Welcome
Presentation on
Industrial initiative on
medical biotechnology in Bangladesh
Presented by -
Abdul Muktadir
Managing Director, Incepta
Pharmaceuticals Ltd
•
B.Pharm, University
of Dhaka
•
M.Pharm, University
of Dhaka
•
M.S. in Industrial Pharmacy, Long Island University , USA
Research on –
1. Anti-tumor antibiotic,
University of Dhaka & IPGMR (BSMMU)
2. Dosage Form Design, Long Island University , USA
3. Special research interest on
Aerosol, Nanotechnology, Sustain
release drug, Lyophilyzation, Design of
Pharmaceutical Factory
l
Pharmaceutical is the most promising industrial
sector in our country
l
There are 257 pharmaceuticals companies
registered & among them 197 are operational
l
Annual 2011 sales was 8,048 crore taka (1.06 B$)
with a growth rate of 24.63%
l
The industry is providing employment for about
1,00,000 skilled personnel
l
Technological excellence has always been the
highlight of the pharmaceutical industry
l
Export of pharmaceutical finished product is
evolving. This industry contributed 421 crore taka (52.65 million USD) in 2011
by exporting to 83 countries
l
We are manufacturing 97% of country’s
requirement of medicine & only 3% is imported which are mainly
biopharmaceuticals
l
Recombinant human Insulin
l
Recombinant human Erythropoietin
l
PEG-Interferon alpha
l
Low molecular weight heparin (Enoxaparin)
l
Tissue Plasminogen Activator (Alteplase,
Reteplase)
l
Follicle stimulating hormone products
l
Streptokinase Anticancer drugs
l
Monoclonal antibody
Vaccines (Typhoid, Rabies vaccine, Tetanus etc.)
Market status of Major
biopharmaceutical
Products
|
Revenue per year (in crore taka)
|
Growth
|
Vaccine
|
54.17 (without EPI)
|
38.5%
|
Human insulin
|
212.95
|
40%
|
Erythropoietin
|
0.17 (Actual value is much
high)
|
--
|
Anticancer products
|
5.53(Actual value is much high)
|
53%
|
Low molecular heparin
(Enoxaparin)
|
12.07
|
68%
|
Pre-filled filling facility
Enoxaparin Sodium requires some
modern facilities & critical steps in manufacturing process.
Premises
l Separate high-tech, Clean room that contains
laminar airflow to control airborne contamination.
l Room air is filtered through a High Efficiency
Particulate Air (HEPA) filter removing 99.97% of all particles of 0.3 m or
larger.
Machine
Completely automatic filling
machine with a very compact and elegant Programmable Logic Controller (PLC).
Process
Process is validated by media
filling.
Formulation
Pre-filled Syringe filling
Genetic engineering
Biopharmaceuticals are made by
harvesting the proteins that are produced and secreted by specially genetically
engineered living cells
For biopharmaceuticals, compared
to conventional drugs of small molecule, the quality of the end product
(including therapeutic efficacy and safety) is dependent on the manufacturing
process
Medical Bio-technology - a new
era for Bangladesh
Research
How are biopharmaceuticals made?
- Develop host cell
- Establish a cell bank
- Protein production
- Purification
- Analysis
- Formulation
- Storage and handling
Human insulin (rDNA) BP
•
Human insulin is the blessing of modern genetic
engineering technology. Insulin is made ‘biosynthetically’ by recombinant DNA
technology or 'genetic engineering’.
•
The human insulin gene is inserted into either yeast or
bacteria. Which is then programmed to make the human insulin molecule, which
can be harvested on a large scale.
•
This Active Pharmaceutical Ingredient (API) is then
formulated into a finished dosage form.
Technological challenges in
manufacturing Insulin
Unlike normal substance, Insulin
is protein in nature.
•
It can not be heat sterilized
•
Aseptic manufacturing process will have to be ensured
•
Cold chain will have to be maintained
International standard
facility to manufacture world class Insulin
Filtration, filling and sealing of
vial is done in class 100 area
Cleaning In Place (CIP) and Sterilization In
Place (SIP)
To overcome the problem of stirring, Incepta is using
latest technology VIBROMIXER. It creates a gentle and effective vibration for
mixing. So, Insulin chain remains intact.
Formulation
Aseptic filling of Insulin vials
Highly trained and skilled operators
Quality is ensured to
innovators
HPLC (High performance liquid chromatograph) test
This test will ensure that the
product is pure and in accurate amount that has been claimed. Even microgram
amount of impurity can be detected with this quality control test.
