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.


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.


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.


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.


2011


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.


2011


The main outcomes of the Committee:

• First NMPB BE draft guidelines (based on GCC and EMEA

guidelines.


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)




respective reference strengths



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.


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.



• 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.


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

☺

bioequivalence studies submission; a regulatory perspective

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