The use of advanced, innovative, or cutting-edge technology to improve products or processes is referred to as advanced manufacturing.

1. By
Santosh Kumar-MPH/10019/22
Department of pharmaceutical science and Technology
Birla institute of technology,Mesra
Ranchi- 835215(Jharkhand)
A presentationon
Advanced sterile product manufacturing technology

2. • Introduction
• Area planning and environmental control
• Wall and floor areas
• Change room
• Personal flow
• Utilities and utilities equipment location
• Engineering and maintenance
CONTENT

3. INTRODUCTION
• The use of advanced, innovative, or cutting-edge technology to
improve products or processes is referred to as advanced
manufacturing.
• The advanced manufacturing sector is defined by the rate of
technological adoption and the ability to use that technology to
remain competitive and add value.

4. AREA PLANNING AND ENVIRONMENTAL CONTROL
1. Classification of Manufacturing Areas by Air Cleanliness
• Clean areas for the processing of sterile pharmaceutical products
are controlled according to predefined airborne particle and
microbiological standards.
• Depending on the nature of the operation, the areas are
classified as critical, direct support, and indirect support.

6. • The critical area is a processing area where sterilized products and materials
as well as their surfaces are directly exposed to the environment.
• The environmental conditions should be specified to be suitable for the
virtual elimination of contamination risks and preservation of the sterility of
products.
• The following processes are conductedin this area: sterilization activities
(e.g. sterile connections,addition of sterile materials) prior to filling, sterile
filling, and sterile closure.
Critical Area (Grade A)

7. Direct Support Area (Grade B)
• The direct support area is a working area for personnel who operate machines
installed in the critical area and for those who supervise the operation of
machines.
• The direct support area also serves as a route for the transfer of sterilized
products, materials, and equipment to the critical area or for moving sterilized
products from the critical area

8. Indirect Support Areas (Grade C or D)
• The indirect support area is an area used for processing materials and
products prior to sterilization processes and hence materials and
products are directly exposed to the environment.
• Example indirect support areas include an area for preparing drug
solution prior to sterilization and an area for washing and cleaning
sterilization equipment and apparatuses.

9. 2.Heating, Ventilating and Air Conditioning System
• Air in clean areas needs to be maintained at appropriate levels by designing, instituting,
and managing a suitable heating, ventilation, and air conditioning (HVAC) system
• The HVAC system and its management program are comprised of the following basic
elements: temperature, relative humidity, air flow volume, air exchange rate,
unidirection of air flow, pressure difference relative to adjacent rooms, integrity of HEPA
filter, airborne particle count, and micro bacterial count.

10. 3. Air
• It is critical to secure constantairflow from an area of higher cleanliness
level to an area of lower cleanliness level in order to maintain required
environmental conditions of clean areas.
• Changes in flow velocity can alter flow direction when airflow is specified
to be unidirectional. The velocity should be confirmed to be constantat a
predetermined level by monitoring the velocity of airflow from HEPA
filters at time intervals specified in the program.

11. ENVIRONMENTAL MONITORING
• The primary objective of environmental monitoring is to keep manufacturing
environments for sterile pharmaceutical products clean by controlling the
levels of microorganisms and airborne particles within specified limits for
individual APAsand indirect support areas, by monitoring environmental
conditions to prevent environmental deterioration and product
contamination, and by continuously assessing the efficiency of cleaning,
disinfection, and decontamination procedures.

12. • The walls and floors of the areas where manufacture of drugs is carried out shall
be free from cracks and open joints to avoid accumulation of dust.
• These shall be smooth, washable, covered and shall permit easy and effective
cleaning and dis-infection.
• The interior surfaces shall not shed particles.
• A periodical record of cleaning and painting of the premises shall be maintained.
WALLS AND FLOORS AREAS

13. • In pharmaceutical manufacturing, follow of Entry, and exit procedures for staff
and visitors are essential to prevent external environmental dust and
microorganism to enter the cleaned area.
• The following procedure also helps to prevent contaminationand cross-
contamination inside the manufacturing.
• According to pharmaceuticals WHO guidelines, there must be a well-defined
procedure for entry and exit on-premises. Follow the described procedure below
before entering into premises and exit from the premises.
CHANGE ROOM

14. CHANGE ROOM

15. PERSONNEL FLOW
• Many characteristics and functions of material flow also apply to personnel flow. Most importantly,
logical organizationof the personnel flow serves to protect the product in addition to
considerations of economy and labor legislation.
• To optimize the material flow, the appropriate number of persons required to operate, monitor and
maintain the machines and facilities mustbe determined.
• The functions of individual persons must then be described and the routes transferred to the
layout.
The personnel flow and its iterative optimizationare assessedtogether with the layout and material
flow based on the following assumptions:
➢ Access to pharmaceutical areas only via locks/changing rooms
➢ Separate routes for pharmaceutical and non-pharmaceutical personnel
➢ Short routes

16. UTILITIES AND UTILITY EQUIPMENT LOCATION
• UTILITIES: Piping system in particular, must be initially often periodically
cleaned and serviced.
• Exposed overhead piping is not acceptable from a cleanliness or
contamination standpoint since it collect dirt is difficult to clean and may
leak. Buried or concealed pipe may require unacceptable demolition for
cleaning or repair.
• Whenever possible, major utility distribution services should located
outside of clean area.
• Distribution system be exposed and not buried with in walls or ceilings.

17. • Public utilities require space for metering in addition to meeting electrical power system require
for switchgear and transformer.
• Water system usually require treatment to ensure consistent quality. Plant generated utilities
typically require steam boiler room air, compressors and distillation, the typical boiler room
approach.
• Although a central location minimized distribution problems and minimizes service distribution
distances.
• Proper equipment maintenance is difficult in foul weather especially winter, heavy equipment may
damage the roof structure, particularly if the equipment location mayrequires numerous
penetration through the roof which coupled with equipment vibration will invariably lead to
leakage.

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