The recent developments in the life sciences sector in India is an indication of the  increasing business opportunities in this sector  and the emergence of India  as a huge market for biotechnology products. The exponential  growth of the Indian biotechnology sector has significant implications  for policy makers to establish a stringent regulatory framework.

After phenomenal success of IT sectors, India is fast emerging as an important player in the biotechnology in the Asia-Pacific Region. Rich biodiversity, R&D institutions with scientific talents, reasonable cost, IT skills and already flourishing pharmaceutical industry enabled India ranked as third largest in the Asia-Pacific region (CII-KPMG report).

Although, India’s biotechnology regulatory system has come a long way with number of changes since the Rules for the Manufacture, Use, Import, Export and Storage of Hazardous Micro-organisms/ Genetically Engineered Organisms or Cells 1989 (Rules, 1989), which were first notified under the Environment (Protection) Act, 1986, including the elaboration of a series of guidance documents published by the Department of Biotechnology (DBT) in 1990, 1998 and 1999, there is still a strong  need for a well developed legal/regulatory system by following international harmonized standards.

The DCGI is responsible for approvals of pre-clinical and clinical trials, new drug applications, and the importation of drugs from abroad for all pharmaceutical drug products including biologics. The regulatory approval procedure for biotech products (If synthesized through recombinant DNA (r-DNA) technology) is different from that for standard medicinal products.

 Products, which are not r-DNA Technology derived in nature or are not developed from genetically modified material, are treated in a similar way to standard medicines and the Drug Controller General of India (DCGI) can approve them. In the case of biological products however, additional approvals are required.

Once the proposal is made through Institutional Bio Safety Committee (IBSC), the Review Committee on Genetic Manipulation (RCGM) under the Department of Biotechnology (DBT) examines the pre-clinical data and recommends the application to the DCGI for human clinical trials on the basis of pre-clinical data. The Recombinant Drug Advisory Committee (RDAC) under the DCGI approves the protocol and recommends conducting of human clinical trials.

For marketing license, a New Drug Approval Application (Form 44 of the Drug and Cosmetics Rules, 1945) is to be filed before the DCGI. Yet another Committee, – the Genetic Engineering Approval Committee (GEAC) under the Ministry of Environment and Forest (MoEF) examines information on containment facilities and data on clinical trials in respect of Living Modified Organisms (after April 2006 a system of graded scrutiny was introduced) and accords environmental clearance. All protein and vaccine produced by recombinant technology will be regulated by these guidelines, and other relevant Acts & Rules. Proteins emanating from mono-clonals derived from rDNA technology in the form of therapeutic proteins/drugs would be treated under the biotech regulatory pathway.

Further, the State Food and Drug Control Administration approve the manufacturing license based on a GMP audit. It may be noted that all applications for approval of biological medicinal products need not be scrutinized by all the authorities mentioned above. The involvement of the authorities above depends on the type of product for which approval is sought. For Submission of Clinical Trial Application for Evaluating safety and efficacy of the biotech product the general information such as Detailed Chemistry Manufacturing and Control as per the format provided; Non-clinical data and proposed study protocol to be provided to the DCGI.

As a practice for new drugs, India currently conditions the approval of pharmaceutical products whether filed by either the pioneer or a generic competitor based on the prior approval by a Regulatory Authority in another country like the United States Food and Drug Authority (USFDA) or the European Medicines Agency (EMEA), rather than requiring submission of the entire dossier for review by the Drug Controller General of India (DCGI).

A generic applicant does not normally incur the same expense and time in generating the data and are often only required to provide evidence that their products are “bio-equivalent” to an innovator’s medicine. To gain approval, the generic version must (i) contain the same active ingredients as the innovator drug; (ii) be of the same strength, dosage form, and route of administration; (iii) be therapeutically equivalent; (iv) meet the requirements for identity, strength, purity, and quality; and (v) be manufactured under the same strict standards of good manufacturing practice required for innovator products.

At present, for biosimilar (now termed similar biologics-coined by DBT) products, applicants must provide adequate data on bioequivalence and safety on the use of such products. If these data are inadequate, the Review Committee on Genetic Modification (RCGM) may require limited pre-clinical/ clinical studies to establish bioequivalence.

It is noteworthy to mention that the Department of Biotechnology released the Draft Guidelines on Preclinical Evaluation similar biologics and also conducted a consultative meeting with the stakeholders in March and the final version will be released soon. Likewise DCGI also constituted a task.  

Presently there are multiple regulatory bodies like RCGM, DCGI, GEAC, Local FDA and State Drug controller Authority for biosimilar regulation in India. The domestic industry recommends single regulatory authority that has an oversight from the R&D process, pre-clinical protocol approval, and clinical trials to marketing processes. This single regulatory authority should be empowered and strengthened by having retained knowledgeable staff that understands the global regulatory requirements and can assess, evaluate and take decisions on applications for product development force to frame the guidelines for clinical evaluation of similar biologics.

As stem cells are akin to drugs, the Government of India had felt that there was a need for regulatory framework on ethical, social and legal issues while promoting stem cell research & therapy to follow world-class standards of ethics regulation and engage all stakeholders and the society at large in terms of getting their consensus.

 With this intent, the Department of Biotechnology (DBT) under the Ministry of Science and Technology and Indian Council of Medical Research (ICMR) jointly formulated “National Guidelines of Stem Cell Research and Therapy 2007” to lay down general principles on ethics of stem cell research and therapy.  One of the salient features of the guidelines is the classification of stem cell research under permissible, restricted and prohibited categories. These guidelines address both ethical and scientific concerns to encourage responsible practices in the area of stem cell research and therapy.

For marketable products, clearance from Drug Controller General of India (DCGI) is necessary It has also set standards for the collection, processing and storage of cells intended for clinical use

The government has also proposed single-window processing under the proposed Biotechnology Regulatory Authority of India (BRAI) bill 2010, which received the Cabinet approval on august 17, 2010, seeks to create a new body to regulate research, manufacture, import and use of products of modern biotechnology. The actual contents of the Bill as approved by the Cabinet is not in the public domain and we can get back with details about the functioning of the authority once the Bill is tabled in the Parliament.

The additional features in post marketing surveillance requirement in case of biologics both DCGI and GEAC can impose conditions of surveillance on the product during marketing. In case of biologics the marketing surveillance may be governed under the norms of both the Drugs & Cosmetics Act as well as the Environment protection Act (EPA). Marketing under EPA can be for a period of two to four years initially and this can be renewed on the basis of an application. Post-market surveillance data may be required to be generated and submitted to DCGI and GEAC by the applicants on a case to case basis.

The Indian biotechnology sector is one of the fastest growing knowledge-based sectors and is expected to play a key role in shaping India's rapidly developing economy. The science of biotechnology has been a rapidly growing research and intellectual property led sector. The biotechnology sector today largely uses cutting edge science-based research and development techniques for isolation, modification and combination of genetic materials which in turn are used for invention of new combinations of genetically recombinant drugs and vaccines and other pharmaceutical products, genetically modified organisms/plants and foods, hybrid varieties of plants and seeds and other agricultural products.

Hence in order to gain acceptance and recognition in the highly regulated and competitive western market, the  efficacy and quality of the biotech drugs have to be in tandem with the  stringent bio safety  standards of international regulatory framework.