P. K. P. K. MITRAMITRA

DEFINITION OF DRUGS UNDER DRUGS DEFINITION OF DRUGS UNDER DRUGS AND COSMETICS ACT 1940 AND COSMETICS ACT 1940

DRUGS:DRUGS:

Includes all medicines ,substances, components, for internal or Includes all medicines ,substances, components, for internal or external use.external use.

DEVICES:DEVICES:

Meant to treat, mitigate or prevent, diagnose, disease or disorder Meant to treat, mitigate or prevent, diagnose, disease or disorder in human beings and animals.in human beings and animals.

IT INCLUDES BIOSIMILAR DRUGS (BIOLOGICS)IT INCLUDES BIOSIMILAR DRUGS (BIOLOGICS)

BIOTECHNOLOGY

A standard definition of biotechnology was not reached until the United Nations and World Health Organization accepted the 1992 Convention on Biological Diversity and defined biotechnology as:

Any technological application that uses biological systems, living organisms or derivatives thereof, to make or modify products and processes for specific use.

It was during the early 20th century when the term biotechnology came into use. The term was coined in a book by Karl Ereky, a Hungarian engineer and professor who described a technology based on converting raw materials into a more useful product.

BIOPHARMACEUTICAL MEDICINE

A drug created by means of biotechnology, especially genetic engineering derived proteins and act as active pharmaceutical ingredients.

A pharmaceutical inherently biological in nature and manufactured using biotechnology and it is a medicine whose active substance is made by or derived from a living organism.

Insulin can be produced by a living organism (such as a bacterium or yeast), which has been given the gene that enables it to produce insulin.

BIOPHARMACEUTICALS ……... contdBIOPHARMACEUTICALS ……... contd

Biopharmaceuticals have revolutionized the treatment of many diseases like diabetes, malignant disorders etc., and fundamentally different from the conventional small molecule chemical drugs.

They have very large molecules with highly complex structure which is difficult to identify with currently available analytical methods, when compared to simple molecular structure of chemical drugs.

Nature of the manufacturing process - in biopharmaceutical manufacturing process defines the final product (‘process is product’) and even a minor change in manufacturing process may lead to disastrous outcomes.

The safety and efficacy profile of these biopharmaceutical products are highly dependent on the robustness and the monitoring of quality aspects.

BIOPHARMACEUTICALS - PRODUCTION

Develop host cell

Establish a cell bank

Protein production

Purification

Analysis

Formulation

Storage and handling

PROTEIN DRUGSPROTEIN DRUGS

CLASSIFICATION OF PROTEINSAccording to their biological roles

- Enzymes: Catalyses virtually all chemical reactions i.e. 6GDH

- Transport proteins i.e. Haemoglobin of erythrocytes

- Contractile or Motile proteins i.e. Actin and Myosin

- Structural proteins i.e.Collagen

- Defense proteins i.e. Immunoglobulins and Antibodies

- Regulatory proteins i.e. insulin

- Nutrient and storage proteins i.e. Ovalbumin

PEGYLATION PEGylation is the process of covalent attachment of

Poly Ethylene Glycol (PEG) polymer chains to another molecule, normally a drug or therapeutic protein.

PEGylation is routinely achieved by incubation of a reactive derivative of PEG with the target molecule.

The covalent attachment of PEG to a drug or therapeutic protein can "mask" the agent from the host's immune system and increase the hydrodynamic size of the agent which prolongs its circulatory time by reducing renal clearance.

PEGylation can also provide water solubility to hydrophobic drugs and proteins.

ADVANTAGE OF PEGYLATION

PEGylation, by increasing the molecular weight of a molecule, can impart

several significant pharmacological advantages over the unmodified

form, such as:

Improved drug solubility Reduced dosage frequency, without diminished efficacy with

potentially reduced toxicityExtended circulating life Increased drug stability Enhanced protection from proteolytic degradation

PEGylated drugs have the following commercial advantages also:

Opportunities for new delivery formats and dosing regimens Extended patent life of previously approved drugs

WHY PEGYLATED PROTEINS ?

