Current Issues for Conduction of BE
Studies in Pakistan
1st Symposium on Bioequivalence and Bioavailability
Studies
15-16 April 2014, Lahore, Pakistan
Dr. Zeba Ahmed Shuja
TECHNICAL DIRECTOR
SCHAZOO ZAKA Pvt. Ltd.
Lahore, Pakistan
1
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
2
BE Study Regulatory Issues
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.
3
BE Study Regulatory Issues….
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
4
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 Institute
University of Karachi
B, University of Veterinary Animal Sciences Lahore
C, Dow University of Medical & Health Sciences Karachi
D, Faculty of Pharmacy Islamia University Bahawalpur
5
Selection and Arrangement of
Comparator Product
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.
6
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
7
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.
8
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 punctuality & no show problems
9
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
10
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
11
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.
12
BE Study Cost Issues
Estimated cost / BE study in Pakistan is Approx.
20,000 US $. Internationally up to 100,000 US $
1. Cost
of
documentation
preparation,
review
and
i.e.,
bio
aproval.
protocol
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.
13
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
14
Ethics Committee Issues….
1. Should have 5 Members at least. With prime
responsibility to verify safety, integrity & human
rights of volunteers
2. One Independent Member not linked to the Center
and one Physician required.
3. One Community nonscientific member
4. Only independent members should vote on a trial
related matter
15
Recommendations : Laws
1. Proper Law under Federal DRAP by consensus of all
stake holders Should make guidelines based on Int.
Standards to Conduct, Inspect and Approve all
Centers for performing BE studies.
2. System of getting BE Protocol approved in fast track
before start of any study for a minor fee.
3. Duty free and fast track purchase to be allowed of
Comparator
Product
from
ICH
Reference Standard from EP /USP.
countries
&
16
Recommendations : Laws
1. Encourage Centers to get ISO 17025 certification
so that a minimum quality standard of testing is
maintained. Financial subsidy or refund of cost?
2. Encourage The Pharma Industry
by giving a
reasonable timeline of 3-5 years for Compliance to
registration of Generic Drugs with authentic BE
Studies or Biowaver Dissolution Studies. Similar
criteria to be followed for registered Antibiotics and
Life saving drugs.
17
Recommendations : BE Centers
1. Staff ( Phlebotomists, Doctors, Analysts) should be
continuously
trained
to
follow
international
standards for conduction and reporting of BE
Studies. Co-operation among Centers.
2. Adequate Number of Qualified staff must be
employed & Volunteer rights must be ensured by
proper Insurance.
3. Ethics
Committee
Structure
must
be
International Standards with actual powers.
as
per
18
Recommendations :
Pharmaceutical Industry
1. High time the Pharmaceutical Industry realizes the
ethical and moral responsibility of conducting BE
studies to ensure Efficacy, safety and Quality of
Generic Drug Products in Pakistan.
2. Financial benefits of Opening doors for export of
Generic Drugs to ICH countries with highest
expenditure on Health Care.
3. All stakeholders must co-operate with each other to
achieve any success.
19
Thank You
20