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Challenges in the Changing Pharmaceutical Regulatory Scenario In India Keeping in pace with the Indian Pharmaceutical Industry is one of pharmaceutical regulatory bodies have the largest and most advanced among the also come out with major changes. This international regulatory developing countries. It has over the years initiative by the Indian regulatory bodies scenario, the Indian made significant progress in infrastructure will play a pivotal role to put India on development, technological capability and the top of the pharmaceutical map of pharmaceutical regulatory hence produced a wide range of products. the world. In pursuance of the same, bodies have come out with Understanding the regulatory scenario in they have published guidelines on the major changes, which will this sector is extremely crucial not only following topics and now they are in the due to the rapid and ongoing changes at implementation stage and they are going play a pivotal role to put the global level, largely with reference to to bring about revolutionary changes in the India on the top of the Good Manufacturing Practices (GMP), Indian Pharmaceutical Industry. Good Clinical Practices (GCP) and Good pharmaceutical map of Laboratory Practices (GLP) but also due Good Manufacturing Practices (Current the world. In pursuance to the onus on the regulatory bodies to Schedule M) of the same, the article ensure a healthy supply of quality drugs at affordable prices to the Indian masses. GMP aims to ensure that drugs and other describes the guidelines, pharmaceutical products are safe and implementation and The Industry today is in the front rank of effective. Since then, Good Manufacturing India’s science-based industries with wide Practices (GMP) has been considered a revolutionary changes ranging capabilities in the complex field of seal of quality for pharmaceutical products. bring by the Indian drug manufacture and technology. It ranks GMP has been adopted by many countries Regulatory in the domestic very high in the third world, in terms of worldwide and that includes India which technology, quality and range of medicines is now the second largest producer of Pharmaceutical Industry. manufactured. From simple headache pills pharmaceutical products in the world. to sophisticated antibiotics and complex cardiac compounds, almost every type The revised Schedule M advises proper of medicine is now made indigenously. pressure differentials in the areas of operation, Playing a key role in promoting and which can be achieved through dedicated sustaining development in the vital field air handling units with adequate number of “ “ The Indian Pharmaceutical Industry will have to go a long way for the successful compliance of current Schedule M of medicines, Indian Pharmaceutical air changes. These pressure differentials Industry boasts of quality producers will help to eliminate/reduce the chances of and many units approved have been by cross contamination between the products. regulatory authorities in USA, Japan, EU, In addition to these, revised schedule M Canada, Australia and UK. Now there is emphasises proper cleaning validation of no such country in the world where Indian the equipment and the processing areas manufactured pharmaceutical products are whenever there is product change over. It not available. is also mandatory to display status boards Dr. J Ramniwas of each equipment material to avoid mix- CEO Keeping in pace with the international ups, which leads to cross contamination. Sai Pharma Solutions Inc, Vadodara regulatory scenario, the Indian Current Schedule M also gives importance28 June 2012 Pharma Bio World
“The current GCP guidelines of India are at parwith ICH guidelines of GCP and these guidelineswould open new vistas to companies who want “ investigators and premiere medical institutes available in the country along with considerable low per patient trial cost, as compared to developed countries. The current GCP guidelines of India are at par with ICH guidelines of GCP andto locate their clinical programme in this country. these guidelines would open new vistas to companies who want to locate their clinical programme in this country. However, thisto the stability study of drug substances and industries in India. On the other hand, WHO is very challenging but helps making adrug products to claim the re-test date and eyes towards every small aspects of and niche in the clinical trial business withexpiry date. The Government of India has related to the laboratory procedure with a global acceptance.recognised Pharmaceutical Industry as a view to assure the output scientifically proof.technology-driven industry and is focusing on Drug Registration and Regulatorythe growth of the industry both for domestic Schedule L1 Good Laboratory Practices Submission Guidelinesas well as for the expanding global markets. (GLP) requirements are applicable toTo create a confidence about the quality laboratories attached to all manufacturers Drugs defined as New Drugs under theof drug manufactured in this