Aseptic Process Validation
(Process Simulation or Media/Broth Fill Trial) SOP

1.0   PURPOSE:

1.1.  It is established to avoid contamination of microorganisms during manufacturing of sterile products to ensure aseptic manufacturing techniques/practices being used by the personal are satisfactory and capable of producing sterile products..

2.1. This procedure is applicable to liquid injectable & sterile powder filling areas of production department.

3.1.      Quality Control Manager
3.2.      Microbiologist
3.3.      Production Manager
3.4.      Production Pharmacist
3.5.      Officer QA
3.6       Manager QA

4.0    Definitions:

4.1       Aseptic Filling:
Operations whereby the product is sterilized separately, than filled and packed using sterilized containers and closures in critical processing zones.

4.2       Bioburden:

Total number of viable microorganisms on or in pharmaceutical products prior to sterilization.

4.3       Media Fills:

Method of evaluation an aseptic process using a microbial growth medium (Media fills are understood to be synonymous to simulated product fills, broth trials, broth fills etc.)

5.0     FLOW CHART:


a)           Aseptic Process Validation of Liquid Injectable Area

a.            Prepare desired quantity of Tryptic Soya Broth (Soyabean Casein Digest Medium) as per manufacturer’s instruction to fill appropriate number of units but not less than 3000.
b.            Filter the media under the sterile nitrogen gas pressure using the fiberglass prefilter and 0.2µm cartridge filter or 0.2 µm membrane filter.
c.             Fill media aseptically performing all procedures identical to regular manufacturing process except pre & post purging of sterile nitrogen during filling.
d.            Each operator who normally participates in the aseptic fill products should participate in the aseptic fill validation.
e.            Equipment parts that come in contact with media must be sterile and completely free from any substance that could inhibit growth of microorganisms.
f.              Incubate the filled ampoules at 20 – 25ºC for 14 days along with positive & negative controls.
g.            Leak testing of ampoules be carried out before incubation.
h.            Record any contamination must observe during incubation time.
i.              Sterile sample will contain a clear yellowish colored liquid free from any sign of turbidity, mold or bacterial growth.
j.              Aseptic process validation will meet the requirements if contamination is less than or equal to 0.1%.
k.             Perform swab test of the surfaces and equipment at the end of the aseptic media fill.
l.              Perform swab test of uniforms of operators at the end of media filling operation.
m.          Record all the results.

a.      Validation of Aseptic Process (PICS Guidelines)