Bioequivalence Studies Submission; a Regulatory Perspective
Transcript of Bioequivalence Studies Submission; a Regulatory Perspective
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Bioequivalence Studies Submission;
a Regulatory Perspective
By Dr. Rana M.Tahir
Human Medicines Registration
Directorate
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Overview of National Medicines and Poisons Board
Laws and guidance of Bioequivalence
Common BE Studies Deficiencies
Future Plans
OUTLINES
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2008 NMPB seceded from The General Directory of Pharmacy NMPB Department - Registration - Control (inspection) - Q.C Lab - Planning and research
Overview of National Medicines and Poisons Board (NMPB)
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2009 NMPB was created by law consolidated by many regulations to achieve its goals: -Assurance of Medicines quality, safety and efficacy -Assurance of Medical Devices conformity -Assurance of cosmetics safety
Overview of National Medicines and Poisons Board (NMPB)
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2009
Human Medicines Registration Committee (HMRC)
approved list of BE Centers (CROs) based on GCC and
WHOPQ.
Since then, Registration files can only be a provide if BE
study was done at accredited CRO.
Laws and guidance of Bioequivalence
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2009
• BE studies used to be evaluated by internal assessors from the HMRC.
• Each study used to be evaluated by one assessor and the decision on that study is solely dependent on his/her opinion.
Laws and guidance of Bioequivalence
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2010
First comprehensive bioequivalence products list.
The list describes the type of BE required of each medicinal
product, based on:
- US FDA
- European Medicines Agency (EMEA)
- WHO.
Laws and guidance of Bioequivalence
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2011
First BE technical committee.
The main outcomes of the committee:
• Any application will not be received unless the company at
least committed to submit BE study later
• National medicines are only required to submit in-vitro
dissolution comparative studies.
Laws and guidance of Bioequivalence
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2011
First BE technical committee.
The main outcomes of the Committee:
Propose new criteria for CRO accreditation:
• Provide Certified copies of GCP and GLP certificates
• Provide inspection reports from health authorities.
Laws and guidance of Bioequivalence
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2011
First BE technical committee.
The main outcomes of the Committee:
• First NMPB BE draft guidelines (based on GCC and EMEA
guidelines.
Laws and guidance of Bioequivalence
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Reference Product Selection
ICH Innovator product available
from Sudan market
ICH Innovator product available from GCC market
ICH, WHO or Local Any reference (Innovator Brand) is
acceptable
Study Population & Sample Size
18y or older Min. no.= 12
18-50 age, Min. no. = 24 18 may be accepted if
justified
18-50 age, Min. no. = 24
18-50 age, No minimum number
Highly Variable Drugs
Cmax 80-125 %, 69.84 – 143.19% for
replicate
Cmax 80-125 %, 75-133% for replicate
designs
Cmax 80-125 %, 75-133% for replicate
designs
RSABE: Partial or Full replicated
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Fasting or Fed
IR: Fasting MRP: Fast & Fed. If IR is affected by
food, only Fed
IR: Fasting MRP: Fast & Fed
IR: Fasting MRP: Fast & Fed. If IR is affected by
food, only Fed
IR: Fasting MRP: Fast & Fed
If IR is affected by food, only Fed
Comparative Dissolution
All strengths are compared against
bio-batch, except for higher strength(s)
All strengths are compared against
bio-batch, except for higher strength(s)
All strengths are compared against
respective reference strengths
All strengths are compared against
bio-batch, except for higher strength(s)
Bcs-Classification & Bio-waiver
Class 1 Class III
Only Class I Case-By-Case Class 1 Class III
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2014
Adoption of Harmonised Arab Guidelines on Bioequivalence of
Generic Pharmaceutical Products.
Laws and guidance of Bioequivalence
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2015
• Dedicating a group/team of trained reviewers for this purpose.
• Using a standard procedure for evaluation and a report that include all the major points to be considered).
• Decisions made are based on discussion of the reports in group meetings.
Laws and guidance of Bioequivalence
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Common BE Studies Deficiencies
• GLP or GCP / inspection report not provided
• Not including information of the batches.
• Type and size of the bio-batch are not according to the guideline.
• Including the zero time point in the calculation of similarity factor (f2) and points beyond 85% dissolution.
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• Not providing certificates of analysis for test and reference products in the submitted bioequivalence
• Inappropriate selection of calibration curve range and/or QC samples.
• Not submitting chromatograms study.
Common BE Studies Deficiencies
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Future Plans
1. Diversifying the team’s expertise in terms of Pharmacodynamic and clinical trials
2. Enabling the team to carry out CRO inspections in accordance to a set standard of excellence
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Have a Nice Day
☺