A firm has multiple media fill failures. They conducted their media fills using TSB (tryptic soy broth) prepared by filtration through 0.2 micron sterilizing filter. Investigation did not show any obvious causes. What could be the source of contamination?A firm recently had multiple media fill failures. The media fill runs, simulating the filling process during production, were conducted inside an isolator. The firm used TSB (non-sterile bulk powder) from a commercial source, and prepared the sterile solution by filtering through a 0.2 micron sterilizing filter. An investigation was launched to trace the source of contamination. The investigation was not successful in isolating or recovering the contaminating organism using conventional microbiological techniques, including the use of selective (e.g., blood agar) and nonselective (e.g., TSB and tryptic soy agar) media, and examination under a microscope. The contaminant was eventually identified to be Acholeplasma laidlawii by using 16S rRNA gene sequence. The firm subsequently conducted studies to confirm the presence of Acholeplasma laidlawii in the lot of TSB used. Therefore, it was not a contaminant from the process, but from the media source.
Acholeplasma laidlawii belongs to an order of mycoplasma. Mycoplasma contain only a cell membrane and have no cell wall. They are not susceptible to beta-lactams and do not take up Gram stain. Individual organisms are pleomorphic (assume various shape from cocci to rods to filaments), varying in size from 0.2 to 0.3 microns or smaller. It has been shown that Acholeplasma laidlawii is capable of penetrating a 0.2 micron filter, but is retained by a 0.1 micron filter . Acholeplasma laidlawii is known to be associated with animal-derived material, and microbiological media is often from animal sources. Environmental monitoring of mycoplasma requires selective media (PPLO broth or agar).
For now, this firm has decided to filter prepared TSB, for use in media fills, through a 0.1 micron filter (note: we do not expect or require firms to routinely use 0.1 micron filters for media preparation). In the future, the firm will use sterile, irradiated TSB when it becomes available from a commercial supplier. (Firm’s autoclave is too small to permit processing of TSB for media fills, so this was not a viable option.) The firm will continue monitoring for mycoplasma and has revalidated their cleaning procedure to verify its removal. In this case, a thorough investigation by the firm led to a determination of the cause of the failure and an appropriate corrective action.

Keep reading this blog for cGMP and WHO GMP requirements SOP Validations Master Manufacturing documents sample Change control procedure and format water purification system and its validations cleaning validations ,personnel hygiene and guidelines for gmp microbiological procedure SOPS and manufacturing procedures for pharmaceutical dosage forms Master validation plan sample copy and for your WHO GMP requirements
good manufacturing practice guide for pharmaceuticals manufacturing
Quality assuarance guide for pharmaceuticals manufacturing
Quality assuarance for pharma
Q.A guide for pharma
Guide for pharmaceuticals manufacturing
Email this blog to your friends or collegues who are working in a pharmaceutical manufacturing firm
Following are some of articles which;will be useful for you in further understanding of aspects of sterile dosage form manufacturing

Pharmaceutical Validation

Cleen Room Classification

Pharmaceutical Industry

Pharmaceutical Manufacturing

Clinical Trials

To Find Pharmaceutical jobs and make a Pharmaceutical careers see here pharmaceutical companies

Nature-Ally is your guide to Natural Healthy Living, Read health experts’ Opinions, Info on Alternative Health Therapies, Herbal Product Reviews.

%d bloggers like this: