Jun 2017 Jun 2017 Vol.04 Ed.04Vol.04 Ed.04 The Quarterly Newsletter from the Corporate of Aurous HealthCare The Quarterly Newsletter from the Corporate of Aurous HealthCare The Quarterly Newsletter from the Corporate of Aurous HealthCare --- CRO…CRO…CRO…

http://auroushealthcare.wordpress.com/drhttp://auroushealthcare.wordpress.com/dr--vtvt--sriraam/ sriraam/

D r . V T . S r i r a a m M B B S M D D r . V T . S r i r a a m M B B S M D

(Pharmacology) is the founder(Pharmacology) is the founder –– director director

of Aurous HealthCare of Aurous HealthCare -- CRO.CRO.

An alumni of Stanley Medical College, he was An alumni of Stanley Medical College, he was

honored as “The Best Doctor” by the Ministry of honored as “The Best Doctor” by the Ministry of

Health, Maldives at the age of 23. Health, Maldives at the age of 23.

Gaining rich and varied experience at top CRO, Gaining rich and varied experience at top CRO,

Dr. VT. Sriraam founded Aurous HealthCare in Dr. VT. Sriraam founded Aurous HealthCare in

2008. An astute medical entrepreneur, his sharp 2008. An astute medical entrepreneur, his sharp

business sense combined with his rich knowledge business sense combined with his rich knowledge

and experience in the field of clinical research and experience in the field of clinical research

has pushed Aurous HealthCare from strength to has pushed Aurous HealthCare from strength to

strength. strength.

Dr.Sriraam has been recognized with Dr.Sriraam has been recognized with

NATIONAL AWARD NATIONAL AWARD -- “Indian Leadership “Indian Leadership

Award for Healthcare Excellence”, Award for Healthcare Excellence”, for for

his contributions in the field of medical his contributions in the field of medical

researchresearch

A man with strengths so varied and unique, A man with strengths so varied and unique,

Dr.VT.Sriraam is the epitome of the Dr.VT.Sriraam is the epitome of the

entrepreneurial combination of business brains entrepreneurial combination of business brains

and clinicaland clinical--research creatives.research creatives.

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From the Desk of MD…From the Desk of MD… Dear Colleagues and Friends,Dear Colleagues and Friends,

The Clinical Research Special Edition.The Clinical Research Special Edition. Every field has its nuances and experts. A decade ago, the field of clinical Every field has its nuances and experts. A decade ago, the field of clinical research was looked upon either as “gross human experiments” or just plain research was looked upon either as “gross human experiments” or just plain expenses.expenses.

Today, CDSCO along with other Drug Regulatory of the World insists on Today, CDSCO along with other Drug Regulatory of the World insists on Clinical Trials to prove the safety and efficacy of an investigational product, Clinical Trials to prove the safety and efficacy of an investigational product, before marketing.before marketing.

Apart from ethics, there are various dimensions, rules, mandates and Apart from ethics, there are various dimensions, rules, mandates and guidelines that one has to keep in mind even while designing a clinical trial.guidelines that one has to keep in mind even while designing a clinical trial.

The objective of every clinical trial designed byThe objective of every clinical trial designed by Aurous HealthCare CRO Aurous HealthCare CRO is not just to validate the safety and efficacy of the product, but also work is not just to validate the safety and efficacy of the product, but also work towards understanding compliance, patient feedback and observations to the towards understanding compliance, patient feedback and observations to the client to aid them with comprehensive product placement and effective client to aid them with comprehensive product placement and effective marketing.marketing.

Visit AuroBlog & click on category Visit AuroBlog & click on category -- “Learn Clinical Research” “Learn Clinical Research” for the basics of Clinical Research and terminologies.for the basics of Clinical Research and terminologies.

