PRAKTISI IF Inovasi Produk dan daya saing Industri Farmasi rev
Inovasi Produk dalam meningkatkan
daya saing Industri Farmasi
Key Drivers of Change in
Global Pharma Industry
“Kegagalan”
Increasing regulatory
pharmaceutical R&D
(biaya Penemuan obat baru (NAS) scrutiny
measures/reforms
: 1300-2000 juta US$)
Increasing acceptance of
generics and pricing
pressures
?
Pharma Industry
Innovative Dosage form (DDS) &
“supergeneric”
Changing Technology
Landscape
1.
2.
3.
Biotechnology
Stem-cell
Future :”Personalized
Medicine”
Trends that will impact the Pharmaceutical
Industry: Indonesia
• BPOM following PIC
regulation for GMP
implementation
• Asia harmonization
implementation
Social
• Growing middle class customer
in 11.3% (151 million to 168
million).
• Trend using technology savvy
and globally interconnected (in
virtual world).
Regulation
Technology
Political
• Implementation of
universal coverage
(BPJS) to all citizen
• Increasing pressure
for good and clean
government
• E-commerce spending is
increasing (expected to
increase by 28% in 2014
5.9M)
• Health care mobile
application (IVD)
• Developing Biotechnology
Economy
Environment
• Environmentfriendly / green
manufacture
• Indonesia economy is
expected to growth +/6%
• Indonesia healthcare
spending projected 2.75% of GDP
• Pharma market growth
10.7% by 2017
• Exchange rate volatility
• Cheap revolution
Growth engine
Indonesia Pharma Market
•GDP GROWTH
•SJSN (Universal Coverage)
Who has the right to get SJSN?
All Citizens of Indonesia (UUD 45 ps. 28 & 34)
Existing Healthcare Insurance Coverage
54 % of Indonesia population
without health insurance
coverage
TOTAL POPULATION = 234.18 MIO
46
%
54
%
Pasien
Layanan kesehatan
Fasilitas kesehatan baik
pemerintah maupun sebagian
besar swasta akan ikut dalam
program JKN
COB & OPE menjadi pilihan pada
private sector untuk menjaga
sustainabilitynya
Challenge di profitability outlet
Primary care akan makin
berkembang terkait perbaikan JKN
Pasien lower segment dan
chronic disease menikmati
layanan JKN
Saat ini upper level masih
berobat seperti semula (OPE)
Private insurance
Diduga Peran asuransi swasta
akan makin meningkat jika ada
implementasi yg jelas dari JKN
untuk layanan COB & TopUp
market
Profesi kesehatan
Pengaruh JKN-BPJS
terhadap Industri
kesehatan
Indonesia
Industri Farmasi
Market obat2 untuk common
diseases akan terjadi
commoditization
Market share obat2 generik akan
terus meningkat (2014 :13.8%
2020 :20%)
Pengembangan produk dengan
added value menjadi pilihan ke
depan (Orphan drugs, Biology, DDS,
Vaccine )
Pada layanan kesehatan yang
menerima JKN, terjadi load
pelayanan pasien yang tinggi,
namun terjadi
penurunan/peningkatan income
Pilihan obat possibility ke low
cost product
Prediksi dampak JKN/PKJS terhadap Industri Farmasi
Non BPJS
Kondisi
sebelum JKN
• Innovative products,
biosimilar, biology
products, etc
• Special Product for Private
Insurance
• M&A
BPJS
•OGB
•Common Dissease
•Brandedd Generic
(Increased in Volume)
2015
2019
OBAT PATENT, OFF PATENT & GENERIK
OBAT
PATENT
− UU Paten
− Privilege
− Biaya R & D sangat tinggi ( > USD
350 juta )
− Research based comp
BOLAR PROVISION
≤ 2 tahu dapat
OFF PATENT
e gajuka Registrasi
Generik
INN
• OGB
• Commodity
• Social marketing
• Peraturan
penggunaan OGB
di sarana R.S.
Pemerintah
Branded
Follower/me too
• Marketing cost
• Corporate image
• Brand/product value
• Intangible asset
• Same playing field
• Pilihan dokter
• Pilihan pasien
Off Patent/
Originator
Indonesia
Arah Strategi Inovasi Industri Farmasi Indonesia
Inovasi Produk
Industri
Farmasi
• UU Paten
•Harmonisasi
•Price
•CGMP-Regulated
Business
• Formulasi “me too”,
BA/BE
• Pengembangan Produk
lisensi
• OTC, Natural Prod,
Health food
• DDS / Innovative
Dosage Form
Inovasi Proses
• New Molekul??
