INVOLVEMENT OF HEALTHCARE REGULATORY AFFAIR PROFESSIONAL IN OVERSEAS REGISTRATION PROCESS

Pharma courses

pharma courses



New Drugs approved in India within period of 1 year:-
1.      Application in Form-44 duly signed, by the competent authority with name and designation.
2.      Treasury Challan of Rs. 25000/- as per Drugs & Cosmetic Rules.
3.      Undertaking by the Principal Investigator (PI) as per appendix VII of schedule “Y” of Drugs and Cosmetic Rules.
4.      A copy of the approval of the BE study centre from CDSCO.
5.      Sponsor’s Authorization letter duly signed by the competent authority on their letterhead.
6.      The study protocols.
7.      Clinical study data and published report of pharmacokinetic and pharmacodynamic study carried out in healthy volunteers data published in reputed journals.
8.      Package literature on the international product.
9.      Complete Certificate of Analysis of same batches (both test & reference formulations) to be used in the BE study.
10.  In the case of multiple dose BE study adequate supporting safety data should be submitted.
11.  In the case of Injectable preparation the sub-acute toxicity should be submitted on the product of the sponsor, generated in two species for adequate duration.
12.  Depending on the nature of the drug like cytoxic agent, hormonal preparations etc.  Proper justification for conducting studies on healthy volunteers/patients or male/ female should be submitted.

New Drugs approved within period of more than 1 year & less than 4 years:-
1.      Application in Form-44 duly signed, by the competent authority with name and designation
2.      Treasury Challan of Rs. 15000/- as per Drugs & Cosmetic Rules.
3.      Undertaking by the Principal Investigator (PI) as per appendix VII of schedule “Y” of Drugs and Cosmetic Rules.
4.      A copy of the approval of the BE study centre from CDSCO.
5.      Sponsor’s Authorization letter duly signed on their letterhead by the competent authority.
6.      The study protocols.
7.      Complete Certificate of Analysis of same batches (both test & reference formulations) to be used in the BE study.
8.      In the case of multiple dose BE study adequate supporting safety data should be submitted.
9.      In the case of Injectable preparation the sub-acute toxicity should be submitted on the product of the sponsor, generated in two species for adequate duration.
10.  Depending on the nature of the drug like cytoxic agent, hormonal preparations etc.  Proper justification for conducting studies on healthy volunteers/patients or male/ female should be submitted.

BE NOC for all the drug products in modified release form irrespective of their approval status:-
1.      Application in Form-44 duly signed, by the competent authority with name and designation
2.      Treasury Challan of Rs. 15000/- as per Drugs & Cosmetic Rules.
3.      Undertaking by the Principal Investigator (PI) as per appendix VII of schedule “Y” of Drugs and Cosmetic Rules.
4.      A copy of the approval of the BE study centre from CDSCO.
5.      Sponsor’s Authorization letter duly signed on their letterhead by the competent authority.
6.      The study protocols.
7.      Complete Certificate of Analysis of same batches (both test & reference formulations) to be used in the BE study.
8.      In the case of multiple dose BE study adequate supporting safety data should be submitted.
9.      In the case of Injectable preparation the sub-acute toxicity should be submitted on the product of the sponsor, generated in two species for adequate duration.
10.  Depending on the nature of the drug like cytoxic agent, hormonal preparations etc.  Proper justification for conducting studies on healthy volunteers/patients or male/ female should be submitted.

All above requirements are general in nature, however depending on the nature of the drug, disease and studies further specific information may also be required to be furnished by the firm.

Regulatory Control of Pharmacovigilance System
Pharmacovigilance is the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other possible drug-related problems. The scope of the Pharmacovigilance has been to:
* improve patient care and safety in relation to the use of medicines and all medical and paramedical interventions
* improve public health and safety in relation to the use of medicines
* contribute to the assessment of benefit, harm, effectiveness and risk of medicines, encouraging their safe, rational and more effective (including cost-effective) use
* promote understanding, education and clinical training in Pharmacovigilance and its effective communication to the public.

