Hetero Drugs Limited - Indian Pharmaceutical Association

Hetero Drugs Limited
Global Challenges in Quality Assurance of APIs
The Perspective of Indian Manufacturers
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Hetero Drugs Limited
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Hetero Drugs Limited
Laws Governing GMPs/Quality
‣United States – Food, Drugs and Cosmetics Act
‣Europe – European Pharmaceutical Legislation
– GMPs for APIs
‣India – Drug and Cosmetic Act (Schedule –M –
APIs)
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Hetero Drugs Limited
Additional requirements by ICH, adopted by
Authorities
‣ICH Q7
‣Adoption of Q8, Q9, Q10 Principles to Drug
Substance
‣ICH Q11
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Hetero Drugs Limited
Inspection History In India – The Evolutionary
Process
‣ Early 1980s – The Start of FDA Inspections for sites in
India
‣ Early 2000s – The start of WHO Inspections
‣ Mid 2000s – The onset of European Inspections, TGA
Inspections etc.
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Hetero Drugs Limited
Inspection History In India – The Evolutionary
Process
‣ Increased number of API manufacturing facilities
with Approvals from Agencies, over the past decade
‣ Success Rates in terms of the inspections of the APIs
by Authorities such as USFDA, EU Agencies, EDQM,
TGA, etc., reflects the commitment by the API
manufacturers to gear up to the continuous changes
in the Regulations and their implementation.
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Hetero Drugs Limited
Inspection History In India – The Evolutionary
Process
‣ Several Companies from India are part of WHO Pre-
Qualification Programme particularly for the Supply
of Anti-Retroviral APIs, reflecting the efforts of the
API manufacturers to ensure compliance to the
Stringent Requirements in terms of Quality and
adherence to cGMPs
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Hetero Drugs Limited
Inspection History In India – The Evolutionary
Process
‣ The number of the Firms that supply the APIs to
the Highly Regulated Markets like US, Canada,
Europe, Australia, Japan have increased over the
past few years, reflecting the understanding that
these organizations have gained on the Laws
governing the Supplies of the Pharmaceuticals /
APIs in those countries.
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Hetero Drugs Limited
Inspection History In India – The Evolutionary
Process
‣ Efforts and steps increased manifold by the
Manufacturers to imbibe the philosophy of building in
Quality right from the Development of the process to
Distribution of the API, minimizing all the risks
associated with the manufacture
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Hetero Drugs Limited
Changes in Inspectional Approaches –
Preparedness of Industry
‣ The Approach by the Inspectors adopted by the Inspectors
from Different Authorities changed over the period of time,
with the stress being on Documentation at some time and
on the Practices at some time, ultimately culminating into
the Stress on The Quality Management Systems as a whole,
thus laying the importance on the Involvement of Top
Management of the Firms in implementation and
propagation of the current Regulatory Requirements.
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Hetero Drugs Limited
Changes in Inspectional Approaches –
Preparedness of Industry
‣ Thus, the most important aspect in the current
Scenario is that the Improvements could be
expedited with the decision-making Authorities
themselves getting involved, following the
systems, within the Regulatory Framework.
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Hetero Drugs Limited
Regulatory Submissions – Quality Aspects
‣ Changing Approaches to Submissions – Quality of
Information /Adequacy
‣ Increased levels of Criticality in Evaluation of
process vis-à-vis Specifications
‣ Time-bound review framework – response in time
(Particularly the Centralised / Decentralised
Procedures approach in the EU)
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Hetero Drugs Limited
Regulatory Submissions – Quality Aspects
‣ Understanding on Variations – Current Scenario
in the US/Europe and other Regulated Markets –
Minimizing queries and speedier response,
following the right approach ( from development
to commercial
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Hetero Drugs Limited
Regulatory Submissions – Quality Aspects
‣ The Indian API manufacturers are geared up to
meet all the current challenges posed w.r.t the
review process, of particular importance to
mention is the current trend on the queries related
to the Impurities of Genotoxic concerns and
Definition of Starting Materials
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Hetero Drugs Limited
Regulatory Submissions – Quality Aspects
‣ Proactive approach in the Choice of the Process,
thus optimising the specifications in terms of the
Impurities, adoption of the suitable validated
methods, use of advanced techniques in
Characterisation are the important aspects of
current day API Development
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Hetero Drugs Limited
Emphasis
‣ The Emphasis of API Manufacturers has always
been on continuous improvement to meet the
changing dynamics of a Regulated Environment
‣ The Primary requirement in this scenario is to
have Trained Staff who upgrade by understanding
the current Regulations.
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Hetero Drugs Limited
Emphasis
‣ Periodic Training to all levels of Staff in various
functions related to the Manufacture to ensure
current Understanding w.r.t. Regulations /
Guidances
‣ Periodic Self Audits to ensure compliance to the
Quality Systems and initiating the necessary
actions to improve the system.
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Hetero Drugs Limited
Emphasis
‣ Continuously improving upon the Procedures
(SOPS), Documentation and Record-keeping is
also on of the most important aspect which the
Industry is always focused on. Improvement
followed by Implementation in addition to
constant monitoring and reviews are also part of
the current systems being followed.
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Hetero Drugs Limited
Emphasis
‣ Emphasis is also on learning from past Industry
experiences, Inspection Observations, etc., as part
of improvement.
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Hetero Drugs Limited
Operational Challenges vis-à-vis Complexities of
API Manufacture - Maintaining the Quality
‣ Facilities ( w.r.t product nature, e.g. Oncology,
Hormones, High Potent Drugs etc.)
‣ Equipment (Design based on technologies
adopted)
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Hetero Drugs Limited
Operational Challenges vis-à-vis Complexities of
API Manufacture - Maintaining the Quality
‣ Technologies
‣ Others (Specifications/Process changes)
‣ Skilled Manpower
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Hetero Drugs Limited
Operational Challenges vis-à-vis Complexities of
API Manufacture - Maintaining the Quality
‣ The Operations of the API Facilities need to be in
sync with the changing dynamics, particularly w.r.t
to the current Regulatory scenario, thus constantly
upgrading within the limits of the Regulations,
without affecting the Approval status of the
Marketing Authorisations (of the Finished dosage
manufacturer)
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Hetero Drugs Limited
Current Challenges
GDUFA – USFDA
‣ Industry has already begun working on the plans
to meet the requirements of the new regulation,
starting October, 2013
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Hetero Drugs Limited
Current Challenges
New EU Directive for Importing APIs
‣ The Industry is already in discussion with the
Government of India in trying to find the right
approach to meet the New regulations of
European Authority
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THANK YOU
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