Prio to 2010, Pfizer Health AB produced its legacy products
Genotropin® and Somavert® in separate facilities. Somavert was sourced from a
contract manufacturer while Gentropin was manufactured at a Pfizer facility in Strängnäs, Sweden.
The two drugs have opposite effects on the human physiology
- Genotropin is used to treat growth hormone deficiency and Somavert is a
growth hormone antagonist - but the proteins used in each are very similar.
Pfizer’s development scientists saw an opportunity to exploit this similarity
to develop almost identical unit operations that could be used for both
products within the same facility.
The project - dubbed Project Pegasus - had two fundamental
ground rules: The new Bio 7 facility would not require an increased head count
and a two-shift pattern would be sufficient to produce two batches per week. To
achieve this, the project team went back to the drawing board and re-evaluated
a number of steps in the manufacturing process, including some thought to be
standard in pharmaceutical processing.
Today, the Bio 7 facility is able to produce the two
products much more efficiently - exceeding the goal of two batches per week
with 3.5 batches per week - and is recognized in this year’s Facility of the
Year Awards (FOYA) as the winner of the Operational Excellence category. Here’s
how Pfizer made it happen.
Time is Money
The FOYA judging panel recognized the effort that Pfizer put
into reducing equipment turnaround times. A major focus of the de-bottlenecking
projects was to optimize the clean-in-place (CIP) and steam-in-place (SIP)
procedures.
Four CIP skids are used to provide dedicated cleaning
functions to the various processing areas. Skids 1, 2 and 3 are used to clean
equipment, vessels and lines that have been exposed to proteinaceous material,
and require both chemical make-up and water rinse tanks. The cool water
pre-rinse is executed at the same time as the hot chemical solution is
prepared, creating a seamless CIP sequence.
CIP time is further reduced by eliminating the purified
water pre-rinse compressed air blowdown sequence. Inline conductivity
measurements conducted at the facility showed that air blowdown was not
required to remove residual pre-rinse water from the object prior to preparing
the cleaning solution.
Further tests found that the manual removal and
reinstallation of vent filters before and after vessel CIP was unnecessary. As
a result, the vent filter housings at the Bio 7 facility are designed so that
the vent line can be cleaned without removing the filter element or housing.
This also eliminated delays and potential accidents caused by fittings that are
not secured properly.
SIP Realities
Conventional wisdom suggests that SIP functionality should
be allowed for in downstream processing areas. SIP was included in the original
downstream design specifications, but the functionality was removed when the
project team determined that materials with the highest risk of retaining
contaminating microbes cannot be steamed-in-place - chromatography gels and
some TFF membranes, for example.
The Project Pegasus team found that the added value from
SIPing vessels and lines was questionable, and in some instances may in fact
hide a cleaning problem. The decision to eliminate downstream SIP made a
significant contribution to the reduction in equipment turnaround times and
increased facility capacity.
Pharmaceutical Counterculture
The ability to improve efficiency by questioning and
changing processes that many think are standard in biopharmaceutical processing
requires an environment where operational improvements and innovation are
encouraged and applied.
“Every voice and idea counts no matter where it comes from.
Everyone on the team is continuously encouraged to contribute ideas,” explains
Kim Sandell, receiving project manager for the Bio 7 facility and Pfizer Health AB’s
director of Operational Excellence.
“We also communicated that not everything could be
implemented directly, but we track proposals so that we can pick them up as the
facility evolution continues. I like to think of a process and a facility as a
journey, and that by finalizing the project we have just left the station; we
need to improve and get better as we move along over the years,” adds Sandell.
Risk-based approaches helped Sandell’s team challenge
“common practice” with scientifically sound arguments.
“We used risk-assessment technologies such as failure mode
and effects analysis (FMEA) to ensure that we focused on the important stuff.”
And what is Sandell most proud of?
“We built Bio 7 in a platform technology - I like to compare
it to the car industry’s way of building many different models on one common
platform. This makes it simpler to introduce new processes in the future.”