Biomedical Engineering Reference
In-Depth Information
difficult to remove. Examples are polymethylacrylates as coating polymers
and residues in bioreactor after production campaign. In some cases, it is
possible that after drying of the residue during normal manufacturing, fur-
ther increase in hold time will have no effect on the difficulty of cleaning to
remove product residue. For example, this may be the case when process-
ing conditions are significantly more severe than idle hold time conditions
(e.g., drying a product in a Rosenmund filter for three days at 70 C versus
idle hold time of the empty noncleaned filter at room temperature). In some
cases, it may become easier to clean when dried as residues flaking onto
plastic-type surfaces.
2. Adhesion of material on surface: If exposed to humid conditions, hygro-
scopic materials may become sticky and more difficult to remove (e.g.,
starch).
3. Solubility of residue in cleaning agents: In some cases, where the solubility
of the residue in the cleaning agent is very high, dirty equipment hold time
does not affect cleanability.
4. Potential for degradation: Degradants may have different solubility, tox-
icity, and cleanability characteristics than the original compound. These
may be easier or more difficult to clean and should be evaluated on a
case-by-case basis.
5. Equipment surfaces: The nature of the equipment surface such as aluminum,
steel, hastelloy, plastic, or rubber may be affected by the duration of the
contact or porosity of materials. For example, staining may result from
certain APIs or dyes that can cause this quickly on contact. Also, residues
dried onto plastics may completely flake off, making it easier to vacuum
or blow down before cleaning.
6. Microbiological accumulation and proliferation: Organisms may grow
exponentially if wet residues or stagnant water is left in equipment.
Microbiological considerations should be evaluated when water rinsing is
used. A microbiological assessment of residual product over time on the
noncleaned equipment should be considered. Conditions of temperature,
exposure, time, and product history should be evaluated with respect to
the ability of microorganisms to proliferate. The ability of the cleaning
process to reduce microorganisms would also be a factor, along with
the subsequent dosage form of the next product to be produced in the
equipment.
7. Data on cleaning and failure history: A product or equipment piece with
a history of cleaning problems may be an indication that dirty equipment
hold times is a factor that should be considered. On the other hand, data
may point to a noncritical condition by having the following:
• Routine verification after each changeover cleaning (e.g., routine rinse
sampling and testing for major equipment, routine visual inspection for
Search WWH ::




Custom Search