This document discusses the contamination risk posed by Leptospira bacteria in sterile drug manufacturing processes. Leptospira has been found to pass through sterilizing grade membrane filters. Manufacturers need to assess if Leptospira poses a hazard to their operations and ensure processes are protected from any impacts. Risk management practices should consider this unusual microorganism and involve monitoring methods to rapidly detect contamination. Appropriate preventative measures and mitigation procedures are necessary to control potential contamination risks from Leptospira throughout the product lifecycle.

1. [Case Study (C) : 6-1]
Sterile Operations for Parenteral Preparations
Roohi B. Obaid
23 Jun 2018 at Karachi

2. Leptospira
Opinion & Perspective
FDA
Challenge continues … A probable issue

3. Leptospira
Gram -ve, aerobic, spirochete, flexible, highly motile,
spiral shape with internal flagella
? in diameter & 10 to 20 um in length
Leptospira licerasiae found pass through 0.1 um pore
size rated sterilizing grade membrane

4. Leptospira
Apparently it is a rare contamination risk but may be
more wide spread
Manufacturer needs to assess probable hazard to their
relevant operation
Usually associated with biotechnological products

5. Leptospira
Penetrate sterilizing grade membrane filter & be
present in the manufacturing site environment
Impact in process production (e.g. production yield,
impurity level, process performance)
Go undetected due to limitation of current compendial
bio-burden test in detecting this microbial genus
Be aware, these type
of bacteria can
potentially

6. Leptospira
Use sound risk management (cell culture biotechnology &
conventional sterile drug manufacturing)
Be aware of unusual microbiota reported in
the literature
Ensure manufacturing process is safe from any impact
of such contamination

7. Leptospira
Manufacturer should assess their operation, be aware
of potential risk
Apply appropriate risk management based on understanding
of possible or emerging contamination risk
Preventive measures should be implemented to the
product & process lifecycle as appropriate

8. Leptospira Review of scientific literature & technical report
Get understanding how to mitigate this
contamination hazard
Molecular or non-conventional microbial monitoring
methods at appropriate intervals may be used
If +ve or possible
risk mitigation
procedure &
practice for this
microorganism
should include at
least

9. Leptospira
Use specialized media on which this organism
typically grows rapidly
Use of validated PCR for rapid screening & detection
Special stain techniques for identification
(Frank & Kohn 1973)
Molecular
Methods

10. Leptospira
Use of conventional approaches, properly employ basic,
standard lab practice to detect contamination
For e.g. microscopic examination is part of its routine
cell culture process control program
QRM into initial design for PA &
Promptly implementing an appropriate CA to respond
If +ve or possible
risk mitigation
procedure &
practice for this
microorganism
should include at
least