PHR514-Pharmacy Law and Regulatory Affairs

Lecture 10

Dr Shaouki Munir
MBBS (DU), MGMP (UTS), MPH (UNSW)
 Module Contents

This module covers the following topics:

• Basics of pharmacovigilance
• Clinical development of medicines & their limitations
• Bioequivalence study: definition and importance
• Adverse Drug Reactions: definition, examples, reporting criteria
and sample form
• Biological vs chemical medicines
• Basics on biosimilar medicines & their approval process
• Interchangeability, Substitution and Switching
What is Pharmacovigilance?
Why do we need it?
Learning
from the
history…..
Limitations of clinical trials
Bioequivalence study and it’s importance

Bioequivalence studies are a special type of study where two drugs or

two sets of formulations of the same drug are compared to show that
they have nearly equal bioavailability and PK/PD parameters. These
studies are often done for generic drugs or when a formulation of a drug
is changed during development.

Bioequivalence studies are very important for developing

pharmaceutical preparation in the pharmaceutical industry. Their
rationale is the monitoring of pharmacokinetic and pharmacodynamics
parameters after the administration of tested drugs.
What is Adverse Drug Reaction (ADRs) ?

WHO’s definition of an
adverse drug reaction, which
has been in use for about 30
years, is “a response to a drug
that is noxious and
unintended and occurs at
doses normally used in man
for the prophylaxis, diagnosis
or therapy of disease, or for
modification of physiological
function."
Examples of serious ADRs
Major four criteria for a valid pharmacovigilance report
Who should report?
Adverse Drug Reactions Reporting Form
What is a biosimilar medicine?

A biosimilar is a biological medicine highly similar to another

biological medicine (reference product) already approved for
patient use.
A biosimilar is not a generic
• Only comes on the
market after the
patent of the
reference product
has Expired

• Encourages
competition which
can lead to price
reductions and
improve patient
access to high-cost
medicines
Biosimilar approval process
Manufacturers must demonstrate to regulators that biosimilars have
similar quality, safety and efficacy to the reference product and there
are no clinically meaningful differences between the two

The tailored approach which involves a comparability exercise against

the
reference product
First step: quality comparability
Second step: pre-clinical comparability
Third step: clinical comparability
Quality comparability

✓Quality testing is the cornerstone of bio-similarity

✓ A large number of physiochemical and biological tests
✓Quality comparability exercise must show biosimilar is
highly similar to reference
✓Potential impact of any (minor) quality differences on
safety and efficacy must be addressed
Pre-clinical comparability

• Pre-clinical studies are required for all new

medicines. Involves testing in cell culture and in
animals to determine safety profile before use in
humans
• For biosimilars, preclinical studies related to
mechanism of action of the medicine and could
uncover subtle differences between reference and
biosimilar
• Testing in animals may not always be necessary
Clinical comparability

• Clinical trials are designed to see if clinically

meaningful differences exist between reference and
biosimilar

• Generally includes data on pharmacokinetics,

pharmacodynamics, safety and efficacy

• Testing for immunogenicity required

 Indication extrapolation

• Clinical data may not be required for the biosimilar in all

indications
• Must be scientifically justified
• Similar approach is used to justify post-approval changes for
other biological medicines
• Approved on case by case basis
.
Traceability of biological medicines
Important definitions
Interchangeability: the medical practice of changing one medicine for
another that is expected to achieve the same clinical effect in a given
clinical setting and in any patient (prescriber is involved).

Substitution: dispensing one medicine instead of another equivalent

and interchangeable medicine at the pharmacy level without
consulting the prescriber.

Switching: decision from treating physician to exchange one medicine

for another with the same therapeutic intent in patients undergoing
treatment.