JAMU, OBAT HERBAL TERSTANDAR, FITOFARMAKA DAN KONDISI GLOBAL
JAMU, OBAT HERBAL
TERSTANDAR,
FITOFARMAKA
REGULATORY
FRAMEWORK
DAN KONDISI GLOBAL
Drs. Hary Wahyu T., Apt.
Direktorat Standardisasi Obat Tradisional,
Jakarta, 9-10 September 2014
Kosmetik dan Produk Komplemen
Badan Pengawas Obat dan Makanan
2017
Pengelompokkan Obat Bahan Alam
(Peraturan Kepala Badan POM No.HK.00.05.4.2411 Tahun 2004
Tentang Ketentuan Pokok Pengelompokkan dan Penandaan
Obat Bahan Alam Indonesia).
OBAT BAHAN
ALAM
INDONESIA
JAMU
OBAT HERBAL
TERSTANDAR
FITOFARMAKA
Catatan :
Perbedaan dari ketiga komoditi diatas adalah pada klaim yang
diperbolehkan (tergantung dari bukti dukung)
JAMU :
• Bukti dukung berasal dari bukti
empiris {berdasarkan riwayat turun
temurun penggunaan obat bahan
alam (bagian tertentu atau
keseluruhan bagian tumbuhan)
untuk tujuan tertentu}
OBAT HERBAL TERSTANDAR :
• Merupakan wadah sementara jamu (yang
memiliki bukti empiris) sebelum menuju
fitofarmaka
• Bukti dukung berasal dari uji pada hewan coba.
• Penggunaan hewan coba pada tahapan uji pada
dasarnya untuk melihat profil awal (toksisitas
dan farmakodinamik/khasiat). Dan untuk
pemastian profil keamanan-khasiat selanjutnya
dilakukan tahap uji pada manusia.
• Untuk OHT dikarenakan sudah memiliki data
empiris, penguatan melalui uji praklinik
(toksisitas dan farmakodinamik) dapat diterima.
FITOFARMAKA (1) :
• Dapat berasal dari jamu (dengan bukti
dukung empiris) maupun dari non
jamu (non empiris).
• Bukti dukung berasal dari uji pada
hewan coba dan uji pada manusia.
FITOFARMAKA (2):
• Fleksibilitas yang diberikan
Data toksisitas sub kronik dan kronik bisa diabaikan
(case by case)
Fase I bisa diabaikan (case by case)
Fase II dan III bisa digabung (case by case)
• Kendala lambatnya penambahan jumlah fitofarmaka
kurangnya kompetensi industri/pelaku di bidang uji
klinik (misal metodologi diuji pada hewan coba dan
pada manusia)
perlunya upaya dan biaya yang lebih
industri/pelaku sudah merasa nyaman berada pada
kelompok OHT
KONSEP EMPIRIS
Long historical use of many practices of traditional
medicine, including experience passed on from
generation to generation, has demonstrated the safety
and efficacy of traditional medicine. In conducting
research and evaluating traditional medicine,
knowledge and experience obtained through the long
history of establised practices should be respected.
(General guideline for methodologies on research and
ecvaluation of traditional medicine, 2000)
KONSEP GLOBAL :
Obat bahan alam terbagi menjadi 2 (dua) yaitu
1. Traditional medicine (di Indonesia
dianalogikan dengan Jamu) dengan bukti
dukung empiris. Klim indikasi biasa diawali
dengan Traditionally used for... dan
2. Herbal medicine (di Indonesia dianalogikan
dengan Fitofarmaka) dengan bukti dukung
ilmiah (uji pada hewan coba dan pada
manusia)
KONSEP DI GLOBAL PEMENUHAN DATA
DALAM PENGEMBANGAN
OBAT BAHAN ALAM
1. Berikut gambaran obat bahan alam yang masih
berbasis pada penggunaan tradisional maupun
setelah ada perubahan dari penggunaan
tradisionalnya (berdasarkan WHO Guidelines for the
Regulation of Herbal Medicines in the South-East Asia
Region, 2003)
WHO Guidelines for the Regulation of Herbal Medicines
in the South-East Asia Region
2. Kondisi/persyaratan tersebut diatas juga
diterapkan oleh negara-negara di timur
tengah dan tercantum pada Guidelines on
minimum requirements for the registration of
herbal medicinal products in the Eastern
Mediterranean Region, 2006
Guidelines on minimum requirements for the registration of herbal medicinal
products in the Eastern Mediterranean Region
3. Bagaimana dengan di ASEAN
saat implementasi Harmonisasi ASEAN
di Bidang Obat Tradisional?
