-yellow-fever-cholera-measleshttp://www.healthdata.org/democratic-republic-congohttp://www.who.int/gho/countries/cod.pdf?ua=1https://www.severemalaria.org/countries/democratic-republic-of-congohttps://www.precisionvaccinations.com/democratic-republic-congo-cdc-travel-alerts-include-ebola-measles-polio https://www.precisionvaccinations.com/democratic-republic-congo-cdc-travel-alerts-include-ebola-measles-polio
Nattha Kerdsakundee, Ph.D.
Regional Manager, Department of International Trials
© 2018 National Center for Global Health and Medicine 29
Outline
❖Update Infectious Disease in 2018
❖Antimicrobial Resistance Situation
❖Pharmaceutical Market in Thailand
© 2018 National Center for Global Health and Medicine 30
Health status in Thailand
Source: WHO
• The Non-communicable diseases are the major cause of
death.
The prevalence of NCD is also on the rise due to
• changing lifestyles: smokers, high in meat, salt, fat, and
sugar content meal
• Aging society, the increasing of developing respiratory
diseases, cancer, and diabetes
• Infectious diseases remain an issue of Thailand due to its
tropical climate.
- Nearly 450,000 people in Thailand are living with HIV/AIDS,
but the number of new HIV cases per year decreased
- Dengue fever affects tens of thousands annually
- Other infectious diseases including influenza, tuberculosis,
and malaria
© 2018 National Center for Global Health and Medicine 31
No. Disease No. of case No. of death
% of death
1 Diarrhea 1,055,271 8 < 0.01
2 Pneumonia 247,683 199 0.08
3 Influenza 156,280 30 0.02
4 H.conjunctivitis 82,196 - -
5 Tuberculosis 74,940 4,971 6.63
6 Dengue 78,762 105 0.13
7Hand, foot and mouth
disease58,182 1 < 0.01
8 Chickenpox 53,984 - -
9 Scrub Typhus 8,249 4 0.05
10 Hepatitis B 6,246 - -
11 Malaria 6,329 1 0.02
12 Measles 4,030 15 0.37
13 Scarlet fever 2,813 - -
14 Leptospirosis 2,507 30 1.20
15 Melioidosis 2,344 5 0.21
Infectious disease in 2018
Thailand’s health ministry has confirmed 2 infectious disease outbreak in 2018• Dengue• Measles
Re-emerging Infectious Diseases by WHO definition
Source: Department of disease control, Thailand
© 2018 National Center for Global Health and Medicine 32
Dengue outbreak
Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec
In 2018, the updated no. of Dengue cases are 78,762 case and Death 105 case
In 2013, Thailand experience the largest dengue epidemic in more than two decades
2018 est.
2017
0
20000
40000
60000
80000
100000
120000
140000
160000
2013 2014 2015 2016 2017 2018
No
. of
Susp
ects
Source: Bureau of Vector-borne Disease, Department of disease control, Thailand
© 2018 National Center for Global Health and Medicine 33
Measles outbreak
❑Measles outbreak in the southern provinces
❑ The morbidity rate in Yala province is 132.61 /
100,000 population
❑ Low vaccination rates in the South
❑Misunderstanding about vaccinations that
spread around Muslim communities
© 2018 National Center for Global Health and Medicine 34
Tuberculosis
• HIV- positive with TB is around 10%
• 2.2% of new cases with MDR/RR-TB
• 24% of previously treated cases with MDR/RR-TB Source: WHO Global TB report 2017
Source: Bureau of Tuberculosis Department of disease control, Thailand
0
10000
20000
30000
40000
50000
60000
70000
80000
90000
100000
2014 2015 2016 2017 2018
No
. ofr
egis
tere
d p
atie
nts
Thailand is among the 30 high-burden TB countries globally
© 2018 National Center for Global Health and Medicine 35
Malaria
- P. vivax 80% - P. Falciparum 20%- P. Malariae 0.1%- mixed Pv and Pf 0.7%
Source: Bureau of Vector-borne Disease, Department of disease control, Thailand
Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec
0
5000
10000
15000
20000
25000
30000
35000
2014 2015 2016 2017 2018
No
. of
Susp
ects
Number of malaria patients in Thailand gradually decrease every year
© 2018 National Center for Global Health and Medicine 36
Outline
❖Update Infectious Disease in 2018
❖Antimicrobial Resistance Situation
❖Pharmaceutical Market in Thailand
© 2018 National Center for Global Health and Medicine 37
Antimicrobial Resistance
(Average) every 15 minute; 1 Thai people death from AMR= 100 people per day= 20,000-38,000 people per year
Economic lost around 46,000 mil. baht
Misuse or excessive use of antibiotics81% in public hospital25-91% in university hospital64-80% in drug store
About 88,000 infections were attributed to antimicrobial resistance (AMR) in Thailand
At least 3.24 million additional days in hospital
Source: National Antimicrobial Resistance Surveillance Center, Thailand
© 2018 National Center for Global Health and Medicine 38
Important resistant pathogens
• Imipenem resistant Acinetobacter spp.
