Seminars

Seminar 1: European pharmaceutical regulatory environment

Content

  • The European Pharmaceutical Legislation
  • The regulatory institutions and other stakeholders
  • Interaction of international regulatory agencies
  • General requirements for the Common Technical Document (CTD), the Marketing Authorisation Dossier - Modules 1 and SmPC, Module 2, Risk Management Plan
  • Special legal provisions for biopharmaceuticals
  • Orphan Drug Designation - provisions and procedures
  • SME - provisions and procedures
  • Principles of registration and certification of medical devices and device/drug combinations

The subject area regulatory affairs ensures that the quality, safety and efficacy of the medicinal product is in line with legal requirements for the purpose of marketing safe and efficacious medicinal products solely in the interests of public health. Regulatory affairs is primarily a specialty of the pharmaceutical industry. The function encompasses all strategic, operational and administrative activities required to obtain official authorisation for Clinical Trials, marketing and distributing of medicinal products, post-marketing changes and obligations and manufacture and the activities related to pharmacovigilance. Seminar 1 provides the basis for all activities of a regulatory affairs professional since it imparts detailed knowledge on the pharmaceutical legislation, the regulatory institutions and stakeholders and their interaction and on the Modules 1 and 2 of the marketing authorisation dossier. Modules 3, 4 and 5 of the marketing authorisation dossier are dealt with in Seminar 4 of this course, specifically describing what is relevant for biopharmaceuticals. This seminar furthermore deals with the particulars of small and medium size enterprises and all regulations related to biopharmaceuticals. It also provides the legal details on orphan drug regulations and on the role and activities of the ICH process.

Learning Objectives

  • Understand the legal basis of authorisation of medicinal products and registration of medical devices and drug/device combinations
  • Provides you with a clear understanding of the EU regulatory system and its stake holders
  • Understand the structure of the EMA and its role
  • Understand the special legal requirements for biopharmaceuticals
  • Understand the principle of the orphan drug designation
  • Understand the incentives dedicated to SMEs and the process to obtain a SME status
  • Provides you with hands-on knowledge on the Common Technical Document, Modules 1and 2

Agenda

Day 1

09.15 - 10.15 Welcome and introduction to the whole MSc EUCRAF course on biotech-related regulatory affairs


10.15 - 11.00 Introduction into the European regulatory system

  • How are medicines and devices regulated and why? 
  • What is regulatory affairs?

11.00 -11.30 Coffee break

11.30 - 13.00 The European Pharmaceutical Legislation

Essential terms and provisions of the framework defining the marketing of pharmaceutical medicinal products in the EU/EEA

  • The Common Market in the EU/EEA
  • Approval and distribution of medicinal products in the EU
  • Regulations and directives determining the pharmaceutical legislation applicable to the EU/EEA and national pharmaceutical law of the EU member states
  • Notice to applicants
  • Obligations of the marketing authorisation holder
  • Global Marketing Authorisation
  • Data protection and patents
  • Types and procedures of referrals

13.00 - 14.00 Lunch

14.00 - 15.00 Continued

15.00 - 16.00 The regulatory framework for drug/device combination products

  • The EU regulatory framework for drug/device combination products
  • The specific case of combined ATMP
  • The US regulatory framework for drug/device combination products
  • The key challenges raised by drug/device combination products

16.00 - 16.30 Coffee break

16.30 - 18.30 continued

18.30 End of Day 1

19.00 Get-together with food and wine

Day 2

09.15 - 11.15 Regulatory institutions and other stakeholders of the European system of pharmaceuticals, their functions and role

  • Role of the Parliament, Council, EU Commission, DG SANCO
  • Working effectively with the EMA

o Legal basis, role, structure and procedures

o Executive Director

o Management Board

o Secretariat: EMA’s support of the authorisation process of medicinal products

o Involvement of external experts

o QRD product information, invented name requests

o Transparency, communication and publications

o European Public Assessment Report (EPAR)

o Annual Report

  • EMA Scientific Committees, their interaction and their working parties

o CHMP, PRAC, COMP, PDCO, CAT

o Expert committees SAG

  • Involvement of patient organisations
  • The national agencies of the EU/EEA member states
  • The HoA network
  • The Industry trade associations
  • Involvement of patient organisations

11.15 - 11.45 Coffee break

11.45 - 13.45 Continued

13.45 - 14.45 Lunch

14.45 - 16.15 Why are biopharmaceuticals special? What legal particulars for biopharmaceuticals do we have?

  • Advanced therapies
  • Emerging therapies and technologies
  • Biosimilars
  • Plasma and Vaccine Antigen Master Files
  • Genetically Modified Organism (GMO)
  • Batch release
  • Small and Medium Size Enterprises (SME)

16.15 - 16.45 Coffee break

16.15 - 18.15 continued

18.15 End of Day 2

Day 3

The Common Technical Dossier (CTD)

09.15 - 10.30 Format and content of the marketing authorisation application: The Common Technical Dossier (CTD)

  • General aspects of the harmonised CTD
  • eCTD

Module 1 of the CTD: General information

  • Application form
  • Application numbering
  • Multiple applications: co-marketing and co-promotio
  • Strengths
  • Fees and reduced fees
  • Proposals (Mock-ups) for packaging, labelling and package inserts
  • Specimens
  • INN
  • ATC codes
  • Environmental Risk Assessment (ERA)

