Critical and Comparative Analysis of Marketing Authorization Procedures in

Developing Countries & Developed Countries

Submitted to:

College Mentor: Corporate Mentor:

Dr. Shibu John Mr. Srikant B

Head of Department Senior Manager (RA)

Jamia Hamdard TherDose Pharma Pvt Ltd.

• TherDose Pharma Private Ltd., is a Research and Development company established in December 2003 at Hyderabad, India.

• Build with a vision of creating technology and therapeutic research based speciality pharmaceutical company, with core expertise in the area of dosage form design and development

History

• TherDose Pharma Private Limited, a company incorporated as 100% Export Oriented Unit incorporated in the year 2003.

• Founded by Dr. Nagesh Palepu, a US-Indian Citizen with Dr. Bulusu B Teja, Managing Director.

• SciDose is US based company co-founded by Dr. Nagesh and Joseph Bohan, in the year 2006.

• TherDose became subsidiary for SciDose in the year 2008.

• TherDose was initially a dedicated R&D Company and entered into manufacturing, only, in the year 2012.

Products

Our Distribution Network

ObjectivesBroad Objective

• To understand about international marketing in the pharmaceutical sector, on how a manufacturer can start marketing its medicines in various countries.

Specific Objectives

• To study about the procedures of Marketing Authorization in developing and developed countries.

• To study on how a pharmaceutical company can start marketing of medicines in various countries by following the guidelines and protocols set up by their health regulatory body.

Research Methodology

Research Design• An observational study was done in TherDose Pharma Pvt Ltd, Hyderabad to

study the marketing authorization procedures in developing and developed countries.

• The main purpose of the study was to scrutinize the approvals which are necessary to market a drug in different countries. The approval must be granted so as to market a drug as well as to sell drugs. Without the knowledge of marketing authorization procedure, marketing cannot be followed.

Cont..Data Collection• Data collection was done in TherDose Pharma Pvt Ltd, Hyderabad in

the time period of June-July, 2015.

• Secondary data was studied and compiled. Journals, marketing & RA research reports, dossiers of different countries and websites were referred.

• Also, documents & certificates like IND form #44, WHO GMP certificate, MAA of Kenya, MAA of Moldova and MAA of Philippines was also studied to obtain necessary data for the study.

Cont..Research Tools

• Mostly secondary data was collected, studied, analysed and consolidated to form the report.

• For flow charts and diagrams, Gliffy and SmartDraw softwares were used.

Method of Analysis• Qualitative analysis of the gathered information was done which was

obtained mainly through secondary data.

Marketing Authorization• Marketing Authorisation Application (MAA) is an application submitted by a drug

manufacturer to the regulatory bodies, seeking permission to bring a developed medicinal product to the market.

• Marketing authorization applications can be classified broadly in three groups, which comprise applications for:

1. Products containing new chemical or biological active pharmaceutical ingredients (APIs);

2. Multisource pharmaceutical products (generic products);

3. Variations to existing marketing authorizations.

What does MAA consist of?

• MAA is a comprehensive dossier of information and data describing all aspects (Administrative/Quality/Safety/Efficacy) of a medicinal product demonstrating that it is appropriate for use in patients.

• There is an internationally agreed standard for the overall content and format for this dossier which is referred to as the Common Technical Document (CTD).

ICH• ICH produces guidelines on data

requirements for MA of new chemical entities and biologicals for use in the member regions of ICH.

• ICH has developed over 50 harmonised guidelines aiming at eliminating duplication in the development and registration process, so that a single set of studies can be generated to demonstrate the quality, safety and efficacy of a new medicinal product.

Certificate of Pharmaceutical Product (CPP/COPP)

• A CPP is a certificate issued by the national health authorities upon request from either the manufacturer, the customer or the authorities in the importing country.

• The certificate is issued for a specific product and states whether or not the product is marketed in the country of origin.

• Furthermore, it states that the manufacturer of the product complies with GMP and that they are inspected regularly by the national health authorities.

CDSCO (Central Drug Standard Control

Organization)• CDSCO is the national regulatory body for Indian pharmaceuticals

and medical devices, and serves parallel function to the European Medicines Agency (EMA) of the European Union, the Pharmaceutical and Medical Devices Agency (PDMA) of Japan and the Food and Drug Administration (FDA) of the United States.

• Within the CDSCO, the Drug Controller General of India (DCGI) regulates pharmaceutical and medical devices.

Variation in MA• After a product has been authorized for marketing, the manufacturer

will often wish to make changes (variations) for a number of reasons. The two common areas for change are

1. pharmaceutical aspects of the product (quality control, manufacturing, shelf-life, etc.) or

2. Product information (post marketing findings)

MA in Developed Countries

• Developing countries comes under the Regulatory Market. The following countries are known as Regulatory Market.

1. EU2. USA3. Canada4. Japan

• All these developed countries follow ICH guidelines while marketing and as well as in creating dossier.

MA Procedure in EU• The EMA and the authorisation procedure

In 1993 the European Medicines Agency (EMA) was founded with the primary task of providing scientific advice of the highest possible quality to the Community Institutions on all matters relating to medicinal products for human and veterinary use.

• EMA's main task is to co-ordinate the scientific evaluation of the safety, efficacy and quality of medicinal products which undergo either procedure.

• The European system offers three routes for the authorisation of medicinal products:1. The Centralised procedure2. The Decentralized procedure3. The Mutual Recognition procedure

The Centralised Procedure

The Decentralized Procedure

The Mutual Recognition procedure

MA Procedure in USA• The regulatory body is USFDA.• MAA is accomplished in two

phases:1. Clinical Trials2. NDA

• Takes about 180 days to grant MAA approval.

