INTRODUCTION:

The Marketing authorization (MA) is a process of reviewing and assessing the dossier to support the medicinal product in view of its marketing which is also called licensing, registration, etc. It is finalized by granting offer document called Marketing Authorization Application (MAA). This process is performed within a legislative framework which defines the requirements necessary for application to the competent regulatory authority. The details on the assessment procedure which will be based on quality, efficacy and safety criteria and the grounds for approval or rejection of application, and also the circumstances where a marketing authorization already granted may be withdrawn, suspended or revoked.¹

BRIC COUNTRIES:

The acronym BRICS was initially formulated by economist of Jim O’neill, of Goldman Sachs. In 2006, the four countries started a regular informal diplomatic coordination with annual meetings of foreign ministers at the margins of regular debate of the UN general assembly. Originally the first four were grouped as BRIC. Brazil, Russia, India and China were the four initial countries and then the induction of South Africa in 2010.

The Bric members are all leading developing or newly industrialized countries. Since its insumption, the Brics have expanded its activities in 2 main streams of work.

· Coordination in meetings and international organization.

· The development of an agenda for multi sectorial cooperation within its members. The Brics nation since 2009 have met annually at formal summits. Five nations conduct their bilateral relations on the basis of equality, mutual benefit, non-interference. While brics has received both critism and praise. Intra brics cooperation has also been gaining density. A broad agenda has been developed compromising areas such as health, education, finance, agriculture, economy and trade, science and technology, corporate, combating transnational crime and academic dialogue and security among others. The fortalza summit launched a new cycle for brics. Brazil will follow up on initiative aiming at increasing existing cooperation. Its success can be judged by the desire of Turkey, Argentina, Indonesia with several other emerging economics taking it with full membership of Brics.²

GENERIC DRUG:

A Generic drug means a drug which is not branded but similar to a branded drug of its performance, administration and dosage. The Generic drug is bioequivalent with the branded drug which has same active ingredient but may contain different inactive ingredients (texture, smell and taste). A Generic drug should not be compared with counterfeit medicines which are illegally manufactured. A Generic drug can be marketed after the patent of the brand name drug has been expired. A Generic drug are safe as a branded name drug, the FDA first approves it.³

METHODOLOGY:

Selection of study parameters in terms of: As of BRICS countries the generic drug registration is a sequential process that consists of four parameters which are selected for the understanding and studying of the regulatory requirements.

Part- I:

The requirements for filling an application: The generic drug registration which should be done in local language of the countries application in which needed registration of generic drug.

Part-II:

The Documents and study materials which are required for submission: The most important parts of any kind of regulatory submission should collect the information about the extent of information and data.

A) Legal documents: free sale certificate should be notarized, the letter of authorization, GMP certificate, certificate of pharmaceutical product.

B) Pharmaceutical information: The normative documents contain the main pharmaceutical information of the BRICS countries dossier it should be filed in local language only.

C) Bioequivalence study information: Literature studies should be added.

Part-III:

Dossier compilation and submission: Certain paths from the original documents need to be filed in local language or translated to local language as per country regulatory requirements. The documents should be notarized after translation.

Part-IV:

Bioavailability and bioequivalence study information: While conducting bioequivalence study it should be done according to their regulatory legislation of the country which contains various differences like the fasting and fed condition, statistical application, study population, the study pattern of the BRICS countries for bioeqvalent studies.

DISCUSSION OF VARIOUS REGULATORY REQUIREMENTS:

BRAZIL: (ANVISA) Agencia Nacional de Vigilancia Sanitaria:

Brazilian health regulatory agencies which is in Portuguese is one of the regulatory body of Brazilian government which was created by Fernando henrick Cardoso in 1999 during his term of presidential office which is responsible for the regulation and approval of branded drugs. It is worth highlighting the following stake holders in this process. The sector and in charge of delivering service and safe products; the legislative body should act based on qualified technical information, the national congress. The society which should be increased aware of health risk and able to consume the services and evaluate the products.