With best regards,With best regards,

Dr. VT.Sriraam MBBS MD (Pharmacology)Dr. VT.Sriraam MBBS MD (Pharmacology) Managing Director | Medical DirectorManaging Director | Medical Director

Aurous HealthCare CROAurous HealthCare CRO

Inside…Inside… BA BA -- BE Clinical Trials..BE Clinical Trials.. ..................Page 4..................Page 4

Schedules in D&C Act..........Schedules in D&C Act.......... ............Page 5............Page 5

Intent to Treat Analysis in Trials....Intent to Treat Analysis in Trials....Page 6Page 6

How do companies benefit from investing How do companies benefit from investing

in Clinical Trials???.......................in Clinical Trials???.......................Page 7Page 7

AurouSAurouSpeakpeak in your INBOX !!!in your INBOX !!!

Send a test mail and receive quarterly Send a test mail and receive quarterly

updates on Clinical Trials & Drug Research updates on Clinical Trials & Drug Research

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Drugs and Cosmetics ActDrugs and Cosmetics Act

The Drugs and Cosmetics Act, 1940 is an Act

of the Parliament of India which regulates

the import, manufacture and distribution of

drugs in India. The primary objective of the

act is to ensure that the drugs and cosmetics

sold in India are safe, effective and conform

to state quality standards.

This act was originally known as the Drug

Act and was passed in 1940. The original act

was prepared in accordance to the

recommendations of the Chopra Committee

formed in 1930. The related Drugs Rules was passed in 1945. Since

1940, the act has undergone several amendments and is now known

as the Drugs and Cosmetics Act, 1940

Amendments in Drugs and Cosmetics Act that impact clinical

research (As amended up to 2016)

An Act to regulate the import, manufacture, distribution and sale

of drugs, Cosmetics and medical devices, to ensure their safety,

efficacy, quality and conduct of clinical trials and for matters

connected therewith or incidental thereto”

Definitions such as Ayurvedic, Siddha or Unani drug,

bioavailability study, bioequivalence study, Board, Central Drugs

Laboratory, Central Licensing Authority, clinical trial in respec-

tive drugs, cosmetics, medical devices etc.

No clinical trial is to be conducted without taking permission

from Central Licensing Authority in such form and manner as

may be prescribed.

Whether the injury or death of a person in the

course of a clinical trial, has been caused due to such clinical

trial or not, shall be determined by such authority and in such

manner as may be prescribed

Where a participant is injured or disabled in a clinical trial, the

person or body permitted under section 4A and the sponsor shall

provide such medical treatment and compensation in such man-

ner as may be prescribed

Where death of a participant is caused due to the

clinical trial, the person or a body permitted under section 4A

and the sponsor shall provide to his legal heir, such compensa-

tion ,in such manner as may be prescribed.

The Drugs Control Officer or any other officer authorised by the

Central Licensing Authority shall have the power to enter with or

without prior notice into any premises related to clinical trial to

inspect the facilities, record, data, documents, books, drugs in-

cluding investigational new drugs, notified category of medical

devices and cosmetics.

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ASSESSING BIOEQUIVALASSESSING BIOEQUIVALENCE & BIOAVAILABILITY OF GENERIC DRUGS ENCE & BIOAVAILABILITY OF GENERIC DRUGS ……

Bioavailability studies are intended to measure the rate and extent

to which an active drug ingredient or therapeutic moiety is absorbed

from a drug product and becomes available at the site of action.

Bioavailability is usually assessed by determining the area under the

plasma concentration–time curve or total amount excreted in the urine

after drug administration.

AUC is directly proportional to the total amount of unchanged drug that

reaches systemic circulation. Drug products are generally considered

bioequivalent in extent and rate of absorption if their plasma concentra-

tion curves are essentially super imposable.

Plasma drug concentration increases with extent of absorption and the maximum (peak) plasma concentration is reached

when drug elimination rate equals absorption rate. Bioavailability determinations based on the peak plasma concentration

can be misleading because drug elimination begins as soon as the drug enters the bloodstream. Peak time is the most widely

used general index of absorption rate; slower the absorption, later the peak time.