Types of TM claims
Type of TM claim
Traditional
Scope
Examples to illustrate the scope
(as determined by the regulatory
authority of each Member State)
Health Traditionally used for general health maintenance or • Traditionally used to maintain health for people
enhancement
Use
above 40 yrs old
• Tonic traditionally used to restore energy and
health in women after childbirth/puerperium
• Tonic traditionally used to strengthen body by
nourishing blood and invigorating vital energy
Traditional
Treatment
Scientifically
Established
Treatment
Traditionally used to relieve or alleviate a symptom,
or treat a disease or medical condition according to
the principles of traditional medicine, with the
exception of the prohibited diseases according to
each Member State
• A Traditional medicine for dizziness/vomiting
during travel in car, boat and airplane
• Traditionally used to prevent cold or flu
• Traditionally used to relieve cold and sore throat
To prevent/stop/slow down the progress of a mild or • Traditionally used to treat stomachache
self-limiting disease or medical condition, based on • Traditionally used to treat constipation
principles of traditional medicine
• A traditional medicine to relieve itchiness
To relieve a symptom or treat a disease, disorder or • For treatment of hypertension
medical condition substantiated by scientific
• To treat or relieve arthritis
evidence, which corroborates TM principles*
• Used to lower blood pressure
*as determined by the regulatory authority of each
Member State
• Used to reduce blood sugar
Claim Substantiation
Jenis Klaim TM
Level bukti
Bukti untuk mendukung klaim TM
Kriteria Well-documented
Untuk klaim TM
Traditional
Health Use
Evidence from
documented
traditional use and
knowledge
- Claims for general health maintenance Evidence of documented traditional use or history of use
or enhancement are documented in TM that may be found in the following:
references
Classical TM Texts
- In accordance with TM principles and Pharmacopoeias and Monographs
practice
Reference Textbooks/Journals
Traditional
Treatment
Evidence from
documented
traditional
treatment
- Claims for treatment and prevention
are documented in TM references
Scientific data and
TM principles
- Claims for treatment supported by
scientific data
Scientifically
Established
Treatment
- In accordance with TM principles and
practice
Evidence of documented history of traditional treatment
that may be found in the following:
Classical TM Texts
Pharmacopoeias and Monographs
Reference Textbooks/Journals
Compulsory evidence:
Substantiation of TM claims based on scientific data as
(such as in vitro, in vivo, epidemiological required by the regulatory authority to be conducted on
and/or
finished product or ingredient(s).Justification will have to
be provided to the regulatory authority if evidence
human intervention studies)
provided is based on ingredient
At least 1 additional evidence:
- In accordance with TM principles and
practice
Evidence of documented history of traditional treatment
that may be found in the following:
Note: Refere es that are used to su sta tiate a TM lai
i lude ASEAN Me
Classical TM Texts
Pharmacopoeias and Monographs
Reference Textbooks/Journals
er States’ offi ial phar a opoeias a d
o ographs.
16
Decision tree on the evidence required to support the
different types of TM claims
A proposed TM claim
Traditional Health Use Claim
Scientifically Established
Treatment Claim
Traditional Treatment Claim
Refer to Table 2 and Sections 4.2 and 4.3
Evidence of documented
traditional use or history
of use that may be found
in the following:
• Classical TM Text
• Pharmacopoeias and
Monographs
• Reference Textbooks /
Journals
Does it meet the
criteria of well
documented TM
claim based on
substantiation of
evidence?
YES
NO
Not a welldocumented
Traditional
Health Use
Claim
Evidence of documented
history of traditional
treatment that may be
found in the following:
• Classical TM Text
• Pharmacopoeias and
Monographs
• Reference Textbooks /
Journals
Does it meet the
criteria of well
documented TM
claim based on
substantiation of
evidence?
NO
Compulsory evidence:
Substantiation of TM claims based on scientific
data, as required by the regulatory authority to be
conducted on finished product or ingredient(s).
