An Audit Approach To Address Microbial C PDF
An Audit Approach To Address Microbial C PDF
An Audit Approach To Address Microbial C PDF
TO ADDRESS MICROBIAL
CONTAMINATION IN
PROCESS EQUIPMENT
Paul Lopolito and Elizabeth Rivera
AN AUDIT APPROACH TO
ADDRESS MICROBIAL CONTAMINATION
IN PROCESS EQUIPMENT
INTRODUCTION
Regulatory agencies require that drug manufacturing processes be
designed to ensure that end-products are safe for the user.
Responsibility lies with the manufacturer to evaluate the hazards of
drug preparations per the intended use, the bioburden that the
product may contain, and the suitability of testing to ensure a safe
product. The emphasis of this regulatory expectation is to
investigate, identify and correct contamination events that may
compromise product quality, safety and efficacy, as well as to
establish controls that prevent future contamination.
323
324 Contamination Control in Healthcare Product Manufacturing
sterile, shall be established and followed. Such procedures shall
include validation of all aseptic and sterilization processes.”
The above statements indicate that, in the eyes of the United States
Food and Drug Administration (US FDA), microbial contamination
is a concern for both sterile and non-sterile drug products. This
concern may also be extended to other regulated industries and
international regulatory agencies. For example, the statements
below may imply that a substance that threatens end-user safety
may include microbial contamination.
Microorganism Examples
More
Resistant Prions Creutzfield-Jacob Disease (CJD), Bovine
Spongiform Encephalopathy (BSE),
Chronic Wasting Disease (CWD), Scrapie
(McDonnell, 2007)
330 Contamination Control in Healthcare Product Manufacturing
PART 2: INSPECTION
Time is critical during a microbial contamination investigation, and
an internal or external auditor is a valuable resource for identifying
plausible root causes and the formulation of a corrective and
preventative action plan. The auditor provides an experienced eye
and has advanced knowledge of critical factors including
microorganism identification, historical information, material flow
diagrams, equipment drawings, and cleaning procedures, which
can help reduce the scope of the investigation. A reduction in scope
saves both internal resources and time in correcting the issues and
getting back to manufacturing product.
• the contact time of the cleaning solution with the dirty surface
An Audit Approach to Contamination in Process Equipment 341
Figure 15.4 Effect of process related changes on cleanability
(a) Cotton swab collecting Type 1 rouge (b) Steam trap with multiple in situ
from a piece of process piping dark spots typical of Type 3 rouge
The flow rate required for proper spray and cascading effect in
a vertical cylindrical tank can be estimated by multiplying 2.5 times
An Audit Approach to Contamination in Process Equipment 347
• Inspect the surfaces again while wet with a UV lamp and check
for residual riboflavin
348 Contamination Control in Healthcare Product Manufacturing
legs and fill vertical downward piping. This fluid velocity is quite
enough for pipe diameters of four inches or less.
Dead legs are sites in a piping system where liquid or gases can
become stagnant and where cleaning agents and water are not
properly exchanged during flushing. For obvious reasons, dead legs
should be minimized or, if possible, avoided. Bacteria and soil in
dead legs become sheltered from cleaning, flushing, and sanitization
procedures. Dead ends in piping are unacceptable unless they can be
physically inspected and sampled for cleanliness. Branches and/or
tees used for instrumentation should be horizontally positioned,
with their length limited to 1.5 times the pipe diameter.
CONCLUSION
Contamination of a product with an objectionable microorganism is
a costly and time-consuming problem that needs to be addressed
quickly and efficiently by a cross-functional team. The cross-
functional team should consist of, but not be limited to, personnel
from quality, engineering, operations and microbiology. It is critical
to identify the microorganisms early in the investigation and
determine whether they are from an intrinsic (of the manufacturing
An Audit Approach to Contamination in Process Equipment 355
REFERENCES
American Society of Mechanical Engineers (ASME) (2009)
Bioprocessing Equipment (BPE) pp.1–232.
Beech, I. et al. (2000) Simple methods for the investigation of the role of bio-
films in corrosion, Task 1: Biofilm Publication. September, pp. 1–28.
P3-A 003: 2008 P3-A End Suction Centrifugal Pumps for Active
Pharmaceutical Ingredients.