AUC is inversely proportional to the clearance of the drug. That is, the higher the clearance, the less time the drug spends in

the systemic circulation and the faster the decline in the plasma drug concentration. Therefore, in such situations, the body

exposure to the drug and the area under the concentration-time curve are smaller.

For drugs excreted primarily unchanged in urine, bioavailability can be estimated by measuring the total amount of drug

excreted after a single dose.

Ideally, urine is collected over a period of 7 to 10 elimination half-lives for complete urinary recovery of the absorbed drug.

After multiple dosing, bioavailability may be estimated by measuring unchanged drug recovered from urine over a 24-h pe-

riod under steady-state conditions.

Bioequivalence Studies

If two medicines are bioequivalent there is no clinically

significant difference in their bioavailability. Although

bioequivalence is most commonly discussed in relation to

generic medicines, it is important to note that

bioequivalence studies are also performed for innovator medi-

cines in some situations such as:

Between early and late clinical trial formulations or

between the formulations used in clinical trials and the product

to be marketed for new medicines.

When changes in formulation have occurred after an

innovator product has been approved, for example a change in one or more excipients (inactive ingredients).

Bioequivalence is determined based on the relative bioavailability of the innovator medicine versus the generic medicine. It is

measured by comparing the ratio of the pharmacokinetic variables for the innovator versus the generic medicine.

The acceptance criteria are such that to be classified as bioequivalent, plasma concentrations of the generic medicine will

not differ significantly compared with the innovator medicine.

Studies have demonstrated that actual differences between observed mean plasma concentrations of generic and innovator

medicines were no greater than 5%.

In order to determine that two medicines are bioequivalent there must be no more than a 20% difference between the

AUC and C max. This is based on international consensus that differences less than this are not clinically significant. In order

to establish this, the AUC and C max for the generic medicine are compared to that for the innovator medicine.

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SCHEDULES IN DRUGS ASCHEDULES IN DRUGS AND COSMETICS ACT...ND COSMETICS ACT...

Schedule A: Forms and applications

Schedule B: Fees for test or analysis by the Central Drugs Laboratories or State Drugs Laboratories

Schedule C: Biological and Special Products

Schedule C(1): Other Special Products

Schedule D: Class of Drugs: Extent and conditions of exemption

Schedule E: Omitted

Schedule E(1): List of Poisonous Substances under the Ayurvedic (including Siddha) and Unani Systems of Medicine

Schedule F: Omitted

Schedule F(II): Standards for Surgical Dressings

Schedule F(III): Standards for umbilical Tapes Schedule FF: Standards for Ophthalmic Preparations

Schedule H: Prescription Drugs

Schedule I: Omitted

Schedule J: Disease and ailment (by whatever name described ) which a drug not purport to prevent or cure.

Schedule K: Class of drug: Extent and conditions of exemption

Schedule L1 : Good Laboratory Practice

Schedule M: Good manufacturing practices and requirements of premises, plant and equipment for Pharmaceutica

Schedule M-I:

1. Requirements of factory premises for manufacture of homoeopathic preparations.

2. Requirements of plants and equipments.

Schedule M-II: Requirements of factory premises for manufacture of cosmetic.

Schedule M-III: Requirements of factory premises for manufacture of medical devices.

Schedule N: List of Minimum Equipment for the Efficient Running of a Pharmacy

Schedule O: Standard for Disinfectant Fluids

Schedule P: Life Period of Drugs

Schedule P1 : Pack Sizes of Drugs

Schedule Q: List of Dyes, colours and Pigments permitted to be used in Cosmetics and Soaps as given under IS : 470 BIS

Schedule R: Standards for condoms made of rubber latex intended for single use and other mechanical contraceptives

Schedule S: Standard for cosmetics.

Schedule T: Good manufacturing practices for Ayurvedic, Siddha and all Unani medicines.

Schedule U:

I – Particulars to be shown in the manufacturing records.

II – Records of Raw Materials.

III – Particulars to be recorded in the analytical records.

Schedule U(I):

I – Particulars to be shown in manufacturing records.