EIGHT PEGylated proteins have been commercialized following

FDA approval:

1. ADAGEN (pegademase bovine),

2. ONCASPAR (pegaspargase),

3. NEULASTA (pegfilgrastim),

4. PEGASYS (peginterferon alfa-2a),

5. PEGINTRON (peginterferon alfa-2b),

6. MIRCERA (methoxy polyethyleneglycol-epoietin beta),

7. SOMAVERT (pegvisomart).

8. CIMZIA (certolizumab pegol ),a PEGylated recombinant humanized anti-TNFα Fab’ fragment)

PEGYLATED PROTEINSPEGYLATED PROTEINS

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

Biological ProductBiological Product

Biological products include a wide range of products such as Biological products include a wide range of products such as vaccines, blood and blood components, allergenics, somatic cells, vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins. gene therapy, tissues, and recombinant therapeutic proteins.

Biologics can be composed of sugars, proteins, or nucleic acids or Biologics can be composed of sugars, proteins, or nucleic acids or complex combinations of these substances, or may be living complex combinations of these substances, or may be living entities such as cells and tissues.entities such as cells and tissues.

BIOLOGICSBIOLOGICS

Biologics are isolated from a variety of natural sources:Biologics are isolated from a variety of natural sources:

Human, Animal, or Microorganism and may be produced Human, Animal, or Microorganism and may be produced

by biotechnology methods and other cutting-edge by biotechnology methods and other cutting-edge

technologies. technologies.

Gene-based and Cellular biologics:Gene-based and Cellular biologics:

Example - often are at the forefront of biomedical research, and Example - often are at the forefront of biomedical research, and

may be used to treat a variety of medical conditions for which no may be used to treat a variety of medical conditions for which no

other treatments are available.other treatments are available.

GENESIS OF BIOLOGICSGENESIS OF BIOLOGICS

THERAPEUTIC BIOLOGICAL PRODUCT

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

A biologic is a medicinal product such as a vaccine, blood, or blood component, allergenic, somatic cell, gene therapy, tissue, recombinant therapeutic or living cells that are used as therapeutics to treat diseases.

Biologics are created by biological processes, rather than being chemically synthesized.

THERAPEUTIC EQUIVALENCE – US FDA

Therapeutic Equivalence (TE) :

Drugs 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:

Pharmaceutical equivalents containing the same active ingredients, dosage, and route of administration, 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).

BIOSIMILARS ..… CONCEPT Biosimilars are generic version of biopharmaceutical

medicines which try to mimic products which are derived from recombinant technology.

These are near identical products which use a separate process for its bio formulation and need to pass strict mandates of regulatory bodies like US FDA and EMEA in Europe.

As these compounds need to the process of manufacture requiring fermentation and not traditional reverse chemistry it is difficult to mimic bio identical compounds.

BIOSIMILAR …… CONCEPTFor 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.

If this complex molecule has similar action as that of 1st innovator …. Its biosimilar

There are clear cut differences in the manufacture process and protein folding of biosimilars.

BIOSIMILARS …… contd

Due to the sophisticated nature of these bio-molecules and their 3-D structure its an new area of research for pharmaceutical scientists and drug regulators.

Apart from Biogenerics, a host of molecules especially have Biosimilar compounds in endocrinology namely insulin, growth hormone, PTH like peptides in India.

These need evidence based validation if they have clinically relevant effects or side effects.

BIOSIMILARS ….. contd

Approved biologic version of innovator biopharmaceutical products made by a different sponsor following patent and exclusivity expiry on the innovator product.

Ex. Etanercept (Pfizer)

Because biosimilars 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.

BIOLOGICS vs BIOSIMILARSBIOLOGICS vs BIOSIMILARSProteins produced by living cells, including

monoclonal antibodies, soluble receptors, receptor antagonists, novel molecules derived by genetic engineering and other types of proteins that can be used to treat human diseases.

