Challenges and opportunities in implementing ICH Q8, Q9

Challenges and opportunities in implementing ICH Q8, Q9 and Q10.

Jacques Morénas

pharmacien général de santé publique, assistant director

Inspectorate and Companies DepartmentThe French Health Products Safety Agency (AFSSAPS)

telephone : 33 1 55 87 39 17fax : 33 1 55 87 39 12

e-mail : [email protected]

Workshop on implementation of ICH Q8/Q9/Q10 and other quality guidelines : Beijing 3-5 December 20082

Contents

General considerations

Main challenges

Main opportunities

Conclusions



After all these presentations, we may think that we are really entering in a new world ……

But looking at this figure made by Kowid Ho, (AFSSAPS’sassessor in the field of biotech products), comparing traditional approach versus QbD approach for requesting marketing authorisation, I am not so sure ….


CQA

non-CQA

CPP

Specification

Enhanced

IPT + PAT

Specification 1 Attribute Y

Specification XAttribute Z

End testing and/or

alternative approach

non-CPP

Traditional versus "Enhanced approach"

Process

Starting/raw material 1

Starting/raw material X

… Product

Output

Intermediate

RE

LE

ASE

TraditionalSpecification 1

Specification X

CQA

non-CQA

CPP

non-CPPSpecification

IPT + PAT

End testing and/or

alternative approach

Inputs

Design space

CONTROL STRATEGY

CONTROL STRATEGY



For an EU regulator’s point of view, it seems that many ideas expressed in ICH Q8, Q9 and Q10 are traditional ones with a new look or stabilised definitions between the 3 ICH regions.

So, we need to be very careful not introducing confusions and throwing old good sense into the rubbish bin and explaining we are facing amazing new concepts.


Main challenges

Many seminars, workshops, meetings, publications for explaining these 3 documents in which self-proclaimed “experts” :- develop new concepts never defined in one of the 3 documents as “clinical quality”,- use concepts defined in one of the 3 documents but developing their own interpretation using “ICH based definitions”,- invent systems impossible to understand as PQS based on Quality by Design,- propose very complicated pictures which are extraordinary mazes for good sense as in the following slide ….


Main challenges


Main challenges

So, from harmonised guidance it is still possible for developingdifferent implementations and uses between the 3 regions.

These documents have been drafted between regulators and industry representatives coming mainly from big pharmaceutical companies. It is very important to explain that medium and smallones can also use these documents for obtaining the same benefits. They are not only reserved to big pharmaceutical companies use.


Main challenges

These documents should be confusing by themselves with other ICH guidance. They are using same wording but with different meanings and it is very important to carefully linked concepts and the reference of ICH document.

A good example should be ….


Main challenges

Design space

The multidimensional combination and interaction of input variables (e.g., material attributes) and process parameters that have been

demonstrated to provide assurance of quality (ICH Q6A).

CPPSpecification 1 Attribute Y

Specification XAttribute Z

Design spacenon-CPP

Y

W

Z


Main challenges

Quality (ICH Q6A) : The suitability of either a drug substance or drug product for its intended use. This term includes such attributes as the identity, strength and purity.

Quality (ICH Q9) : The degree to which a set of inherent properties of a product, system or process fulfills requirements.


Main challenges

These documents are shared between ICH regions (and some observers). Local regulations should be impacted by them for increasing the level of harmonisation (as for example the changes in the variations regulation in the EU).

Industry and Regulatory Authorities are putting a lot of resources for developing and implementing these documents. And all are nowfacing decreasing of resources or increasing of tasks (or both).

It is important to convince non-ICH regions to use these documents.


Main challenges

Confusion should be also between PQS as proposed in ICH Q10 (dedicated to a product through its entire lifecycle) and PQS asimplemented in a manufacturing site (as mentioned in GMP guides).


Main opportunities

Facilitating regulatory and industry activities in the 3 regions.

Sharing of resources between Industry but also between Regulatory Authorities.

Developing an integrated assessment for new request for marketing authorisation between assessors and GMP inspectors.

Using risk management in both Industry and Regulatory Authorities (for example planning GMP inspections or assessing quality defects and avoiding unnecessary recalls).


Main opportunities

At the EU level, works done into the PAT team located at the EMEA.

It is consisting of assessors and inspectors coming from various Member States, leaded by Keith Pugh (MHRA).


Main opportunities

EFPIA/ PAT seminar course in Ireland in April 2008 :

-- Multidisciplinary experience with biotech and chemical Multidisciplinary experience with biotech and chemical representatives, including inspectors and assessors, EMEA representatives, including inspectors and assessors, EMEA and EDQM,and EDQM,

-- Two companies volunteered for mock inspectionsTwo companies volunteered for mock inspections : : WyethWyeth(Dublin) and Pfizer (Cork),(Dublin) and Pfizer (Cork),


Main opportunities

-- Very interesting outcomes have been discussed as for Very interesting outcomes have been discussed as for example :example :

* * Knowledge transfer process (Development Knowledge transfer process (Development Manufacturing) Manufacturing) and knowledge management should be formalised,and knowledge management should be formalised,

* Design space and its parameters should be managed under* Design space and its parameters should be managed underQuality Management System.Quality Management System.


Main opportunities

* * Review of Raw Data during Inspections :Review of Raw Data during Inspections :

Ensure appropriate Quality Management Systems are in Ensure appropriate Quality Management Systems are in place to support development,place to support development,

Assessor needs to ensure Design Space and Real Time Assessor needs to ensure Design Space and Real Time Release Testing are based on valid data.Release Testing are based on valid data.


Conclusion

After this presentation, you might think :

So many challenges for a successful implementation of Q8, Q9 and Q10 …. !!!

And be fully desperate !!


Conclusion

In fact, my advice is “be reasonably optimistic !!!

Looking from where we come and the journey for drafting ICH Q8, Q9 and Q10 and starting work in the implementation group ….

I think the more complicated is behind us.


Conclusion

It is obviously a big challenge for regulators and industry to have this understanding and implementation but, in 5 years, I saw :

How confidence between regulators and industry is beginning to grow,

The interest to better define concepts already existing sharingcommon understanding and way to use them,

The shared will to work together from virtual concepts to practical implementation,

The strong wish to facilitate innovation and envisage “regulatory flexibility” within the common interest of protecting patients and public health.


Thanks

to you for your attention

Documents

Challenges and opportunities in implementing ICH Q8, Q9