•
Both the formulations are stable, because
incompatible formulation will show more than 4 peaks.
•
Retention time is similar, it indicates that
similar API has been used
•
Peaks are acceptable, because the peaks are very
sharp and raised from the base line
Vibrenta
Insulin Glargine (rDNA)
Injection
A new generation of bio-insulin
for management of diabetes
Storage and handling
l
The formulated product is stored, handled, and
administered to patients
l
Biopharmaceuticals are very sensitive to
temperature changes and/or shaking
l
Most of the products are needed to store in cold
chain system of 20 C to 80 C
l
Strict storage and handling conditions are
therefore essential for maintaining
product integrity and stability
Poor adherence to (cold) storage requirements can affect clinical
efficacy and safety
Recombinant DNA Erythropoietin
is manufactured in Bangladesh
Quality Control test
Purity of Erythropoietin is measured by
HPLC method.
Epoetin's comparison showed the
following result:
Epoetin is comparable to
innovator as the peak appeared in the same place & peak height was same.
Biological activity test,
performed in ICDDRB, Dhaka
Randomly distribute the mice of
suitable weight (preferably 8-week old; 16 to 18 gms wt.) into six cages
comprising eight mice per cage.
-
Inject 3
standard doses in 24 mice for 4 days
-
Inject 3 sample doses in 24 mice for 4 days
Inject daily each mice subcutaneously
with 0.2 ml of the appropriate treatment applying one solution per cage; for
four days and then put the animal in new cage.
FLOWCYTOMETRY
Flowcytometry is a powerful tool
in modern biology and in recent years has become widely used in all branches of
biological science. The applications to which it can be applied have expanded
rapidly from cell sorting, to measurement of cell surface and intracellular
antigens, and the analysis of DNA.
Purity & Identity test by
Electrophoresis
•
The purity of Filastin is determined by Electrophoresis
method by comparing protein band of innovator & Filastin
•
Purity: Single band of Filastin is found in the same
horizontal line with the standard, which indicates the purity and identity of
Filastin is same like innovator
Biological activity test
•
The reference standard and Filastin is cultured in
NFS-60 cells (extracted from mice). Then, high technology inverted microscope
is used for checking the growth of NFS-60 cell
•
Uniform growth of NFS-60 cell indicates product will
increase neutrophil inside body
Peginterferon alfa 2a
Hepatitis C
•
The currently recommended therapy of chronic HCV
infection is peginterferon alfa recommended by AASLD, EASL, APASL etc.
Hepatitis B
•
HBsAg loss is more likely to achieve during
peginterferon alfa than oral drugs which is the closest outcome to a cure.
•
Sustained off-treatment response is achieved in
approximately one-third of patients
OPTIPEG-A
Quality
The potency of Optipeg-A is determined by in-vitro
biological activity test using MDBK cell & VSV virus, and compared with the response of
Certified Reference Standard CRS).
Product
|
Potency
|
|
Optipeg-A
|
Critical Reference Standard (CRS)
|
|
Peginterferon alfa2a 180
|
0.6 X 106 IU/ 0.5 ml
|
>0.36 X 106 IU/ 0.5 ml
|
Peginterferon alfa2a 135
|
0.8 X 106 IU/ 0.5 ml
|
>0.27 X 106 IU/ 0.5 ml
|
Safe-guarding Doctors, Nurses and other health-care
professionals from unwanted needle prick with “Automatic Needle
Shielding” device
Vaccine facilities
World Class Vaccine Facilities
•
For catering global need and that of Bangladesh ,
Human vaccine plants are fully operational .
•
They have state
of art facility fully compliant with WHO-GMP & International Standard
•
They are self
sufficient unit with its own dedicated technical manpower, utilities and Animal
house.
Vaccines already launched by
local manufacturer
Incepta Vaccine Ltd - Capacity
The yearly capacity is 180
million vials and ampoules.
Capacity/ Hour
|
Capacity/ Day
|
Capacity/ Year
|
|
Vials
|
18,000
|
360,000
|
108,000,000
|
Ampoules
|
12,000
|
240,000
|
72,000,000
|
Total capacity per year
|
180,000,000
|
||
A number of exciting vaccines
are in pipeline:
- Tetanus
immunoglobulin
- Hepatitis B
both for adult and children
- Haemophilus
influenzae b (HIB)
- Meningococcal
- Measles &
Rubella
- Polio
- Pentavalent
(DPT,HIB,HB)
Research & Development
As a research-driven pharmaceutical company, Incepta is committed to the
goal of discovering and developing products which represent high therapeutic value
for patients, physicians, and health care providers.
