INTRODUCTION TO BIOEQUIVALENCE REGULATIONS IN INDIA:

BIOEQUIVALENCE is the term connected to pharmaceutical equivalents whose

rate and extent of absorption are not factually different when administered to
patients or subjects at a similar molar measurements under comparable test
conditions.
Bioequivalent studies are employed for the development of suitable dosage
form for a new drug entity and new drug formulations for existing
drugs,determination of influence of expients ,patient related factors &
possible interactions with other drugs , control of quality of drugs and
comparison of same drug produced by different manufacturers
In India, CENTRAL DRUGS STANDARD CONTROL ORGANISATION(CDSCO)
provides the "Guidelines for bioavailability and boiequivalence studies"
mentioned in 'Schedule Y 'and as per the "Drugs and Cosmetic Rules (II nd
Ammendment ) 2005", all bioequivalent studies should be conducted
according to those guidelines.
BIOEQUIVALENCE STUDY NOC FOR DRUGS APPROVED WITHIN ONE
YEAR:
Indias Central Drugs Standard Control Organization (CDSCO) needs a certain
list of documents that are required to apply for conducting bioequivalence
studies.
The list of the requirements in terms of documents to be submitted for grant
of permission to conduct Bioequivalence studies for export of drugs
approved within one year are:

Application in Form-44 duly signed, by the competent authority with

name and designation.

A challan of 25,000 rupees /- as per Drugs & Cosmetic Rules.

Undertaking by the Principal Investigator (PI) as per appendix VII of

schedule Y of Drugs and Cosmetic Rules.

A copy of the approval granted to the BE study centre by CDSCO.

Sponsors Authorization letter duly signed by the competent authority

on their letterhead.

The study protocols.

Clinical study data and published report of pharmacokinetic and

pharmacodynamic study carried out in healthy volunteers/patients

data published in reputed journals.

Package literature on the international product.

Complete Certificate of Analysis of same batches (both test &

reference formulations) to be used in the BE study.

In the case of multiple dose BE study adequate supporting safety data

should be submitted.

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.

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.

BIOEQUIVALENCE STUDY NOC FOR MODIFIED RELEASE

PRODUCTS:
The list of the requirements in terms of documents to be submitted for grant
of permission to conduct Bioequivalence studies for export of modified
release products are:

Application in Form-44 duly signed, by the Authorized signatory with

details of name and designation.

A Challan (TR 6) of 15000/- as per Drugs & Cosmetic Rules (Medical

and Public Health Account: 0210) for approved in India or if not
approved in India ,a challan of Rs. 25000/-.

Undertaking by the Principal Investigator (PI) in original duly signed on

a company letterhead as per appendix VII of Schedule Y of Drugs and
Cosmetic Rules.

Regulatory status of the Drug in India.

BA/BE Centre approval copy issued by DCG(I), New Delhi, along with
details of number of beds provided at the centre (CRO) including ICU
beds for effective handling of SAEs in emergency situations.

Sponsors Authorization letter duly signed by the Authorized Signatory

on company letterhead.

The study protocols, Informed Consent Form (ICF) or Patient

Information Sheet (PIS) along with audio-visual recording system as per
Schedule Y guidelines; & copy of approval of protocol from the IEC, if
available.

Copy of registration of Independent/Institutional Ethics Committee

(IEC) under Rule-122DD from the Office of Drugs Controller General
(India), New Delhi.

The study synopsis

Undertaking letter from the sponsor stating that you will provide
complete medical care as well as compensation for the injury or Death
and statement to this effect should be incorporated in the Informed
Consent Form further in case of such injuries or Deaths the details of
compensation provided should be intimated to this Directorate as per
Rule 122 DAB of D&C Act 1940 & Rules there under.

Chemical and Pharmaceutical data including stability data.

Certificate of Analysis (COA) of representative batches (both Test &

Reference formulations) to be used in the BE study along with
dissolution profile in case Oral Solid dosage forms.

For Multiple dose BE study adequate supporting safety data & PK/PD
data should be submitted covering the duration of period for which the
study has to be conducted. If Regulatory Guidance is available provide
a copy of the same.

For all Injectable, the sub-acute toxicity should be submitted on the

Test product of the sponsor, studied in at least two species for
minimum 14 days.

For conducting BE studies with reference to Cytotoxic drugs, Hormonal

preparations, Narcotic and Psychotropic substances etc in Healthy
Human subjects a Scientific justification with special emphasis on
Safety of subjects with a proper Risk Mitigation Strategy should be
submitted.

For conducting BE studies with reference to Cytotoxic drugs, Hormonal

preparations, Narcotic and Psychotropic substances etc in Patients a
Scientific justification with special emphasis on Safety with a proper
Risk Mitigation Strategy should be submitted.

Report of any study related deaths during last 3 years.

Address details of the IEC Location and study site location.

CONCLUSION:
The concept of Bioequivalence has been adopted by pharmactical
industries and national regultory boards all over the world for over two
decades.There have been continuous efforts for developing efficient
approaches to access bioequivalence of various dosage
forms.Bioequivalence approaches have been adopted by India long ago
and there has been growing significance.
REFERENCES:
1.NEWS ARTICLE :
Bibliography:
Clarifications on Bioequivalence (BE) study requirements in India (2009)
Available at: http://www.pacificbridgemedical.com/newsbrief/clarifications-on-bioequivalence-be-study-requirements-in-india/
(Accessed: 9 January 2017).
In-line Citation: (Clarifications on Bioequivalence (BE) study requirements
in India, 2009).
2.WEBSITE:
Bibliography:
CDSCO (2014) Available at:
http://www.cdsco.nic.in/writereaddata/BABE_Prescreening%20checklist
%202014.pdf (Accessed: 9 January 2017).
In-line Citation: (CDSCO, 2014)
3.WEBSITE:
Bibliography:
CDSCO (2014) Available at: http://www.cdsco.nic.in/writereaddata/BABE
%20website%202014%20revised%20document%20required.pdf
(Accessed: 9 January 2017).
In-line Citation: (CDSCO, 2014)
4.BOOK:
Bibliography:

Niazi, S.K. (2014) Handbook of Bioequivalence testing, Second edition.

Available at: https://books.google.co.in/books?
id=jpPaBAAAQBAJ&pg=PA463&dq=bioequivalent+studies+india&hl=en&s
a=X&ved=0ahUKEwjHgfmF_7PRAhUELI8KHW23BJ0Q6AEILjAA#v=onepage
&q=bioequivalent%20studies%20india&f=false (Accessed: 9 January
2017).
In-line Citation: (Niazi, 2014)