validation

validation

the term widely used in the pharmaceutical industry

valid

means can be justified or legally defined

validation

is demonstration and documenting that something does what is supposed to do

validation

a full detailed documentation that all processes and procedures are functioning in the manner that they are designed for

validation

is a documented act of proving that any procedure, process, equipment, material, activity, or system actually leads to the expected result

method validation

process of proving that an analytical method is acceptable for its intended purpose

analytical procedures

_________________ must be shown to be acceptable for their intended use and must provide accurate and reliable results at every stage of development

evidence

validation of analytical test methods provides ________________ that systems and methods are suitable for the intended use

accuracy, sensitivity, specificity, reproducibility

the _________, ____________, __________, and ________________ of test methods employed by the firm shall be established and documented

purpose

there should be evidence that validated analytical procedures meet their ___________ through its life cycle

validation

the process by which it is established, by laboratory studies, that the performance characteristics of the procedure meet the requirements for the intended analytical applications

alternative method or procedure

is defined as any method or procedure other than the compendial method of procedure for the article in question

fully validated

the alternative method and procedure must be ____________ and must produce comparable results to the compendial method or procedure within allowable limits in a case by case basis

controlled, monitored

the FDA has strict guidelines for process validation in manufacturing because the process has to be _____________ and ___________ throughout all stages of manufacturing

efficacy, safety, cleanliness, sterility

validation is necessary if a company wants its product to have enough ____________, ______________, ______________, or ___________

qc, verifying system suitability, part of registration application, for submission to compendium

4 reasons why analytical method validation

identification tests, quantitative tests for impurities content, limit tests for the control of impurities, quantitative tests of active moiety in samples of drugs

4 types of analytical procedures to be validated

suitability of instrument, suitability of materials, suitability of analyst, suitability of documentations

4 considerations prior to method validation

suitability of instrument

involves status of qualification and calibration

suitability of materials

involves status of reference standards, reagents, etc.

suitability of analyst

involves status of training and qualification records

suitability of documentation

involves written analytical procedures and proper approved protocol with pre-established acceptance criteria

validation of an analytical procedure

is the process by which it is established, by laboratory studies, that the performance characteristics of the procedure meet the requirements for the intended analytical applications

method validation

the process for providing documented evidence that the method does what it is intended to do

verification

"am i building the product right?"

validation

"am i building the right product?"

validation

means confirmation by examination and provision of objective evidence that the particular requirements for specific intended use can be consistently fulfilled

verification

means confirmation by examination and provision of objective evidence that specified requirements have been fulfilled

validation

a process of seeing whether the product satisfies the customers needs or not

validation

it is performed to build the right product

validation

activities include testing of the product itself

verification

evaluating the process and product in development stage

verification

it is performed to build a product in right way

verification

document reviews and inspection are examples of these activities

validation

Characterizes performance characteristics

verification

Confirms that the validated methods works as intended under
Conditions of actual use.

a drug should be produced that is fit for its intended use

the basic principle of quality assurance

validation

"did we build the right model?"

validation

"Is the model useful?"

validation

"have we accurately modelled the decision problem?"

verification

"Did we build the model right?"

verification

"Is the model correctly built and functioning?"

verification

"Is the model free from errors?"

ICH Q2 R1

validation of analytical procedure

validation

is a process of establishing documentary evidence demonstrating that a procedure, process, or activity carried out in production or testing maintains the desired level of compliance at all stages

method validation

is the process used to confirm that the analytical procedure employed for a specific test is suitable for its intended use

international council for harmonisation of technical requirements for pharmaceuticals for human use

meaning of ICH

user required specification

a document stating the specified user requirement for a select piece of equipment, system, or facility

validation

is a process to provide assurance that instrumentations are functioning properly

validation master plan

a document that summarizes the firm's overall philosophy, intention, and approach to be used for establishing performance adequacy

Operational Qualification of HPLC (high performance liquid chromatography)

to assure that the equipment used for analysis, is operated, and qualified according to the specifications mentioned in the equipment catalog and complies with company and regulatory standards and guidance

UV/VIS variable wavelength detector

the objective of this test is to verify and document that the critical instruments used to monitor or control the system are operated and tested in accordance with available specification documentation

accuracy

an assessment of the difference between the measured value and the real value

precision

a measure of the agreement for multiple measurements on the same sample

specificity

the ability to assess the analyte when in the presence of other components

limits of detection and quantitation

the lowest amounts of analyte that can be detected / determined accurately, respectively

linearity and range

the proportionality of the measurement to the concentration of the analyte within a specified range

robustness

a check of the effect of deliberate small changes to the method on the results

trueness

unbiased results; measurement agreement with true value

trueness

comparison with well characterized samples and reference methods

precision

characterization of the agreement among test results

precision

involves statistical metrics

repeatability

precision among short term variations

ruggedness

precision among intermediate variations

reproducibility

precision among longer term variations

repeatability

under instrument precision

ruggedness

under intermediate precision

reproducibility

under interlaboratory precision

repeatability

it is the variation in measurements obtained

equipment, people

2 possible causes of poor repeatability

ruggedness

is a measure of reproducibility of test results under the variation in conditions normally expected from laboratory to laboratory and from analyst to analyst

specificity or selectivity

method sensitivity to potential interferences, assessments

method sensitivity to potential inferences

involves impurities, contaminants, degradation products; closely related compounds

assessment

involves chromatographic studies, peak purity tools, use of orthogonal methods, etc

limit of detection

lowest quantity of a substance that can be distinguished from a blank sample

limit of detection

point at which a measured response is larger than its uncertainty

limit of quantitation

meaning of LOQ

limit of detection

meaning of LOD

signal to noise ratio

meaning of SNR

detection limit

the lowest amount of analyte in a sample which can be detected but not necessarily quantitated as an exact value

quantitation limit

is the lowest amount of an analyte in a sample which can be quantitatively determined with suitable precision and accuracy

quantitation limit

is a parameter of quantitative assays for low levels of compounds in sample matrices, and is used particularly for the determination of impurities and/or degradation products

limit of detection

the smallest concentration of an analyte in a test sample that we can easily distinguish from zero

limit of quantitation

the smallest concentration of an analyte in a test sample that we can determine with acceptable repeatability and accuracy

linearity

is the ability of an analytical procedure (within a given range) to obtain test results which are directly proportional to the concentration (amount) of analyte in a sample

range

is the interval between the upper and lower concentration of analyte in the sample for which it has been demonstrated that the analytical procedure has a suitable level of precision, accuracy, and linearity

robustness

a measure of an analytical procedure's capacity to remain unaffected by small, but deliberate variations in method parameters and provides an indication of its reliability during normal usage