• Lean Mnufacturing, Lean
Supply Chain
•Improved lead time
•Improved cost, NOC
PROGRAM PENUNJANG:
• ‘Networking’ antara Industri, Pemerintah dgn
Institusi/Lembaga penelitian
The Innovation Approach
•Short term range
•Improves BA-BE Product
•Natural product
•Process Innovation
•Medium term range
•Small Molecule & Super Generics
• NDDS, Nanotechnology
•Long term range (NCE/NAS ??)
•Biotechnology & Genomics
• Stem Cell
Produksi BBO
Short term range
• Generic Dosage Form
– Pengembangan Produk dalam bentuk sediaan yang umum seperti effervescent, tablet,
kapsul, sirup, powder, injeksi dan sebagainya.
– Dalam kategori ini tidak diperlukan uji klinis hanya BA/BE saja kalau diperlukan
– Kunci utama : Speed and Cost
- 12 -
Process Innovation
Lean production
Goals - highest quality, lowest cost,
shortest lead times
Business as usual
Wastes:
Overproduction
Transportion
Inventory
Waiting
Overprocessing
Rework
Motion
Ignorance of Employee intellectual
Lean system
Waste
• Faster Leadtime
• Optimum cost
• High Quality
13
3 MUSUH UTAMA LEAN:
Pemborosan, tidak fleksibel dan variasi pada seluruh proses
Menghilangkan waste /
pemborosan
Mengurangi ketidak-fleksibelan
("mura"): mampu
("muda") :
mengirimkan barang sesuai dengan
kebutuhan pelanggan sesuai dengan
waktu dan jumlah yang diminta
menurunkan biaya,
meningkatkan kualitas dan
mencapai hasil yang konsisten
Customer demand
Wast
e Inflexibility
Variability
Output
Customer demand
Output
Menurunkan variasi
("muri") :
memperbaiki kehandalan
proses, misal meningkatkan
kualitas dan menurunkan
biaya
14
Leadtime Study
Nonvalue
added
Assembly
Casting
Machining
Waiting
Transportation
Staging
Inv entory
Non
Value
Added
Staging
5%
Value
Added
Raw
Material
Time
= Value
Added Time
= Non-Value
Added Time
(WASTE)
Finished
Parts
Waktu yang menghasilkan value
added hanya 5 % dari total leadtime
Penghematan biaya dengan cara
tradisional hanya fokus pada aktivitas
Value Added
LEAN fokus pada aktivitas NON-
VALUE ADDING
15
Contoh : Integrated Production System- Lean Manufacturing di Farmasi
Production Pull System - Value Stream Mapping
Too Many WIP
between Process
(Potential to Improve)
PPIC
RKHP
Daily
RKHP
WH
1. Weighing
2. Supply per batch
3. Over supply
4. Handling process
SCH
RKHP
RKHP
RKHP
RKHP
Daily
Daily
Daily
Daily
Daily
1. Waiting QC
2. Documentation
WH
RM
Bind
Staging
Gran
ulasi
Staging
Dry
ing
Final
Mixing
Tablet
Strip
ping
Catch
Covering
Storage
Storage
PM
1. Nonstandard handling
2. Unbalanced machine 1. Nonstandard handling
2. Over capacity
3. Other waste
3. Big production volume
4. Handling distance
Staging
Storage
1. Nonstandard handling
1. Nonstandard handling 1. Nonstandard handling
2. Waiting QC
2. Over supply
3. Transfer
2. Transfer
3. Handling distance 3. Documentation
4. Over supply
Max LT
2.00 D
0.7 D
0.3 D
0.04 D
0.26 D
2..2 D
3.2 D
3.07 D
0.5 D
4.00 D
0.3 D
0.04 D
0.26 D
1.25 D
2.09 D
1.41 D
0.5 D
4.00 D
11.39 D
Before
1,25 D
Target
16.56 D
0.625 D
0.08 D
1.25 D
1.50 D
1.0 D
0.25 D
4.00 D
8.90 D
0.625 D
0.08 D
1.25 D
1.375 D
1.0 D
0.25 D
1.15 D
6.05 D
0.625 D
0.08 D
1.25 D
1.375 D
0.68 D
0.25 D
0.77 D
0.30 D
0.08 D
0.47 D
0.625 D
0.3 D
0.25 D
0.77 D
1
2
3
4
5
5.35 D
3.09 D
Few innovation in production equipment
Some innovations
• Granulation
– Single-Pot Granulation + Microwave drying
– Closed system for solid dosage form
• Injection filling
– Isolators in filling machines
– Laser ampoule closing
– Pre-filled syringe & Blow-Fill-Seal technology