Biosimilars may represent a cost-saving alternative to reference biologics.

Currently FDA has not provided details of the kind of testing required to demonstrate sufficient similarity in efficacy and safety for approval.

A similar production process does not ensure that the biosimilar is functionally equivalent to a reference biologic. Extensive human testing will be required.

BIOLOGICS vs BIOSIMILARS

Even though the FDA has been establishing standards for licensure to ensure the safety and effectiveness of biosimilars and issued a guidance in February 2012 [7], the FDA has not approved a biological product as biosimilar or interchangeable.

Several companies are developing biosimilars and will almost certainly submit applications for licensure under the new law.

It is not yet known when the first biosimilar product will be on the U.S. market.

BIOSIMILARS – GLOBAL TRACKINGOver 425 biosimilars and 350 biobetters in the development pipeline, from preclinical through marketed, plus over 350 companies involved globally.

US and EU patent and market and data exclusivity expirations have been calculated for over 100 currently-approved reference products.

India is one of the leading contributors in the world biosimilar market. India has demonstrated the greatest acceptance of biosimilars, which is reflected from over 50 biopharmaceutical brands getting marketing approval.

Indian biotechnology industry was 2.0 billion USD in 2006, 70% of which is biopharmaceuticals. These are projected to reach up to US$ 580 million by 2012.

BIOSIMILAR & BIOBETTER

biosimilars = 427; biobetters = 367; ref. products = 117 pipeline products (biosimilars + biobetters) = 788 Note, this study covers protein products, now nearly all recombinant proteins. Vaccines, blood-derived, cellular, cultured tissues and other types of biologics are not included

LAUNCH OF BIOSIMILARS & BIOBETTERSLAUNCH OF BIOSIMILARS & BIOBETTERS

Note, "2011" indicates marketable before or in 2011.

BIOSIMILARS IN THE LAUNCH PIPELINE

"N.A." columin on right refers to pipeline products for which the reference product cannot be determined (e.g., which of several interferon alfa-2 reference products a biosimilar seeks to

emulate).

US BIOSIMILARS FOR LAUNCH

CONTINENT WISE POSITIONING OF BIOSIMILARS

The number of companies in different regions. Products can have multiple companies involved.

BIOSIMILARS – TOP COMPANIES

Roche/Genentech 35

Harvest Moon Pharmaceuticals USA, Inc.

29

Novo Nordisk A/S 25

Novartis AG 25

Pfizer Inc. 20

BioXpress Therapeutics S.A. 18

Biogen Idec 18

Lilly, Eli & Co. 18

Merck KGaA 17

Merck & Co., Inc. 16

Biocon Ltd. 14

Inbiopro Solutions Pvt Ltd. 14

Green Cross Corp. 14

Baxter 14

Bio Sidus S.A. 13

LG Life Sciences Ltd. 13

Bioton S.A. 13

Sanofi S.A. 12

Bayer AG 12

Dong-A Pharmaceutical 12

Bolder BioTechnology, Inc. 12

Amega Biotech 11

AXXO GmbH 11

Teva Pharmaceutical Industries Ltd.

11

Chemo Group (Grupo Insud ) 11

BIOSIMILARS - IMPLICATIONS

Products that have been shown to be similar to the reference product in appropriate comparative, head to head quality, non-clinical and clinical studies.

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

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.

FIRST BIOSIMILARSOMNITROPE: Having similar action in human beings as that of HUMAN

GROWTH HORMONE (2006)

INFLIXIMAB:A monoclonal antibody, works by binding to (TNF-α). TNF-α

is a chemical messenger (cytokine) and a key part of the autoimmune reaction.

Acts as an anti-inflammatory and used to treat ankylosing spondylitis, Crohn’s disease, psoriatic arthritis & psoriasis, rheumatoid arthritis, ulcerative colitis.

