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