COMPARATIVE STUDIES FOR FILING AND MARKETING …

www.wjpps.com │ Vol 9, Issue 11, 2020. │ ISO 9001:2015 Certified Journal │

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Ramakrishna et al. World Journal of Pharmacy and Pharmaceutical Sciences

COMPARATIVE STUDIES FOR FILING AND MARKETING

AUTHORIZATION OF GENERICS IN EUROPE, UNITED STATES &

INDIA

G. Ramakrishna*, M. Bhavya Shalini, Brahmaiah Bonthagarala, M. V.

Nagabhushanam and Y. Ratna Sindhu

Department of Pharmaceutical Regulatory Affairs, Hindu College of Pharmacy, Amaravathi

Road, Guntur-522002, A.P., India.

ABSTRACT

The main aim of the topic to review and compare the generic drug

filing process and different aspects of approval between United States

Food and Drug Administration (USFDA), European Medical Agency

(EMA), and DCGI Drug Controller General Of India approval„s for

Marketing Authorization of a drug in US & Europe and India, and their

role in improving the standard laid down by them. The goal of the

approval process is to provide enough information about the drug

which should show safety and efficacy in human beings. ANDA is a

regulatory submission for marketing authorization of generic version

of drugs in United States. Marketing authorization application (MAA)

is the relevant regulatory submission procedure to be followed in the

Europe to market a drug. In India Marketing authorization application

for generic drugs is the regulatory submission procedure laid down by Drug Controller

General of India (DCGI). The Common Technical Document is a common format. A set of

specifications for application dossier, for registration of medicines and designed to be used

across Europe, United State and India. Quality, Safety and Efficacy information is assembled

in a common format through CTD.

KEYWORDS: USFDA, API, DCGI, MAA, EMEA.

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 7.632

Volume 9, Issue 11, 1091-1102 Review Article ISSN 2278 – 4357

*Corresponding Author

Prof. G. Ramakrishna

Department of

Pharmaceutical Regulatory

Affairs, Hindu College of

Pharmacy, Amaravathi

Road, Guntur-522002, A.P.,

India.

Article Received on

13 Sept. 2020,

Revised on 03 October 2020,

Accepted on 23 October 2020

DOI: 10.20959/wjpps202011-17676


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1. INTRODUCTION

Generic Drug market is a vast and cost effective market for all the developing pharmaceutical

companies. Hence, the following topic was selected based on the current scenario of generic

drug market and regulations involved for generic manufacturing as well as marketing. Hence,

the purpose of this work is to gather information about various technical document

requirements and also study of various procedures involved in the generic drug filing process,

approval and marketing.[1-3]

Generic drug are usually cheaper than the innovatory drug because of the following reasons:

1. No cost of identification and isolation of New Chemical Entity (NCE),

2. No cost of research and development,

3. Minimum marketing cost because branded drugs is already approved as safe and

effective.

A generic drug is simply a copy if innovator / brand name drug and is bioequivalent to a

brand name drug with respect to pharmacokinetic and pharmacodyanmic properties. Branded

drug play an important role in medications, but generic are their cost effective alternatives. A

generic drug is identical or bioequivalent to a branded name drug in.

Dosage form,

Safety,

Strength,

Route of Administration,

Quality,

Performance characteristics and

Intended use.

Role of regulatory authorities[3,4]

The United States of America & Europe are two main regulatory agencies in the world. US is

a single country but EU is a union of countries. The regulatory requirements of various

countries of the worlds vary from each other. The role of the regulatory authorities is to

ensure the quality, safety, and efficacy of all medicines in circulation in their country.

The International Council for Harmonization of Technical Requirements for Pharmaceutical

for Human Use (ICH) is unique in bringing together the regulatory authorities &

pharmaceutical industry to discus scientific and scientific aspects of drug registration. ICH„s


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mission is to achieve greater harmonization worldwide to ensure that safe, effective, and high

quality medicines are developed and registered in the most resource-efficient manner.

Regulatory agencies of different countries[5,6,7]

USA

Centers for Disease Control and Prevention

Department of Health and Human Services (DHHS)

The Food and Drug Administration (FDA)

National Center for Complementary and Alternative Medicines (NCCAM)

National Institutes of Health (NIH)

National Library OF Medicine

National Science Foundation

Office of Disease Prevention

Europe

EU Legislation – Eudralex

European Directorate for the Quality of Medicines and Healthcare (EDQM)

European Medicines Agency (EMEA)

Heads of Medicines Agencies (HMA)

INDIA

Central Drug Standard Control Organization (CDSCO)

Government of India Directorate of Health and Family Welfare

Indian Council of Medical Research (ICMR)

Ministry of Health and Family Welfare.