DRUG PRODUCT REGISTRATION:

GENERIC MEDICINE:

A drug similar to the pharmaceutical drug which has a same active ingredient which is generally produced after the patent protection expiration or wavier its quality, safety and efficacy being proven and designated by common Brazilian denomination or failing by the common international denomination.

· For registering drug product one has to be requested by the local office of the foreign company or its agent distributors.

· The product is valid for five years after registration which can also be renewed continuously by the same period.

· According to the law, within 180 days the registration process will be completed.

· ANVISA will access the documentation for registration, alteration or revaluation. The decision will be issued through publication of the federal government organization (DOU).

· The assessment of the documentation can be done its taken under the legal conditions and periods which are in Brazilian sanitary legislation.

· According to the documentation stipulated in resolution RDC n 185/01, in order to request an alteration for to registration of the medicinal product, the manufacturer or importer should at least submit these documentation completed, together with other documents required for the original registration of the product whose information has to be modified drug registration requirement.^3,4

POST-REGISTRATION MEASURES:

After publication of the registration, the generic medicine manufacturer must supply ANVISA with:

1. The first three batches manufactured must be submitted as a proof of submission, then if it wishes samples are collected for control analysis.

2. According to the timetable approved by ANVISA, the results of evaluation of long duration stability studies of first three batches must be produced. But the stability studies of registered medicines will not confirm the description of stability studies, then a fresh stability studies must be produced.

3. If there is any incidence of adverse reaction and therapeutic inefficacy, reports must be produced.

4. After registration of generic medicine in DOU, within 1 year the manufacturer has to produce the evidence of initiating the sales of the medicine by producing the duplicate copy of three sales bill to ANVISA, for updating of generic medicines sold in market according to specific legislation available at pharmacies an drug store.

5. Official laborites are excluded from producing the bill of sales, but they must produce the proof of production and distribution of medicines.⁴

REGISTRATION REQUIREMENTS:

· Technical information of Active pharmaceutical ingredient.

· Pharmacokinetic and Pharmacodynamics.

· Quality control analysis of raw materials used in manufacturing.

· Quality control analysis of finished products.

· All the documents must be submitted in hard copy signed on last page and the technician responsible for the company must sign on every page. A copy of technical reports must be produced to ANVISA.

· For the launched of product locally, methodology must be transferred.⁴

RUSSIA: (ROSZDRAVNADZOR):

(Federal Service on Healthcare and Social Development Supervision)⁸

The ministry of health care and social development (ministry of health) and subordinated to it falls under the Russian federal government, the federal services on healthcare and social development supervision (federal health service or roszdravnadzor). The ministry of health amends state regulation and issues an administrative healthcare regulation according to the preparation, quality and distribution of pharmaceutical products. The control and supervisory functions of this process is performed by the federal health service. The federal health service has a primary responsibility for registration of medicinal products and coordinating the activities within the department.

The federal regulation in the production and distribution of pharmaceutical products is done by

· State registration of pharmaceutical products

· Activities related to distribution of pharmaceutical products is licensed by federal health service.

· Certification of Activities related to pharmaceutical product development and distribution and expert review are performed by federal health service.

· Production, preparation, quality, safety and effectiveness of pharmaceutical products are controlled by federal health services.

· State regulation of pharmaceutical pricing^4,5

REGISTRATION OF ORIGINAL AND GENERIC PHARMACEUTICAL PRODUCT–STAGES Registration process conditionally can be divided into 3 basic stages:

Stage I:

Submission of completed registration dossier in Russian to the national center of pharmaceutical product expertise (FGU).

Stage II:

Expertise the quality, safety and efficacy of pharmaceutical product to the national center of pharmaceutical product expertise (FGU).

