Professional Documents
Culture Documents
Review Article
Abstract
It has always been known that facilities and processes involved in pharmaceutical production
impact significantly on the quality of the products. The processes include raw material and
equipment inspections as well as in-process controls. Process controls are mandatory in good
manufacturing practice (GMP). The purpose is to monitor the on-line and off-line performance
of the manufacturing process, and hence, validate it. Thus validation is an integral part of
quality assurance.
This overview examines the need for pharmaceutical validation, the various approaches and
steps involved, and other pertinent considerations.
study with details of performance procedure as laid down in the protocol must
characteristics; be considered as potentially compromising
• Installation and qualification the validity of the study itself and requires
requirement for new equipment; critical evaluation of all the impact on the
• Any upgrading requirement for existing study. The final certification of the validation
equipment with justification for the study should specify the pre-determined
change(s) and statement of acceptance criteria against which success or
5
qualification requirement; failure was evaluated .
• Detailed stepwise statement of actions
to be taken in performing the study (or Validation of Analytical Assays and Test
studies); Methods
• Assignment of responsibility for
performing the study; Method validation confirms that the analytical
• Statement on all test methodology to procedure employed for a specific test is
be employed with a precise statement suitable for its intended use. The validation
of the test equipment and/or materials of an analytical method is the process by
to be used; which it is established by laboratory studies
• Test equipment calibration require- that the performance characteristics of the
ments; method meet the requirement for the
• References to any relevant standard intended application. This implies that
operating procedures (SOP); validity of a method can be demonstrated
7
• Requirement for the current format of only though laboratory studies . Methods
8, 9
the report on the study; should be validated or revalidated :
• Acceptance criteria against which the
success (or otherwise) of the study is • before their introduction and routine
to be evaluated; and use;
• The personnel responsible for • whenever the conditions change for
evaluating and certifying the accept- which the method has been validated,
ability of each stage in the study and e.g., instrument with different
for the final evaluation and certification characteristics; and
of the process as a whole, as • wherever the method is changed and
measured against the pre-defined the change is outside the original
criteria. scope of the method.
• Define the performance parameters conclusion that residues have been reduced
14 14
and acceptance criteria; to an “acceptable level” . Harder cited five
• Define validation experiments; crucial elements:
• Verify relevant performance charact-
eristics of the equipment; 1. A standard operating procedure (SOP)
• Select quality materials, e.g., for cleaning with a checklist;
standards and reagents; 2. A procedure for determining clean-
• Perform pre-validation experiments; liness (rinse or swab);
• Adjust method parameters and/or 3. An assay for testing residual drug
acceptance criteria, if necessary; levels;
• Perform full internal (and external) 4. Pre-set criteria for testing chemical
validation experiments; and microbial limit to which to
equipment must be cleaned; and
• Develop SOPs for executing the
5. Protocol for cleaning validation.
method routinely;
• Define criteria for revalidation; 14
Harder recommended that the procedure
• Define type and frequency of system be tested for, requiring it to be successful on
suitability tests and/or analytical quality three successive cleanings and there should
control (AQC) checks for the routine; be periodic revalidation as well as
and revalidation after significant changes.
• Document validation experiments and 15
Jenkins and Vanderwielen presented an
results in the validation report. overview of cleaning validation covering
strategy and determination of residue limits,
Environmental Considerations: Cleaning method of sampling and analysis noting that
and Clean Room Standards “increased use of multi-purpose equipment”
has produced increased interest in cleaning
Cleaning validation is documented proof that validation. The cleaning protocol must be
one can consistently and effectively clean a thorough and must be checked. Training is
system or equipment items. The procedure essential. A validation program requires
11, 12
is necessary for the following reasons :
• criteria for acceptance after cleaning,
• It is a customer requirement – it • appropriate methods of sampling,
ensures the safety and purity of the • a maximum limit set for residues, and
product; • test methods that must themselves be
• It is a regulatory requirement in active tested.
pharmaceutical product manufacture;
and Products to be tested may be put into groups
• It also assures from an internal control 16
rather than testing all of them . The most
and compliance point of view the important may not be the highest volume
quality of the process. product but those capable of causing the
13
largest possible problems if contaminated or
The FDA guide to inspections intended to if they contaminate the products (solubility of
cover equipment cleaning (chemical the drug is an important issue). Equipment
residues only) expects firms to have written may also be tested in groups.
procedure (SOPs) detailing the cleaning
processes and also written general Process Validation
procedure on how cleaning processes will be
validated. FDA expects a final validation Process validation is the means of ensuring
report which is approved by management and providing documentary evidence that
and which states whether or not the cleaning processes (within their specified design
process is valid. The data should support a
119 Trop J Pharm Res, December 2002; 1 (2)
E Jatto & AO Okhamafe