CMC Strategy Forum

Prague 2013

Enda Moran

EBE Satellite Session, 06 May 2013

European Biopharmaceutical Enterprises

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EBE’s VISION:

fostering innovation, and promote favorable business and regulatory conditions

for biopharmaceutical enterprises of all sizes in Europe.

• Increasing awareness of the tangible benefits of biopharmaceutical innovation to

patients and society

• Promoting connectivity between big and small pharma and biopharma

• Helping the development of policies at European level that support biopharmaceutical

innovation, regulatory and entrepreneurial conditions

• Delivering resources and access to technical & regulatory expertise, research and

funding partnership opportunities, education & training on all aspects of the

biopharmaceutical sector

• Through collaboration within EFPIA and its working groups, strengthen representation on

specific issues relating to biotech and small & medium size enterprises in

biopharmaceutical sector.

EBE’s MISSION:

advocating the benefits of a healthy biopharmaceutical industry vis-à-vis all key

stakeholders and to nurture a healthy membership base by:

European Biopharmaceutical Enterprises European Biopharmaceutical Trade Association

• Non-profit organisation, governed by a board of

directors and annual general assembly. Managed by an

executive team based in Brussels.

• Established in 2000 as a specialised group of EFPIA,

European Federation of Pharmaceutical Industries and

Associations.

• 53 members to date.

• 9 working groups on variety of key topics related to

biopharmaceutical industry.

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European Biopharmaceutical Enterprises

Members ( April 2013 )

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EBE Structure

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Biosimilars Rare Diseases and

OMP Advanced Therapies BioManufacturing Pharmacovigilance

Personalised Medicines

Models for innovation and funding

Public Affairs & Regulatory – Technical expertise

EBE Board – Strategy Setting

Value Add to EBE Members

Connectivity

Pharma - Biotech

European Policy

Development

Biotech Sector

Awareness

Resources:

Information &Training

EBE TEAM – Execution and Management of Working Groups

European Biopharmaceutical Enterprises

www.ebe-biopharma.org

( Our website is currently under re-construction. We apologise for any

inconvenience and look forward to welcoming to our new EBE website

as from July 2013. )

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Reflection – 2012 Concept papers discussed at CMC Forum Berlin 2012

• Satellite session at the

CMC Strategy Forum,

Berlin.

• Concept Papers

- Setting specifications

- Platform

manufacturing

CMC Strategy Forum Europe 2012 Monday, April 23, 2012 - Wednesday, April 25, 2012

Concept papers on Setting Specifications &

Platform Manufacturing now available

Will be accessible via www.ebe-biopharma.org July2013: site being updated.

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Industry representatives & BWP Discussed Process

Validation at EMA, London on 09 Apr 2013

• Industry / BWP workshop

on Process Validation

• A valuable ‘check-in’

before furthering the

forthcoming PV guideline

for biotechnology-derived

drug substances

• More later...........

New Concept Paper. I Forced Degradation Studies

• Describe approaches and best practices amongst biopharmaceutical

companies in the design and execution of Forced Degradation Studies

(FDS).

• Rationale & drivers:

• Very few regulatory guidances on FDS

• Lack of clarity on what should be done at each development phase,

both from a regulatory and a scientific perspective.

• New topic group lead by Annick Gervais, UCB and involving 6 other EBE

Member Companies

Janssen Biologics

MedImmune

Merck-Serono

Novo Nordisk

Sanofi Swedish Orphan BioVitrum

Expected Content

• Why a FDS?

• When to initiate a FDS?

• Which clinical Phase?

• Which Stressing Agents?

• What are the relevant

stressing conditions? In which

case?

• How to design a FDS?

• What are the limitations?

• What is the extent of

degradation to achieve?

• How to define the acceptance

criteria for comparability?

Forced Degradation Studies

Possible Degradation

Pathways

Understand CQA Candidate

Selection

Manufacturing Process

Development

Formulation Development

Product Related Species

Characteri-sation

Comparability

Method Development

Stability Indicating Methods

Temperature Excursions

Storage / freeze-thaw

Stability Predictor

New Concept Paper. I Forced Degradation Studies

• Describe approaches and best practices amongst biopharmaceutical companies in the design and execution of Forced Degradation Studies (FDS).

• 2013 Plans:

Kick-off meeting 3rd May 2013

Shape and structure of

paper laid out Table of Contents, subject matter to

be discussed, types of study

examples to be described, data to

be included….

Q4 2013

New Concept Paper. I Forced Degradation Studies

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• Problem statement - By reference to Ph. Eur. Monograph # 2031 “Monoclonal antibodies for

human use”, EU Health Authorities can request to define as acceptance criteria “without visible particles” for the Drug Product appearance during assessment of late stage Clinical Trial Application or Marketing application “Practically free of visible particles” is challenged as a QC acceptance

criterion

- Even with best formulation optimization effort supported by excellent long term stability studies, stress stability studies (e.g. agitation), without (zero) Visible Particles is an unrealistic requirement for QC release/shelf life testing the baseline should be practically free of visible particles

- Setting acceptance criteria corresponding to “practically free of visible particulates or setting acceptance criteria when visible proteinaceous particles are unavoidable is a topic that require some discussion/ harmonization in the industry

New Concept Paper. II Visible Particles

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New Concept Paper. II Visible Particles Topic Group

• Lead: Serge Mathonet, Sanofi, Global Reg Aff R&D - Biotherapeutics CMC

+ Experts from Sanofi, Roche, Novo Nordisk, MedImmune, Abbvie, J&J

• Deliverable: Concept paper: available for consideration by industry, BWP, EDQM etc. - Scope:

Monoclonals - Filled vials, syringes and pens (clinical and commercial supplies)

- Content Problem statement Best practices in the industry in term of visual inspection process and

associated operator training, QC sampling, testing and setting acceptance criteria corresponding to “practically free of visible particles” or settting acceptance criteria when visible proteinaceous particles are unavoidable.

Consideration for particles ID, characterization and qualification

- Timelines Development of position paper in 2013 Kick off 20 Feb 2013 2nd draft being discussed

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New Concept Paper. II Visible Particles: On-going discussion items

• Categorisation of extrinsic/intrinsic particles defects into minor, major or critical

• 100 % visual inspection: Number of units to be re-inspected if one defect is found

• Operator certification program (manual/semi-automated 100 %inspection and AQL verification):

• Non destructive versus destructive particle testing and influence on sample size - vials, pre-filled syringe and pre-filled pens

• Acceptance criteria: AQL and QC testing (release/stability)

• Role of Quality investigation into the cause of an initial failure for decision making (re-inspection or lot release)

• Pre-Clinical/Clinical qualification of intrinsic particles

EBE Satellite Session Agenda

09:00 – 09:15 Welcome and Introduction to the European Biopharmaceutical Enterprises (EBE) Ongoing Activities and Initiatives.

Enda Moran, Pfizer Ltd., Grange Castle, Ireland 09:15 – 09:30 EBE Interest Topic

Bioburden Control at the Sterile Filtration Step: A risk-based approach Ray Field, MedImmune, UK