Stage III:

For issuing of registration certificate, the dossier has to be completed and submitted to roszdravnadzor.¹³

The following information must be presented in the Russian language:

Manufacturer details:

· Trademark

· Net weight

· Composition

· Nutritional value

· Storage conditions

· Expiry date

· Documents in which products are identified.¹⁴

INDIA: Central Drug Standard Control Organization (CDSCO)

DRUG REGULATORY AUTHORITY^{7, 8}

The drug and cosmetic act founded in 1940 is governed by both central and state government. The central government governs the approval of new drugs, clinical trials, quality of imported drugs and expert advice whereas the state government controls the regulation of manufacture, sale and distribution. Some specialized drugs like blood products, IV fluids, vaccines and sera are licensed by Drug controller general of India. (16)

GENERIC DRUG REGISTRATION REQUIREMENTS:

Dossier is the document submitted for registration to central drug standard control organization. India started to follows the international acceptance format of ICH M4 Common Technical Document (CTD) for completion of registration file from November 2010. It consist of

· General information of the drug.

· CTD summaries.

· Quality reports

· Non clinical studies reports.⁸

CHINA: State Food and Drug Administration (SFDA)

DRUG REGULATORY AUTHORITY:¹¹

The government of china in march 1998 declared that the ministry of health department of drug administration will be joining with the state pharmaceutical administration of china (SPAC) that will be called the state drug administration (SDA). Therefore, SDA maintains all the drug manufacturing, trade and registration.

SFDA:

As of 2003 the SDA was reformed to become the state food and drug administration and the other pharma functions that of the ministry has been assigned to various government bodies. The ministry of labour and social security has been assigned with the responsible of medical insurance. An important step brought in action by the Chinese government was single drug regulatory authority. Western and TCM medications as well as advertising is taken care by SFDA.

GENERIC DRUG REGISTRATION REQUIREMENTS¹¹

It consists of five modules:

· Information of administration

· CTD summaries

· Quality reports

· Non clinical study report

· Clinical study reports

RESULTS AND DISCUSSION:

· The relation being critical with emerging BRICS healthcare climate and pharmaceutical market and the strategies that are best to enhance their growth in every emerging markets.

· The generic shares that has been increased to over 70% and still improving. while in developed countries, the pharmaceuticals CAGR has been declined. The manufacturers in need to drive or maintain profit margins will be seeking new opportunities elsewhere.

· The development of upcoming markets has brought us to a new trend particularly in BRICS countries. The rise in demand plays a particular part in middle class emerges.

· Brazilian government gives incentives for the registration of new generic drugs and discounts the registration fee for generic drugs. This leads to a drawback of short evaluation time for generic and similar products.

· Lifetime validity–Russian government has declared new technical regulation in 2007 that lead to the lifetime validity of registration certificate.

· The drug registration process is simplified in India and requirements of bioavailability and bioequivalence is different from other countries.

· To enhance the drug safety in china the SFDA amended measures on the administration of drug registration. The amended measures results in the improving registration procedures which is done by upgrading drug appraisal and approval standards and tighter supervision during the process of application which is done for both product and on production.

· In 2017, South Africa regulatory authority – MCC has been changed to South Africa health products regulatory authority (SAHPRA). This results in faster commercialization and increased returns on investments.

· The language barrier and understanding of regulation is the primary challenge in registration of generic drug in BRICS countries.

· In Brazil, Russia and china total registration format should be in respective local language and this becomes more difficult in administrative work for foreign manufacturers.

CONCLUSION:

The basic purpose of this study was to compare generic drug registration process between countries and to outline the differences in procedures. Brazil, Russia, India, China and South Africa are typically rendered as "the BRICS" or "the BRICS economies". Moreover India china and south Africa follows the CTD format procedures, the registration process for brazil and Russia is different. It is concluded that the world pharmaceutical economy, there is increase in growth in marketing economies of BRICS countries are on increasing growth and still more increasing in direct foreign investments by creating more opportunities for pharmaceutical companies in world market. In brazil, Russia and china total registration format should be in respective local language and this becomes more difficult in administrative work for foreign manufacturers. It takes more time to understand the rules and regulations for registration process for new generic drugs. Harmonization is the only way in decreasing the differences of procedures. The information provided above is satisfactorily translated from different languages like Portuguese, Russian and Chinese and compiled in a sequence as a part of my dissertation work.

