BIOSIMILAR DRUGS

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5 Δεκ 2012 (πριν από 4 χρόνια και 10 μήνες)

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RM SHARMA

1

BIOSIMILAR DRUGS

FOOD AND DRUGS
ADMINISTRATION
PERSPECTIVE

RM SHARMA

2

DEFINITION OF DRUGS

UNDER DRUGS AND COSMETICS ACT
1940


INCLUDES


ALL MEDICINES ,SUBSTANCES,
COMPONENTS, FOR INTERNAL OR
EXTERNAL USE



DEVICES


MEANT TO TREAT, MITIGATE OR PREVENT,
DIAGNOSE, DISEASE OR DISORDER,IN
HUMAN BEINGS AND ANIMALS

IT INCLUDES BIOSIMILAR DRUGS (BIOLOGICS)


RM SHARMA

3

BIOLOGICALS


ARE DRUGS IF THE INTENDED
-
USE IS TO TREAT CURE
MITIGATE AND DIAGNOSE DISEASE IN HUMAN BEINGS:


Biological Product


Biological products include a wide range of products such as
vaccines, blood and blood components, allergenics, somatic cells,
gene therapy, tissues, and recombinant therapeutic proteins.
Biologics can be composed of sugars, proteins, or nucleic acids or
complex combinations of these substances, or may be living entities
such as cells and tissues. Biologics are isolated from a variety of
natural sources


human, animal, or microorganism


and may be
produced by biotechnology methods and other cutting
-
edge
technologies. Gene
-
based and cellular biologics, for example, often
are at the forefront of biomedical research, and may be used to treat
a variety of medical conditions for which no other treatments are
available.

RM SHARMA

4

THERAPEUTIC BIOLOGICAL
PRODUCT


Therapeutic Biological Product


A therapeutic biological product is a
protein derived from living material (such
as cells or tissues) used to treat or cure
disease.

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THERAPEUTIC EQUIVALENCE

AS PER US FDA


Therapeutic Equivalence (TE)


Drug products classified as therapeutically equivalent can be
substituted with the full expectation that the substituted product will
produce the same clinical effect and safety profile as the prescribed
product. Drug products are considered to be therapeutically
equivalent


only

if they meet these criteria:


they are


pharmaceutical equivalents

(contain the same


active
ingredient(s)
;

dosage form

and

route of administration
;
and

strength
.)


assigns therapeutic equivalence codes based on data that a drug
sponsor submits in an
ANDA

to scientifically demonstrate that its
product is bioequivalent (i.e., performs in the same manner as the
Reference Listed Drug).

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BIOLOGIC


A

biologic

is a

medicinal

product such as a

vaccine
,

blood

or blood
component,

allergenic
,

somatic cell
,

gene
therapy
,

tissue
,

recombinant therapeutic protein
, or living cells that
are used as

therapeutics

to treat diseases.[

Biologics are created
by

biologic

processes, rather than being

chemically

synthesized.


Biologics can be composed of sugars, proteins, or nucleic acids or
complex combinations of these substances, or may be living entities
such as cells and tissues. Biologics are isolated from a variety of
natural sources


human, animal, or microorganism


and may be
produced by biotechnology methods and other technologies. Gene
-
based and cellular biologics, for example, often are at the forefront
of biomedical research, and may be used to treat a variety of
medical conditions for which no other treatments are available

RM SHARMA

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BIOSIMILAR DRUGS


With the more common

small
-
molecule

drugs, an exactly
identical

generic drug

can be reliably produced and
marketed. Because biologics are vastly more complex,
other manufacturers cannot guarantee that their version
is exactly identical to the original manufacturer's version,
although it is similar to the original biologic.

The
subsequent manufacturer may use a slightly different
manufacturing process, which can occasionally produce
significantly different effects.
The follow
-
on manufacturer
does not have access to the originator's molecular

clone
bank

and original cell bank. Finally, nearly undetectable
differences in impurities and/or breakdown products are
known to have serious health implications.

RM SHARMA

8

BIOSIMILAR DRUGS


Biosimilars

or

Follow
-
on

biologics

are terms
used to describe officially
-
approved subsequent
versions of
innovator

biopharmaceutical

products.



Biosimilars

made by a different sponsor
following patent and exclusivity expiry on the
innovator product.


Biosimilars

are also referred to as

subsequent
entry biologics (SEBs)

in Canada.Reference to
the innovator product is an integral component
of the approval.

RM SHARMA

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Ist BIOSIMILAR DRUG

OR INTERCHANGEABLE


OMNITROPE: Having similar action in
human beings as that of HUMAN
GROWTH HORMONE (2006)

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CONCEPT OF BIOSIMILAR


FOR COMPLEX MOLECULAR DRUG AN INNOVATOR
PUTS A DRUG IN MARKET AFTER PROPER
APPROVAL FOR REGULATORY AUTHORITIES:
OBVIOUSLY IT HAS A BRAND NAME IT IS
PROTECTED UNDER PATENT RIGHTS ITS
STRUCTURE MAY BE CORRECTLY KNOWN OR NOT
KNOWN


ANOTHER MANUFACTURER MAY DISCOVER
COMPLEX MOLECULE USING DIFFERENT SOURCE
OF CLONING OR PROCESS WITH STRUCTURE
KNOWN OR NOT KNOWN. THE COMLEX MOLECULE
HAS SIMILAR ACTION AS THAT OF IST INNOVATOR.


