Pilot Programs Improve Performance
CONTAMINATION CONTROL IN AND OUT OF THE CLEANROOM
BFK Solutions LLC
As an undergraduate, Barbara and her fellow biology and chemistry majors regularly sampled prototype cookies courtesy of a classmate’s dad, formulator for a large commercial baker. The prototype cookies were invariably far superior to the final product. Issues arise
in moving from R&D to large-scale production.
Problems can be averted by using a pilot program,
but the pilot program has to be well-designed.
Pilot programs are useful in development of
pharmaceuticals, cosmetics, nutritional supplements, medical devices, and aerospace components. In critical and precision cleaning, we often
suggest that one way of hedging your bets is to set
up a pilot plant before making a large commitment in new capital equipment. We suggest you
purchase or lease smaller-scale cleaning equipment and use that equipment for cleaning process
Managing a pilot program involves many cleaning and contamination control challenges. In most
instances a pilot plant is one where process equipment is used for many types of product. Therefore,
equipment must itself be cleaned between projects.
A pilot program is larger than bench-scale research
and smaller than production. While there is often a
limited budget, there are usually high expectations,
time constraints, and pressure from management
and marketing. There can be false perceptions that
pilot programs don’t require much care.
Soil is matter out of place; a benign ingredient in one
pilot study may interfere with product produced in a
subsequent pilot study. People involved in pharmaceutical and related manufacturing are concerned
about reducing the API (Active Pharmaceutical
Ingredient) or AI (Active Ingredient) to an acceptable level. The API is the part of the formulation
that is biologically active. However, given the range
of products being produced in pilot programs, it is
important to consider API as well as all potential
interfering residue, whether or not it is biologically
The problem of residue is universal. In metal fabrication and finishing, fine metal particles from one
application can interfere with subsequent production.
This can include particulate contamination and galvanic interaction. In precision optics, many manufacturing professionals deem that dedicated equipment,
even for a pilot study, is a must.
Residue can be liquid, gas, or solid. Where the product
is a powder, the program for residue removal depends
on the situation. Equipment manufacturers sometimes recommend vacuuming to remove dry powder.
However, such an approach may not adequately
remove the contaminant, particularly if the equipment
is to be used for disparate processes. Sometimes the
residue is not quite a powder that can be readily dusted off or vacuumed away. Instead, the residue may
be an emulsion or a caked-on material. Fine particles
are particularly adherent, as they can be retained in
areas of surface roughness; even what appears to be a
smooth surface may have enough microscopic roughness to hold tiny particles. One logical strategy is to
remove as much of the powder as possible without
liquid, then resort to traditional CIP (Clean in Place)
and/or COP (Clean Out of Place) processes using
cleaning agents and processes including immersion,
agitation, and ultrasonics.
Things change during scale-up. For example, it was
recently reported that during scale-up of what was
considered a relatively straightforward formulation,
even using careful process controls, process times had
to be increased from 50 to 70 minutes.1 Process parameters may need to be reevaluated yet again in moving
from the pilot process to full production.
Unexpected reactivity can be damaging. A highly
exothermic reaction can pose a safety hazard to workers
and to the product. Other forms of reactivity include
unexpected precipitation of residue in a liquid process
bath, cleaning bath, or reactor. Remove such residue
before using the same equipment for subsequent pilot
studies. Figure out the root cause of the precipitation.
Unexpected residue in the pilot program can be a sign
that the process technique needs refinement. Even with
extensive written instructions, important details can be
lost. Therefore, consider paying a visit to your research
group and observing as the process is performed.
Ideally, process equipment should be dedicated to
a narrow range of applications. In reality, however,
equipment in a pilot lab may be used for many different applications — perhaps ranging from ingestible to
Even if great care is taken to clean promptly and
appropriately, there may be applications where the
risks of using pilot plant equipment outweigh potential