Implementation of ICH Q8, Q9, Q10

Workshop C
Pharmaceutical Quality
System (PQS)

International Conference on Harmonisation of Technical

Requirements for Registration of Pharmaceuticals for Human Use
 ICH Quality Implementation Working Group - Integrated Implementation Training Workshop

Workshop C: Pharmaceutical Quality System

Disclaimer

The information within this presentation is based

on the ICH Q-IWG
Q IWG members expertise and
experience, and represents the views of the ICH
Q-IWG members for the p purposes
p of a training
g
workshop.

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 ICH Quality Implementation Working Group - Integrated Implementation Training Workshop

Workshop C: Pharmaceutical Quality System

Introduction
• Structure of this session

- Presentation of key messages on Pharmaceutical

Quality System
- Examples
p from the Case Studyy
- Discussion in one or more sub groups on
the key questions
- Wrap up
- Breakout report

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 ICH Quality Implementation Working Group - Integrated Implementation Training Workshop

Workshop C: Pharmaceutical Quality System

Key message on Pharmaceutical

K Ph ti l Q
Quality
lit
System as proposed by ICH Q10
• Building quality into the product during development is fundamental.
• ICH Q10 is one model of a PQS which reinforces and introduces
some elements beyond GMP
• N intent
No i t t in
i ICH Q10 tto create
t new expectations
t ti beyond
b d currentt
regulatory requirements
• Introduces the involvement and role of senior management
• Introduces a product life cycle perspective
• Implementation of PQS should provide enhanced assurance of quality
• Quality Risk Management principles are essential to build an accurate
PQS along the lifecycle of a product
• Knowledge Management and PQS are interrelated
• PQS approach applies to Drug Substance/ Active Pharmaceutical
Ingredient (small molecule & biotech) and Drug Product/ Medicinal
Product/ Pharmaceutical Product

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 ICH Quality Implementation Working Group - Integrated Implementation Training Workshop

Workshop C: Pharmaceutical Quality System

What is ICH Q10?

• ICH Q
Q10 is a guideline
g on the essential elements of a PQS
Q
through out the life cycle of a product
- GMP is applicable to the Manufacturing part of the life cycle
- Manufacturing of Investigational (medicinal) Product
- Manufacturing of commercial products
- A ICH Q10 type PQS reinforces/introduces some elements e.g.
- Link manufacturing and development (incl. feedback)
- Continual improvement
- Involvement of senior management
g
- Quality Risk and Knowledge management
- Product Transfer and discontinuation
- Management of Outsourcing and purchasing material

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 ICH Quality Implementation Working Group - Integrated Implementation Training Workshop

Workshop C: Pharmaceutical Quality System

IIntroduces
t d the
th involvement
i l t and
d role
l off
senior management
• The decision to have enhanced development approaches
(QbD) reinforces the need for a strong link between quality
systems in development and manufacturing
• Senior management demonstrate commitment to the PQS by :
- Granting adequate resources to implement, support and manage
the PQS
- Communicating g the importance
p of the PQS
- Ensuring strong interfaces between all relevant functions e.g.
Development, manufacturing, Quality Unit (QA, QC, QP),
engineering, supply chain and management of outsourced
activities
- Participation in the system through the conduct of management
review (including process performance) of the PQS and product
quality review

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 ICH Quality Implementation Working Group - Integrated Implementation Training Workshop

Workshop C: Pharmaceutical Quality System

I
Introduces
d a lif
life cycle
l perspective
i

• The development of a product is done under the framework of

a PQS that is appropriate and proportionate e.g.
- It should be
- a general system (not product specific) such as organisation,
quality policy, general documentation e.g. procedures,
records, decisions, archiving
- a system dedicated to products
for example facilitating a
comprehensive
p understandingg
of the development that feeds
into manufacturing

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 ICH Quality Implementation Working Group - Integrated Implementation Training Workshop

Workshop C: Pharmaceutical Quality System

P d
Product lif
life cycle
l – Example
E l ffrom a
case study

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 ICH Quality Implementation Working Group - Integrated Implementation Training Workshop