• Tabletting
– Fast change over : detachable turret, tool-less setting
down/up
– Fully automated production
Pharma technology trend
Single Pot Granulation
+ Microwave Drying
Ultima (Collette N.V)
ULTIMA 25
ULTIMA
75
Isolators are invading SDF
territory
Isolated tablet press with
Reference :Symposium : German Technology for The Pharmaceutical Industry
additional
mobile
isolators Pharma technology trend
Singapore,
November 22-23,
2001
Continuous coating [L.B.Bohle]
Pharma technology trend
... another provoking
concept
Pharma technology trend
Medium term range
SMALL MOLECULES & SUPERGENERICS
Dds-sistem Penghantaran Obat Inovatif
= Riset Alternatif
Riset Senyawa Obat
Sintesis
Uji Pra Klinis
Uji Klinis
success rate
Riset Penghantaran
Obat
5%
10 %
50 %
Uji Pra Klinis
Uji Klinis
Registrasi
US$ 800 juta
10-15
tahun
80 %
Registrasi
Biaya
US$ 10-20 juta
Waktu
3-5 tahun
Denti-Patch
Asthma Patch
Estrogen Patch
Impotence Patch
Supergenerics is developed to face competition in generics
markets after patent expiry or to develop modified products
with non infringe patent
•Supergenerics are developed through improvement on
drug delivery, manufacturing or reformulation technology
Efficacy of drugs are still not optimum and may have serious side effects
Modification of products for increase solubility, passing barrier and reduce
side effects
•There are top five technologies in DDS :
1. Oral thin films
2. Microneedles
3. Extended release
4. Aerosol
5. Liposomes
NANOTECHNOLOGY
Nanotech has been used widely as platform for pharmaceutical and healthcare
application due to ability of nano particles to penetrate into body, brain, cells
• New and advanced medicine and materials for treatment and drug release
• Products with better bioavailability reduced dosing enabled better efficacy,
reduced side effects
• Nanotech is used in drug formulation and delivery
– Doxil (doxorubicin hcl liposome)
– Abraxane (nanoparticle albumin bound paclitaxel)
– Daunoxome (daunorubicine liposome)
• Some materials are developed as nano particles nano ginseng, nano tea,
etc
• Other forms: Nanocarbon (buckysomes) from buckyballs as nanocarrier
Nano Capsules for Endoscopies
from Given Imaging Technology.
Next: NEMO (Nano-based capsuleEndoscopy with Molecular Imaging
and Optical biopsy)
Long term range
New Chemical Entity
New Active Substances
World pharmaceutical R&D productivity declines
• R&D productivity: Increasing R&D Spending, Less NMEs & New Biologics Approved
• Few Successful new product launch
• Only 5 Big Pharma companies earned > 10% from major products launched after 2001.
90% came from medicines that have been in market > 5 yrs.
Main Steps during Drug Development
IDEA
Clinical trial authorization
(IND)
CLINICAL DEVELOPMENT:
•Phase I
•Phase II/III
Life Cycle Management
Evaluation Report
Renewal of Registration etc
DRUG SUBSTANCE:
•Synthesis
•Analytics
•Dosage Forms
PRECLINICS:
•Pharmacology
•Toxicology
•Pharmacokinetics
Marketing authorization
(NDA, PL)
LAUNCH
Duration and Cost of Drug Development
Duration
Research
Costs (Mio US$)
3-6 yr
140
110
Phase I
1.5 yr
30
Phase II
2 yr
80
Phase III
3.5 yr
330
Authority”s
Assesment/NDA Phase
1.5 yr
60
Preclinical Phase
Development/
Clinical Phase
11 – 15 yr
ca. 750 Mio US$
•
•
•
•
•
STEM CELL
Cells are the basic units of all life.
Stem cells are the first cells formed in the
development of a human being,
immediately after fertilization of an ovum
by a sperm.
