The Production Environment

BUILDINGS

The design features for facilities for manufacture of sterile products should ensure that the
areas in which product contact components are to be prepared and which products are to
be processed, filled and sealed should be segregated from other manufacturing areas and
not used for any other procedures.

Cleanrooms should be effectively flushed with air supplied under positive pressure and
delivered through HEPA air filters located where the air enters the processing environment.

Cleanrooms should contain the minimum of “ dead” space, i.e. space not effectively flushed
with clean air, the minimum of obstructions to flow of clean air, such as fittings, ledges and
shelves and no extraneous equipment.

Cleanrooms should be provided with suitable anterooms or equivalent separation facilities

through which staff or articles may enter or leave the area.

The surfaces of walls, floors and ceilings should be smooth, impervious and unbroken in
order to minimize the shedding or accumulation of particulate matter, and to permit the
repeated application of cleaning agents and disinfectants where used.

 Ceilings should be adequately sealed to prevent contamination from the space

above them.

 Pipes and ducts should be installed so that they do not create recesses that are
difficult to clean. They should be sealed into walls through which they pass.

 Drains should be avoided wherever possible and excluded from sterile areas unless
essential

 Sinks should be excluded from aseptic processing.

 Room temperature and humidity should be maintained at a level that will not cause
excessive sweating of operators clad in protective garments.

 Airlock doors should not be opened simultaneously

 Conveyor belts should not pass through walls enclosing sterile areas. They should
end at the wall, products passing onwards across at stationary surfac
 EQUIPMENTS

All equipment, including sterilizers, air-filtration systems, and water-treatment systems

including stills, should be subject to planned maintenance, validation and monitoring; its
approved use following maintenance work should be documented.

Equipment shall be technically suitable, well sited (so as not to interfere with other
operations), easy to clean and maintain. The design, siting and operation of equipment shall
ensure that no contamination from foreign materials such as rust, lubricants, abraded
particles or foreign ingredients should occur.

CLEANLINESS and HYGIENE

Personnel entering clean or sterile areas should change into special garments, which
include head, and foot wears. These garments should shed virtually no fibres or particulate
matter, and retain particles shed by the body.
They should be comfortable to wear, and loose fitting to reduce abrasion. The garments
should be restricted for use only in the relevant clean or sterile areas.

QUALITY CONTROL

Quality control involves all analytical functions conducted in the laboratory, including
sampling, inspecting and testing of starting materials, intermediate, bulk and finished
products. It also includes stability test, environmental monitoring program, validation tests,
review of batch documentation, sample retention program and establishing and maintaining
current specification of materials, products and their test methods.

RECORDS

 Records of calibration shall be provided and maintained

 The maintenance records are kept
 For equipment used solely for one product the record can be included in the production
batch record
 Records of cleaning, sanitizing, sterilization and inspection prior to use shall be
maintained

TRANSPORTATION and STORAGE

Manufacturing operations are divided into three categories

 Terminally sterilized products:
 Solutions should generally be prepared in a grade C environment in order to give low
microbial and particulate counts, suitable for immediate filtration and sterilization
 For parenterals,filling should be done in a laminar-airflow workstation (grade A) in a
 grade C environment.
 Sterile filtered products: The handling of starting materials and the preparation of
solutions should be done in a grade C environment.

After sterile filtration, the product must be handled and dispensed into containers under
aseptic conditions in a grade A or B area with a grade B or C background respectively.

 Other sterile products prepared from sterile starting materials in an aseptic way.

Validation

The process of confirming by recognized appropriate means or manner, that any material,
process, procedure, activity, system, equipment or mechanics used in production and
control consistently achieved the desired results.