Recently, its concerns have been widened to include herbals, traditional and complementary medicines, blood products, biologicals, medical devices and vaccines. Pharmacovigilance also concerns substandard medicines, medication errors, lack of efficacy reports, use of medicines for indications that are not approved and for which there is inadequate scientific basis, case reports of acute and chronic poisoning, assessment of drug-related mortality, abuse and misuse of medicines and adverse interactions of medicines with chemicals, other medicines, and food.

Importance of Pharmacovigilance:
It highlights the need for critical examination of the Strengths and weakness of present Pharmacovigilance systems in order to increase their impact. It anticipates developments necessary to meet the challenges of the next ten years. It argues that the distinctive approaches adopted by different countries in response to their individual needs should be supported and fostered. The document also highlights the importance of collaboration and communication at local, regional and international levels, to ensure Pharmacovigilance delivers its full benefits.

CONSTITUTES OF THE PHARMACOVIGILANCE PROCESS
Pharmacovigilance process starts at the way beginning of clinical development process of a drug product and continues throughout the life cycle of the product. Broadly it can be divided into two phases:
1) Pre Marketing Pharmacovigilance Process
2) Post Marketing Pharmacovigilance Process

Pre Marketing Pharmacovigilance Process:
The assessment of clinical data and Safety and Efficacy data during the drug product development known as the pre marketing Pharmacovigilance process. It involves the measuring of the adverse drug reactions in whole the phases of the clinical trials. On the basis of these data or case report form informs the agencies and manage the risk benefits ratio of the drug product. During the clinical data the adverse drug reaction occur are known as the expected adverse drug reaction and those which are comes during the post marketing Pharmacovigilance process are known as the unexpected adverse drug reaction.

Post Marketing Pharmacovigilance Process:
Phase 2nd of the Pharmacovigilance process after a medicines gets launched in the market and until the time that it remain in the market is the post approval Pharmacovigilance process. It is the post marketing Pharmacovigilance process that’s the regulatory agencies of the world vigilant about the reporting of adverse events happens spontaneously.

Pharmacovigilance in different countries/regions
All the regions of the world have their own particular Pharmacovigilance system, through based on WHO guidelines.

Pharmacovigilance in Europe
Pharmacovigilance system in Europe is coordinated by the European Medicines Agency (EMA) and conducted by the National Competent Authorities (NCAs). The EMA maintains and develops the Pharmacovigilance database comprising all suspected serious adverse drug reaction observed in the European region. Here, the Pharmacovigilance system is called EUDRA Vigilance and contains separate but similar database of human and veterinary reactions. EMA Pharmacovigilance legislation regulated by Article 106 of Directive 2001/83/EC, Directive 2001/20/EC & Article 26 of Regulation (EC) No. 726/2004 EMEA& EC

Pharmacovigilance in United States
Here Pharmacovigilance has a multi faced approach. Three branches of the Pharmacovigilance in the USA has been defined by the FDA to evaluate product risks and promote the safe use of products by the American people. These three division / branches comes in the office of Surveillance and epidemiology (OSE).

Three Divisions within OSE:
1. Division of Drug Risk Evaluation (DDRE)
2. Division of Medication Errors and Technical Support (DMETS)
3. Division of Surveillance, Research and Communication Support (DSRCS)

In United State the Pharmacovigilance Legislation Regulated 21 CFR 314.80, 314.98 FDA, CDER, CBER.[7]

Pharmacovigilance in India
The central drugs Standard control organisation (CDSCO), ministry of health and family welfare, Govt of India launched the national Pharmacovigilance programmed (NPP) in November, 2004 based on the WHO recommendations made in the document titled” safety monitoring of Medicinal products-guidelines for setting up and Running a Pharmacovigilance Centre” the whole country is divided into zones and regions for the operational efficiency, CDSCO, new Delhi is at the top of the hierarchy by two zonal Pharmacovigilance centre viz. seth GS medical college , Mumbai and AIIMS, New Delhi.