Stem cells are characterized by two
properties:
– replicate to form other identical stem
cells
– can alternatively give rise to
differentiated cells
Form the 200-plus cell types in the human
body.
A major object of stem cell research is to
develop the means to use them as the raw
material for tissues which are lacking in the
body due to disease.
Burn wound
Chronic wound
Hematopoietic Stem Cells ->
Endothelial Progenitor Cells
Myocardial Infarction
Umbilical
Cord Blood
alopecia
Condition
medium
(content
media)
Bone marrow
stem cells ->
Mesenchymal
Stem Cells
Skin rejuvination
Osteoarthritis
STEM CELL u
ALLOGENEIC
cheaper and more convenient
AUTOLOGOUS
Safety - ot reje ted y the patie t’s i
u e syste
PENGEMBANGAN BAHAN BAKU OBAT
DI INDUSTRI FARMASI INDONESIA
Indonesia
Fakta-fakta
tentang BBO di Indonesia
Sekilas Industri Bahan baku obat Indonesia
• Diawal Orde baru atau tahun 70-an, dipersyaratkan
untuk MNC setelah 5 Tahun berbisnis Di Indonesia
harus membuat minimal 1 Bahan Baku Obat
– Beberapa yang pernah membuat BBO diantaranya , Merck
(Vit B1), Carlo Erba, Meiji dsb, tetapi tidak berlanjut
• Kebjakan Pemerintah memberi perlindungan
IndustrinBBO dengan pemberian tambahan Tax untuk
Bahan Import
– Beberapa sempat berproduksi seperti Sandoz (amoxicylin),
Riasima (paracetamol), tteetapi menjadi terhenti ketika
perlindungan Tax nya di cabut
• Industri BBO yang masih eksis antara lain : Kinin
(Kimia Farma), Vaksin ( Biofarma)
Pasar Bahan Baku Obat Indonesia
Nilai (Rp.Triliun)
2011 : Rp. 9,59 T
2012 : Rp.11,40 T
2013: Rp.13,00 T
4-5% Bahan Baku obat
yang di produksi
Indonesia kebanyakan
Bahan pembantu
seperti Sorbitol, ethyl
alkohol, Fructose.
Sedang API sangat
sedikit, seperti Kina,
Iodium, sedikit
Paracetamol dsb
China;
60%
India; 30%
Eropa;
10%
Tantangan Industri Bahan Baku Obat
• Konsumsi / Pasar dalam negeri relatif Kecil
(Economic of Scale)- Profit margin kecil –
Investasi awal besar
• Ketersediaan bahan dari Industri lokal Kimia
Hilir
• Ketersediaan lokal Teknologi pembuatan BBO
Tidak bisa bersaing dalam ͞global Price͟
PENUTUP
Alternative Solutions
• Companies are increasingly dispersing R&D networks to
• 1) cost-effectively access critical knowledge that
could not otherwise be tapped, and
• 2) to locate capabilities where they can deliver
results better, faster, and cheaper than elsewhere in
the network
• In-licensing new compounds
– Companies buy the rights to use compounds that others
have discovered
• Contract research organizations (CROs)
–Cost reductions less than 8% of drug development cost
Ope I
ovatio
Open Innovation
Speaker Profile
Drs Pre Agusta Siswantoro, Apt , MBA (31st July 1962)
Education Background
Pharmacy Graduated, Gadjah Mada University, 1985
MBA Graduated in IPPM Jakarta, 1992
WORKING EXPERIENCES
1. R&D - Production manager , PT PRAFA, 1987 - 1992
2. Production Manager- Assisten Director R&D, PT KALBE FARMA, 1992-2000
3. Plant /Manufacturing Director PT BINTANG TOEDJOE, 2000- 2008
4. Corporate R&D Director KALBE FARMA 2006 -2008
5. Director of PT Global Chemindo Megatrading (GCM)- Raw Material Trading, 2011- present
6. Supply Chain Director KALBE Group 2008 – present
OTHERS
1. Jury of I do esia’s I ovatio organized by BIC and KNRT, 2008 – 2010
2. Wakil Ketua, Pengurus Pusat, IKATAN APOTEKER INDONESIA, 2009 -2014
3. Ketua Hisfardis (Himpunan Seminat Farmasi Distribusi)
3.Pengurus Pusat Gabungan Perusahaan Farmasi Indonesia –GPFI ,2011-2015
Excellence
Execution
daya saing Industri Farmasi
Key Drivers of Change in
Global Pharma Industry
“Kegagalan”
Increasing regulatory
pharmaceutical R&D
(biaya Penemuan obat baru (NAS) scrutiny
measures/reforms
: 1300-2000 juta US$)
Increasing acceptance of
generics and pricing
pressures
?