Justification will have to be provided to the
regulatory authority if evidence provided is based
on ingredient
At least 1 additional evidence:
Evidence of documented history of traditional
treatment that may be found in the following:
• C
• lassical TM Texts
• P
•harmacopoeias and Monographs
• R
•eference Textbooks/Journals
Not a welldocumented
Traditional
Treatment
Claim
Does it meet the
criteria of well
documented TM
claim based on
substantiation of
evidence?
NO
YES
YES
Traditional Health
Use Claim
Traditional
Treatment Claim
Scientifically Established
Treatment Claim
Not a welldocumented
Scientifically
Established
Treatment
Claim
Types of HS claims (1)
Type of HS
claim
Scope
Examples to illustrate the scope
- as determined by the regulatory
authority of each Member State
General or
Nutritional
For Nutritional Support and General Health
Maintenance. Benefits derived from supplementation
beyond
a perso ’s daily dietary i take.
• Supple e ts utritio
• Supports healthy gro th a d
Development
• Nourishes the ody
• Relie es ge eral tired ess, eak ess
• Helps to ai tai good health
Functional
Relate to a positive contribution to health or to
the improvement of a function or to modifying
or preserving health in the context of the total
diet on normal functions or biological activities
of the body.
• Mai tai s/Supports healthy joi ts
• Mai tai s/Supports i
u ity
• Mai tai s healthy li er fu tio
• Mai tai s/Supports alert ess
• Mai tai s/Supports e tal
performance
• Pro otes healthy ski
• Helps to relie e post-menopausal
discomforts
• Aids i digestio to relie e i digestio
• Bifidobacteria in product A helps to
improve slow transit system in 14 days
• Supports health i agei g
• Supports health i
e opause
• Supports health i preg a y
Maintains or enhances structure or function of
the body, excluding disease related claims.
Supports health and to relieve/reduce/
lessen/ease minor body discomforts in some
physiological processes (e.g. ageing, Menopause,
pregnancy)*.
*as determined by the regulatory authority of each
Member State
Types of HS claims (2)
Type of
HS claim
Disease
Risk
Reduction
Scope
Significantly altering or reducing a
risk factor of
a disease or health related
condition*.
*as determined by the regulatory
authority of each Member
State
Examples to illustrate the scope
- as determined by the
regulatory
authority of each Member State
• Helps to redu e risk of
osteoporosis by
strengthening bone
• Helps to redu e the risk of
dyslipidaemia
OBAT HERBAL
TERSTANDAR DAN
FITOFARMAKA
REGISTRASI OHT
• Protokol Uji Praklinik diajukan ke
BPOM untuk persetujuan
• Data praklinik sebagai bukti dukung
khasiat keamanan registrasi Obat
Herbal Terstandar
• BPOM melakukan pendampingan
REGISTRASI FITOFARMAKA
• Data praklinik bisa berasal dari data praklinik
Obat Herbal Terstandar (namun bila perlu
disesuaikan) atau data praklinik baru (tidak
perlu protokol uji praklinik, tidak perlu
dimintakan persetujuan BPOM)
• Pengajuan persetujuan pelaksanaan uji klinik
diserahkan dokumen Protokol Uji Klinik,
Informed concern, dan Investigator Brochure)
• Data klinik sebagai bukti dukung khasiat
keamanan registrasi fitofarmaka
• BPOM melakukan pendampingan
CONTOH KEKURANGAN SAAT EVALUASI DOKUMEN & PROTOKOL UJI KLINIK
UJI PRA KLINIK
UJI KLINIK
1.
1.
2.
3.
4.
Data uji farmakodinamik belum
menggambarkan penyakit yang
dikondisikan namun sudah ada
tindakan/prosedur lanjutan.
Data keamanan berupa toksisitas sub
kronis dan teratogenik yang masih
memerlukan klarifikasi lebih lanjut
dikarenakan misalnya paparan
histologi yang inkonsisten
Kurangnya jumlah hewan coba yang
digunakan
Terdapat kejadian serius di ginjal dan
lever di semua hewan coba yang
digunakan, baik di mencit maupun di
kelinci
2.
3.
4.
5.