R & D Center is located in Savar, Dhaka .
The activities involve the therapeutic areas of respiratory, oncology,
immunology, cardiovascular, central nervous system, virology, and Medical
Biotechnology.
Biotechnology Derived Product
Facility (BDPF), Biotech Division
Production Corridor of Biotechnology Derived Product Facility (BDPF).
Liquid Chromatography Mass Spectrometer Triple Quadrupole Time of Flight
(LC-MS-3TOF), AB Sciex , USA /Germany .
(the MS-3TOF is the most advanced and powerful state of the art
instrument to quantify and qualify unknown molecules including protein and
peptide structure of low to high molecular weight. It is coupled with LC.
Eight capillary DNA Sequencer, Applied BioSystem, USA/Germany. This is
used for sequencing DNA of interest to confirm cloning, mutagenesis and other
modification in DNA. This provides evidence to amino acid sequence using DNA
sequence software.
Polymerase Chain Reaction (PCR) machine, Applied Biosystem, USA/Germany
(used for amplification of DNA of interest).
Incubators 3M, Germany
at Microbiology Lab for R&D and Formulation (Used for incubation of cell
culture).
Fermenter (Bioreactor), Bioengineering ,
Switzerland
Washing and depyrogenation tunnel as part of Bausch and Stroebel , Germany
Combi filling line from Bausch and Stroebell ,
Germany
Reverse Osmosis Water System (Milli Q Water grade), Pall, USA (This
special grade of water is used for doing molecular biology work at molecular
research lab)
Gel Documentation System, Cell Biosystem, USA (used for documentation of
traceable bands of DNA and Protein in gel at Molecular Research Lab)
Bio-safety Cabinet class II,
ESCO, Singapore
(for aseptic handling of
biological agents used in cloning, transformation, sub culture, inoculation
techniques at Molecular Research Lab.)
Magnehelic pressure gauge, data logger for temperature (Ocia Soft
France), humidity and pressure reading and access control panel at entry to
gowning room for clean area .
Inverted Microscope, Med Line France at IPQC lab of R&D Pilot
line
Cell homogenizer,
GEA, Germany
(used for disrupting cell biomass)
Tangential Forward Flow (TFF) system, GE Health care, USA (used for filtration of
protein)
Research &Developmen
l The facility is equipped with all kinds of
production equipments suitable for production of API, Pre-filled syringes,
lyophilized injections, liquid injections etc.
l The facility is also fully equipped for
stability study and analytical method development.
l The company has now expanded its R&D
facility to a new area and it is operational from 2012
Global Pharma Market
The total market is divided into two different broad categories
v Generic drugs
v Branded drugs
Branded drugs are usually patented and are
marketed by the innovator company
Generic drugs are copy of the innovator
brands and are introduced only after expiry of patent life of the brand
Comparison of drug price in between
UK & Bangladesh
Branded products:
Price per tablet
Patent product
|
Price
|
Price in
|
|
in Pound
|
in taka
|
in taka
|
|
Esomeprazole
|
0.66
|
92
|
5
|
Atorvastatin
|
0.64
|
90
|
10
|
Valsartan
|
0.53
|
74
|
9
|
Adefovir
|
10.5
|
1470
|
35
|
Duloxetine
|
0.80
|
112
|
7
|
•
Governments
of Western countries are increasingly relying on generics to save on healthcare
costs
•
The
generic business experience spiraling
reduction of prices of generic drugs with the introduction of same drug by many
competitors.
Global Generic Market
•
Major
supplier of this generic market is India
& China
•
But, China is more diverting towards Intermediates
& Solvents and India
is more focused in API
•
All
countries are looking for an English speaking alternative source
•
World
class facility. 5 of our local companies have already received approval from UK , Australia , EU, GCC etc.
•
We are
already exporting to 83 countries
•
API park
is going to be ready very soon
•
Availability
of highly skilled English Speaking professionals
Expectation of the Industry
from Biotechnologists
Bangladesh Pharma Industry
has already started to prepare itself with the technological knowledge of
biopharmaceutics.
At this stage we need supply of knowledgeable & skilled
biotechnologist who can handle the technology from raw material to finished
product.
l Product design
l Identification of expressed proteins
l Separation
l Purification
l
Assay of the
finished product
We need to acquire the technological knowledge to manufacture different
known biopharmaceutical products like Insulin, Erythropoietin etc. in small
scale laboratory settings.
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