country, it is covered under rules 74 and 78 of Drugs Drugs and Cosmetics Act are subjectedessential that the regulators of the country & Cosmetics Rules, which include to bioavailability/bioequivalence (BA/BE)define standard, which are on par with global manufacture of ‘medical devices’, evaluations through clinical trials, whichstandards through proper legislation. ‘diagnostic reagents’, ‘surgical dressings are reviewed by the Drugs Controller such as gauges and bandages’, General (India). A drug has a New DrugThe Indian Pharmaceutical Industry will ‘disinfectant fluids’ and ‘sanitising fluids’, status for four years from the date of firsthave to go a long way for the successful etc and hold licenses in forms 25 and permission. After four years, the Statecompliance of current schedule M but 28. These laboratories even though tiny Licensing Authority grants license but theyonce compliance is achieved, the Indian sized, shall be in conformity with all GLP do not insists for BA/BE and clinical trialpharmaceutical industry will be able to requirements even laboratories attached to studies which are essential to establishbeat any GMP global standard. Change the manufacturing units too. the efficacy of the drugs. Central Drugscan be good or difficult at times; this Standard Control Organisation (CDSCO)largely depends on how prepared a person This will be particularly useful to the has come out with new draft guidelines onor an organisation is to adapt and survive laboratories that already comply with the the approval of clinical trials and new drugs.with the new set up. Apparently, the requirements of Schedule L1 and want tosmall players in India’s pharmaceutical move ahead towards WHO compliance. CDSCO has decided to adopt Commoncompanies have to buckle down to be Technical Document (CTD) format formore equipped with the changes that Good Clinical Practices (GCP) technical requirements for registrationGMP brings into their businesses. of pharmaceutical products for human Clinical research is the key to the use. The same is in use for biologicalGood Laboratory Practices (Schedule L1) discovery of latest diagnostic methods and products since 2009 and now this guidance to develop modern drugs for treatment of document describes the format forThe Drugs & Cosmetics Rules were diseases. Good Clinical Practices (GCP) preparation of CTD for marking approvalamended to incorporate Schedule L1 is an ethical and scientific quality standard of pharmaceuticals for human use otheron Good Laboratory Practices and for designing, conducting and recording than biological products. It is apparentRequirements of premises and Equipments trials that involve the participation of that Indian Pharmaceutical Regulatorypublished under notification GSR 780 (E) human subjects. Compliance with this bodies will be able to expedite the reviewdated 10 th November 2010; a period of two standard provides assurance to public that process of new drug application marketingyears was granted for the Pharmaceutical the rights, safety and well being of trial approval. These guidelines are applicableindustry to make necessary arrangement subjects are protected, consistent with the to for import, manufacture and marketingto comply with the requirement of Schedule principles enshrined in the Declaration of approval of new drug applications.L1 before these are made mandatory. Helsinki and ensures that clinical trial data is credible. The adoption of Drug Master File (DMF)Rules laid by Schedule L1 are terse and and drug product dossier concepts CTDminimum with an objective to improve the It has been widely recognised that India format in tune with the global requirementsreliability of data without much adding to offers unique opportunities for conducting will help the Indian pharmaceutical Industrythe cost to the company, particularly for clinical trials in view of the large patient to contribute production and speedy entrythe small to medium scale pharmaceutical pool, well-trained and enthusiastic to the global markets and simultaneouslyPharma Bio World June 2012 29
Indian patients would also receive to adapt its business model to recent development concept and Qualityquality and safe medicines. The Indian changes in the operating environment. design has become the buzzword inRegulatory Agencies and Regulatory the pharmaceutical world and to thatAffairs professionals will be of immense India’s Patents Act should ensure that India is no exception. The US Food andimportance to address these challenges it does not exceed the requirements of Drug Administration (FDA) is planningin the right perspective to make Indian Trade-Related Aspects Of Intellectual to make the submission of Quality byPharmaceutical Manufacturers competent Property Rights (TRIPS), and that Design (QbD) document mandatoryand regulatory savvy. prioritizes access to medicines and for all the New Drug Application (NDA) public health, while retaining the right applicants from January 2013. All thePharmacovigilance Programme of India to participate in the compulsory license manufacturers exporting to the