Pharma Industry
Innovative Dosage form (DDS) &
“supergeneric”
Changing Technology
Landscape
1.
2.
3.
Biotechnology
Stem-cell
Future :”Personalized
Medicine”
Trends that will impact the Pharmaceutical
Industry: Indonesia
• BPOM following PIC
regulation for GMP
implementation
• Asia harmonization
implementation
Social
• Growing middle class customer
in 11.3% (151 million to 168
million).
• Trend using technology savvy
and globally interconnected (in
virtual world).
Regulation
Technology
Political
• Implementation of
universal coverage
(BPJS) to all citizen
• Increasing pressure
for good and clean
government
• E-commerce spending is
increasing (expected to
increase by 28% in 2014
5.9M)
• Health care mobile
application (IVD)
• Developing Biotechnology
Economy
Environment
• Environmentfriendly / green
manufacture
• Indonesia economy is
expected to growth +/6%
• Indonesia healthcare
spending projected 2.75% of GDP
• Pharma market growth
10.7% by 2017
• Exchange rate volatility
• Cheap revolution
Growth engine
Indonesia Pharma Market
•GDP GROWTH
•SJSN (Universal Coverage)
Who has the right to get SJSN?
All Citizens of Indonesia (UUD 45 ps. 28 & 34)
Existing Healthcare Insurance Coverage
54 % of Indonesia population
without health insurance
coverage
TOTAL POPULATION = 234.18 MIO
46
%
54
%
Pasien
Layanan kesehatan
Fasilitas kesehatan baik
pemerintah maupun sebagian
besar swasta akan ikut dalam
program JKN
COB & OPE menjadi pilihan pada
private sector untuk menjaga
sustainabilitynya
Challenge di profitability outlet
Primary care akan makin
berkembang terkait perbaikan JKN
Pasien lower segment dan
chronic disease menikmati
layanan JKN
Saat ini upper level masih
berobat seperti semula (OPE)
Private insurance
Diduga Peran asuransi swasta
akan makin meningkat jika ada
implementasi yg jelas dari JKN
untuk layanan COB & TopUp
market
Profesi kesehatan
Pengaruh JKN-BPJS
terhadap Industri
kesehatan
Indonesia
Industri Farmasi
Market obat2 untuk common
diseases akan terjadi
commoditization
Market share obat2 generik akan
terus meningkat (2014 :13.8%
2020 :20%)
Pengembangan produk dengan
added value menjadi pilihan ke
depan (Orphan drugs, Biology, DDS,
Vaccine )
Pada layanan kesehatan yang
menerima JKN, terjadi load
pelayanan pasien yang tinggi,
namun terjadi
penurunan/peningkatan income
Pilihan obat possibility ke low
cost product
Prediksi dampak JKN/PKJS terhadap Industri Farmasi
Non BPJS
Kondisi
sebelum JKN
• Innovative products,
biosimilar, biology
products, etc
• Special Product for Private
Insurance
• M&A
BPJS
•OGB
•Common Dissease
•Brandedd Generic
(Increased in Volume)
2015
2019
OBAT PATENT, OFF PATENT & GENERIK
OBAT
PATENT
− UU Paten
− Privilege
− Biaya R & D sangat tinggi ( > USD
350 juta )
− Research based comp
BOLAR PROVISION
≤ 2 tahu dapat
OFF PATENT
e gajuka Registrasi
Generik
INN
• OGB
• Commodity
• Social marketing
• Peraturan
penggunaan OGB
di sarana R.S.
Pemerintah
Branded
Follower/me too
• Marketing cost
• Corporate image
• Brand/product value
• Intangible asset
• Same playing field
• Pilihan dokter
• Pilihan pasien
Off Patent/
Originator
Indonesia
Arah Strategi Inovasi Industri Farmasi Indonesia
Inovasi Produk
Industri
Farmasi
• UU Paten
•Harmonisasi
•Price
•CGMP-Regulated
Business
• Formulasi “me too”,
BA/BE
• Pengembangan Produk
lisensi
• OTC, Natural Prod,
Health food
• DDS / Innovative
Dosage Form
Inovasi Proses
• New Molekul??
