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Quality%20Management%20for%2021st%20Century

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Title: Quality%20Management%20for%2021st%20Century


1
Quality Management for 21st Century
S. Srinivasan CEO Managing Director Matrix
Laboratories Limited
2
Indian Pharmaceutical Companies geared up for
global market Quality Management for 21st
Century Quality Risk Management Product
Development Process Analytical Technology
(PAT) Regulatory Review Conclusion
3
Indian Pharmaceutical Companies geared up for
global market
  • Current size of the global Pharma market is
    around US 800 billion
  • Generic market US 93 billion
  • the API market US 37 billion
  • (Source Espicom business intelligence)
  • Global demand of APIs is expected to increase at
    CAGR of over 8 over the next 5 years (Source
    Chemical Pharmaceutical Association (CPA))
  • A recent study by EY indicates projected growth
    in Pharma outsourcing out of India of over 40.
  • India projected as an excellent destination for
    cost efficiency in manufacturing, coupled with
    strong supply of skilled manpower, in comparison
    to China, Eastern Europe, Puerto Rico, Singapore
    Ireland

4
Indian Pharmaceutical Companies geared up for
global market
  • India has maximum number of USFDA approved plants
    outside the US and last few years filed the
    maximum number of DMFs.
  • Indian companies play a predominant role in the
    WHO pre-qualification programme related to
    Malaria, TB and HIV/AIDS.
  • Indian pharmaceutical and API players are well
    positioned to take advantage of this market
    opportunity.
  • Indian companies have created good infrastructure
    with cGMP compliant plants over the last decade.

5
Indian Pharmaceutical Companies geared up for
global market Quality Management for 21st
Century Quality Risk Management Product
Development Process Analytical Technology
(PAT) Regulatory Review Conclusion
6
Quality Management for 21st Century
  • An integrated quality system should cross into
    all areas of operations.
  • QMS to be designed to assure quality into the
    manufacturing and control processes.
  • ICH Q10 is not intended to create any new
    expectation beyond current regulatory
    requirements. This guideline has been formed by
    integrating GMP requirements (ICHQ7) and ISO QMS
    guidelines. It serves as a bridge between
    regional requirements, facilitating harmonization
    of pharmaceutical quality system.
  • Implementation of ICH Q10 should facilitate
    innovation and continual improvement and
    strengthen the link between pharmaceutical
    development and manufacturing activities.

7
Quality Management for 21st Century
  • Main objectives of Q10 are
  • To achieve product realization
  • Establish and maintain a state of control, and
  • Facilitate continual improvement
  • Pharmaceutical quality system should include the
    following elements -
  • Process performance and product quality
    monitoring
  • Corrective and preventive actions
  • Change management and management review
  • Key performance indicators should be identified
    and used to monitor effectiveness of processes.
    These indicators can be derived during the
    development process and also from manufacturing
    experience. They can be used as enablers for
    continual improvement.

8
Quality Management for 21st Century
The quality management system presents continuous
validation -concept to replace the current
three-batch process validation concept, i.e. move
from paradigm of testing to assure quality to
designing to assure quality and increase
process capability to minimize risk. Implementati
on of this framework will place tremendous
responsibility on the pharmaceutical
manufacturers to have the Operations and Quality
teams well-trained in quality management
initiatives In integrated QMS, there is an
interplay of several ICH guidelines - - ICHQ8
on Product Development - ICHQ9 on Quality Risk
Management
9
Indian Pharmaceutical Companies geared up for
global market Quality Management for 21st
Century Quality Risk Management Product
Development Process Analytical Technology
(PAT) Regulatory Review Conclusion
10
Quality Risk Management
  • ICH Q9 should serve as a foundation and
    complement existing quality practices, standards
    and guidelines within the pharmaceutical
    industry.
  • Appropriate use of quality risk management can
    facilitate regulatory compliance to a substantial
    degree and also improve quality of communication
    between industry and regulators.
  • A rational approach to risk management has to
    begin with the question What is the impact on
    the product?

11
Quality Risk Management
  • This guideline provides a framework that may be
    applied to all aspects of pharmaceutical
    business, including
  • development, manufacturing and distribution
  • inspection and submission /review processes
    throughout the lifecycle of drug substances,
    biological and biotechnological products and
  • use of raw materials, solvents, excipients,
    packaging and labeling materials.

12
Quality Risk Management
  • Risk Management is about
  • knowing our processes (manufacturing and
    business)
  • understanding what is truly important
  • not spending time on a low risk activity,
    process, event or system because it just doesnt
    matter!
  • focusing our money, time, energy and people on
    the things that are really important
  • focusing our efforts and resources on the things
    that provide quality assurance to our customers
  • Risk Management is not about
  • making do with insufficient time, money or people
  • providing an excuse not to do the right things
  • deciding what to do based on what might be
    observed during an inspection

13
Quality Risk Management
  • It is imperative therefore, that we as API
    manufacturers are able to and perform a
    scientific and practical risk management process
    as a part of the quality management and
  • document the observations
  • the actions and other related details based on
    current knowledge about assessing the probability
  • the severity and detectability of the risk.
  • Output of a risk assessment could either be a
    quantitative estimate of risk or a qualitative
    description of a range of risks.