CTD

The Common Technical Documents (CTD) is a set of specification for application dossier for

the registration of Medicines and designed to be used across Europe, Japan and the United

States.

It is an internationally agreed format for the preparation of application regarding new drugs

intended to be submitted to regional regulatory authorities in participating countries. CTD is

maintained by the International Conference on Harmonization of Technical Requirements for

Registration of Pharmaceutical for Human Use (ICH).


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2. Filing & Marketing authorization of generic drugs in europe, united States & India

2.1. Marketing authorization of generics in europe[8-12]

European Medical Agency (EMA)

EMA is the regulatory agency / decentralized body its mainly responsible in the protection

and promotion of public and animal health, through the evaluation and supervision of

medicines for human and veterinary use. The EU has one of the most highly regarded

regulatory systems in the world.[8]

EU consists of 27 member states

Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland, France,

Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxemburg, Malta,

Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, and the United

Kingdom and three countries which are member of European Free Trade Agreement (EFTA)

Iceland, Norway, and Liechtenstein.

EU establishes 4 different drug approval processes

Centralized Procedure

Decentralization Procedure

National Procedure

Mutual Recognition Procedure

All medicines must be authorized before they can be marketed and made available to

patients.

In Europe Union (EU), there are two main routes for authorized medicines:

A centralized route

A national route.


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Fig. 1: Marketing authorization procedures in european union (EU).

According to European Generic Medicines Association (EGA), the marketing authorization

for a pharmaceutical product in more than one country in the European Union must currently

be applied for through one of two procedures:

Centralized Procedure”

“Mutual Recognition Procedure” (MRP).

“Decentralized Procedure,” came into force with the newly revised EU pharmaceutical

Directive in November 2005

National procedure

Decentralized procedure[9,10]

The 'centralised procedure' for authorising medicinal products is laid down in Regulation

(EC) No726/2004. The centralised procedure, which is compulsory for products derived from

biotechnology, for orphan medicinal products (Fees Exemption will be given in this case) and

for medicinal products for human use which contain an active substance authorised in the

Community after 20 May 2004 (date of entry into force of Regulation (EC) No 726/2004)

and which are intended for the treatment of AIDS, cancer, neurodegenerative disorders or


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diabetes. The procedure is also compulsory for the products which are used as performance

enhancers or to increase yields from animals.

Pre-submission

A draft summary of product characteristics;

Eligibility

Strength

Type of application

Statement of intention to request for accelerated assessment

Statement of whether Orphan designation valid or pending

Proposed invented name

Request for total fee exemptions

Fig. 2: Process of decentralized procedure.


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National procedure[12-14]

The national procedure is like the other procedures but in this case only one member state is

involved. The documents submitted to an authority are very specific to that particular

authority and evaluation of the application is carried out by the same member state. The

evaluation time for an application for a national marketing authorization is 210 days from the

receipt of the application. But this procedure is stringently limited from 1 January 1998 to the

early phase of mutual recognition (granting of the marketing authorisation by the Reference

Member State) and to medicinal products which are not to be authorised in more than one

Member State.

Fig. 3: Process of national procedure.


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Centralized procedure

Fig. 4: Process of decentralized procedure.

2.2. Filing procedures in united states[13, 14]

Investigational new drug application (IND)

It is an application file to the FDA in order to start clinical trials in humans on the basis of the

data obtained from the preclinical trials.

New drug application (NDA)

If clinical studies confirmed that new drug is relevantly safety and effective will not pose

risk to patients, the manufacturer file a New Drug Application (NDA) in the United states.

Abbreviated new drug application (ANDA)

It‟s an application made for approval of Generic Drugs. The sponsor is not required to

reproduce the clinical studies that were done for the original, brand name product.


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Fig. 5: Process of generic drugs regitsration process in USA.

2.3. Regulatory guidelines for dossier submission in india[15,16]

The Indian pharmaceutical industry, which is the third largest globally in terms of volume.

CDSCO: A licensing authority for approval of new dug proposed to be imported

Head office located in New Delhi & functioning under the control of directorate general of

Health services, MHFW, Govt of India.

DCGI: It is Responsible for approval of new drugs & Clinical trails to be conducted in India

Appointed by Central Govt of India.

Process of filing as per CTD

The filing of a dossier in CTD format compulsory in India (or) The CTD is only a format for

submission of information to CDSCO.