• Lean Mnufacturing, Lean
Supply Chain
•Improved lead time
•Improved cost, NOC
PROGRAM PENUNJANG:
• ‘Networking’ antara Industri, Pemerintah dgn
Institusi/Lembaga penelitian
The Innovation Approach
•Short term range
•Improves BA-BE Product
•Natural product
•Process Innovation
•Medium term range
•Small Molecule & Super Generics
• NDDS, Nanotechnology
•Long term range (NCE/NAS ??)
•Biotechnology & Genomics
• Stem Cell
Produksi BBO
Short term range
• Generic Dosage Form
– Pengembangan Produk dalam bentuk sediaan yang umum seperti effervescent, tablet,
kapsul, sirup, powder, injeksi dan sebagainya.
– Dalam kategori ini tidak diperlukan uji klinis hanya BA/BE saja kalau diperlukan
– Kunci utama : Speed and Cost
- 12 -
Process Innovation
Lean production
Goals - highest quality, lowest cost,
shortest lead times
Business as usual
Wastes:
Overproduction
Transportion
Inventory
Waiting
Overprocessing
Rework
Motion
Ignorance of Employee intellectual
Lean system
Waste
• Faster Leadtime
• Optimum cost
• High Quality
13
3 MUSUH UTAMA LEAN:
Pemborosan, tidak fleksibel dan variasi pada seluruh proses
Menghilangkan waste /
pemborosan
Mengurangi ketidak-fleksibelan
("mura"): mampu
("muda") :
mengirimkan barang sesuai dengan
kebutuhan pelanggan sesuai dengan
waktu dan jumlah yang diminta
menurunkan biaya,
meningkatkan kualitas dan
mencapai hasil yang konsisten
Customer demand
Wast
e Inflexibility
Variability
Output
Customer demand
Output
Menurunkan variasi
("muri") :
memperbaiki kehandalan
proses, misal meningkatkan
kualitas dan menurunkan
biaya
14
Leadtime Study
Nonvalue
added
Assembly
Casting
Machining
Waiting
Transportation
Staging
Inv entory
Non
Value
Added
Staging
5%
Value
Added
Raw
Material
Time
= Value
Added Time
= Non-Value
Added Time
(WASTE)
Finished
Parts
Waktu yang menghasilkan value
added hanya 5 % dari total leadtime
Penghematan biaya dengan cara
tradisional hanya fokus pada aktivitas
Value Added
LEAN fokus pada aktivitas NON-
VALUE ADDING
15
Contoh : Integrated Production System- Lean Manufacturing di Farmasi
Production Pull System - Value Stream Mapping
Too Many WIP
between Process
(Potential to Improve)
PPIC
RKHP
Daily
RKHP
WH
1. Weighing
2. Supply per batch
3. Over supply
4. Handling process
SCH
RKHP
RKHP
RKHP
RKHP
Daily
Daily
Daily
Daily
Daily
1. Waiting QC
2. Documentation
WH
RM
Bind
Staging
Gran
ulasi
Staging
Dry
ing
Final
Mixing
Tablet
Strip
ping
Catch
Covering
Storage
Storage
PM
1. Nonstandard handling
2. Unbalanced machine 1. Nonstandard handling
2. Over capacity
3. Other waste
3. Big production volume
4. Handling distance
Staging
Storage
1. Nonstandard handling
1. Nonstandard handling 1. Nonstandard handling
2. Waiting QC
2. Over supply
3. Transfer
2. Transfer
3. Handling distance 3. Documentation
4. Over supply
Max LT
2.00 D
0.7 D
0.3 D
0.04 D
0.26 D
2..2 D
3.2 D
3.07 D
0.5 D
4.00 D
0.3 D
0.04 D
0.26 D
1.25 D
2.09 D
1.41 D
0.5 D
4.00 D
11.39 D
Before
1,25 D
Target
16.56 D
0.625 D
0.08 D
1.25 D
1.50 D
1.0 D
0.25 D
4.00 D
8.90 D
0.625 D
0.08 D
1.25 D
1.375 D
1.0 D
0.25 D
1.15 D
6.05 D
0.625 D
0.08 D
1.25 D
1.375 D
0.68 D
0.25 D
0.77 D
0.30 D
0.08 D
0.47 D
0.625 D
0.3 D
0.25 D
0.77 D
1
2
3
4
5
5.35 D
3.09 D
Few innovation in production equipment
Some innovations
• Granulation
– Single-Pot Granulation + Microwave drying
– Closed system for solid dosage form
• Injection filling
– Isolators in filling machines
– Laser ampoule closing
– Pre-filled syringe & Blow-Fill-Seal technology