US,(PvPI) for Assuring Drug Safety scenario. India should lead a movement will now have to submit an entire set of developing nations and create a of documents supporting their product,The CDSCO, Directorate General of Trade-Related Aspects Of Intellectual right from its inception stage to theHealth Services, under the aegis of Property Rights (TRIPS) south and G-20 US regulatory authority while filing forMinistry of Health & Family Welfare, alliance is a step in that direction. approval. The documents submittedGovernment of India, in collaboration should support the companies claimwith Indian Pharmacopeia commission Price Control on how effective and efficacious their(IPC), Ghaziabad is initiating a product is from the design stage itself.nation-wide Pharmacovigilance programme The Pharmaceutical Price Control Policy Failing which there are chances offor protecting the health of the patients by carried forward earlier governmental their application being rejected by theassuring drug safety. The programme shall initiatives in terms of ensuring quality FDA officials.be coordinated by the IPC, Ghaziabad as a drugs at reasonable prices, strengtheningNational Coordinating Centre (NCC). The of indigenous capability for cost-effective QbD is a concept that is introduced bycentre will operate under the supervision production, reducing trade barriers the US FDA with an aim to understandof a Steering Committee. and providing active encouragement to the design and development of the in-house R&D efforts of domestic firms. pharmaceutical formulations andSince, there are considerable social and The objective is to increase revenue and manufacturing processes to help ensureeconomic consequences of Adverse Drug lower prices of medicines by using fiscal quality of the end product. On thisReactions (ADRs) there is a need to deterrent on Maximum Retail Price (MRP). occasion, the International Pharmaceuticalengage health-care professionals, in a well Excipients Council (IPEC) has urged all thestructured programme to build synergies This change may have had some impact Indian manufacturers exporting to the USfor monitoring ADRs. The purpose of the in terms of magnifying the advantage to update and prepare themselves on thePharmacovigilance Programme of India is to industries located in the excise free procedural requirements so that they willto collect, collate and analyse data to arrive zones. This also succeeded in attracting not be taken by surprise while filing anyat an inference to recommend regulatory some small pharmaceutical firms to these NDA applications.interventions, besides communicating risks zones. This development indicates theto healthcare professionals and the public. heightened sensitivity of the government Design of Experiments (DOE) is the most towards consumer access to medicines at effective method to achieve product andIPR Issues Concerning Global Pharma reasonable prices and keeping a check on pro¬cess efficiency and optimisation.Market profit mongering by the industry. Design of Experiment (DOE) studies can help develop process developmentAs per World Trade Organization (WTO), In addition to the Quality (GMP, GLP, knowledge by revealing relationships,from the year 2005, India granted product GCP), Intellectual Property Rights (IPR) including multifactorial interactions,patent recognition to all New Chemical and drug price control change initiative between the variable inputs (e.g.,Entities (NCEs) i.e., bulk drugs developed by the Indian Pharmaceutical Regulatory component characteristics or processingthen onwards. This introduction of Agencies, the Indian Pharmaceutical parameters) and the resulting outputsproduct patent regime from January 2005 manufacturers will have to face the (e.g., in-process material, intermediates,is leading into long-term growth for the challenges in the subsequent areas to or the final product).future, which mandated patent protection remain in completion in to the globalon both products and processes for a market, which are listed below: The application of Quality by Designperiod of 20 years. Under this new law, principles is beginning to be wellIndia will be forced to recognise not only • Quality by Design – New Perspective to established in the pharmaceutical industry.new patents but also any patents filed Product Development: With the advent In particular, the demonstration of theafter January 1, 1995. Under changed of ICH-Q8 and ICH-Q11, guidelines science and risk-based approaches beingenvironment, the industry is being forced have revolutionised the product applied to specific subsets of the drug30 June 2012 Pharma Bio World
