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Cleaning Validation Protocol For Pharmaceuticals
Cleaning Validation Protocol For Pharmaceuticals
1. Introduction:
The validation of the cleaning procedures is establishing documented evidence that the procedure
is effective and capable for removing the contaminants associated with previous products,
residues agents as well as the control of potential microbial contaminants.
The cleaning validation is not only ensure the compliance of the regulatory requirements, but a
more important benefit for performing cleaning procedure validation is the identification and the
correction of the potential problems which could compromise the safety, efficacy or quality of
the subsequent batches of drug product.
2. Objective:
The objective of the cleaning validation is to verify the effectiveness of the cleaning procedure
for removal of product residues, degradation products, preservatives, excipients and/or cleaning
agents so that the analytical monitoring may be reduced to a minimum in the risk associated with
cross-contamination of active ingredients.
The objective of Validation of the cleaning procedure (SOP No :___________) being used for
the cleaning of machine name (Machine No :___________) is to prove that the product contact
parts of the Machine name (Machine No :__________) have been cleaned and that the
contamination level (Chemical and Microbial Contaminants) had been reduced below to an
acceptable level.
To achieve these acceptable levels, cleaning procedure (SOP No :___________) need to be
established and validated; sampling and analysis will be carried out for this purpose to assure
that the cleaning of machine complies with specified limits.
Cleaning validation will verify the effectiveness of cleaning procedure.
3. Scope:
a) This document on cleaning validation is intended to address special consideration and issues
pertaining to validation of cleaning procedure (SOP No :____________) of Machine Name
(Machine No :___________) used for tablets Compression of Pharmaceutical products.
b) This document is also intended to establish inspection consistency and uniformity with respect to
equipment cleaning procedures.
c) This document is intended to cover validation of equipment cleaning for removal of
contaminants associated to the previous product, residues of cleaning agents as well as the
control of potential microbial contaminants.
4. Responsibility:
Equipment cleaning validation may be performed concurrently with actual production steps
during process development and bulk manufacturing. Validation programs should be continued
through full scale commercial production.
The concept “Test-Until-Clean” will be applied. This concept involves cleaning, sampling and
testing with repetition of this sequence until an acceptable residue limit is attained.
A validation program generally encompasses at least three consecutive successful replicate to
establish that the procedure is reproducibly effective.
If the equipment of the similar size, design and construction is cleaned by the same procedure,
studies need not to be conducted on each unit as long as a total of three successful replicates are
done on similar piece of equipment; this concept is known as equipment grouping.
Any of the following proposed changes are evaluated fully for their impact on the validated state
of the procedure. Changes may be,
If any of the above-cited changes are required it should be performed in accordance with the
change control procedure (SOP No :____________).
a) Area difficult to clean and which are reasonably clean can be evaluated by direct surface
sampling method (Swab Method), leading to establish a level of contamination or residue per
given area i.e. 60-100 in2. The residue that are dried out or are insoluble can be sampled by swab
Method.
b) The suitability of the method to be used for sampling and of sampling medium should be
determined. The ability to recover the sample accurately may be affected by the choice of
sampling method. It is important to assure the sampling medium and solvent (Used for extraction
from the medium) are satisfactory and can be readily used.
c) For determination of the microbiological contamination on surfaces is to use sterile cotton swabs
moistened with sterile peptone water, WFI, or Phosphate Buffer. Using sterile forceps and
aseptic technique, an area of predetermined size, e.g. 60-100 in2, is wiped with a sterile swab.
The swab is then aseptically transferred to a sterile tube containing a suitable diluents. The tube
is then agitated to suspend any viable microorganisms and aliquots are placed in a semisolid
medium to obtain quantitative results.
Write down the analytical procedure for determination of traces at least three active
pharmaceutical ingredients.
Swab test
i. Intimate the Production Department for the cleaning validation of Machine name
(Machine No.______________) before starting the activity through cleaning Validation
Schedule.
iii. Validation Officer takes the swab sample for chemical determination, whereas
microbiological Determination.
iv. Send the sample to quality control along with Technical information sheet for analysis.
v. QCD analyzes the sample according to procedure and provide the results to validation
section.
vi. Repeat the steps ii, iii, and iv after the change of consecutive three different products.
vii. Validation section analyzes all the results and compiles the report.
viii. If the result comply with the specified limits than the machine name (Machine
No.______________) is considered as cleaned and the cleaning procedure (SOP
No.______________) is considered as validated.
ix. If the result do not comply with the specified limits, then repeat the overall validation
actives for further two consecutive changes of different products i.e. to provide the validation
data of three consecutive API’s.
x. If the validation results do not comply with the specification, improve the cleaning
procedure and continue it until all the results comply with the specified limits.
12.1
12.2
12.3
13.1 Facilities:
The validation of cleaning procedure being used for the cleaning of Machine Name (Machine
No.___________) was performed in ______________ section of ___________Product at
company Name and address.