The document outlines the importance of instrument and analytical validation in the pharmaceutical industry, detailing the processes and qualifications necessary to ensure compliance and quality assurance. It covers types of validation, stages of qualification, and specific methodologies like analytical method validation, emphasizing the necessity of equipment validation and testing at various stages including user requirements, factory acceptance, and site acceptance tests. The content also discusses performance characteristics such as accuracy, precision, and robustness necessary for effective analytical procedures.

1. Instrument and Analytical Validation and Qualification
Name
Shopnil Akash
Department of Pharmacy
Daffodil International University
Session: 2018-2019

2. Content/ Topics
• Validation
• Purpose of Validation
• When should be validated?
• Qualification
• Quality concept
• Importance of qualification
• Validation VS Qualification
•
•
• Types of validation
• Equipment validation
• Stages of Qualification
• Short Description of steps of Instrument qualification
• User requirement specification
Factory acceptance test
• Site acceptance test
• Application of Equipment validation:

3. Validation
Validation is the process of establishing documentary evidence
demonstrating that a procedure, process, or activity carried out in testing
and then production maintains the desired level of compliance at all
stages
It is an Essential to ensure the quality Of a product and Good Manufacturing
Practices including all other regulatory requirements

4. Purpose of Validation
Validation is the process of establishing the
• Performance characteristics
• Limitations of a method
• Which analytes can be determined in which matrix in the presence of which
interferences?
• Within these conditions what levels of precision and accuracy can be achieved

5. • Before development of a new method in to routine use.
• Whenever condition change for which method has been validation e.g. instrument with different characteristics.
• Whenever the method is changed and the change is outside the scope of the original method.
• Change in raw material.
• Change in manufacturing process.
• Change in equipment/system.
• Change in supporting systems.
• Change in packaging materials
When should be validated?

6. Qualification
Qualification is defined as an action of providing that equipment or ancillary systems are
properly installed, work correctly, and actually lead to the expected results. Qualification is part
of validation, but the individual qualification steps alone do not constitute process validation.
Pharmaceutical
Industry
Quality
Approach
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manufacture
medicine
Affordabl
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Maximizin
g Profit
Quality Approach
Adopted
by
GMP/cGMP
Quality concept

7. Importance of qualification
The current equipment qualification programs and procedures used within the
pharmaceutical industry are based on
 regulatory requirements,
 voluntary standards,
 vendor practices, and
 industry practices
Qualification will help to increase the longevity of the instruments along with the
repeatable and reliable performance which ultimately can be applied to achieve
validation process.

9. Types of validation
Validation is divided into following subsections which include
• Analytical method validation
• Process validation
• Cleaning validation
• Equipment validation
• Let’s take an overview of different types of the validation process and discuss in detail
about equipment validation and and its phase with their importance in pharmaceutical
industries.

10. Equipment validation
Equipment validation:
Equipment validation is established documented set up that proves any equipment works correctly and leads to
accepted and accurate results (predetermined result). The process of equipment validation is based on the principle that
equipment must be designed, constructed, maintained, and adapted to perform the operations which are to be carried
out. Equipment’s are the basic component of pharma industries; therefore, before performing a process in pharma
industries, it becomes primary important to issue equipment validation (documented evidences of equipment)
The process of equipment validation is mainly divided into three phases:
• Phase – 1: Pre-validation phase.
• Phase – 2: Process validation phase.
• Phase – 3: Validation maintenance phase

11. Stages of Qualification
Design Qualification (DQ)
Installation Qualification (IQ)
Operational Qualification (OQ)
Performance Qualification (PQ)
Maintenance Qualification (MQ)

12. Short Description of steps of Instrument qualification

13. • User requirement specification is to provide appropriate design and performance requirements for procurement of
equipment/system/instrument/utility including major add-on component or major modification/expansion of area,
to meet in house requirement as well as compliance with cGMP. The requirement for preparation of URS shall be
evaluated at initial stage i.e. during procurement phase. The preparation of URS shall be applicable to the items
intended for use as part of pharmaceutical/nutraceutical manufacturing and control and which impacts GMP.
Benefits of a well-defined URS-
• Time and cost-efficient
• Quality end product
• Qualified Instruments that comply with regulatory requirements
• No duplication of work
• Reliable analysis data
User requirement specification

14. • Factory acceptance test is a way to ensure that equipment/system/utility being purchased
meet the agreed upon design specifications. Ideally this happens before arriving at the
customer’s site, however, for complex systems with high integration, tests may need to be
performed at the customer’s location. Factory acceptance tests allows any issues to be
corrected either at the vendor location or before operational qualification, leveraging the
technical expertise and resources of the vendor preventing any potential cross-
contamination with the customer’s site and improving the overall quality of the product
delivered to the customer.
Factory acceptance test