“product design or processing has beendiscussed intensively during the pastseveral years. Therefore, it is now time towiden the scope of QbD across multiple unitoperations, including important aspects of With the advent of ICH-Q8 and ICH-Q11, guidelines have revolutionised the product development concept and Quality design has become the “the drug substance. buzzword in the pharmaceutical world.Model development and implementationis a core principle to employing a QbDapproach in drug product design and Flexible facility design will contribute to monitoring. Pharmacy profession shouldprocess scale-up. The advantages in reduced financial risk as products progress orient concept of pharmacy practice attaking this approach are realised through from Phase 1 to Phase 3. Traditional community and hospital pharmacies throughthe ease of visualisation or mathematical approaches require investment of millions appropriate training and compensation.expression of data sets for greater process of dollars into a facility for a product tounderstanding, which leads to clear be manufactured in the hope that the The pharmacy profession will make the clinicaldecision making and results in superior candidate will succeed in Phase 3 testing. trial industry in India to grow to over a billionproduct quality. While agile and adaptable facility designs dollars in the next ﬁve years and position itself will become more widespread, dedicated as a destination of choice for CRO servicesThere are several model types that can be manufacturing facilities will still be required by way of strict implementation of patentdeveloped and used at every stage in the under certain conditions, including laws, single window clearance of clinical trialQbD process. A favored approach is to large-volume products with high API and/ protocols by regulatory clearances and shallbegin with the end in mind by outlining up or drug product demands, manufacture of accord industry status to this sector. India willfront a clear plan toward model design and highly potent or toxic drug substances, and emerge as a major global player in the ﬁelddevelopment for the drug product process, the need for specialised processes. of pharmaceuticals exports and as a providerconsidering how each model will be used, of quality medicines at low costs. It shalllimitations, assumptions, qualification, and The Indian pharmaceutical industry shall also emerge as a major player in the genericmaintenance. The experimental approach ensure that essential drugs at affordable drugs market in USA and Europe. India shallto the development of each model should prices are available to the vast population attain new heights in herbal drugs researchconsider the type of model (mechanistic of this sub-continent and also continue in shaping Indian Systems of Medicine into aor empirical), selected variables, scale providing employment for millions. popular system of medicine of the future fordependency and relationship to the overall India shall implement all the rules and holistic health care and ensuring health care fordrug product process. Once a model has regulations, which guide, monitor and all - especially for the welfare of the poor.been developed, steps are needed toward control the activities of the providers ofimplementation through qualification of the healthcare system in the country and The focus of Indian Pharmaceuticalthe model and evaluating uncertainty in shall examine the way to bring them up to Regulatory bodies is now shifting towardspredictions. Finally, for models selected international standards. the risk management and science basedfor use in commercial manufacture, a GMP regulations with the affordability ofmaintenance plan is needed to support The government should implement the quality medicines. The need of the hourproduct life cycle. recommendations of Mashelkar committee is to change the attitude by the Indian and constitute the Central Drug Authority at the Pharmaceutical Manufactures from What• New Concept in Facility Design: earliest. The basic course of education should will happen to others, will also happen to Manufacturing plants will increasingly be designed to ensure that the newly qualiﬁed me to We resolve to make our industries utilise modular building strategies. pharmacist has the necessary knowledge and compliant to regulatory requirements Facilities will include disposable skills to commence practicing competently in by converting industries research and process equipment, enclosed clean a variety of settings including community and innovation driven. This too is true that when rooms around process equipment, and hospital pharmacy and the pharmaceutical our intentions are clear and our efforts are lean design concepts. This approach industry. Continuing professional development consistent in the right direction, nothing provides significant cost savings must then be a lifelong commitment for every is impossible. and reduces start-up time frames for practicing pharmacist. new facilities. Designing outcomes All changes and challenges are always into manufacturing processes via Concept of National schools of pharmacy tough but facing them with determination quality-by-design concepts will should be established to develop and yields a long lasting success! be critical to reducing costs, introduce model curriculum. Pharmacists increasing efficiencies, and assuring should become knowledgeable to participate Contact: jramniwas@saipharmasolutions. regulatory compliance. in medication management and outcome comPharma Bio World June 2012 31