Metodologi uji yang kurang
sesuai
Kriteria inklusi dan eksklusi yang
belum sesuai
Jumlah subjek yang kurang
Endpoint efikasi tidak menjawab
apa yang menjadi tujuan uji
Dokumen informed consent
tidak mencerminkan apa yang
ada dalam protokol
TERSTANDAR,
FITOFARMAKA
REGULATORY
FRAMEWORK
DAN KONDISI GLOBAL
Drs. Hary Wahyu T., Apt.
Direktorat Standardisasi Obat Tradisional,
Jakarta, 9-10 September 2014
Kosmetik dan Produk Komplemen
Badan Pengawas Obat dan Makanan
2017
Pengelompokkan Obat Bahan Alam
(Peraturan Kepala Badan POM No.HK.00.05.4.2411 Tahun 2004
Tentang Ketentuan Pokok Pengelompokkan dan Penandaan
Obat Bahan Alam Indonesia).
OBAT BAHAN
ALAM
INDONESIA
JAMU
OBAT HERBAL
TERSTANDAR
FITOFARMAKA
Catatan :
Perbedaan dari ketiga komoditi diatas adalah pada klaim yang
diperbolehkan (tergantung dari bukti dukung)
JAMU :
• Bukti dukung berasal dari bukti
empiris {berdasarkan riwayat turun
temurun penggunaan obat bahan
alam (bagian tertentu atau
keseluruhan bagian tumbuhan)
untuk tujuan tertentu}
OBAT HERBAL TERSTANDAR :
• Merupakan wadah sementara jamu (yang
memiliki bukti empiris) sebelum menuju
fitofarmaka
• Bukti dukung berasal dari uji pada hewan coba.
• Penggunaan hewan coba pada tahapan uji pada
dasarnya untuk melihat profil awal (toksisitas
dan farmakodinamik/khasiat). Dan untuk
pemastian profil keamanan-khasiat selanjutnya
dilakukan tahap uji pada manusia.
• Untuk OHT dikarenakan sudah memiliki data
empiris, penguatan melalui uji praklinik
(toksisitas dan farmakodinamik) dapat diterima.
FITOFARMAKA (1) :
• Dapat berasal dari jamu (dengan bukti
dukung empiris) maupun dari non
jamu (non empiris).
• Bukti dukung berasal dari uji pada
hewan coba dan uji pada manusia.
FITOFARMAKA (2):
• Fleksibilitas yang diberikan
Data toksisitas sub kronik dan kronik bisa diabaikan
(case by case)
Fase I bisa diabaikan (case by case)
Fase II dan III bisa digabung (case by case)
• Kendala lambatnya penambahan jumlah fitofarmaka
kurangnya kompetensi industri/pelaku di bidang uji
klinik (misal metodologi diuji pada hewan coba dan
pada manusia)
perlunya upaya dan biaya yang lebih
industri/pelaku sudah merasa nyaman berada pada
kelompok OHT
KONSEP EMPIRIS
Long historical use of many practices of traditional
medicine, including experience passed on from
generation to generation, has demonstrated the safety
and efficacy of traditional medicine. In conducting
research and evaluating traditional medicine,
knowledge and experience obtained through the long
history of establised practices should be respected.
(General guideline for methodologies on research and
ecvaluation of traditional medicine, 2000)
KONSEP GLOBAL :
Obat bahan alam terbagi menjadi 2 (dua) yaitu
1. Traditional medicine (di Indonesia
dianalogikan dengan Jamu) dengan bukti
dukung empiris. Klim indikasi biasa diawali
dengan Traditionally used for... dan
2. Herbal medicine (di Indonesia dianalogikan
dengan Fitofarmaka) dengan bukti dukung
ilmiah (uji pada hewan coba dan pada
manusia)
KONSEP DI GLOBAL PEMENUHAN DATA
DALAM PENGEMBANGAN
OBAT BAHAN ALAM
1. Berikut gambaran obat bahan alam yang masih
berbasis pada penggunaan tradisional maupun
setelah ada perubahan dari penggunaan
tradisionalnya (berdasarkan WHO Guidelines for the
Regulation of Herbal Medicines in the South-East Asia
Region, 2003)
WHO Guidelines for the Regulation of Herbal Medicines
in the South-East Asia Region
2. Kondisi/persyaratan tersebut diatas juga
diterapkan oleh negara-negara di timur
tengah dan tercantum pada Guidelines on
minimum requirements for the registration of
herbal medicinal products in the Eastern
Mediterranean Region, 2006
Guidelines on minimum requirements for the registration of herbal medicinal
products in the Eastern Mediterranean Region
3. Bagaimana dengan di ASEAN
saat implementasi Harmonisasi ASEAN
di Bidang Obat Tradisional?