A biosimilar of Johnson & Johnson’s blockbuster Remicade, which had sales of US$8 billion in 2010.

DANGER OF BIOSIMILARSThe two biosimilar products have different origin

The two biosimilars may have same therapeutic effect

They may have different side effect and toxicology

Hence Biosimilars require thorough testing

Similarity between a biosimilar and its reference biotherapeutic product should be evaluated in all respects (quality, safety and efficacy). 

Purported copies of biotherapeutic medicines that have not undergone head-to-head comparisons with an appropriate reference product put patient safety at risk and should not be licensed via biosimilar pathways.

BIOSIMILARS vs SIMPLE DRUGS

Chemical structures of simple drugs are known and are same in patent and generic as well.

Generic version and innovators of simple drugs the have same therapeutic effect.

The side effects are also same for both generic & innovators of simple drugs.

Follow up drugs are usually generic.

• Chemical structure and composition is most likely to be different and unknown.

• Always under brand name but have same therapeutic use.

• The side effects may be different for originator & biosimilar.

• Follow up drugs are not generic in nature.

BIOSIMILARS - FDA APPROACHLegislation in the 21st century has attempted to

address this by recognizing an intermediate ground of testing.

This 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.

BIOSIMILARS – FDA APPROACHThis 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 phamacovigillance plan.

BIOSIMILARS - FDA CONCERNUnlike 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.

Neither to the exact fermentation and purification processes,nor to the active drug substance.

They only have access to the commercialized innovator product.

BIOSIMILARS - FDA CONCERN

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

PROCEDURAL STATUS - FDAGenotropin, originally approved as a biologic drug under

the FD&C Act but now considered as reference product.

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.

BIOSIMILARS – PAN GLOBEBIOSIMILAR REFERENCE

PRODUCTSPONSOR 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

Remsima (Infliximab)

Remicade ( Merck )

Celtrion July 2011

Reditux( Rituximab )

Rituxan ( Roche /Biogen )

Dr.Reddys July 2007

Insugen (Recombinant human

insulin)

Insulin (Novonordisc)

Biocon Oct 2011

BIOSIMILAR EXCLUSIVITY

Reference Products

• 12 years market exclusivity

• No exclusivity for supplements, new indications, dosing schedules,

dosage forms, delivery systems/devices or strengths

• But, exclusivity for “modification to structure”that results in change in

safety, purity or potency

First Interchangeable Biosimilar Product

• Up to one year of being only interchangeable product

• Can be shortened if unable to launch

BIOSIMIALR – MKT PROPSECTS

BIOSIMILARS – INDIAN PLAYERS 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.

INDIA - BIOSIMILARSINDIA - BIOSIMILARSNeed to study the issue in detail

Need to organize 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 pharmaco-vigillence with special design and plan

CRESP – DR. REDDY’S BIOSIMILAR

Darbepoetin alfa is a 37 kDa glyco-protein which was developed to be a hyper-glycosylated long lasting form of recombinant human erythropoietin (rHuEPO).

Increased glycosylation results in higher sialic acid content per molecule. This is responsible for increased half-life of darbepoetin alfa when compared to rHuEPO.

Like all biopharmaceuticals, darbepoetin alfa is synthesized in living organisms by modifying their DNA using recombinant DNA technology.

CRESP - DARBEPOETINMechanism of Action: DARBEPOETIN ALFA

Stimulates erythropoiesis by binding to erythropoietin receptors (EPO-R) on hematopoietic cells.

Binding to EPO-R results in activation of the JAK-STAT signal transduction pathway.

Activation of the signal transduction pathway results in survival, differentiation, proliferation, and maturation of Red Blood Cells (RBCs).

