You are hereVALIDATION OF ANALYTICAL PROCEDURES: A COMPARISON OF ICH Vs PHARMACOPOEIA Vs FDA

VALIDATION OF ANALYTICAL PROCEDURES: A COMPARISON OF ICH Vs PHARMACOPOEIA Vs FDA


4. Validation Protocol

The text of 21 CFR Part 211, ICH guidelines and general chapter <1225> all provide terms and definitions, there is no specific discussion on Validation protocol and methodology. In ICH guidelines (Q2B) on method validation methodology, the applicant has been made responsible for appropriate validation protocol and procedure suitable for the product. Therefore prior to initiating a validation study, a well planned validation protocol is required. The validation protocol should include a detailed test procedure, basic experimental design, elements for validation, predefined acceptance criteria, reference or related methods and management approval.

A test procedure is description of the “analytical method” to be used as a guide in validating the method and serve as basis for preparation of validation protocol. It should include

  1. A listing of reagents, solvents and other supplies
  2. Instructions for preparation of standards, samples and solutions
  3. A listing of equipments to be used or equivalents
  4. Instrumental parameters and chromatographic conditions
  5. System suitability requirements
  6. Standard and sample analysis sequence
  7. Calculation sequence to include result formatting 2

5. Types of Analytical Procedures to be Validated

There are 3 types of analytical procedures:

·         Regulatory analytical procedures

·         Alternative analytical procedures

·         Stability indicating assay

Regulatory analytical procedures are those procedures which are official in compendia of standards recognized by legislation of country for example, he drug and cosmetic rues recognize official procedures given in I.P. and other pharmacopoeia such as B.P.&  U.S.P

Alternative analytical procedures are alternative procedures for regulatory analytical procedures. Generally pharmacopoeia state that alternative method can be used provided their performance is equivalent or more then pharmacopoeial analytical procedure.

Stability indicating assay is a validated quantitative method that can detect changes with time in particular properties of drug substance and drug product. It accurately measure the active ingredient without interference from degradation products, process impurities excipients or other potensial impurities 11

Validation of analytical procedures is directed to the four most common types of analytical procedures:

-     Identification tests;

-     Quantitative tests for impurities' content;

-     Limit tests for the control of impurities;

-     Quantitative tests of the active moiety in samples of drug substance or drug product or other selected component(s) in the drug product.

A brief description of the types of tests considered in this document is provided below.

- Identification tests are intended to ensure the identity of an analyte in a sample.  This is normally achieved by comparison of a property of the sample (e.g., spectrum, chromatographic behaviour, chemical reactivity, etc) to that of a reference standard;

- Testing for impurities can be either a quantitative test or a limit test for the impurity in a sample.  Either test is intended to accurately reflect the purity characteristics of the sample. Different validation characteristics are required for a quantitative test than for a limit test;

- Assay procedures are intended to measure the analyte present in a given sample.  the assay represents a quantitative measurement of the major component(s) in the drug substance.  For the drug product, similar validation characteristics also apply when assaying for the active or other selected component(s).  The same validation characteristics may also apply to assays associated with other analytical procedures (e.g., dissolution).

  Typical validation characteristics which should be considered are listed below:

1. Accuracy

2. Precision

2.1 Repeatability

2.2 Intermediate Precision

3. Specificity

4. Detection Limit

5. Quantitation Limit

6. Linearity

7. Range

The degree of revalidation required depends on the nature of the changes. Certain other changes may require validation as well.

TABLE 1 – Different Characteristics

Type of analytical procedure

Identification

Testing  for impurities

Assay

- dissolution

(measurement only)

- content/potency

characteristics

 

quantitat.   limit

 

Accuracy

-

       +            -

                       +

Precision

    Repeatability

    Intermediate.Precision

 

-

-

 

       +            -

       + (1)       -

 

                       +

                      + (1)

Specificity (2)

+

       +            +

                       +

Detection Limit

-

       - (3)        +

                       -

Quantitation Limit

-

       +            -

                       -

Linearity

-

       +            -

                       +

Range

-

       +            -

                       +

-      signifies that this characteristic is not normally evaluated

+     signifies that this characteristic is normally evaluated

(1)   in cases where reproducibility has been performed, intermediate precision is not needed

(2)   lack of specificity of one analytical procedure could be compensated by other supporting analytical procedure(s)

(3)   may be needed in some cases

6. DEFINITIONS

· ANALYTICAL PROCEDURE
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.