Types of TM claims
Type of TM claim
Traditional
Scope
Examples to illustrate the scope
(as determined by the regulatory
authority of each Member State)
Health Traditionally used for general health maintenance or • Traditionally used to maintain health for people
enhancement
Use
above 40 yrs old
• Tonic traditionally used to restore energy and
health in women after childbirth/puerperium
• Tonic traditionally used to strengthen body by
nourishing blood and invigorating vital energy
Traditional
Treatment
Scientifically
Established
Treatment
Traditionally used to relieve or alleviate a symptom,
or treat a disease or medical condition according to
the principles of traditional medicine, with the
exception of the prohibited diseases according to
each Member State
• A Traditional medicine for dizziness/vomiting
during travel in car, boat and airplane
• Traditionally used to prevent cold or flu
• Traditionally used to relieve cold and sore throat
To prevent/stop/slow down the progress of a mild or • Traditionally used to treat stomachache
self-limiting disease or medical condition, based on • Traditionally used to treat constipation
principles of traditional medicine
• A traditional medicine to relieve itchiness
To relieve a symptom or treat a disease, disorder or • For treatment of hypertension
medical condition substantiated by scientific
• To treat or relieve arthritis
evidence, which corroborates TM principles*
• Used to lower blood pressure
*as determined by the regulatory authority of each
Member State
• Used to reduce blood sugar
Claim Substantiation
Jenis Klaim TM
Level bukti
Bukti untuk mendukung klaim TM
Kriteria Well-documented
Untuk klaim TM
Traditional
Health Use
Evidence from
documented
traditional use and
knowledge
- Claims for general health maintenance Evidence of documented traditional use or history of use
or enhancement are documented in TM that may be found in the following:
references
Classical TM Texts
- In accordance with TM principles and Pharmacopoeias and Monographs
practice
Reference Textbooks/Journals
Traditional
Treatment
Evidence from
documented
traditional
treatment
- Claims for treatment and prevention
are documented in TM references
Scientific data and
TM principles
- Claims for treatment supported by
scientific data
Scientifically
Established
Treatment
- In accordance with TM principles and
practice
Evidence of documented history of traditional treatment
that may be found in the following:
Classical TM Texts
Pharmacopoeias and Monographs
Reference Textbooks/Journals
Compulsory evidence:
Substantiation of TM claims based on scientific data as
(such as in vitro, in vivo, epidemiological required by the regulatory authority to be conducted on
and/or
finished product or ingredient(s).Justification will have to
be provided to the regulatory authority if evidence
human intervention studies)
provided is based on ingredient
At least 1 additional evidence:
- In accordance with TM principles and
practice
Evidence of documented history of traditional treatment
that may be found in the following:
Note: Refere es that are used to su sta tiate a TM lai
i lude ASEAN Me
Classical TM Texts
Pharmacopoeias and Monographs
Reference Textbooks/Journals
er States’ offi ial phar a opoeias a d
o ographs.
16
Decision tree on the evidence required to support the
different types of TM claims
A proposed TM claim
Traditional Health Use Claim
Scientifically Established
Treatment Claim
Traditional Treatment Claim
Refer to Table 2 and Sections 4.2 and 4.3
Evidence of documented
traditional use or history
of use that may be found
in the following:
• Classical TM Text
• Pharmacopoeias and
Monographs
• Reference Textbooks /
Journals
Does it meet the
criteria of well
documented TM
claim based on
substantiation of
evidence?
YES
NO
Not a welldocumented
Traditional
Health Use
Claim
Evidence of documented
history of traditional
treatment that may be
found in the following:
• Classical TM Text
• Pharmacopoeias and
Monographs
• Reference Textbooks /
Journals
Does it meet the
criteria of well
documented TM
claim based on
substantiation of
evidence?
NO
Compulsory evidence:
Substantiation of TM claims based on scientific
data, as required by the regulatory authority to be
conducted on finished product or ingredient(s).