14
Quality Risk Management
Based on the risk analysis, one could arrive at
appropriate risk control measures to reduce and
/or accept risks. Training of industry
personnel in quality risk management process
provides for greater understanding of decision
making processes and builds confidence in quality
risk management outcomes.
15
Example 1 Quality Risk Management
  • Recent examples of improper evaluation of
    manufacturing processes
  • (Source http//www.emea.europa.eu/humandocs/PDFs
    /EPAR/Viracept/Viracept-H-164-Z-109-AR.pdf)
  • Nelfinavir
  • Europe wide recall of the HIV drug Nelfinavir
  • Patients reported strange smell on the tablets
  • Investigation revealed high level of Ethyl
    Mesylate (EMS) a potential genotoxic impurity
  • Investigation at the manufacturing plant
    identified ethanol contamination in a holding
    tank of Methane Sulphonic Acid (MMS)
  • Ethanol was used as a cleaning solvent which was
    not part of a regular procedure
  • Residual ethanol got converted to EMS in presence
    of MMS
  • Lack of knowledge understanding of the
    manufacturing process

16
Example 2 Quality Risk Management
  • Recent examples of improper evaluation of
    manufacturing processes
  • (Source http//www.ibc-asia.com/GenericsAsia/Day
    201/Ron20Tomer.pdf)
  • Terbinafine
  • A potential impurity was identified in the
    manufacturing process of the API
  • Launch of the Generic version was delayed due to
    lack of knowledge
  • Impurity was expected to be generated due to two
    starting materials (Acrolein and PCl5)
  • EDQM initially set a limit of 6 ppm and after
    additional studies fixed the limit at 500 ppm
  • This impurity now appears as a listed impurity in
    the EP monograph

17
Indian Pharmaceutical Companies geared up for
global market Quality Management for 21st
Century Quality Risk Management Product
Development Process Analytical Technology
(PAT) Regulatory Review Conclusion
18
Product Development
  • Another integral part of the new quality
    management system is ICHQ8 on pharmaceutical
    development.
  • The aim of pharmaceutical development is to
    design a quality product and its manufacturing
    process to consistently deliver the intended
    performance of the product.
  • The information and knowledge gained from
    pharmaceutical development and manufacturing
    experience provide scientific understanding to
    support the establishment of specifications and
    manufacturing control.
  • Information from pharmaceutical development
    studies can be a basis for Quality Risk Management

19
Product Development
  • Changes in formulation and manufacturing
    processes during development and lifecycle
    management are opportunities to gain additional
    knowledge.
  • Movement out of the controls window should be
    considered a change and would normally initiate a
    regulatory post-approval change process.

20
Example 3 Trend Analysis before CAPA
21
Example 3 Trend Analysis after CAPA
22
Indian Pharmaceutical Companies geared up for
global market Quality Management for 21st
Century Quality Risk Management Product
Development Process Analytical Technology
(PAT) Regulatory Review Conclusion
23
Process Analytical Technology (PAT)
  • Process analytical technology approach should
    encourage voluntary development and
    implementation of innovative approaches to
    pharmaceutical manufacturing and quality
    assurance.
  • Many new technologies that provide information on
    physical, chemical, biological characteristics of
    materials will help in improving process
    understanding, predict quality and performance.
  • Regulatory expectations are so high that
    manufacturers are expected to use such
    technologies to improve efficiency and
    effectiveness of process design, manufacturing
    controls and quality assurance.

24
Process Analytical Technology (PAT)
  • Gains in quality and efficiency from PAT could
    vary and are likely to come from
  • reducing production cycle times by using on-line
    measurements and controls
  • preventing rejects, scrap and re-processing
  • real time release
  • increased automation to improve operator safety
    and reduce human errors
  • improving energy and material use and increasing
    capacity
  • facilitating continuous processing to improve
    efficiency and manage variability
  • The integrated quality system orientation affords
    a flexible regulatory approach for implementation
    of PAT under the facilities own quality system

25
Indian Pharmaceutical Companies geared up for
global market Quality Management for 21st
Century Quality Risk Management Product
Development Process Analytical Technology
(PAT) Regulatory Review Conclusion
26
Regulatory Review
  • Regional differences in the regulatory review
    processes such as filing of changes are adding
    complexity to manufacturers during the product
    life cycle.
  • Now considerable emphasis is being placed on
  • Assessment of possible Genotoxic impurities
  • Crystal characteristics
  • Polymorphism
  • Enantiomeric purity besides residual solvents,
    organic and inorganic impurities
  • Metal catalytic residues

27
Regulatory Review
  • The regional differences in the regulations and
    the different requirements for the same monograph
    as per different Pharmacopoeias pose its own
    challenge to the Industry.
  • Compelling necessity to develop a bank of
    reference standards
  • Increasing emphasis by the WHO and its
    expectation for the APIs for WHO markets to be
    compliant with the international pharmacopoeia,
    has raised an additional point of complexity.
  • One hopes that WHO also joins the initiative of
    harmonization and international pharmacopoeia
    gets harmonized with other standards of
    reference.
  • It is important for the manufacturers to design
    and develop their operations with the aim of
    avoiding excessive changes to their products
    during its lifecycle.
  • This would save precious time as well as
    resources for the organization.

28
Indian Pharmaceutical Companies geared up for
global market Quality Management for 21st
Century Quality Risk Management Product
Development Process Analytical Technology
(PAT) Regulatory Review Conclusion
29
Conclusion
Quality Guru Deming has the following to say on
variability inspection - Depending on
inspection is like treating a symptom while the
disease is killing you. The need for inspection
results from excessive variability in the
process. The disease is variability. Ceasing
dependence on inspection means you must
understand your processes so well that you can
predict the quality of their output from upstream
activities and measurements. To accomplish this,
you must have a thorough understanding of the
sources of variation in your processes and then
work toward reducing the variation. Ceasing
dependence on inspection forces you to reduce
variability.
30
Conclusion
To conclude, the API industry needs to evolve to
a desired quality system
Present Focus Desired Focus
Documentation Trend Data analysis
Have SOPs Understand parameters that are critical to quality attributes
Follow SOPs Measure process capability
Validate process Perform continuous quality verification
Meet specifications dont change Undertake continuous improvement
31
Thank you
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