1 Current Issues for Conduction of BE Studies in Pakistan 1 st Symposium on Bioequivalence and Bioavailability Studies 15-16 April 2014, Lahore, Pakistan.

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Current Issues for Conduction of BE Studies in Pakistan

1st Symposium on Bioequivalence and Bioavailability Studies

15-16 April 2014, Lahore, Pakistan15-16 April 2014, Lahore, Pakistan

Dr. Zeba Ahmed ShujaTECHNICAL DIRECTOR

SCHAZOO ZAKA Pvt. Ltd.Lahore, Pakistan

BE Studies Current Issues

1. BE Study Regulatory issues

2. Selection and arrangement of comparator

product and Reference Standard

3. BE Study Volunteers issues

4. BE Study Organizational issues

5. BE Study Costing issues

6. Ethics Committee issues

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1. Currently BE Studies rule not enforced at the

time of registration of Generic Drugs by Drug

Regulatory Authority Pakistan, MOH

2. No procedure in place for Contract Research

Organizations Public/Private inspection and

approvals

3. Similarly currently BE study Protocols not being

approved by MOH.

BE Study Regulatory Issues

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4. According to the drug act 1976, Section

11 point 5(g) page 37

Provincial Quality Control Board:

The following shall be the powers of the

Provincial Quality Control Board……

g) Identify and accredit on payment of fee other laboratories in the province with suitable facilities and expertise

BE Study Regulatory Issues….

BE Study Regulatory Issues….

5. Health Department Punjab has adopted BE

studies as compulsory for Bid evaluation for the

procurement of drugs/medicines for the financial

year 2014-2015? A, Center for BE Studies and Bioassay Research A, Center for BE Studies and Bioassay Research

Institute University of Karachi Institute University of Karachi

B, University of Veterinary Animal Sciences LahoreB, University of Veterinary Animal Sciences Lahore

C, Dow University of Medical & Health Sciences Karachi C, Dow University of Medical & Health Sciences Karachi

D, Faculty of Pharmacy Islamia University Bahawalpur D, Faculty of Pharmacy Islamia University Bahawalpur

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1. WHO recommended comparator product

should be used to conduct BE study from

ICH countries (EU, Japan, UK)

2. On line pharmacies not reliable: delivery

and storage condition problems

3. Government support needed in duty free

custom clearance.

Selection and Arrangement of Comparator Product

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Arrangement of Reference Standard

1. An authenticated analytical reference

standard of known identity and purity

should be purchased either from USP,

WHO & EP or from well reputable source

like Sigma etc. should be used to prepare

solutions of known concentrations

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BE Study Volunteers Issues

1. There is no proper system of volunteers

insurance.

2. Difficult to arrange 60-80 healthy volunteers

for initial screening. Women do not volunteer

in Pakistan. Generally 24 volunteers are

essential for any single cross over study

according to WHO guidelines. Studies using

12-18 volunteers are also conducted.

BE Study Volunteers Issues….

3. Difficulties in blood sampling due to lack of trained stuff

resulting in blockage of cannula during blood sampling

causing Direct sampling, Less volume sampling &

Haemolysis, leading to Volunteer discomfort

4. Problem related to volunteers next follow up visit, Time Problem related to volunteers next follow up visit, Time

punctuality & no show problemspunctuality & no show problems

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BE Study Organizational Issues

1. Lack of proper standard operating procedures i.e.,

weak documentation in case of deviation from

Protocol.

2. Lack of resource like skilled Phlebotomists /

Analysts, calibrated and qualified analytical

instruments i.e., HPLC/LCMS instrument

3. Non availability of validated bio-analytical methods.

No studies done on the stability of the analyte in

the plasma indifferent storage conditions

BE Study Organizational Issues….

4. BE center’s do not meet the international WHO

current Good Laboratory Practices, and Good

Clinical Practices requirements

5. No timeline commitment for bioanalytical method

development, bioanalytical method validation,

protocol preparation, study execution and report

preparation in the Centers

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BE Study Organizational Issues….

6. Insufficient stock of Chemicals, analytical

columns and guard columns etc.

7. Documents eg. like Case Report Form not

filled and signed on time

8. No Quality Assurance System established or

followed properly.

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Estimated cost / BE study in Pakistan is Approx.

20,000 US $. Internationally up to 100,000 US $

1.Cost of documentation i.e., bio protocol

preparation, review and aproval. Report

preparation about 2000-3000 pages

2.Cost of subject’s recruitment, complete blood

and urine testing, ECG, X-RAY, subject’s

insurance, follow up and confinement and

catering etc.

