qbd approach and regulatory challenges in europe · implementation of ich q8-10 using actual...

An agency of the European Union

QbD approach and Regulatory Challenges in EuropeDIA 26th Annual EuroMeeting, Vienna 2014

Dr Peter Richardson

Head of Quality, European Medicines Agency

QbD approach and Regulatory Challenges in Europe1

Disclaimer

The views and opinions expressed in the following PowerPoint slides are those of the individual presenter and should not be attributed to Drug Information Association, Inc. (“DIA”), its directors, officers, employees, volunteers, members, chapters, councils, Special Interest Area Communities or affiliates, or any organization with which the presenter is employed or affiliated.

These PowerPoint slides are copyright of the European Medicines Agency. Reproduction is permitted provided the source is acknowledged.

Re-organisation of the EMA

Focus on how to better:

• support the scientific work of the of the EMA committees; • share the knowledge and information the Agency holds

throughout the EU medicines regulatory network; • meet the need of the Agency’s stakeholders and partners.

• Therapeutic area Offices lead Product Teams.

• Additional functions – Offices / Services support to procedures and processes, rationalising activities where possible.

• Administrative / procedural aspects separated from scientific –regulatory support.

• Quality Office : further integration of chemicals and biologicals..


New EMA Structure - Quality

Management structure: Divisions / Departments / Offices

• Human Medicines Research and Development Support Division• Human Medicines Evaluation Division,

- Scientific and Regulatory Management Department

- Specialised Scientific disciplines Department

- Quality Office (chemicals and biologicals)

• Procedure Management and Business Support Division


http://www.ema.europa.eu/ema/index.jsp?curl=pages/about_us/general/general_content_000112.jsp&mid=WC0b01ac0580028c2c

What is Quality by Design (QbD) – ICH Q8(R2)

• Systematic approach to development

– may include, e.g. incorporation of prior knowledge, results of experimental studies using design of experiments, use of quality risk management, and use of knowledge management throughout the lifecycle of product

• Science applied across the lifecycle of the product / process within a Quality Management System.


Purpose of QbD ?

Primarily:

• Develop robust manufacturing processes, increased understanding of important factors and explanation of sources of variability.

Consequently:

• Provide increased assurance on process control and consistency, may alleviate regulatory oversight.


Evolution of QbD: ICH Guidelines / Q&A / Training


‘Questions and Answers’ ‘Points to consider’ ‘Training & Workshop’http://www.ich.org/products/guidelines/quality/article/quality-guidelines.html

Evolution of QbD:some EU Experiences

• QWP, BWP, GMP IWG & PAT Group

- PAT Group : Landing point for Applicants

- Evolving expertise within network

• More activity for Chemicals v Biologicals

• Diversity in each application

- Expectation, Creativity, Complexity

• Considerable effort invested

• International regulator’s interacting


EMA-FDA QbD pilot


•Allow EU and US assessors exchange their views on the implementation of ICH Q8-10 using actual applications and facilitate harmonisation

•Share knowledge gained with the EU network and Industry through lessons learnt

•Japan joined as an observer

Aim

•Submissions that include an enhanced approach to pharmaceutical development leading to the use of at least one of the following:

•Design space,

•PAT tools for control,

•Continuous process verification,

•Models to support real time release testing,

•Continuous processes

•Post-approval regulatory flexibility

Scope

http://www.ema.europa.eu/docs/en_GB/document_library/Other/2011/03/WC500103621.pdfhttp://www.fda.gov/downloads/InternationalPrograms/FDABeyondOurBordersForeignOffices/EuropeanUnion/UCM259808.pdf

EMA-FDA QbD pilot


Two options:

•The application is submitted to both agencies at about the same time, for MAAs/NDAs for parallel evaluation by both agencies

Parallel assessment: 1 application

complete

•The application is submitted to either EMA or FDA and the agency doing the evaluation requests to obtain consultative advice from the other agency

Consultative advice: Several ongoing

•Chemicals•There are also interactions on biologicals.Type of products:

EMA / FDA – parallel assessment


Renewed for 2 years

(until March 2016)

EMA-FDA Pilot for QbD – Progress to Date

• Applications in program

- 1 parallel assessment complete, another accepted

- 5 consultative advice

- 1 biotech product that followed the consultative advice pathway

• Meetings

- Multiple teleconferences on applications and on general topics

- 3 face-to-face meetings

• Communications

- 2 sets of Q&As published, others being developed

- Many conference presentations

• Japanese participation

- Parallel assessment application and in multiple meetings


EMA-FDA QbD Pilot Question & Answers

• Two sets of Q&As have been published jointly as a result of the pilot (8/20/13 and 11/4/13):

http://www.ema.europa.eu/docs/en_GB/document_library/Other/2013/08/WC500148215.pdf

http://www.ema.europa.eu/docs/en_GB/document_library/Other/2013/11/WC500153784.pdf

• Topics include:

- Expectations for Quality Target Product Profile (QTPP)

- Expectations for Critical Quality Attributes (CQAs)

- Classification of criticality in 3 tiers (e.g., Key Process Parameters)

- Expectations for the manufacturing process description

- Use of QbD for analytical methods (e.g., Analytical Target Profile (ATP) and Method Operational Design Ranges (MODR)

- Design space verification



13

Preliminary feedback: QbD Pilot

Close Agreement on:

- QTPP and CQAs

- Criticality

- Design Space verification

- Level of detail in manufacturing process descriptions

- QbD for Analytical Methods


http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/UCM359265.pdf

Quality by Design : Current Status

A lot of progress in the recent past- More science based applications- More scientific understanding (DoE), emphasis on

• Robust manufacturing processes• Control Strategy

Opportunities:- Real Time Release Testing- Manufacturing flexibility (Design Space)- Focused dossier / reduced variations ?


Quality by Design : issues

Problems raised by Regulators and Industry

• More science but more questions !?

• Level / amount of data / information requested or submitted in an application not clear.

• Quality of information submitted in some cases.

• Why invest in systematic or QbD approach if no benefit ?

• Terminology !


QbD Workshop - Jan 2014


Six case studies (1 Bio). Team for each composed of industry and regulators. FDA & PMDA repesented.

Best practices – proposed recommendations.

Highly successful, with many participants, also online.

Outcomes, presentations and meeting video will be published on Agency website.

http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/events/2013/12/event_detail_000808.jsp&mid=WC0b01ac058004d5c3

Discussion Topics

1. Risk Assessment and Criticality

2. Design Space

3. Use of Models

4. Control Strategy

5. Lifecycle management

6. The Development Story and presentation of Information in Submissions

7. Dossier – Quality System interactions


e.g. Risk Assessment

FMEA: numbers should be objectivehowever not absolute.

Important to provideevidence basis (i.e. thesupporting science for proposals).

Level of detail needed?


e.g. Risk Assessment

Perjeta (mAb) - EPAR


QbD Approach:

QbD: Challenges and way forward


020406080

100

Step 0 Step 1 Step 2 Step 3

Investissement Regulatory Challenges Benefits

Step 0-1 Investment

Immediate benefit :

Process understanding

Efficiency & yield improvement

OOS & Recall decrease

Supply Secured

Step 1-2 LearningTraining & pilot

Implementation of

Regulatory Trust & harmonisation

Step 3 full BenefitTrust & predictability

Streamline regulatory review

Regulatory flexibility

Global Regulatory Alignment

Continuous improvement

Post-approval changesCritical

step

G. France: QbD Workshop Jan14

Thank you

Peter Richardson Head of Quality

Specialised Scientific Disciplines DepartmentEuropean Medicines Agency

[email protected] | www.ema.europa.eu

Acknowledgements:

• Jean Louis Robert (QWP)

• Evdokia Korakianiti (EMA)

• Christine Moore (FDA)

• Georges France (Novartis)


qbd approach and regulatory challenges in europe · implementation of ich q8-10 using actual...

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