• Tabletting
– Fast change over : detachable turret, tool-less setting
down/up
– Fully automated production
Pharma technology trend
Single Pot Granulation
+ Microwave Drying
Ultima (Collette N.V)
ULTIMA 25
ULTIMA
75
Isolators are invading SDF
territory
Isolated tablet press with
Reference :Symposium : German Technology for The Pharmaceutical Industry
additional
mobile
isolators Pharma technology trend
Singapore,
November 22-23,
2001
Continuous coating [L.B.Bohle]
Pharma technology trend
... another provoking
concept
Pharma technology trend
Medium term range
SMALL MOLECULES & SUPERGENERICS
Dds-sistem Penghantaran Obat Inovatif
= Riset Alternatif
Riset Senyawa Obat
Sintesis
Uji Pra Klinis
Uji Klinis
success rate
Riset Penghantaran
Obat
5%
10 %
50 %
Uji Pra Klinis
Uji Klinis
Registrasi
US$ 800 juta
10-15
tahun
80 %
Registrasi
Biaya
US$ 10-20 juta
Waktu
3-5 tahun
Denti-Patch
Asthma Patch
Estrogen Patch
Impotence Patch
Supergenerics is developed to face competition in generics
markets after patent expiry or to develop modified products
with non infringe patent
•Supergenerics are developed through improvement on
drug delivery, manufacturing or reformulation technology
Efficacy of drugs are still not optimum and may have serious side effects
Modification of products for increase solubility, passing barrier and reduce
side effects
•There are top five technologies in DDS :
1. Oral thin films
2. Microneedles
3. Extended release
4. Aerosol
5. Liposomes
NANOTECHNOLOGY
Nanotech has been used widely as platform for pharmaceutical and healthcare
application due to ability of nano particles to penetrate into body, brain, cells
• New and advanced medicine and materials for treatment and drug release
• Products with better bioavailability reduced dosing enabled better efficacy,
reduced side effects
• Nanotech is used in drug formulation and delivery
– Doxil (doxorubicin hcl liposome)
– Abraxane (nanoparticle albumin bound paclitaxel)
– Daunoxome (daunorubicine liposome)
• Some materials are developed as nano particles nano ginseng, nano tea,
etc
• Other forms: Nanocarbon (buckysomes) from buckyballs as nanocarrier
Nano Capsules for Endoscopies
from Given Imaging Technology.
Next: NEMO (Nano-based capsuleEndoscopy with Molecular Imaging
and Optical biopsy)
Long term range
New Chemical Entity
New Active Substances
World pharmaceutical R&D productivity declines
• R&D productivity: Increasing R&D Spending, Less NMEs & New Biologics Approved
• Few Successful new product launch
• Only 5 Big Pharma companies earned > 10% from major products launched after 2001.
90% came from medicines that have been in market > 5 yrs.
Main Steps during Drug Development
IDEA
Clinical trial authorization
(IND)
CLINICAL DEVELOPMENT:
•Phase I
•Phase II/III
Life Cycle Management
Evaluation Report
Renewal of Registration etc
DRUG SUBSTANCE:
•Synthesis
•Analytics
•Dosage Forms
PRECLINICS:
•Pharmacology
•Toxicology
•Pharmacokinetics
Marketing authorization
(NDA, PL)
LAUNCH
Duration and Cost of Drug Development
Duration
Research
Costs (Mio US$)
3-6 yr
140
110
Phase I
1.5 yr
30
Phase II
2 yr
80
Phase III
3.5 yr
330
Authority”s
Assesment/NDA Phase
1.5 yr
60
Preclinical Phase
Development/
Clinical Phase
11 – 15 yr
ca. 750 Mio US$
•
•
•
•
•
STEM CELL
Cells are the basic units of all life.
Stem cells are the first cells formed in the
development of a human being,
immediately after fertilization of an ovum
by a sperm.