Justification will have to be provided to the
regulatory authority if evidence provided is based
on ingredient
At least 1 additional evidence:
Evidence of documented history of traditional
treatment that may be found in the following:
• C
• lassical TM Texts
• P
•harmacopoeias and Monographs
• R
•eference Textbooks/Journals
Not a welldocumented
Traditional
Treatment
Claim
Does it meet the
criteria of well
documented TM
claim based on
substantiation of
evidence?
NO
YES
YES
Traditional Health
Use Claim
Traditional
Treatment Claim
Scientifically Established
Treatment Claim
Not a welldocumented
Scientifically
Established
Treatment
Claim
Types of HS claims (1)
Type of HS
claim
Scope
Examples to illustrate the scope
- as determined by the regulatory
authority of each Member State
General or
Nutritional
For Nutritional Support and General Health
Maintenance. Benefits derived from supplementation
beyond
a perso ’s daily dietary i take.
• Supple e ts utritio
• Supports healthy gro th a d
Development
• Nourishes the ody
• Relie es ge eral tired ess, eak ess
• Helps to ai tai good health
Functional
Relate to a positive contribution to health or to
the improvement of a function or to modifying
or preserving health in the context of the total
diet on normal functions or biological activities
of the body.
• Mai tai s/Supports healthy joi ts
• Mai tai s/Supports i
u ity
• Mai tai s healthy li er fu tio
• Mai tai s/Supports alert ess
• Mai tai s/Supports e tal
performance
• Pro otes healthy ski
• Helps to relie e post-menopausal
discomforts
• Aids i digestio to relie e i digestio
• Bifidobacteria in product A helps to
improve slow transit system in 14 days
• Supports health i agei g
• Supports health i
e opause
• Supports health i preg a y
Maintains or enhances structure or function of
the body, excluding disease related claims.
Supports health and to relieve/reduce/
lessen/ease minor body discomforts in some
physiological processes (e.g. ageing, Menopause,
pregnancy)*.
*as determined by the regulatory authority of each
Member State
Types of HS claims (2)
Type of
HS claim
Disease
Risk
Reduction
Scope
Significantly altering or reducing a
risk factor of
a disease or health related
condition*.
*as determined by the regulatory
authority of each Member
State
Examples to illustrate the scope
- as determined by the
regulatory
authority of each Member State
• Helps to redu e risk of
osteoporosis by
strengthening bone
• Helps to redu e the risk of
dyslipidaemia
OBAT HERBAL
TERSTANDAR DAN
FITOFARMAKA
REGISTRASI OHT
• Protokol Uji Praklinik diajukan ke
BPOM untuk persetujuan
• Data praklinik sebagai bukti dukung
khasiat keamanan registrasi Obat
Herbal Terstandar
• BPOM melakukan pendampingan
REGISTRASI FITOFARMAKA
• Data praklinik bisa berasal dari data praklinik
Obat Herbal Terstandar (namun bila perlu
disesuaikan) atau data praklinik baru (tidak
perlu protokol uji praklinik, tidak perlu
dimintakan persetujuan BPOM)
• Pengajuan persetujuan pelaksanaan uji klinik
diserahkan dokumen Protokol Uji Klinik,
Informed concern, dan Investigator Brochure)
• Data klinik sebagai bukti dukung khasiat
keamanan registrasi fitofarmaka
• BPOM melakukan pendampingan
CONTOH KEKURANGAN SAAT EVALUASI DOKUMEN & PROTOKOL UJI KLINIK
UJI PRA KLINIK
UJI KLINIK
1.
1.
2.
3.
4.
Data uji farmakodinamik belum
menggambarkan penyakit yang
dikondisikan namun sudah ada
tindakan/prosedur lanjutan.
Data keamanan berupa toksisitas sub
kronis dan teratogenik yang masih
memerlukan klarifikasi lebih lanjut
dikarenakan misalnya paparan
histologi yang inkonsisten
Kurangnya jumlah hewan coba yang
digunakan
Terdapat kejadian serius di ginjal dan
lever di semua hewan coba yang
digunakan, baik di mencit maupun di
kelinci
2.
3.
4.
5.
Metodologi uji yang kurang
sesuai
Kriteria inklusi dan eksklusi yang
belum sesuai
Jumlah subjek yang kurang
Endpoint efikasi tidak menjawab
apa yang menjadi tujuan uji
Dokumen informed consent
tidak mencerminkan apa yang
ada dalam protokol