15. • Site acceptance test is the stage where the customer conducts testing for the
components supplied under the project scope and tests the conformance of the delivered
resolution through the resolution definition document and functional specifications. SAT
is performed at the site when the system is installed at the permanent operation position.
The SAT is to test and check functionalities with other interfaces at the site. ISPE
GAMP 5 defines SAT as a process that shows the system to be working as expected in
its operational environment. The test show whether the system interacts correctly with
all other systems at the site.
Site acceptance test

16. Application of Equipment validation:
• Application of Equipment validation: The following is the importance of equipment validation in
pharmaceutical industries.
1. Validation of equipment reduces costs by reducing rejects, reworks, and downtime.
2. Decrease the risk of non-compliance regulatory.
3. High rate of customer satisfaction.
4. Analytical tests methods and calibrations are proceeded.
5. It also reduces testing in in-process and final product.
6. Also improve employee’s awareness.
7. Make maintenance of equipment easier.

17. ANALYTICAL METHOD VALIDATION

18. TYPICALANALYTICAL PERFORMANCE CHARACTERISTICS
USED IN METHOD VALIDATION
 Specificity (Selectivity)
 Linearity
 Range
 Accuracy
 Precision
 Detection Limit
 Quantitation Limit
 Robustness
 System Suitability Testing

19. The analytical procedure refers to the way of performing the analysis. It should describe in detail the steps
necessary to perform each analytical test. This may include but is not limited to: the sample, the reference
standard and the reagents preparations, use of the apparatus, generation of the calibration curve, use of the
formulae for the calculation, etc.
Or
Validation of an analytical method is the process by which it is established, by laboratory studies, that the
performance characteristics of the method meet the requirements for the intended analytical applications.
ANALYTICAL METHOD VALIDATION

20. Selectivity of an analytical method is its ability to measure accurately an analyte in the presence of interferences
that may be expected to be present in the sample matrix.
The specificity of an analytical method is the ability to assess unequivocally the analyte in the presence of
components that may be expected to be present, such as impurities, degradation products, and matrix components.
Selectivity Specifity
A selective method gives correct
results for all interesting analytes
whereas a specific test method
gives correct results for the
interesting analyte whereas other
analytes might interfere each
other.
Outlines the analytical extent
to which an analytical
substance or substance group
can be determined without
interference from sample
related components.
The difference between selectivity and specificity

21. LINEARITY
The linearity of an analytical procedure is its ability (within a given range) to
obtain test results which are directly proportional to the concentration (amount)
of analyte in the sample
• For the establishment of linearity, a minimum of 5 concentrations is
recommended. • The correlation coefficient, y-intercept, slope of the regression
line should be submitted

22. RANGE
• The range of an analytical procedure is the interval between the upper and
lower concentration (amounts) of analyte in the sample (including these
concentrations) for which it has been demonstrated that the analytical
procedure has a suitable level of precision, accuracy and linearity.

23. ROBUSTNESS
The robustness of an analytical procedure is a measure of its
capacity to remain unaffected by small, but deliberate variations
in method parameters and provides an indication of its reliability
during normal usage. •
typical variations are: - • different columns (different lots and/or
suppliers); - temperature; • - flow rate.

24. Ruggedness, according to USP
Ruggedness is the degree of reproducibility obtained
under a variety of conditions, expressed as relative SD,
e.g.: different analysts,
different equipment,
different trade marks of reagents etc.

25. Accuracy
The accuracy of an analytical procedure expresses the closeness of agreement
between the value which is accepted either as a conventional true value or an
accepted reference value and the value found.
This is sometimes termed trueness.

26. Precision
The precision of an analytical procedure expresses the closeness of agreement (degree of scatter) between a series
of measurements obtained from multiple sampling of the same homogeneous sample under the prescribed
conditions. Precision may be considered at three levels: repeatability, intermediate precision and reproducibility.
Precision should be investigated using homogeneous, authentic samples. However, if it is not possible to obtain a
homogeneous sample it may be investigated using artificially prepared samples or a sample solution. The
precision of an analytical procedure is usually expressed as the variance, standard deviation or coefficient of
variation of a series of measurements.
• Intermediate precision
• reproducibility.
• repeatability,

27. Description of Precision
Repeatability expresses the precision under the same
operating conditions over a short interval of time.
Repeatability is also termed intra-assay precision
Intermediate precision Intermediate precision expresses
within-laboratories variations: different days, different
analysts, different equipment, etc.
Reproducibility expresses the precision between
laboratories (collaborative studies, usually applied to
standardization of methodology).