Cresp is available in thefollowing presentations:

• Single-use vials: 25 μg/1 mL and 40 μg/1 mL

• Pre-filledsyringes:25μg/0.42mL & 40μg/0.4mL

REDITUX – DRL’s 1ST BIOSIMILAR

Rituximab is a 144 kDa chimeric mouse/human monoclonal antibody consisting of a glycosylated IgG1kappa immunoglobulin with murine light- and heavy chain variable regions (Fab) and human kappa and gamma-1 constant regions (Fc domain).

Produced by using recombinant DNA technology in Chinese Hamster Ovary (CHO) cells.

Binds to CD20 antigen which is expressed on B-lymphocytes in non-Hodgkin’s lymphoma patients.

The binding of rituximab with the CD20 antigen is the first step in the elicitation of its biological function.

It induces cell death through antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) or apoptosis pathways.

Targeted B cell therapy via an infusion of rituximab ectively depletes B cells resulting in a reduction in inflammation.

Therefore, it is also used to treat patients suffering from rheumatoid arthritis.

DR. REDDY’s BIOSIMILAR

BIOCON - BIOSIMILAR PRODUCTS

BIOCON IS THE 4TH LARGEST PRODUCER OF RECOMBINANT HUMAN INSULIN USING PROPRIETARY TECHNOLOGY.

BIOSIMILARS PRODUCT DESCRIPTION

ERIPRO Recombinant human erythropoietin

BIOMAB Bioximilar nimotuzumab (humanized mAb targeting epidermal growth factor receptor)

NUFIL Filgrastim, recombinant G-CSF

MYOKINASE Recombinant streptokinase biosimilar

INSUGEN Recombinant human insulin

INTAS - BIOSIMILARS

BIOSIMILAR PRODUCT DESCRIPTION

NEUKINE Filgrastim ( recombinant G-CSF )

NEUPEG PEGylated G-CSF

INTALFA Recombinant human interferon alpha-2b

EPOFIT Recombinant erythropoietin

The only Indian Biotech facility that has been audited and approved for GMP bythe EMEA, MCC, South Africa and RCC DR of the Middle East countries for cGMP.One of the Biosimilars developed has completed Phase 1 & 3 clinical trials in the EU.

RELIANCE LIFE SCIENCE - BIOSIMILARS

RLS was incorporated in 2001 and operates the country's largest mammalian cell culture facility. Its UK subsidiary, Reliance Gene Medix develops biosimilars for the European market. 70 % of the TOP line of the company is accounted for biosimilars.

BIOSIMILAR PRODUCT DESCRIPTION

RELIPOETIN Recombinant erythropoietin

RELIGRAST Recombinant G-CSF

RELIFERON Recombinant interferon alpha-2b

MIREL Recombinant reteplase (tissue plasminogen activator)

INDIAN BIOSIMILAR MARKET Indian biosimilar market in 2008 was estimated to be worth $200

million & expected to reach $580 million by 2012.

More than 130 companies in the biopharmaceutical market in India.

Only 7-10 companies are involved in the manufacture of recombinant products as of now.

• 48 drugs off patent within 10 yrs world wide ($ 73 billion)

Molecules in pipeline: Insulin, granulocyte colony-stimulating factor (G-CSF), Interferons, monoclonal antibodies (MAbs).

mAb is the most demanding segment for many Indian players (mAbs with a global revenues US$20 billion, the fastest-growing segment within the pharmaceutical industry).

BIOSIMILARS IN EUROPE

EMA GUIDELINES - BIOSIMILARS

BIOSIMILARS APPROVED IN EU

BIOSIMILARS IN EU : AN UPDATE

GLOBAL SITUATIONS

UNWANTED IMMUNOGENICITY

THREAT OF IMMUNOGENICITY

IMMUNOGENICITY : CLINICAL CONSEQUENCES

IMMUNOGENICITY

ANTIBODY DETECTION

IMMUNOGENICITY & DISSIMILARS

ANTIBODY FREQUENCY FOR BIOSIMILARS

ARE BIOSIMILARS REALLY BIOSIMILARS

Terms ‘Biosimilars’, ‘Similar Biological Products’ & ‘Non-Innovator Products’ etc often used interchangeably. Canbe incorrect.

