Regulatory Guidance on Bioavailability and Bioequivalence Studies
Bioequivalence Studies Submission; a Regulatory Perspective
Transcript of Bioequivalence Studies Submission; a Regulatory Perspective
Bioequivalence Studies Submission;
a Regulatory Perspective
By Dr. Rana M.Tahir
Human Medicines Registration
Directorate
Overview of National Medicines and Poisons Board
Laws and guidance of Bioequivalence
Common BE Studies Deficiencies
Future Plans
OUTLINES
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)
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)
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
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
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
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
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
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
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
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
2014
Adoption of Harmonised Arab Guidelines on Bioequivalence of
Generic Pharmaceutical Products.
Laws and guidance of Bioequivalence
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
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.
• 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
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
Have a Nice Day
☺