Globally pharmaceutical regulatory norms are getting more stringent, for product development and registrations. Because of this the cost of development, innovative research (value-added branded generics), manufacturing, clinical trials, bioequivalence, analytical & stability studies, data management quality, and compliance during the lifecycle of the product are significantly impacting margins.
To maintain consistent growths in the future, big players in the pharmaceutical industry are focusing on the fast growing emerging markets to outsource their drug developmental activities, and are also seeking licensing partners for marketing their products. This paradigm shift has moved the main focus from the regulated markets of EU and North America to the Rest of World (ROW ) markets. India is emerging as a strong contender riding on its inherent competencies and capabilities in process innovation, cost -effective drug development supported by a well established industry of CMOs (Contract Manufacture Organizations) & CROs (Clinical Research Organizations) catering to the pharmaceutical industry. A growing number of Indian sites are being inspected and approved by global regulatory agencies meeting ICH-GXP compliances. Motivated by cost -effectiveness and availability of trained and experienced technical expertise, the total outsourcing business in Indian pharmaceutical industry is expected to cross around $2.5 billion by 2012.
Recent data tracking the growth in emerging markets including India confirms that the share of emerging markets is expected to increase from 22 per cent in 2008 to 26 per cent in 2013. Indian pharma market is also expected to grow at a CAGR of 12-14 per cent and will be $20-24b in 2015. Further India's share of global contract manufacturing is expected to grow at a CAGR of 25 per cent to be worth $10b by 2015. The Indian API manufacturing industry is the third largest in the world, growing at 19.3 per cent with Indian bulk drug exports increasing from $ 1.56 billion to $ 4.8 billion. Increased emphasis of contract manufacturing has increased the scope of captive API demand from Indian supplier.
The Indian scenario for API and generics
Regulatory: In keeping with global standards India is in the process of harmonizing its regulatory practices with guidelines on GMP, GCP , GLP supported by a more stringent IPR norms to gain the confidence of the developed world, against stiff competition from other outsourcing destinations such as China, Ireland, Brazil, Spain, Hungary etc in the global generic market. Major generic players in collaboration with global research companies are seeking market differentiation to move up the value chain by manufacture of complex generics based on NDDS, chiral molecules, controlled drugs, biosimilars etc .New Indian guidelines and regulations are also proposed for biosimilars, food additives, herbals, cosmetics etc.
Manufacturing facilities: The Indian sites are well equipped with infrastructure meeting regulated market standards in terms of design & development to manufacture R&D and commercial batches supported with automated testing equipments and systems. The manufacturing facilities have GMP approvals from USFDA, TGA, EMEA, UK-MHRA and several global regulatory agencies.
Technical resources: The technical staff supporting manufacturing operations in India is highly knowledgeable, competent and experienced with handling technical issues to support submissions to global markets (regulated and ROW) for API & formulations. Regulatory services provider can assist with regulatory and QA documentation to efficiently respond to enquiries from agencies on dossier review and site inspections.
Outsourced projects
Given that the generic pharma market, both globally and in India is expected to grow as per the trends quoted above, it is incumbent for global companies to form key partnerships now with appropriate service providers to address future development needs. The best provider is one that understands the regulatory environment in the country of interest (manufacture and marketing) in order to successfully move the drug development programs forward in an efficient and cost effective manner thereby avoiding loss of time, money and potentially market opportunities.
Bringing together the global pharma companies and the Indian contract manufacturers is now of critical importance as a majority of the new DMF's filed globally are from India, and therefore most API's will be manufactured and supplied from either India or China. Consequently, the role of the Indian regulatory services provider has become more significantly, to ensure harmonization of the high quality standards to be maintained by the API & formulation manufacturers in India meeting global standards.
In order to ensure quality and speedy regulatory approvals of outsourced projects, it is imperative for the regulatory service provider to provide resources with both technical and market domain expertise. Besides close working with the company's internal team for a seamless integration, other critical aspects to be managed by a local regulatory consultant to ensure meeting of budgets and timeliness are listed below.
Bridging role between the stakeholders: Due to cultural and communication challenges, regulatory services provider play a vital bridging role between the technical and business teams of multiple sponsors based abroad and Indian manufacturing and services companies engaged in outsourced projects. The bridging exercise assists with understanding and managing realistic expectations relating to project deliverables to gain buy -in from all stakeholders.
Sourcing: Due diligence and qualification of vendors: Due to increasing costs of travel and the evolving regulatory requirements, Indian regulatory service provider plays a critical role on behalf of global pharma companies to conduct initial technical due diligence and vendor qualification to ensure sourcing and contracts with reliable, high quality, cost -effective GXP facilities in India which significantly minimizes the risk of huge investments in capital-intensive facilities and subsequent delayed timelines as an outcome of alliance with an in appropriate partner, for starting materials, packaging materials, contract testing sites etc. for API as well as finished products are sourced from India to build the product with desired global quality standards.
Subject experts: Besides regulatory and QA support provided by Indian service provider, development and manufacturing efficiencies can be significantly approved by engaging subject experts (chemistry, engineering etc) with relevant hands on experience to assist in solving specific challenges faced during outsourced product or processes development leading to successful regulatory approvals and commercialization.
Project management: Technical & regulatory oversight: Continuous monitoring of the outsourced project is critical to meet budgets and timelines.
Regular monitoring visits to the Indian sites include overseeing the process development and production activities to resolve issues immediately ensuring continuous regulatory compliance and quality of final product. (Use of recovered solvents/raw materials, optimization of solvents, raw material quantities etc).
Dossier management: Harmonization of dossier in content and format: Regulatory submission requirements differ in content and format across regulatory agencies. Besides review and reconciliation or data (administrative & technical: quality, safety, efficacy), there may be a need to harmonize the existing DMFs and submit in the specified format according to agency/region specific requirements including support for electronic submissions.
Preparedness for audit
Mock audits are conducted for Indian sites to face global inspections & regulatory GMP compliance audits with greater degree of preparedness and confidence
Conclusion
A globally harmonized; networked and outsourced world of virtual companies brings not only new opportunities, but also includes related challenges as seen in the outsourced development of generics in India. Selection of the correct regulatory service provider is critical to the success of the outsourced project to gain a competitive edge via quality speedy approvals translating to early market access. Outsourcing strategies allows the global pharma companies to focus on their key strengths relating to discovery technologies and marketing, whilst their outsourcing partners (CMOs ,CROs) and the regulatory service provider work in close collaboration to efficiently bring an economically viable value- added generic drug to the market.
The author is Technical, Director, PharmaLeaf India Pvt Limited, Bangalore