Drug Manufacturing Process - 2 PDF

DRUG MANUFACTURING
PROCESS
DRUG MANUFACTURING PROCESS
Manufacturing process concerns itself with four major
themes-
s Manufacturing facilities (Infrastructure)

s Source of biopharmaceuticals
s Upstream and downstream processing (Production of
final product)
s Analysis of final products (QC analysis)
Manufacturing facilities
In pharmaceutical industries, the central issue for safe
and effective production of drugs are-
Appropriate design and
layout of the pharmaceutical facilities

Manufacturing facility
Clean room
s Clean rooms are environmentally control and all critical

manufacturing steps (especially for sterile products) must be
undertaken here.
s Clean room protect the product from contamination
s The basic feature of clean room design is the presence in their

ceiling high efficiency particulate air (HEPA) filter.
s Floor, walls and ceiling can be coated with durable chemical

resistant material such as epoxy resigns.
Clean room may be grade-A,B,C,D

Cleaning, decontamination and sanitation (CDS)
Cleaning→ involves the removal of dirt, ie, miscellaneous

organic and inorganic material which may accumulate in
process areas or equipments during production
Decontamination→ refer to the inactivation and

removal of undesirable substances, which generally
exhibit some specific biological activity likely to be
detrimental to health of patient receiving the drug.
Sanitation→ refer specifically to the destruction and

removal of viable microorganisms.
Effective CDS procedures are routinely applied to-
a) Surface in manufacturing which are not come into

direct contact with product (room wall, floor)
Process-
1 st → cleaning with water or detergent
2nd → Use of disinfectant such as alcohol,
phenol,
chlorine, iodine.
3rd → Fogging the room using fine disinfectant
b) Surfaces come into direct contact with product
( vessel, chromatographic column)
Process:
• It is important that no trace of the CDS agents
subsequently remain on the surface, as this would
result in automatic product contamination.
s The final stage of most CDS procedures as applied to

process equipments, involves exhaustive rising with
high pure water.
Specific cleaning in place (CIP)
Procedure can generally be used to accommodate equipment

such as internal surface of fermentation equipment,
chromatographic column etc.
First→ Detergent solution pump through fixed pipe

work followed by WFI
Secondly→ passage of sterilizing live steam generated

from WFI
Internal surface of fermentation/processing vessel can be

scrubbed down. Such vessels are generally jacked.
FIG-VESSEL
Some chemicals used in CIP are-
s 0.5-2.0 M Nacl
s Non ionic detergent
s NaOH (0.1-1.0 M)
s Acetic acid (20-50%)
s Ethanol (20%)
s EDTA (-1.0 mM)
s Protease solution
s Dilute buffer
WATER
Water of two different levels of quality is usually required-
Purified water→ Limited use as less pure than WFI. Such as –

-As solvent in aqueous based oral product
-primary cleaning procedure
Water for Injection (WFI)→ Extensive application. Such as –

-Microbial fermentation media
-Culture media
These are distinguished on the basis of the range and quality of

allowable contaminants.
GENERATION OF PURIFIED AND WFI
Potable water
Depth filtration
(Contain mixture of granular anthracite, Washed sand and Gravel)
Solid and colloidal materials are retained as the water percolates
through the filter bed. The bed may be generated every few
days by backwashing
Organic trap
(Contain Resign and Carbon such as activated charcoal)
Resign→ absorb organic matter
Activated charcoal→ absorb residual organic (humic acid) and
any disinfectant such as chlorine present in potable water
Activated charcoal
absorb residual organic (humic acid) and any disinfectant such as
chlorine present in potable water
Anion exchanger
Anions (Cl-, SO 3-2) are exchanged with OH- of the anion exchanger
Cation exchanger
Cations in water (Na +, Ca +) are retained on the cat ion exchanger by
displacing H - ion
Cation exchanger
Filtration Purified water
Distillation
Filtration or UV treatment
often constitutes the next step
(to remove microbial contamination)
DOCUMENTATION
s Essential for good manufacturing
s Every aspect is characterized by existence of extensive