· SPECIFICITY
Specificity is the ability to assess unequivocally the analyte in the presence of components which may be expected to be present. Typically these might include impurities, degradants, matrix, etc.
Lack of specificity of an individual analytical procedure may be compensated by other supporting analytical procedure(s).

This definition has the following implications:

Identification: to ensure the identity of an analyte.

Purity Tests: to ensure that all the analytical procedures performed allow an                    accurate statement of the content of impurities of an analyte, i.e. related substances test, heavy metals, residual solvents content, etc.
Assay (content or potency):  to provide an exact result which allows an accurate statement on the content or potency of the analyte in a sample.

· 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.

· 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.

· Repeatability
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
Reproducibility expresses the precision between laboratories (collaborative studies, usually applied to standardization of methodology).

· DETECTION LIMIT
The detection limit of an individual analytical procedure is the lowest amount of analyte in a sample which can be detected but not necessarily quantitated as an exact value.

· QUANTITATION LIMIT
The quantitation limit of an individual analytical procedure is the lowest amount of analyte in a sample which can be quantitatively determined with suitable precision and accuracy. The 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.

· 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.

· 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.

· 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

NOW YOU CAN ALSO PUBLISH YOUR ARTICLE ONLINE.

SUBMIT YOUR ARTICLE/PROJECT AT articles@pharmatutor.org

Subscribe to Pharmatutor Alerts by Email

FIND OUT MORE ARTICLES AT OUR DATABASE


Anonymous (not verified)
Pharma Graduate

Dear All,

With respect to the current scenario of the Indian pharma graduate and outlook of the government and the industry, we need to address the following problems with the demands as mentioned below for the pharma graduate:-

1) To ensure there are quality graduates coming out of the colleges as there are poor quality of the students coming out from the universities.

2) Our Indian degrees should be recognized all over the world and registered pharmacist in India should be able to register in any European or American Countries without much hassle.

3) As per the regulation of the price of the essential drugs in the DPCO, the salary provided to the pharma graduate should be also be regulated per the pay commission.

4) PIC (The Great Pharmacy Council of India) should work proactively for the maintaining the high standards of the pharma profession by making the employment of the pharma graduate compulsory in the production area and not allowing the other graduates including the Msc and Bsc in working in the company.

5) The DPharm graduation should be phased out immediately as there should not be any advantages or disadvantages for both the B or the D graduate.

6) The PharmD should not start as there is no scope for the further learning after Bpharm, as per the syllabus for the PharmD there is no scope for any specialization and may have no effect on any job performance. Eventually he will be standing behind a pharmacy counter which even a D pharm would be able to stand and dispense the medicine as prescribed by the doctors.

7) New Colleges having such courses should be stopped with immediate effects, as more graduates are eventually been fooled for the course and no happiness is gained by being a graduate of Pharm.

8) For Marketing Jobs, also they should be reserved only for the trained person like Dpharm or BPharm, no other untrained person should be selling the pharma products.

9) More Government Employment schemes for the further progress of the pharma profession and national strength. And allowing the Pharma graduate to have better roles in research.

For the above demands if completed, provide a perfect healthy and fairly competitive environments for the level playing of the pharma graduate. But how make the government listen to your demands, how will the bloody buggers will answer to the questions which are pertinent to their activities which are corrupt enough.

There is a solution to this question. I can make this thing happen, I require only 50 persons who can help me. The only things required:-
1) Incurring expense of rupees 50Rs (This is No payment to me)
2) Time to post an application.

If you are interested in participating in the movements, please contact me at hvk159@hotmail.com

Regards,

manav2229
Offline
Joined: 2011-11-24
GOOD WORK

I WANT TO CONGRATULATE TO ALL OF U.U ALL HAVE DONE A NICE JOB.I AM WORKING AS Sr. OFFICER VALIDATION SECTION IN MACLEODS PHARMA IN ARD FROM LAST THREE YEARS. Its A GOOD ARTICLE CAN U SEND A COPY OF THIS ON MY MAIL ID;manav2229@gmail.com. so i can read it thoroughly and give u some good suggestions.

GOOD LUCK.

Anonymous
Hi

Very Informative article. Keep it your hard work

Dr Tushar Lokhande

FIND MORE ARTICLES

Subscribe to RSS headline updates from:
Powered by FeedBurner