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MIKROBIOLOGI TERAPAN:

PERAN MIKROBIOLOGI
DI INDUSTRI VAKSIN
Bandung, 22 Oktober 2016
IIN SUSANTI
Bio Farma

Pendahuluan: Mikrobiologi Terapan


Mikrobiologi terapan adalah interaksi antara mikroba dengan isi
dunia lainnya
Efek mikrobiologi terhadap tanah, air, makanan, obat-obatan, pertanian

Mikroorganisme hampir bisa ditemukan di semua aspek


kehidupan kita
memegang peranan kritikal pada kelangsungan hidup kita di bumi

to be a successful ecosystem on Earth, BE NICE to the


microorganisms!
Sebagian besar bakteri: NOT harmful to human.
Most are beneficial in food, agriculture, medicine, and for
energy production.
Applied Micobiology is to understand microorganisms and to get
them to work for us.

The number of normal bacterial cells that live on the


body is in the region of 100 million. This number is
10 times greater than the 10 million cells that make
up the human body.
(http://www.microbiologyonline.org.uk/about-microbiology/microbes-and-the-human-body)

Pendahuluan: Mikrobiologi Terapan


Makanan & Minuman: microorganisme untuk produksi
keju, yoghurt dan roti, wine, bier, dan distilled alcoholic
beverage. Khas Indonesia: Tape, Brem
Pharmaceuticals : antibiotik, vitamin ( B12 and B2),
steroid (Cortisone), dan Vaksin.
Chemicals : ethanol, citric acid dan vinegar
Biochemical cycles: Carbon cycle, nitrogen cycle,
nitrogen fixation in plants.
Energy/Environment: Biofuels, bioremediation (clean
up pollution)
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Use of Microorganisms

Use of Microorganisms

Keberhasilan Mikrobiologi
Salah satu contoh sukses besar di bidang mikrobiologi adalah
control of disease causing by organisms.

Diseases caused by microorganisms


Life style diseases
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Pendahuluan: Pharmaceutical
Microbiology
Industri farmasi hendaknya menghasilkan produk
sesuai dengan persyaratan:
Quality
Identity
Strength
Purity
Safety

Microbiology memegang peranan penting untuk


memenuhi sebagain dari persyaratan kualitas di atas:
Sterile products
Non-sterile products: freedom from objectionable
micoorganisms

Key Elements
Pharmaceutical
Microbiology

Production

Quality
Assurance /
Quality Control

R&D

Regulasi

Peran Mikrobiologi dalam Produksi


Produksi bahan baku dan senyawa aktif dalam
industri farmasi:
Bio-konversi
Natural metabolites
Metabolit yang diproduksi melalui genetically
engineered microorganism (rekombinan)
Vaksin (mikroorganisme atau bagian/metabolit
dari organisme yang digunakan dalam usaha
pecegahan penyakit)

Vaksin
Tujuan: menginduksi sistem imun tubuh untuk
membentuk antibodi terhadap antigen
tertentu
Traditional Vaccines:
Attenuated: strain mutan hidup dari patogen yang
telah hilang sifat virulennya tapi masih
mempunyai sifat antigenitas, co/: BCG, Campak,
Polio oral
Killed bacteria or viruses: sel atau virion yang
dimatikan dengan panas atau penambahan zat
kimia; co/: influenza, pertusis, polio inaktif
Toxoid (Metabolite): Diphtheria, Tetanus

Second Generation Vaccines:

Conjugate vaccine: bagian dari organisme yang


dikonjugasikan dengan protein sebagai carrier;
co/: HiB, Meningococ
Subunit vaccine: mengandung satu atau lebih
komponen selular dari organisme; co/: Aselular
pertusis, Influenza HA
Genetically engineered: Hepatitis B

Future Vaccines:

Recombinant vector vaccine


Skin patches (Koyo)
Inhalasi
Edible vaccine

Bio Farma
State-owned enterprise under the auspices of the
Ministry of State-owned Enterprise.
Sole vaccine manufacturer in Indonesia
Mission :

o Support National Immunization Program through supply of


vaccines
o Provide shareholder with dividends

One of a few WHO prequalified vaccine manufacturers


in the world
Export vaccines through UNICEF and other countries

Bio Farma
Core products :
DTP, TT, DT, BCG
OPV, Measles, Hepatitis B
Combination vaccines : DTP-HepB
Pentavalent: DTP-HepB-HiB
Other products : sera & diagnostik
Vaccines under development:
Influenza avian influenza
sIPV
Rotavirus
Pneumococ
Thypoid

MICROBIOLOGICAL
IN
VACCINES PRODUCTION

Production Processes
Production based on concepts of biotechnology

1 000 liter fermentors for tetanus cultivation

Production Processes

Harvesting equipment

Measles Production (Up-stream)

Measles Production (Down-stream)

Microbiological
Quality Assurance
Deteksi
Kontaminan
Monitoring
Proses

Quantitative
Analysis

Deteksi Kontaminan

Bakteri
Jamur
Endotoksin
Mycoplasma
Virus

Sterility Test Membrane filtration

Sterility Test Direct Inoculation

Mycoplasma Testing
Direct Inoculation: media PPLO
DNA Staining
PCR

Note: PPLO = PleuroPneumonia Like


Organisms

Endotoxin - Pyrogen
Pyrogen Rabbit test
LAL test:
Gel clot
Chromogen
Turbidimetry

Limulus (horseshoe crab)

Bioburden

Raw material
Active substances
Water
Media sblm sterilisasi

Viruses
Cell culture
PCR
Sel RK

Virus
Herpes

Sel Vero

Virus
Foamy

Sel MK

Virus
Herpes

Sel MRC-5

Virus
CMV

Sel VK

Virus
SV40

Monitoring Process
Environment monitoring
Sterilisasi
Validasi

CLEAN ROOM
WHAT IS A CLEAN ROOM ?
A specially constructed environment wherein
precise control is maintained over
temperature, humidity, pressurization, degree
of air filtration, number of air change,
direction of air flow, noise, vibration and
electrostatic potential and to type and count
of microbial contamination

Clean room:
Class A (kelas 100)
Class B (kelas 1000)
Class C (kelas 10000)
Class D (kelas 100000)
Containment
Four Biosafety levels:
Biosafety Level 1 (BSL 1)
Biosafety Level 2 (BSL 2)
Biosafety Level 3 (BSL 3)
Biosafety Level 4 (BSL 4)

BACTERIA & PARTICLES CARRIED BY


PEOPLE
BACTERIA

PARTICLES

Hands
Forehead
Scalp
Armpits
Nasal
Saliva
Skin surface
Skin replacement
Shedding of

100-1000/cm2
10000-100000/cm2
1 million/cm2
1-10 million/cm2
10 million/g
100 million/g
1.75m2
every 5 days
> 10 millions/day
particle

Ruang Berkelas

Laminair Air Flow / Biosafety Cabinet

Gowning

Environment Monitoring
Air sampler

Contact plate

Particle count

Settling plate

Finger dab

Proses Sterilisasi
Biological indicators:
Oven (dry heat)
: B. subtilis
Autoclave (steam) : B. stearothermophillus

Validasi Sterilisasi

Validasi Proses Aseptis

Media Fill
Media Transfer
Sterile Filtration
SIP / CIP (sterilization/cleaning in place)
Cleaning validation

Quantitative Analysis
Antibiotik
Vitamin

TERIMA KASIH

TERIMA KASIH