associate documentation
s It is essential due to-

-Help to prevent error
-Facilitate the tracing of manufacture history
of any batch documentation
-Ensure reducibility in all aspect
DOCUMENTATION
Documentation fall into one of the four categories-
a) Standard operating procedure (SOP): Detail

how staff undertake particular process/procedure. It
may be different categories. Such as-
s -SOPs detailing step by step operational procedures

for specific items of equipment (eg. autoclave)
s - SOPs detailing maintenance/validation
s - SOPs detailing to testing/ analysis
s - SOPs detailing CDS procedure
DOCUMENTATION
b) Specification:
s Normally written by QC personnel. They detail the exact

qualitative and quantitative requirement to which individual
raw materials or product must confirm (% of active ingredient,
permitted level)
s Specification for packaging materials will for example lay down

exact dimension of product packaging carton.
s Specification for product level will detail level dimension and

exact detail of level text.
s QC personnel ensure that the raw material meet their

specification before being released to production.
DOCUMENTATION
c) Manufacturing formulae, processing and packaging
instruction:
Manufacturing formulae→ Indicates product name, potency,

batch size, raw materials,
Processing→ Indicates Equipment to be used, location in

which each step undertaken, precautions if any etc.
Packaging→ indicates packaging instruction, level to be used
A copy of level to be used is generally attached to the

documents to allow supervisor and operators to verify easily
that the correct level has been dispensed for the product in
questions
DOCUMENTATION
d) Record:
Any given batch of product, records relating to every
aspect of manufacture will retained. It includes-
- Specification results obtained on all raw materials

- Manufacturing, processing and packaging record
- QC analysis result
Generation of manufacturing records
Print out of manufacturing formulae, processing and
packaging instruction by production personnel prior
to commencement
Responsible person fills in the batch no. in the space

provided
After completion of each step responsible operator/

personnel written information including the time and
date of undertaken on printed form

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DRUG MANUFACTURING

s Manufacturing facilities (Infrastructure)

Appropriate design and

layout of the pharmaceutical facilities

s Clean rooms are environmentally control and all critical

s Clean room protect the product from contamination

s The basic feature of clean room design is the presence in their

s Floor, walls and ceiling can be coated with durable chemical

Clean room may be grade-A,B,C,D

Cleaning, decontamination and sanitation (CDS)

Cleaning→ involves the removal of dirt, ie, miscellaneous

Decontamination→ refer to the inactivation and

Sanitation→ refer speciﬁcally to the destruction and

Eﬀective CDS procedures are routinely applied to-

a) Surface in manufacturing which are not come into

s The ﬁnal stage of most CDS procedures as applied to

Procedure can generally be used to accommodate equipment

First→ Detergent solution pump through ﬁxed pipe

Secondly→ passage of sterilizing live steam generated

Internal surface of fermentation/processing vessel can be

Puriﬁed water→ Limited use as less pure than WFI. Such as –

Water for Injection (WFI)→ Extensive application. Such as –

These are distinguished on the basis of the range and quality of

Filtration Puriﬁed water

s Every aspect is characterized by existence of extensive

s It is essential due to-

a) Standard operating procedure (SOP): Detail

s -SOPs detailing step by step operational procedures

s Normally written by QC personnel. They detail the exact

s Speciﬁcation for packaging materials will for example lay down

s Speciﬁcation for product level will detail level dimension and

s QC personnel ensure that the raw material meet their

Manufacturing formulae→ Indicates product name, potency,

Processing→ Indicates Equipment to be used, location in

Packaging→ indicates packaging instruction, level to be used

A copy of level to be used is generally attached to the

- Speciﬁcation results obtained on all raw materials

Responsible person ﬁlls in the batch no. in the space

After completion of each step responsible operator/

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