• Imipenem resistant Pseudomonas aeruginosa
• Vancomycin resistant enterococci
• Carbapenem resistant Enterobacteriaceae
• Extended spectrum β-lactamase producing Enterobacteriaceae
• Multidrug resistant and extensive drug resistant tuberculosis
Source: National Antimicrobial Resistance Surveillance Center, Thailand
© 2018 National Center for Global Health and Medicine 39
Rate of Imipenem resistance Acinetobacter spp.
Distribution of MDR-TB Cases, Thailand(639 cases in 2018)
Source: Bureau of Tuberculosis Department of disease control, Thailand
Percent resistance of E. faecium, E. faecalis to vancomycin
Source: National Antimicrobial Resistance Surveillance Center, Thailand
© 2018 National Center for Global Health and Medicine 40
Causes of AMR in Thailand
❑Misused antibiotics as medicines to fight inflammation or
cold symptom
❑ Improper use of antibiotics by medical personnel, public
health agencies, veterinarians and agriculturalist
Source: National Antimicrobial Resistance Surveillance Center, Thailand
© 2018 National Center for Global Health and Medicine 41
Policies for AMR in Thailand
Lower the number of drug resistance-related deaths by 50%
within the year 2021
❑Monitor cases of antibiotic resistance
❑ Control the distribution of antibiotics
❑ Prevent drug resistance in the farming sector and pets
❑ Offer related education to the public
❑ Developing mechanism to steer forward all attempts to fight it
Source: National Antimicrobial Resistance Surveillance Center, Thailand
© 2018 National Center for Global Health and Medicine 42
Outline
❖Update Infectious Disease in 2018
❖Antimicrobial Resistance Situation
❖Pharmaceutical Market in Thailand
© 2018 National Center for Global Health and Medicine 43
Pharmaceutical Market in Thailand
Share of Pharmaceutical Expenditure (2013-17 average)
The market in medicines now accounts for
approximately a quarter of all domestic
medical expenses with the majority of this
being distributed through hospitals.
Source of Import (2017)
In 2017, the value of the Thai pharmaceuticals
market was THB 169 bn, 5.3% growth YoY(Source: Business Monitor International)
© 2018 National Center for Global Health and Medicine 44
Leading Categories Market Share
❑ Anti-infective drug is around 20% of
drug market in Thailand
❑ Antibiotic value is around 50% of Anti-
infective drug
❑ In 2012, the value of antibiotic drug
(manufacture and import) was THB
17,000 mil.(Source: Thai FDA)
© 2018 National Center for Global Health and Medicine
Source: PwC Health Industries Leader
Thai government and tourismAuthority of Thailand havepromoted medical and healthtourism policy
Healthcare market trend
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Source: EIC SCB, World Health Organization, BMI
Pharmaceutical Market Trend
© 2018 National Center for Global Health and Medicine
Thank you
ありがとうございます
ขอบคณุคะ่Picture: dreamstime
INDONESIA
Marlinang D. Siburian, MSc.
Rubella2017 Sept- 2018 Jan : Asmat, Papua651 cases, 75 died
Facts:• Indonesia is one of the
10th countries with the highest measles and rubella cases
• 2014-2018 : ✓ 5737 Rubella cases✓ 1660 suspect CRS
(Congenital Rubella Syndrome) (surveyed from 12 sentinel hospitals)
• 1982 : Measles vaccine as national program for children age 9 mo
• 2017 : Rubella vaccine was added to national program given in together with measles vaccine → Measles Rubella (MR) vaccine
• Rubella vaccine produced by Serum Institute of India (SII), containing enzyme derived from porcine
• HARAM – against religious law (considered as a sin)
• 50-95% of the society rejected the vaccination
• Threat of coming outbreaks!!