MA Procedure in Canada

In Canada, the MA comes under NDS i.e. New Drug Submission

Takes about 210 days to approve MAA.

MA Procedure in JAPAN• Pharmaceutical and Medical

Devices Agency (PMDA)

• The PMDA provides consultation concerning clinical trials of new drugs and conducts approval reviews of a NDA as well as for ANDA

• Takes about 180 days to approve MAA.

MA in Developing Countries• The countries who follow ICH guidelines are also known as Regulatory

Countries while countries that do not follow ICH guidelines are known as ROW market.

• ROW market is further divided into the following markets:

1. LATAM (Latin America)

2. ASEAN (Association of South East Asian Nations)

3. Africa

4. CIS (Commonwealth of Independent States)

5. India

Overview of ICH – CTD and ACTD

Dossier ICH – CTD ACTD

Administrative Documents & Product Information

Module 1 Part I

CTD Overview and Summaries

Module 2 Incorporated in part II

Quality Documents

Module 3 Part II

Non-Clinical Documents

Module 4 Part III

Clinical Documents

Module 5 Part IV

MA Procedure in LATAM Countries

BRAZIL

• The federal regulatory agency responsible for pharmaceutical product registration in Brazil is ANVISA (Agência Nacional de Vigilância Sanitária/National Sanitary Vigilance agency), which was established in 1999.• Takes about 180 days to approve MAA.

Application Submission

Pre-filling Screening

Review

Review by ANVISA

Regulatory Decision by

ANVISA

Approval

MA Procedure in ASEAN COUNTRIES

 Association of South–East Asian Nations (ASEAN) follows ASEAN – CTD (ACTD). ASEAN is a geo-political and economic organization of ten countries located in Southeast Asia as shown in Figure.

MA Procedure in Philippines

Application Submission

Application Screening by FDA

Application Evaluation

Decision by FDA

Approval/Rejection

COUNTRY REGULATORY BODY TIME LINE FEESSingapore HAS (Health Sciences

Authority)90-240 working days 2,750 USD

Malaysia NPCB (National Pharmaceutical Control Bureau)

80-210 working days 670 USD (1 API) &920 USD (2 or more API)

Philippines FDA 6 months 300 USD (Branded) &220 USD (Generic)

Myanmar FDA 1 year 400 USD

Thailand TFDA (Thailand Food and Drug Administration)

70-110 working days 65 USD

Cambodia Department of Drugs & Food

1 year 300 USD (1 API) &500 USD (2 or more API)

Indonesia NADFC (National Agency for Drug and Food Control)

100-150 working days 650 USD

Vietnam MOH (Ministry Of Health) 1 year 210 USD

MA Procedure in CIS Countries

The Commonwealth of Independent States (CIS) is a regional organisation whose participating countries are former Soviet Republics, formed during the breakup of the Soviet Union.

At its conception it consisted of 12 former Soviet Republics: Armenia, Belarus, Kazakhstan, Kyrgyzstan, Moldova, Russia, Tajikistan, Turkmenistan, Ukraine, and Uzbekistan, Azerbaijan, Georgia.

MA in Russia

• The regulatory processes in CIS countries are led and supervised by Regulatory Agency, Roszdravnadzor closely collaborating with or operating within the respective Ministries of Health.

• Takes about 120 days to approve MAA.

• MA procedure has three stages.

MA in MOLDOVA• Marketing authorization procedure in Moldova is same as in

Russia. The regulatory body in Moldova is AM (Agentia Medicamentului), rest all the procedures are same.

• Takes about 160 days to approve MAA.

MA Procedure in IndiaNDA in India• The NDA registration (using form # 44 along with full pre-clinical and

clinical testing information) is applied after the completion of clinical trials.

• The information regarding the prescription, samples and testing protocols, product monograph, labels, and cartons must also be submitted.

• Takes about 160 days to approve MAA.

NDA Approval Process

Conclusion• The Pharmaceutical market based on the diversity in the regulation region and

marketing interest can be divided into two groups: Regulatory and ROW markets.

• The regulated market involves those countries where there are defined regulatory requirements set by the regulatory bodies of that country and the emerging market countries are those who still lag behind in putting forward the well-defined regulations for drugs.

• The drug approval process comprised mainly the two steps:1. application to conduct clinical trial and 2. application to the regulatory authority for marketing authorization of drug.

Cont• As every country has its own Drug Regulatory Authorities, which is

responsible to enforce the rules and regulations and issue the guidelines to regulate the marketing of a drug.

• Therefore, it is very difficult, especially for the companies with global approach to develop one single regulatory approach for a Marketing Authorization Application (MAA) for a new drug on the basis of one dossier submitted simultaneously to different countries in the world.

Country Regulatory body Time for Regulatory Approval of

CTA/IND Application

Time for Evaluation of MAA

MAA Fee

EU EMA 120 day 210 days $192,400USA USFDA 30 days 180 days $217,787Canada Health Canada 35 days 210 days £254100

Japan PMDA 80 days 160-180 days 11000HKD

Brazil ANVISA 90 days 180 days 37'000 BRL

Russia Roszdravnadzor 30-40 days 120 days $50,000

Moldova AM 30-40 days 160 days $45,000

India CDSCO 30 days 150 days 50,000 INR

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mid .

WHO GMP Certificate OF TherDose Pharma

MAA OF KENYA

MAA OF MOLDOVA

MAA OF PHILIPPINES

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