Manufacturing

practice
in
sterile pharmaceutical
product
 Objectives
Ø To review the basic GMP requirements in the
manufacturing of pharmaceutical sterile products.
Ø To review air classification for activities related
to the manufacturing of sterile products.
Ø To review the different types of sterilization
methods.
Ø To review the quality assurance aspects in the
manufacturing and control of sterile products.
 GMP requirements for
sterile products
Ø Additional rather than replacement.
Ø Specific points relating to minimize risk of
contamination like…
üMicrobiological
üParticulate matter
üPyrogen

 General
considerations
Ø Production in clean areas.
Ø Appropriate standards of cleanliness.
Ø Supply of filtered air.
Ø Airlocks for entry..
üPersonal and/or equipments.
üMaterials.
Ø Separate areas for operations..
üComponent preparation.
üProduct preparation.
üFilling, sterilization, etc.
ü
Facilities for production
area
Ø Designing of area..
ü Smooth,impervious,unbroken & easy to clean.
ü Minimize shedding and accumulation of particles
microorganism.
Ø Environmental control.
ü Microbiological.
 Air sample.
 Surface swabs.
 Personnel swabs.
ü Physical.
Ø Traffic control..
ü Staff movement controlled.
ü Proper changing and washing procedure before
entry to the aseptic room.
Facilities for production
area(continued)
Ø Housekeeping..
ü Frequent and thorough cleaning of aseptic
room.
Ø Irradiation..
ü U.V. radiation.
Ø Disinfection.
Ø Perssonal..
ü Training to all cleaning and maintenance staff.
ü Inspections and controls from outside.
ü Proper clothing.

Facilities for production
area(continued)
Ø Air control..
 Air filtration system..
1.Conventional clean room system.
2.Laminar flow clean room system.
§ Downward air flow system.
§ Horizontal air flow system.
§ Wall to floor air flow system.
 Airflow velocity..
§ Pressure maintenance.
 Maintenance of temperature and humidity.

Layout of sterile production
area
S Storage
T
Compounding
area Aseptic area Quarantine and
O area Transport
C
K

R
O
O Clean up
area Packing and
M Sterilization labeling
Sterilization methods
Ø Sterilization by dry heat.
Ø Sterilization by moist heat.
Ø Sterilization by radiation.
Ø Sterilization by gases and fumigants.
Ø Sterilization by filtration.
Production planning &
processing
Ø Cleaning of equipment.
Ø Cleaning of containers and closures.
Ø Preparation of solution or suspension.
Ø Filtration.
Ø Filing of the product in containers.
Ø Sealing.
Ø Sterilization.
Ø Quality assurance test..
Quality assurance
Ø Sterility test..
As mentioned in Indian Pharmacopoeia

§ Method A(membrane filtration method).

§ Method B(direct inoculation method).
Ø Clarity test.
Ø Leakage test.
Ø Pyrogen test.