Stem cells are characterized by two
properties:
– replicate to form other identical stem
cells
– can alternatively give rise to
differentiated cells
Form the 200-plus cell types in the human
body.
A major object of stem cell research is to
develop the means to use them as the raw
material for tissues which are lacking in the
body due to disease.
Burn wound
Chronic wound
Hematopoietic Stem Cells ->
Endothelial Progenitor Cells
Myocardial Infarction
Umbilical
Cord Blood
alopecia
Condition
medium
(content
media)
Bone marrow
stem cells ->
Mesenchymal
Stem Cells
Skin rejuvination
Osteoarthritis
STEM CELL u
ALLOGENEIC
cheaper and more convenient
AUTOLOGOUS
Safety - ot reje ted y the patie t’s i
u e syste
PENGEMBANGAN BAHAN BAKU OBAT
DI INDUSTRI FARMASI INDONESIA
Indonesia
Fakta-fakta
tentang BBO di Indonesia
Sekilas Industri Bahan baku obat Indonesia
• Diawal Orde baru atau tahun 70-an, dipersyaratkan
untuk MNC setelah 5 Tahun berbisnis Di Indonesia
harus membuat minimal 1 Bahan Baku Obat
– Beberapa yang pernah membuat BBO diantaranya , Merck
(Vit B1), Carlo Erba, Meiji dsb, tetapi tidak berlanjut
• Kebjakan Pemerintah memberi perlindungan
IndustrinBBO dengan pemberian tambahan Tax untuk
Bahan Import
– Beberapa sempat berproduksi seperti Sandoz (amoxicylin),
Riasima (paracetamol), tteetapi menjadi terhenti ketika
perlindungan Tax nya di cabut
• Industri BBO yang masih eksis antara lain : Kinin
(Kimia Farma), Vaksin ( Biofarma)
Pasar Bahan Baku Obat Indonesia
Nilai (Rp.Triliun)
2011 : Rp. 9,59 T
2012 : Rp.11,40 T
2013: Rp.13,00 T
4-5% Bahan Baku obat
yang di produksi
Indonesia kebanyakan
Bahan pembantu
seperti Sorbitol, ethyl
alkohol, Fructose.
Sedang API sangat
sedikit, seperti Kina,
Iodium, sedikit
Paracetamol dsb
China;
60%
India; 30%
Eropa;
10%
Tantangan Industri Bahan Baku Obat
• Konsumsi / Pasar dalam negeri relatif Kecil
(Economic of Scale)- Profit margin kecil –
Investasi awal besar
• Ketersediaan bahan dari Industri lokal Kimia
Hilir
• Ketersediaan lokal Teknologi pembuatan BBO
Tidak bisa bersaing dalam ͞global Price͟
PENUTUP
Alternative Solutions
• Companies are increasingly dispersing R&D networks to
• 1) cost-effectively access critical knowledge that
could not otherwise be tapped, and
• 2) to locate capabilities where they can deliver
results better, faster, and cheaper than elsewhere in
the network
• In-licensing new compounds
– Companies buy the rights to use compounds that others
have discovered
• Contract research organizations (CROs)
–Cost reductions less than 8% of drug development cost
Ope I
ovatio
Open Innovation
Speaker Profile
Drs Pre Agusta Siswantoro, Apt , MBA (31st July 1962)
Education Background
Pharmacy Graduated, Gadjah Mada University, 1985
MBA Graduated in IPPM Jakarta, 1992
WORKING EXPERIENCES
1. R&D - Production manager , PT PRAFA, 1987 - 1992
2. Production Manager- Assisten Director R&D, PT KALBE FARMA, 1992-2000
3. Plant /Manufacturing Director PT BINTANG TOEDJOE, 2000- 2008
4. Corporate R&D Director KALBE FARMA 2006 -2008
5. Director of PT Global Chemindo Megatrading (GCM)- Raw Material Trading, 2011- present
6. Supply Chain Director KALBE Group 2008 – present
OTHERS
1. Jury of I do esia’s I ovatio organized by BIC and KNRT, 2008 – 2010
2. Wakil Ketua, Pengurus Pusat, IKATAN APOTEKER INDONESIA, 2009 -2014
3. Ketua Hisfardis (Himpunan Seminat Farmasi Distribusi)
3.Pengurus Pusat Gabungan Perusahaan Farmasi Indonesia –GPFI ,2011-2015
Excellence
Execution