Cleaning Validation Practical

Cleaning validation practical1
CLEANING VALIDATION PRACTICAL
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Cleaning validation practical 2
Introduction
Validation is a crucial fragment of good manufacturing practices (GMP). It is, thus, a part of the
quality assurance package linked with a specific product or procedure (Forsyth 2016). The
fundamental principle of quality assurance has their objective of manufacture of merchandises
that are appropriate for their planned usage. Equipment is used to produce bio/pharmaceuticals
products ought to be cleaned after use to make sure residues of previous batches and detergents
do not contaminate the subsequent batch of product, degradates of wastes utilised or microbial
pollution (Fan, Phinney and Heldman 2015). The washing routine utilised to clean the appliances
ought to be authenticated and documented in a cleaning validation protocol (CVP). A CVP must
offer documented proof that the cleaning process is sufficient. The FDA or other supervisory
bodies does not set acceptable specification or approaches for assessing whether a washing
routine is certified (Föste et al. 2013). It is unreasonable for the regulatory establishments to do
so due to the broad differences in apparatus and produces used over the bulk and finished dose
form productions. The firm’s justification for the residue parameters established ought to be
logically centred on the producer’s acquaintance of the materials encompassed and be valid,
practical and attainable. It is crucial also to define the analytical techniques sensitivity to set
rational parameters. Some of the restrictions that have been stated by sector councils in the
writings or the demonstrations comprise analytical detection levels such as biological or residue
action level like 1/1000 of the standard therapeutic dose and no visible residue and 10PPM
(Walsh et al. 2013). The direction on the calculation of limit can be established in the articles
denoted to by the FDA in supervisory guidance booklets (Brunkow et al. 2018).
In this validation experiment, the fermenter is utilised to create biopharmaceutical products
which leave residues of the salts, protein, sugars and lipids (Murthy and Chitra 2013). The

Cleaning validation practical 3
vessel is washed by a cleaning standard operating procedure (SOP) or cleaning in progress (CIP).
The microbial levels analysis will be matched to USP criteria for biopharmaceutical products.
The reading for total organic carbon (TOC), pH and conductivity will be taken from final rinse
water and matched to pharmacopeia requirement for USP grade water (Swarbrick 2013).
Cleaning process
A sample was taken from 10L fermentor to act as a positive control. The vessel was then
sterilised for 30 minutes under 1210C. All process took nearly 1 hour and 30 minutes and batch
on the computer was started to record sterilisation graph for the validation documentation. A
sample was taken post sterilisation and then batch on the computer was stopped. The sterile
content on the vessel was emptied. Swab samples from predetermined locations were taken
while ensuring position were marked on the drawing for the documentation. The vessel was
filled with approximately 12L of fresh DI water, and 100ml of 1M NaOH was added. The
cleaning routine was started for 5 minutes at 800C with 1500rpm stirrer speed, which took for
nearly 40minutes for heat and cool down.
As the vessel was being drained, rinse sample was taken. It was expected that the pH could be
neutral and conductivity ought to be low if the vessel had been rinsed effectively (Siegmann-
Hegerfelda et al. 2013). The pH and conductivity were taken to check the above. The second set
of swab samples was made as before from predetermined locations. The swabs and samples were
removed for further biological analysis. The conductivity and pH of the first and second rinse
sample were also read and recorded.

Cleaning validation practical 4
Discussion
Six swab number S1, S2, S3, S4, S5 and S6 comprised base left hand, shaft top left the top side,
wall top right, shaft middle right, agitator bottom right, and right-hand side near turbidity sensor
location respectively. The pH and conductivity reading of first rinse samples were 10.78 and
494u/s at 250C while the pH and conductivity reading of second rinse samples were 12.52 and
12.52u/s at 250C respectively. The microanalysis of the above example gave the positive results.
Additionally, there was no colony forming on agar plates. Therefore, it means no residue
present in a vessel and the system was correctly cleaned that is why there was no growth of
microbial. However, another possibility of having no colony forming a unit on agar plates might
be deviations samples as the swabs were not correctly done or while performing the test for
proper microanalysis, instructions were not followed which could result to no growth of CFU on
agar plates (Lodhi, Padamwar and Patel 2014).
If the washing with a cleaning solution having a high pH, perhaps, due to the presence of caustic
in the cleaning solution, or low pH due to acid in the cleaning solution, pH would be a gauge of
the completion of the rinsing process. As one approaches closer to a baseline pH (for instance
7.0) the slightly lower pH due to picking of carbon dioxide from the air during the CIP process,
there would be confidence of rinsing process being effective (Walsh et al. 2017). However, in
this case, the second rinse had pH above the first rinse and hence going up rather than down,
thus, showing ineffective in a cleaning process. Additionally, it could be problem of using pH
meter which was not calibrated or using a fault one. Conductivity is a measure of ionic species
present in solution. The good thing with conductivity measurement is that it is a linear
measurement. Therefore, a water sample with a conductivity of 494u/s had almost 39-fold the
number of ions as a water sample with a conductivity of 12.52u/s