REFERENCE:

1. Marketing Authorization Available from: http://en.wikipedia.org/ wiki/Marketing authorization

2. Brazilian National Health Vigilance Sanitaria Available from:

3. http://www.ghtf.org/meetings/conferences/9thconference/presentations/latinamerican/waynebrodbeskow.pdf

4. National Health Surveillance Agency: http://www.anvisa.gov. br/hotsite/genericos/legis/ leis/6360_e.htm

5. National Health Surveillance Agency: Resolution no nº 3.675 http://www.anvisa.gov.br/eng/legis/resol/136_03_ redc_e. htm

6. National Health Surveillance Agency: http://www. puntofocal.gov.ar/notific otros_miem bros/bra226_t.pdf

7. National Health Surveillance Agency Legislation Resolution- RE nº 478http://www.silvademoraes.com.br/site_ingles/jurisprudence/ food_drugs_itens.html Drug Registration and Labelling in Brazil: http://www.princeton. edu/~ota/ disk1/ 1993/9321/ 932111.PDF

8. Russian federation [Online]: Available from: www.roszdravnadzor.ru.

9. Registration of Pharmaceutical Products in Russia: http://pharmareg.ru/upload/ReportAChorichFran kfurt.pdf

10. Drug regulatory requirements in Russia [Online]: www.pharmabiz. com/article/detnews.asp

11. G. Sai Hanuja, B. Sai Kumari, M. V. Nagabhushanam, D. Nagarjuna Reddy, Brahmaiah Bonthagarala, Regulatory Requirements for Registration of Generic Drugs in “BRICS” Countries, International Journal of Pharmaceutical Science and Health Care, ISSN 2249 – 5738, Issue 6, Vol. 6, November-December 2016,20-40.

12. B. Sai Kumari, G. Sai Hanuja, M.V. Nagabhushanam, D. Nagarjuna Reddy, 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, Issue 6 volume 6, November-December 2016, 144-157. 15.Shaik Salman Basha, S. M. Shakeel, M. V. Nagabhushanam, D. Nagarjuna Reddy, Brahmaiah Bonthagarala, The Assessment of Current Regulatory Guidelines for Biosimilars- A Global Scenario, World Journal of Pharmaceutical Research, ISSN 2277– 7105, volume 6, Issue 1, 351-369.

13. S.M. Shakeel, Shaik Salman Basha, M.V. Nagabhushanam, D. Nagarjuna Reddy, 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, Issue 6,Vol. 6 , November-December 2016, 1-19.

14. Mounica N.V.N., Sharmila Reddy V, Anusha S, Evangeline L, Nagabhushanam M.V., Nagarjunareddy D, Brahmaiah B, Scale up and Post Approval Changes (SUPAC) Guidance for Industry: A Regulatory Note, ISSN: 2321 – 6794, DOI:https://doi.org/10. 22270/ijdra.v5i1.192, International Journal of Drug Regulatory Affairs; 2017, 5(1), 13-19.

15. Sharmila Reddy V, Mounica N.V.N., Anusha S, Evangeline L, Nagabhushanam M.V., Nagarjunareddy D, Brahmaiah B, Regulatory Requirements of Similar Biologics for Marketing Authorization in India, ISSN: 2321–6794, DOI:https://doi.org /10.22270/ijdra.v5i1.193, International Journal of Drug Regulatory Affairs; 2017, 5(1), 20-24.

Received on 16.09.2018 Modified on 18.10.2018

Research J. Pharm. and Tech. 2019; 12(3): 1403-1408.

DOI: 10.5958/0974-360X.2019.00234.8