ITS BIOSIMILAR

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THE DANGER IN BIOSIMILAR


THE TWO BIOSIMILAR HAVE
DIFFERENT ORIGIN


THE TWO BIOSIMILARS MAY HAVE
SAME THERAPEUTIC EFFECT


BUT MAY HAVE DIFFERENT SIDE
EFFECT AND TOXICOLOGY


HENCE REQUIRE THOROUGH
TESTING

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DIFFERENCE FROM SIMPLE
MOLECULES OF DRUGS


CHEMICAL
STRUCTURE ARE
KNOWN AND ARE
SAME IN PATENT AND
GENERIC


GENERIC VERSION
AND INNOVATORS ONE
HAVE SAME
THERAPEUTIC EFFECT


THE SIDE EFFECTS
ARE ALSO SAME


FOLLOW UP DRUGS
ARE GENERIC


CHEMICAL
STRUCTURE AND
COMPOSITION IS MOST
LIKELY TO BE
DIFFERENT AND
UNKOWN


ALWAYS UNDER
BRAND NAME BUT
HAVE SAME
THERAPEUTIC USE


THE SIDE EFFECTS
MAY BE DEFFERENT


FOLLOW UP DRUGS
ARE NOT GENERIC

RM SHARMA

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FDA APPROACH


Legislation in the 21st century has attempted to address this by
recognizing an
intermediate ground of testing
, which is more testing
than for small
-
molecule drugs proven to be identical to each other,
but less testing than for completely new therapeutics
.


In the European Union a specially adapted approval procedure has
been authorized for certain protein drugs, termed

similar biological
medicinal products
. This procedure is based on a thorough
demonstration of "comparability" of the "similar" product to an
existing approved product.Within the U.S., the

Patient Protection
and Affordable Care Act

of 2010

created an abbreviated approval
pathway for biological products shown to be biosimilar to, or
interchangeable with, an FDA licensed reference biological
product.The acceptance of biosimilars may reduce the profitability of
biologics and the cost to the patients and healthcare systems



Introduction of biosimilars also requires a specifically
designed

pharmacovigilance

plan


RM SHARMA

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FDA CONCERN


Unlike the more common

small
-
molecule

drugs, biologics generally
exhibit high molecular complexity, and may be quite sensitive to
manufacturing process changes


The follow
-
on manufacturer does not have access to the originator's
molecular clone and original cell bank, nor to the exact fermentation
and purification process,nor to the active drug substance. They do
have access to the commercialized innovator product.


Differences in
impurities and/or breakdown

products can have
serious health implications.
This has created a concern that copies
of biologics might perform differently than the original branded
version of the product


Consequently only a few subsequent versions of biologics have
been authorized in the US through the simplified procedures allowed
for small molecule

generics
, namely Menotropins (January 1997)
and Enoxaparin (July 2010), and a further eight biologics through
the 505(b)(2) pathway

RM SHARMA

15

PROCEDURAL STATUS IN US
FDA


Genotropin, originally approved as a biologic drug under
the FD&C Act

.FDA has previously approved biologic
products using comparability, for example, Omnitrope in
May 2006, but this like Enoxaparin was also to a
reference product


On March 17, 2009, the Pathway for Biosimilars Act was
introduced in the House


FDA was given the authority to approve biosimilars
,
including interchangeable

that are substitutable with
their reference product,as part of the
Patient Protection
and Affordable Care Act on March 23, 2010



None have yet been approved under the above said Act.

RM SHARMA

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EXAMPLES OF BIOSIMILAR

BIOSIMILAR

REFERENCE
PRODUCT

SPONSOR

DT. OF
APPROVAL

Omnitrope
(somatropin; human
growth hormone

Genotropin (Pfizer,
New York
)

Sandoz

April 2006


Nivestim

(filgrastim;
G
-
CSF)

Neupogen (Amgen )

Hospira Enterprises


June 2010


TOTAL

12

RM SHARMA

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INDIAN PLAYERS IN
BIOSIMILARS


INDIA IS EXPOSED TO VAST OPPORTUNITIES IN
BIOSIMILARS


COMPETENT HOUSES ARE ALREADY MAKING
GREAT HEADWAY


GOVT HAS TO DEVELOP THE PATHWAYS FOR SAFE
ARRIVAL OF BIOSIMILARS IN INDIAN MARKET


PHARMACOVIGELLENCE IS GOING TO PLAY VERY
PROMINENT ROLE IN THE ADVENT OF BIOSIMILARS


LOT OF CAUTIONS PRECAUTIONS AND WARNINGS
WILL BE ENCOUNTERED


A RESPONSIBLE ROLE IS REQUIRED TO BE PLAYED
BY ALL AND EVERY ONE . EVERY ONE HAS TO RISE
ABOVE ALL MOTIVES TO PROVIDE SAFE
BIOSIMILARS

RM SHARMA

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IN INDIA


NEED TO STUDY THE ISSUE IN DETAIL


NEED TO ORGANISE EXPERT BODY TO TAKE UP
THE TASK


NEED TO IDENTIFY THE SUPER EXPERTS


NEED TO LISTEN FROM THE MOUTH OF HORSES


EVALUATE THE SIZE OF ACTIVITY


IDENTIFY THE INPUTS IN TERMS OF
INFRASTRUCTURE EXPERTS FACILITIES FINANCE,
LEGISLATION UNDER DRUGS AND COSMETICS
RULES


STRENGTHENING OF PHARMACOVIGILLENCE
WITH SPECIAL DESIGN AND PLAN

RM SHARMA

19

R.M.SHARMA

STATE DRUGS CONTROLLER CUM JOINT
COMMISSIONER

FOOD AND DRUGS ADMINISTERATION

HARYANA