Non-Innovator Products or ‘Me-too’ products usually havenot been evaluated using comprehensive comparabilitystudies. They are not biosimilars.

This can be very important from the immunogenicityviewpoint.

EU DEFINITION OF BIOSIMILAR

According to the EU, a biosimilar product is a copy of an already

authorized biological medicinal product (The Reference Product ) with

demonstrated similarity in physiochemical characteristics, efficacy and

safety, based on a comprehensive comparability exercise.

Biological medicinal products are derived from living cells or organisms

and consist of relatively large & highly complex molecular entities that

are often difficult to fully characterize by currently available analytical

methods.

Because of the inherent variability of the biological system used as

manufacturing process, the resulting biological product will also display

a certain degree of variability (micro heterogenicity)

EX: INTERFERON–BETA (IFN-β) PRODUCTS

IMMUNOGENICITY OF IFN-β-1a PRODUCTS

All innovator products are immunogenic:• Incidence of neutralizing antibodies (NAb): Avonex 2-6% (13%); Rebif 12-28% (30 -39%); Blastoferon 8%; loss of efficacy and treatment failure; abs are cross-reactive

• Removal of HSA from formulation of final product reduces immunogenicity: NAb seroprevalence for Rebif New Formulation (no HSA) of 17.4% compared to 27.3% for Rebif with HSA. Also fewer injection-site reactions.

• All non-innovator IFN-β-1a products contain HSA and are likely to be immunogenic!

BIOSIMILAR REGULATORY SCENARIO - USABIOLOGICS PRICE COMPETITION & INNOVATION ACT”(BPCIA)

BPCIA provides a clear regulatory pathway for approval of “biosimilars”

Enacted on March 23, 2010, as a part of the Patient Protection and Affordable Care Act

BPCIA establishes a biosimilar regulatory pathway under Section 351 of the Public Health Service Act (PHSA), 42 U.S.C. §262

In very general terms, BPCIA authorizes FDA to approve “biosimilars”based

on similarity to an already-approved biologic (reference product

Reliance on the safety and efficacy findings of the reference product (subject to data package protection, if applicable); and

reduced package of clinical and non-clinical safety and efficacy data for the biosimilar

BIOSIMILAR REGULATORY SCENARIO - EU

The Committee for Medicinal Products for Human Use (CHMP)guidelines concerning Biosimilars:

• Concept of Biosimilar is applicable to any biological medicinal product and more likely applied to highly purified products, which can be thoroughly characterized

• Pharmacovigilance monitoring: the specific product given to the patient should be clearly identified

• The active substance must be similar in molecular and biological terms to the active substance of the reference medicinal product

Example: IFN alpha 2a is not similar to IFN alpha 2b.

• The same reference product throughout the comparability program

BIOSIMILAR REGULATORY SCENARIO - INDIA

Pre-Clinical studies are requiredPhase I –II trials not requiredPhase III –Non inferiority trial against innovator is required

for the specific indication Regulatory Process–Drug Controller General of India. –May

involve other regulatory bodiesGenetic Engineering Approval Council (GEAC)Recombinant DNA Advisory Committee (RDAC), Review Committee on Genetic Manipulation (RCGM), Institutional Biosafety Committee (IBSC)No separate approval processNo Exclusive Guidelines; applied on a Case-to-Case by Indian Pharmacopoeia Commission (IPC) in collaboration with

National Institute of Biologicals (NIB)

BIOSIMILARS: PATENT STATUS

BIOSIMILARS: INDUSTRY GROWTH IN INDIA

INDIAN BIOSIMILAR INDUSTRY

INDIAN BIOSIMILAR PRODUCTS: CURRENT & FUTURE PIPELINES

WAY FORWARD FOR INDIAN BIOSIMILARS

THANK YOU THANK YOU

P.K. MITRAP.K. MITRA