Production of sterile unit:

Environment control of sterile area:

In HPL, total environment is done properly according to the GMP guideline

1.. Area control

i.. Corridor: Negative pressure

ii.. Room: Positive pressure

2. Temperature control: 18-250 C

3. Humidity Control: 35-650 C

4. Pressure control:

i. Zone E: 5-10 pascal

ii. Zone D: 15-20 pascal

iii. Zone C: 30-35 pascal

iv. Zone B: 45-55 pascal

Clean room behavior:

Clean room is an integral part of production unit especially sterile unit. GMP EU cleanroom standard

Class Maximum Particle/m3

At Rest At Rest In operation In operation

0.5 um 5um 0.5um 5um

Class A 3,520 20 3,520 20

Class B 3,520 29 352,000 2,900

Class C 352,000 2,900 3,520,000 29,000

Class D 3,520,000 29,000 N/A N/A

In HPL,

Grade A: The local zone for high risk operations like filling, stopper, bowls, open ampoules and vials,
making aseptic connection. A laminar flow system provides a homogeneous air speed of 0.45m/s.

Grade B: Background environment for grade A zone items needing aseptic preparation and filling.
Grade D: Used for performing less critical tasks that carried out during less critical stages in the
manufacturing process.

Types of sterile product:

There are 2 types of sterile product. These are

1.. Aseptic product 2. Terminally sterile product

Sterile Product in HPL

 Ampoule
 Liquid vial
 Lyophilized product
 Syringe
 Eye drops
 Nasal drops

Method of sterilization:
1. Physical method:
i.. Dry heat sterilization
ii.. Moist heat sterilization( for 25 min at 1210C)
2. Chemica method:
 Alcohol 70%
 Lysol (cresol with soap)
3. Gaseous sterilization
 Fumigation by liquid formaldehyde
4. Sterilization by radiation:
 UV radiation (225-265nm)

Production of sterile product:

Receiving materials

Washing of vials/ampoules

Depyrogenation of vial/ampoule

Filtration

Filling and sealing

Inspection

Packaging
Washing of ampoules/vials:

Ampules are placed manually on tray

Passed to ampoule washing room

Ampoules tray are placed in washing machine where a lash of DM+

WFI flows from upper and lower part of the machine

After certain period of time, it is removed and the ampoules are

replaced from that tray to another tray

The ampoules are sterilized by dry heat sterilization for

depyrogenation at 2300C for 2.5 hours

Then it is allowed cool and removed for filling and sealing in aseptic
area

Vial Filling and Sealing process:

Receive Ingredient
Deboxing
Passed through change box under laminar air flow
Filling and Sealing in aseptic condition
Lyophilization Technology/ Freeze drying:
Steps of lyophilization

Pretreatment
Freezing (-45 to-600C)
Vaccum
Primary drying/sublimation phase
( -600C to-100C )

Secondary drying
Packaging
Storage
Reconstitution phase

Equipment used in sterile production:

Washing and depyrogenation machine: Germany
Rota ampoule vial
Rota ampoule filling and sealing machine Germany

Mixing vessel India

Automatic inspection machine: Italy

SA5 CMP
Zirbus (Freeze dryer) ermany

Tofflon (Lyophilization machine) China

Ju won Blister machine South Korea

Micro embossing machine Japan