Guidelines for Analytical Method Validation:

INTRODUCTIONS:
The objective of validation of an analytical procedure is to demonstrate that it is suitable for its intended purpose.

Analytical procedures used to measure the quality of pharmaceutical products span almost the entire range of currently available technologies and techniques.

It is important to keep in mind that the most important aspect of any analytical method is the quality of the data it ultimately produces.

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.

All relevant data collected during validation and formulae used for calculating validation characteristics should be submitted and discussed as appropriate.  Well-characterized reference materials, with document purity, should be used throughout the validation study.  The degree of purity depends on the intended use.

TYPES OF ANALYTICAL PROCEDURE TO BE VALIDATED:
The Discussion of  the validation of analytical procedure is directed to the four  most common types of analytical procedures:
Identification tests :
Tests are intended to ensure the identity of analyte in a sample this is normally achieved by comparison of a property of the sample (e.g. spectrum, chromatographic behavior chemically reactivity, etc) to that of a reference sample.

Quantitative tests for impurities content:
For the impurity in a sample either test is intended to accurately.
Limit tests for the control impurities:
Different validation characteristics are required for a quantitative test than for a limit tests.
Quantitative tests of the active tests moiety in sample of drug substance or drug product or other selected component(s) in the drug product.

The assay represents a quantitative measurement of major component (s) applies when assaying for the active or selected component(s). the same validation characteristic may also apply to assays associated with other analytical procedure  (e.g., dissolution).

The objective of the analytical procedure should be clearly understood since this will govern the validation characteristic which needs to be evaluated. Typical validation characteristic which should be considered are listed below:
*    Accuracy.
*    Precision.
*    Repeatability.
*    Intermediate precision.
*    Reproducibility.
*    Specificity.
*    Detection limit.
*    Quantitation Limit.
*    Linearity.
*    Range.
*    Robustness

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

Type of Analytical Procedure

Identification

Testing for Impurities

Assay

Dissolution(Measurement Only)

Content /Potency

Characteristics

Quantitative

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 (see glossary) 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

ANALYTICAL PERFORMANCE CHARACTERISRTICS:
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). Non-Numerical data (Raw Data, Chromatograms).
Comparison of responses from samples with and without analyte present.

Identification:
Identification tests should be able to discriminate between compounds of closely related structure which are likely to be present.
Identification test may be applied to maintain structurally similar to or closely related to the analyte to confirm that a positive response is not obtained.

Assay& Impurity Test (s):
The method was intended to detect trace quantities of the active ingredients for purpose of a cleaning validation the detection and quantification limits are appropriate and necessary. Validation of each assay or test method should be performed on a case basis, to ensure that the parameter is appropriate for the methods intended to use.
The approach is similar for both assay and impurity tests: 

Impurities are Available :
Demonstration of the discrimination of the analyte in the presence of impurities and or excipients;  Practically, this can be done by spiking pure substance with appropriate levels of impurities and/or excipients and demonstrating that the assay result in unaffected by the presence of these materials. Impurity test, the discrimination may be established  by spiking drug substance or drug product with appropriate level of impurities and demonstrating the separation of these impurities individually and /or from other components in the sample matrix./or from other components in the sample matrix.

Impurities are not Available :
If impurity or degradation product standard are unavailable ,specificity may be demonstrated by comparing  the tests results of sample containing impurities or degradation product to a second well – characterized procedure.
E.g. Pharmacopoeial method or other validation analytical procedure. As appropriate, this should include samples stored under relevant stress condition: light, heat, humidity, acid/base hydrolysis and oxidation,
•    For the assay, the two results should be compared.
•    For the impurity tests, the impurity profile should be compared.
Peak purity tests may be useful to show that the analyte chromatographic peak is not attributable to more than one component (e.g., diode array, mass spectrometry).

To the drug formulation were added known amount of API was estimated by the prescribed method to know it.

The values suggest that the method is specific for estimation of API and amounts of other excipients do not have any impact on estimation of the analyte.

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


 

Pages

FIND MORE ARTICLES