II – Records of Raw Material.

Schedule V: Standards for patent or proprietary medicines.

Schedule W: Omitted

Schedule X: Narcotic Drugs & Psychotropic Substances

Schedule Y: Requirements and guidelines for permission to import and/or manufacture New Chemical

Entities (the schedule that gives you complete information regarding guidelines and processes for Clini-

cal Trials and Functioning of Ethics Committees.

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INTENT TO TREAT ANALINTENT TO TREAT ANALYSIS IN CLINICAL TRIALS ...YSIS IN CLINICAL TRIALS ...

Determining the sample of participants to

be analysed is a crucial step in reporting

clinical trials. For such analyses, the gold

standard is the “intention-to-treat”

principle.

Intention-to-treat analysis is a comparison

of the treatment groups that includes all

patients as originally allocated after

randomization. This is the recommended

method in superiority trials to avoid any

bias.

Advantages:

Retains balance in prognostic factors arising from the original random treatment allocation

Gives an unbiased estimate of treatment effect

Admits non-compliance and protocol deviations, thus reflecting a real clinical situation Requirements for an ideal ITT analysis

Full compliance with randomised treatment

No missing responses

Follow-up on all participants Limitations

Estimate of treatment effect is generally conservative because of dilution due to non-compliance

In equivalence trials (attempting to prove that two treatments do not differ by more than a certain amount), this analysis will favour equality of treatments

Interpretation becomes difficult if a large proportion of participants cross over to opposite treatment arms

Full application of intention to treat is possible only when complete outcome data are available for all randomised subjects

Application of ITT Analysis in clinical trials:

About half of all published reports of randomised controlled trials stated that intention to treat was used, but handling of deviations from randomised allocation varied widely.

Many trials had some missing data on the primary outcome variable, and methods used to deal with this were generally inadequate, potentially leading to bias.

Intention to treat analyses are often inadequately described and inadequately applied.

Universal Ethics Committee: Universal Ethics Committee: The Ethics Committee Division of The Ethics Committee Division of Aurous HealthCare Aurous HealthCare -- CRO…CRO…

Universal Ethics Committee (UEC), is a unit of Aurous HealthCare (CRO) that is registered

with CDSCO-DCGI holding registration number ECR/125/Indt/TN/2013 ECR/125/Indt/TN/2013 & OHRP (Office of

Human Rights Protection, Unites States) - IRB00008683. UEC has been serving the Clinical

Research fraternity since 2012 by providing guidance for conduct and ethical clearance for clinical

trial projects. Equipped with a GCP and Schedule Y compliant Expert member team, UEC contributes to the conduct of

justified human (clinical) trials. We also review and approve Post Marketing Surveillance studies...We also review and approve Post Marketing Surveillance studies...

Contact : sriraamvt@gmail.com; universalethicscommittee@gmail.com; or via +91Contact : sriraamvt@gmail.com; universalethicscommittee@gmail.com; or via +91--98409091559840909155

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HOW DO COMPANIES BENHOW DO COMPANIES BENEFIT FROM DOING CLINICAL TRIALS ???EFIT FROM DOING CLINICAL TRIALS ???

AUROUS HEALTHCARE RESEARCH AND DEVELOPMENT INDIA PRIVATE LIMITED

(Formerly Auroville HealthCare R & D India Pvt Ltd.)

#180/109, G1&G2, RR Villa, Rangarajapuram Main Road, Kodambakkam, Chennai-600024.

Phone: +91-44 23720600, +91-44 32472446 • Mobile: +91 9840909155 Fax: +91-4423720600

aurous.cro@outlook.com md@auroushealthcare.com mdahcwins@gmail.com

www.auroushealthcare.com

THE PIONEER THE PIONEER CONTRACT RESEARCH ORCONTRACT RESEARCH ORGANISATION (CRO) GANISATION (CRO) WITH FOCUS ON CLINICAL RESEARCHWITH FOCUS ON CLINICAL RESEARCH

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