Biosimilars and Generics Russia

Biosimilars and Generics: Russia

18-20 September, 2012 Istanbul, Turkey

Natalia Salamova, Business Development Manager

Vladimir Chistyakov, Medical Writer

• Biosimilars vs./and generics: general notions

• Market interest for biosimilars and generics

Generics • Generics: facts and figures • Generics: regulatory

environment • Generics: challenges

• OCT experience • Documents submission • Perspectives

Content

Biosimilars • Biosimilars: facts and figures • Biosimilars: regulatory issues • Biosimilars: challenges

Patented medicinal products

Source: IMS Health

• Generic drugs Drugs having the same active pharmaceutical

substance (or a combination of substances) in the same administration form as the original patented medicinal product and entering the market after the originator product

• Biosimilars Immunobiological medicinal products – drugs

of biological origin aimed at immunological diagnostics, prophylactics, treatment of diseases

Generics vs. Biosimilars: definitions (Russia)

Generics • Mostly small molecules • Produced by means of

chemical synthesis • Essentially similar medicinal

product • Easily reproduced

• Abbreviated pre-clinical

studies • Standardized study designs for

clinical development • Standardized bio-analytical

part

Generics vs Biosimilars

Biosimilars • Large complex molecules • Produced by living organisms

• Similar biological medicinal

product • Manufacturing production

sensitive • Extensive pre-clinical studies

profile • Sophisticated design for

clinical development • More complex bioanalytical

part

• Efficient pharmacoeconomic parameters

• Higher availability for patients

• New opportunities for companies

Generics: advantages

• 2nd quarter of 2012: > 250 clinical trials approved • Bioequivalence studies: > 100 (≈ 40%)

Generics: general statistics (Russia)

Source: Orange Paper

• Federal Law No. 61 On Medicinal Products Circulation as of April 12, 2010

• Guidelines on Bioequivalence Assessment of Medicinal Products as of 2008

• GOST R 52379-2005 “Good clinical practice”

• ICH-GCP Guidelines

Generics: regulatory basis

• A minimum of 18 healthy volunteers aged 18-45

• Cross-over design (mostly) • Usually under fasting conditions • Wash-out period – minimum 6 T ½

• Active substance concentration assessment within 4 T ½

• Active substance concentration assessed in whole blood, plasma, serum

• Equivalence margins for Cmax are 0.75 – 1.33 • In case of psychoactive, anti-tumor, HIV

drugs, and highly toxic drugs – studies in patients

General provisions (I)

Objects of b/e studies – medicinal drugs aimed for administration: - orally (tablets, capsules, suspensions, etc.) - by skin application, - rectally and vaginally providing that its efficacy is mediated by the appearance of the

active substance in the systematic blood circulation. BE studies are not conducted for medicinal products designed

for: - inhalation, - injection, - infusion, - oral solution, - eye drops, - drugs of topical action.

General provisions (II)

Regulatory pathway (I)

Ministry of Healthcare of the Russian Federation (Import/Export)

Documents from CRO

Ministry of Healthcare of the Russian Federation

Federal State Budget Institution “Scientific Centre for Evaluation of Medicinal Products”

Local Ecs Ethics Council within the Ministry of Healthcare of the Russian Federation

60 days CT

approval

30 days

• Pre-clinical studies for the generic product (comparative acute, sub-acute toxicity). Literature data are not applicable

• Lack of commercial phase I units • Lack of GLP laboratories

• Import of investigational product

substance for pre-clinical studies and for method validation

Generics: issues to consider

Part II: Biosimilars in Russia Vladimir Chistyakov

Biosimilars in Russia: facts

• Currently, the legislation in Russia does not contain a definition for biosimilar drugs

• There are no official documents in Russia describing regulatory requirements for the quality, non-clinical and clinical studies for biosimilars

But:

• Biosimilar and biobetter drugs are under development in Russia

• A number of clinical studies with biosimilar drugs have been approved by the Russian Ministry of Health

Examples of approved clinical trials in Russia with biosimilars (2011-2012)

• Rituximab: • TL011 (Teva) • CT-P10 (Celltrion) • GP2013 (Hexal AG) • Rituximab (Biocad)

• Filgrastim: • Tevagrastim (Teva) • MK-4214 (Merck) • EP2006 (Sandoz)

• Avastin: • BCD-02 (Biocad)

Source: http://www.grls.rosminzdrav.ru/

Non-clinical development of biosimilars

In vitro studies • Characterization of the chemical

structure of the biosimilar drug • Comparative studies of

pharmacodynamic effects

In vivo studies • Comparative studies of efficacy • Comparative safety and toxicology

studies in animals

Source: http://www.grls.rosminzdrav.ru/

Clinical development of biosimilars

A study to show comparable pharmacokinetics and pharmacodynamic (PD) effects of the biosimilar drug and originator product, points to consider:

• Study population: patients vs. healthy volunteers

• PK parameters of interest • Availability of relevant PD markers • Number of study subjects • Overall cost of the study including

comparator drug cost

Clinical development of biosimilars (II)

• A study to show comparable safety and efficacy of biosimilar drug and originator product:

• “If dose comparative and highly sensitive PD studies cannot be performed convincingly showing comparability in a clinically relevant manner, similar clinical efficacy between the similar and the reference product should be demonstrated in adequately powered, randomised, parallel group comparative clinical trial(s), preferably double-blind, normally equivalence trials.”

• Consulting

• Medical writing

• Feasibility assessment

• Project management

• Regulatory support

• Clinical monitoring

• CRA training

Services provided by OCT

• Logistics support

• Quality assurance, Audits

• Purchase of concomitant

medication

• Data management

• Statistics

• Safety Management

Contact

Russia HEADQUARTERS: 8/2 Bolshaya Moskovskaya Str., Suite 4-1 St.Petersburg, 191002, Russia

MOSCOW OFFICE: Gamsonovsky per. 2, building 2, Suite 77-82, Moscow 115191, Russia USA BD Office 845 Third Avenue, 6th Floor New York, NY 10022, US Ukraine 34 Lesi Ukrainki Str., Suite 219 PO box 50, 01601, Kiev, Ukraine

Bulgaria Sofia, district Triaditza, 53, Tzarigradsko Shosse, Blvd., bl. 2, floor 1, Apt. 4 The Baltic States Bauskas str. 33-4 Riga, LV-1004, Latvia Belarus Severny per. 13/2, Suite 3 Minsk, 220036, Belarus

Thank you for your time and interest!

Contact OCT: info@oct-clinicaltrials.com

Qualified clinical Investigators with experience in ICH-GCP compliant industry-driven study

www.oct-clinicaltrials.com