Workshop C: Pharmaceutical Quality System

API Unit Operations

Coupling Reaction Coupling of API Starting Materials

Removes unreacted materials Done

Aqueous
q Extractions cold to minimize risk of degradation

Distillative Removes water, prepares API

Solvent Switch for crystallization step

Semi Continuous Addition of API in solution and

Crystallization anti-solvent to a seed slurry

Centrifugal Filtration Filtration and washing of API

Drying off crystallization solvents

Rotary
y Drying
y g

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 ICH Quality Implementation Working Group - Integrated Implementation Training Workshop

Workshop C: Pharmaceutical Quality System

Tablet Formulation

Pharmacopoeial
or other
compendial
di l
specification

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 ICH Quality Implementation Working Group - Integrated Implementation Training Workshop

Workshop C: Pharmaceutical Quality System

Drug Product Process

API and Excipients
Amokinol
D-mannitol Blending
Calcium hydrogen phosphate hydrate
Sodium starch glycolate
Lubricant
Magnesium Stearate Lubrication

Compression
Coating
HPMC，Macrogol 6000
titanium oxide Film coating
iron sesquioxide

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 ICH Quality Implementation Working Group - Integrated Implementation Training Workshop

Workshop C: Pharmaceutical Quality System

Process Steps

Drug Substance Drug Product

Semi-Continuous

Moisture Control
witch

ation

Rotary Drrying

Compresssion
Manufactture
ons

Lubrication
gal

Packagiing
Distillative
ng
on
us

ng
on
Solvent Sw

Coating
Centrifug
Crystalliza
Aqueou
Couplin
Reactio

Extractio

Blendin
Filtratio
CQA

i vivo
in i performance*
f *
Dissolution
Assay
Degradation
C
Content U
Uniformity
if i
Appearance
Friability
Stability-chemical
Stability-physical

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 ICH Quality Implementation Working Group - Integrated Implementation Training Workshop

Workshop C: Pharmaceutical Quality System

Product life cycle – Example from the case

study
• The PQS ensured
- The Quality Risk Management processes were performed at
key stages by involvement of the right technical disciplines
- Selection of appropriate tools respecting the different
aspects of the QRM process and appropriate training
- Defined and documented processes as required in the PQS
- Appropriate management review

• The knowledge gained during the

development process was captured
and shared with manufacturing

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 ICH Quality Implementation Working Group - Integrated Implementation Training Workshop

Workshop C: Pharmaceutical Quality System

The PQS should be fit for purpose

• Applied in a structured and consistent manner that is
appropriate and proportionate to each of the product lifecycle
stages
• Implementation of PQS/Q10 type take into account the size
and complexity of the company’s activities (incl. products)
• The vision,, objectives,
j , design
g and the implementation
p should
be pragmatic, clear and therefore understood
- The PQS must be linked to real practices and integrated into
daily work

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 ICH Quality Implementation Working Group - Integrated Implementation Training Workshop

Workshop C: Pharmaceutical Quality System

Knowledge Management and PQS

• The company should capture and use knowledge gained during
development and manufacturing using a systematic approach
- For continual improvement of the current products as well as
future products
- Each company should consider how this is achieved
• Examples
- QTPP may evolve during lifecycle – during development and
commercial manufacture - as new knowledge is gained
- The Control Strategy is adapted from lessons learned during
product transfer and commercial manufacturing
- Use of prior knowledge of similar products at the manufacturing
site

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 ICH Quality Implementation Working Group - Integrated Implementation Training Workshop

Workshop C: Pharmaceutical Quality System

Topics to discuss (1)

• Is a PQS
Q mandatory?y Is ICH Q10Q mandatory? y
• What is the added value for a company in implementing an ICH
Q10 type PQS across the life cycle?
• Wh t modifications
What difi ti tto a company’s’ existing
i ti PQS iis envisaged
i d tto
meet ICH Q10 intentions?
• How can Q10 type PQS facilitate in handling an enhanced
development approach?
• How might a PQS support continual improvement?
• What do you see as the top 3 ‘high
high risk
risk’ elements that are
managed by a PQS?
• Are there any barriers to practical implementation of an ICH Q10
t
type PQS?

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 ICH Quality Implementation Working Group - Integrated Implementation Training Workshop

Workshop C: Pharmaceutical Quality System

Topics to discuss (2)

• Which PQS elements do you think are most useful in a
development site?
• Is it necessary to describe PQS elements in regulatory submission
(Q-CTD)?
• What is important in a PQS at the global/corporate level and at the
local/site level?
• What are the key elements to settle before designing a PQS ?

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