The biopharmaceutical industry has for a long time suffered inconsistent reliability performance of valves and diaphragms.
The cost of a single batch failure can run into the millions of dollars while unplanned production stoppage and contamination
investigations consume vast amounts of resources. One cause can be poor maintenance practices by the user, but as lessons
are learned and practices improved, the spotlight is shifted. End users increasingly expect valve and diaphragms to deliver
more consistent reliability performance through better product design, reliability testing, and improved change control. To
enable this much needed transition, the time is right for the bio/pharmaceutical industry and valve and diaphragm suppliers
to change the way they do business with each other.
THE ROOTS OF INCONSISTENCY
In the past, it has been impossible to predict the life of a diaphragm until tested in the user's full-size commercial system.
Although expensive and risky, this has also meant that suppliers are often distanced from the end user's real-world application
and reliability experiences. Meanwhile, replacement parts are often supplied through distributors, further distancing suppliers
from end-user's performance issues.
Case Study, Bayer HealthCare, San Francisco
Divakar Amin, engineering manager, final product manufacturing at Bayer HealthCare, described the implications of inconsistent
diaphragm valve performace to the BioPhorum Operations Group:
"I have experienced two recent incidents involving valve failure during the fill-finish process, causing leakage into a final
processing operation. The cost of the lost batch each time was measured in millions of dollars. When we opened each valve
up, we found that the diaphragm material had deformed because the material was not suitable for the thermal cycling of the
"We need to ensure that valve manufacturers match the process application to the capabilities of their products. Bulk tanks
are exposed to high temperatures during sterilization, peaking at 130 °C. Valve manufacturers tell us that their diaphragm
material can withstand 150 °C, but what they don't tell us is how many thermal cycles their material can withstand, especially
if the cycle includes low temperature processing. If the polymer is not tested against the full thermal cycle, we have no
level of confidence that it's not going to fail and leak.
"It's very important that suppliers perform the reliability testing in the lab and tell us how many thermal cycles the diaphragms
will sustain. Without this information I'm left having to change-out my diaphragms every three months because I simply cannot
risk losing another batch."
INCONSISTENT CHANGE CONTROL
Barak Barnoon, director of process engineering and analytics at Pfizer, raised another example of inconsistent diaphragm valve
performance in real-world applications to the BioPhorum Operations Group:
"What is missing currently, is control on their part of their suppliers and their diaphragm raw materials. We have seen impaired
performance due both to changes in their sourcing and also in the manufacturing processes of their diaphragm suppliers. There's
a big opportunity to increase the level of control and good manufacturing practices."
Divakar cites a further example of inadequate change control:
"If very small changes are made to the diaphragm material, then they can have a big impact on performance. We have experienced
a situation where an autoclave valve was replaced with an 'identical' product. Subsequently, the heat-up time of the autoclave
went out of its validated range. After extensive investigations we discovered a very minor, undisclosed change to the valve
that impacted the process."