BE Study Cost Issues

BE Study Cost Issues….

3. No Tax relaxation on the purchase of comparator

product from ICH countries Reference Standard from

USP/EP, Statistical Experts Cost.

4. Cost of blood collection tubes (cryo tubes), Cost of

processing and storage, cost of support staff

(phlebotomist, doctor, pharmacist and biochemist etc.)

5. Maintenance of sensitive analytical instruments like

LCMS, HPLC ( Chemicals, columns)

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Ethics Committee Issues….

1.1. Should have 5 Members at least. With prime Should have 5 Members at least. With prime

responsibility to verify safety, integrity & responsibility to verify safety, integrity &

human rights of volunteershuman rights of volunteers

2.2. One Independent Member not linked to the One Independent Member not linked to the

Center and one Physician required.Center and one Physician required.

3.3. One Community nonscientific member One Community nonscientific member

4.4. Only independent members should vote on a Only independent members should vote on a

trial related mattertrial related matter1515

Recommendations : Laws1.1. Proper Law under Federal DRAP by consensus Proper Law under Federal DRAP by consensus

of all stake holders Should make guidelines of all stake holders Should make guidelines

based on Int. Standards to Conduct, Inspect and based on Int. Standards to Conduct, Inspect and

Approve all Centers for performing BE studies.Approve all Centers for performing BE studies.

2.2. System of getting BE Protocol approved in fast System of getting BE Protocol approved in fast

track before start of any study for a minor fee. track before start of any study for a minor fee.

3.3. Duty free and fast track purchase to be allowed Duty free and fast track purchase to be allowed

of Comparator Product from ICH countries & of Comparator Product from ICH countries &

Reference Standard from EP /USP.Reference Standard from EP /USP. 1616

Recommendations : Laws1.1. Encourage Centers to get ISO 17025 certification so that a Encourage Centers to get ISO 17025 certification so that a

minimum quality standard of testing is maintained. Financial minimum quality standard of testing is maintained. Financial

subsidy or refund of cost?subsidy or refund of cost?

2.2. Encourage The Pharma Industry by giving a reasonable timeline Encourage The Pharma Industry by giving a reasonable timeline

of 3-5 years for Compliance to registration of Generic Drugs of 3-5 years for Compliance to registration of Generic Drugs

with authentic BE Studies or Biowaver Dissolution Studies. with authentic BE Studies or Biowaver Dissolution Studies.

Similar criteria to be followed for registered Antibiotics and Life Similar criteria to be followed for registered Antibiotics and Life

saving drugs.saving drugs.

3.3. System of getting BE Protocol approved in fast track before start System of getting BE Protocol approved in fast track before start

of any study for a minor fee. of any study for a minor fee.

4.4. Duty free and fast track purchase to be allowed of Comparator Duty free and fast track purchase to be allowed of Comparator

Product from ICH countries & Reference Standard from EP /USP.Product from ICH countries & Reference Standard from EP /USP.1717

Recommendations : BE Centers1.1. Staff ( Phlebotomists, Doctors, Analysts) should Staff ( Phlebotomists, Doctors, Analysts) should

be continuously trained to follow international be continuously trained to follow international

standards for conduction and reporting of BE standards for conduction and reporting of BE

Studies. Co-operation among Centers.Studies. Co-operation among Centers.

2.2. Adequate Number of Qualified staff must be Adequate Number of Qualified staff must be

employed & Volunteer rights must be ensured employed & Volunteer rights must be ensured

by proper Insurance.by proper Insurance.

3.3. Ethics Committee Structure must be as per Ethics Committee Structure must be as per

International Standards with actual powers.International Standards with actual powers.1818

Recommendations : Pharmaceutical Industry

1.1. High time the Pharmaceutical Industry realizes High time the Pharmaceutical Industry realizes

the ethical and moral responsibility of the ethical and moral responsibility of

conducting BE studies to ensure Efficacy, safety conducting BE studies to ensure Efficacy, safety

and Quality of Generic Drug Products in Pakistan.and Quality of Generic Drug Products in Pakistan.

2.2. Financial benefits of Opening doors for export of Financial benefits of Opening doors for export of

Generic Drugs to ICH countries with highest Generic Drugs to ICH countries with highest

expenditure on Health Care. expenditure on Health Care.

3.3. All stakeholders must co-operate with each other All stakeholders must co-operate with each other

to achieve any success.to achieve any success.1919

2020

Thank YouThank You