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Fig. 6: The CTD Triangle.

3. SUMMARY AND CONCLUSION

Approval and authorization of drug product in United States, Europe & India are the most

crucial ones compare to other countries in the world. Various countries have different

guidelines and standard for registration and authorization of generic drugs. The primary

purpose of the rules governing medicinal products in US, Europe & India is to safeguarded

public health. It is the role of public regulations so that safe and effective medications reach

the market. Thus the above work helps the applicants in assisting them for the procedure to

be followed for marketing authorization since many regulatory authorities are involved. It

also provides a brief procedure of steps involved in applying an application to till its approval

by the authorities and the common format of filing them.

4. REFERENCES

1. N.V. Gopal, M. Nagarjuna Reddy generic drug registration process in US and Europe

American Journal of pharmacy and health research, 2014; 2(11). www.aiphr.com.

2. Singh DP. Generic Drug access in Global scenario. J. Pharm. Sci. and Res, 2010; 2: 90-8.

Journal of Pharmaceutical sciences and research, 2010; (2): (2). www.

Jspr.pharmainfo.net.

3. Journal of pharmaceutical science and bioscientific research, 2014; 4(4). www.jpsbr.org.


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4. Common technical document available at www.ich.org.

5. Hatch Waxman act.

6. http://www.fda.gov/newsevents/testimony/ucm115033.htm.

7. Paragraph filings guidance compliance regulatory process.

8. http://www.fda.gov/Drugs/DevelopmentApprovalProcess.

9. Process of filing drug application available from.

10. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugs.

11. are Developed and Approved/Approval Applications Abbrevated New Drug Application

ANDA Generics.

12. Pre-assaigned number requisition from.

13. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements

/ElectronicSubmissions/ucm114027.htm.

14. European medical agency, Guiding principles, How we work [internet], 2014; 26. from:

http://www.ema.europa.eu/ema/index.jsp?curl=pages/about_us/general/general_content_0

00125.jsp&mi d=WC0b01ac0580028a46.

15. Introduction to ICH [internet], 2014; 24. Available

from:http://www.ich.org/fileadmin/Public_Web_Site/ABOUT_ICH/Vision/Introduction_t

o_ICH.pdf.

16. Vishal Gupta, NitinKashyap U, Raghunandan H V. Comparison of Drug Approval

Process in United States and Europe. Journal of pharmaceutical science and

research[internet]. 2013; 2014, 20, 5(6): 131 – 136. Available from:

http://jpsr.pharmainfo.in/Documents/Volumes/vol5issue06/jpsr05061302.pdf

17. Sukesh Bhardwaj, Vikaas B Sukesh Bhardwaj, Vikaas Budhwar, Vipul K. Gupta.

Requirements For The Submission Of Generic Drug Application Across US And EU In

CTD/eCTD Format. AJPSR [internet]. October 2011, 2014; 1(5): 3. Available from:

http://www.ordonearresearchlibrary.com/Data/pdfs/AJPSR22.pdf.

18. Brahmaiah Bonthagarala, Current Regulatory Requirements for Registration of

Medicines, Compilation and Submission of Dossier in Australian Therapeutic Goods

Administration, International Journal of Advanced Scientific and Technical Research,

ISSN 2249-9954, 2016; 6(6): 144-157.

19. Brahmaiah Bonthagarala, Comparison of Regulatory Requirements for Generic Drugs

Dossier Submission in United States and Canada, International Journal of Pharmaceutical

Science and Health Care, ISSN 2249 – 5738, 2016; 6(6): 1-19.

http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/ucm114027.htm

http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/ucm114027.htm

http://www.ema.europa.eu/ema/index.jsp?curl=pages/about_us/general/general_content_000125.jsp&mi

http://www.ema.europa.eu/ema/index.jsp?curl=pages/about_us/general/general_content_000125.jsp&mi

http://www.ordonearresearchlibrary.com/Data/pdfs/AJPSR22.pdf


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20. Brahmaiah Bonthagarala, Current Regulatory Requirements for Registration of

Medicines, Compilation and Submission of Dossier in Australian Therapeutic Goods

Administration, International Journal of Advanced Scientific and Technical Research,

ISSN 2249-9954, 2016; 6(6): 144-157.

21. Brahmaiah Bonthagarala, Comparison of Regulatory Requirements for Generic Drugs

Dossier Submission in United States and Canada, International Journal of Pharmaceutical

Science and Health Care, ISSN 2249 – 5738, 2016; 6(6): 1-19.

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