OUTBREAKS
Diphtheriae2017 Jan-Nov :
Nationwide, 596 cases, 32 died
Aceh, 76 casesEast Java, 271 cases
Banten, 81 casesWest Sumatera, 30 cases
West Java, 95 cases
Hepatitis A2018 Sept :
Singkawang, West Kalimantan
189 cases
Hepatitis A2017 Nov-2018 Jan : Lamongan, East Java 33 cases
Hepatitis A2015 Dec: Bogor, West Java28 cases, 1 died
Chikungunya2015 Dec-2018 Jan : Buleleng, Bali96 cases
Dengue 2016 Jan-Feb :
In 15 cities of 11 Provinces608 cases, 34 diedNationwide, 8487 cases, 108 died.Facts: Number of cases >> since 2015 (more in patients age >15 yo)
MERSNo case found in
Indonesia.Two Indonesians got
infected and were hospitalized in Saudi Arabia. Returned to
Indonesia after recovered.
Facts:• One million
Indonesian people travel to Saudi
Arabia every year for religious trip.
• High risk for MERS!!
Facts:Vaccination coverage >> Number of cases >>→AMR (penicillin and
erythromycin)New vaccine?!!
Nati
on
al
Pro
gra
m InfluenzaTetanus, Diphtheriae, Pertussis (Td/Tdap)Varicella, HPV , Zoster, Measles, Rubella, Mumps, Hep A, Hep BHep A and BTyphoidPneumococcal Polysaccharide (PPSV23)/PneumoniaPneumococcal conjugate 13-valent (PCV13)/PneumoniaMeningitis MeningococcalYellow fever
Available Vaccines:
Vaccine suppliers:
1. Bio Farma (since 1890), now supplies
Pentavalent and Measles vaccines for
National Program2. Glaxo Smith Kline (GSK)
3. Novartis4. Sanofi
Vaccination
in Indonesia
76.1 67.8 69.8 75.3 74.1 79.3 83.0 82.7 82.280.0 85.0 90.0 95.0 100.0
84.0
0.0
50.0
100.0
150.0
-30.0
20.0
70.0
120.0
2007 2008 2009 2010 2011 2012 2013 2014 2015
National vaccination coverage
Coverage
Source: Information and Data Center MOH
0-4 yo20,945,43122,953,246
Indonesian Population
2010 2050
#1 Great need for HALAL vaccine supplies
• Measles
59,000 death/year
• Rabies• Diphtheria 7,097 cases in 2016(India (~50%), Madagascar, Indonesia, Nepal, Myanmar)
• Rubella22,361 cases in 2016(India (~37%), China, Indonesia, Sudan, South Africa)
186,605 cases in 2016(India (~38%), Mongolia, China, Nigeria, Indonesia)
25,000 death/year
Infectious Diseases and Muslim
population
• Dengue
Muslim Population: 1.6 billion (2010) ~ 21.9% of the world population
• Since 2012, when the virus was first identified in Saudi Arabia, there have been 2081 laboratory-confirmed cases of MERS-CoV infection reported to WHO from 27 countries, with at least 722 deaths - a fatality rate of 35%
• MERS-CoV is one of the high threat pathogens included in the WHO’s Research & Development Blue Print which provides a road map for research and development of diagnostic, preventive and therapeutic products for prevention, early detection and response
• More than 2 million Muslim people travel every year to Mecca for Hajj pilgrimage
• Many infectious diseases cases occur in countries with Muslim majority including Indonesia (disbelief in vaccination and/or
uninformed)• High demand for halal medical products ~
>1.6 billion people • Pharmaceutical companies should start to
consider halal-haram aspects• Clinical trials for halal recommendation
can be done in countries with Muslim population to get halal certification
• Endorsement from Religious leaders on medical products are required in
countries with Muslim Majority such as Indonesia
• National health program in countries with Muslim majority should be disseminated through well-informed religious leaders
Middle-East respiratory syndrome
coronavirus (MERS-CoV)
© 2018 National Center for Global Health and Medicine 53
ありがとうございます。Terima kasih