Labelling, Package Leaflet and Summary of Product Characteristics (SmPC)

  • Readability test, Braille, Blue Box

10.30 - 11.00 Coffee break

11.00 - 13.00 continued

13.00 - 14.00 Lunch

14.00 - 16.00 Module 2 of the CTD

Table of Contents (Module 2 – 5)

  • Module 2.3 Quality Overall Summary
  • Module 2.4 Nonclinical Overview
  • Module 2.5 Clinical Overview
  • Module 2.6 Nonclinical Summary
  • Module 2.7 Clinical Summary

Risk Management Plan (RMP)

16.00 - 16.30 Coffee break

16.30 - 18.00 continued

18.00 End of Day 3

Day 4

09.15 - 10.45 International collaboration of agencies

  • ICH process: collaboration of the three regions EU, US and Japan
  • Collaboration with FDA
  • Collaboration with other agencies: China, India, Brazil

10.45 - 11.15 Coffee break

11.15 - 12.45 Orphan Medicinal Products in the EU/EEA

  • Legal basis and provisions
  • Orphan designation
  • Orphan status
  • Market exclusivity and further incentives
  • Annual report
  • Register
  • Marketing authorisation procedure
  • Strategy

12.45 - 13.45 Lunch

13.45 - 15.30 continued

15.30 - 16.00 Coffee break

16.00 - 17.00 Small and Medium Size Enterprises (SME)

  • The particular conditions applicable to Small and Medium Size Enterprises (SME) and the SME office of the EMA
  • SME Regulation and Incentives
  • Type of companies assigned SME status
  • What does the SME Office deliver
  • Scientific advice

17.00 End of Seminar 1

For Full Course students:

Day 5

09.15 - 11.15 Questions and answers

11.15 - 12.15 Working Lunch

12.15 - 14.00 Written Exam

14.00 End of Seminar 1 for Full Course students

Dominique Monferrer

Seminar 2: Regulatory Procedures for clinical trial applications, marketing authorizations, variations in the EU, USA, Japan and China

Content

  • The European centralized procedure at the EMA
  • MRP and DCP
  • CTA in Europe – process, VHP, particulars for biopharmaceuticals
  • Variations - changes to the CTD, procedures, data particulars for biopharmaceuticals
  • Changes to the SmPC
  • Approval in other regions - process and essentials of the relevant agencies

Seminar 2 provides in-depth knowledge on the procedures for marketing authorization applications, clinical trial authorisations and variations in the EU, USA, Japan and China. These regions are the most important markets for pharmaceutical products and the appropriate agencies such as the European national agencies, the EMA, the FDA and the Japanese MHLW have major influence on the regulatory strategy in pharmaceutical companies used to develop and submit new medicines. In order to authorise products in these markets successfully companies need to act according to the requirements and procedures of the different regions since they are not harmonised despite increasing efforts. For the EU the centralised procedure and the national mutual recognition and decentralised procedures are described in detail. Furthermore the documentation and steps required to obtain and maintain authorisations for clinical trials are discussed. During the life cycle of products their marketing authorization dossier is changed and the changes are subject to regulatory processes. For biopharmaceuticals these variations are frequently demanding in terms of data and dossier requirements. The seminar focuses in detail on product life cycle activities related to Europe but also provides an overview on the principles to be followed in other regions. 

Learning Objectives

  • Get in-depth knowledge on the European DCP, MRP and centralized procedures for Marketing Authorisation Applications (MAA)
  • Understand the main responsibilities of the European Medicines Agency (EMA) and the details of the centralized procedure
  • Understand the specific requirements of the authorization, clinical trial and post-authorisation procedures in the USA, Japan and China
  • Understand and select the most appropriate registration procedure
  • Manage the particulars of the nationally managed Clinical Trial Applications (CTA) successfully and understand the current Voluntary Harmonisation Procedure and future Procedure for CTAs
  • Delivers the details on the different types of variations valid for biopharmaceuticals
  • Manage to install an effective life cycle system to prepare adequate documentations effectively and the procedures with time-lines successfully
  • Identify which documentation and data are required for each type of variation

Agenda

Regulatory procedures for clinical trial applications, marketing authorizations and variations in the EU, USA, Japan and China 

  • European centralized procedure at EMA
  • MRP and DCP
  • CTA in Europe – Process, VHP, particulars for biopharmaceuticals
  • Variations - changes to the CTD, procedures, data particulars for biopharmaceuticals Changes to the SmPC
  • Approval in other regions - process and essentials of the relevant agencies 


Day 1

..................................................................................

09.15 - 09.30
Welcome and introduction
..................................................................................

09.30 - 10.15
European Centralised Procedure at the EMA

1. Essentials on regulation and procedures

  • Mandatory and optional scope of the centralised procedure Eligibility request
  • Pre-submission activities
  • Conditional marketing authorisation
  • Marketing authorisation under exceptional circumstances Accelerated assessment
  • Appointment and role of the (Co) Rapporteurs and their assessment teams, of the EMEA PTL and of experts of agencies
  • Involvement of working parties and scientific committees other than CHMP

..................................................................................

10.15 - 10.45 Coffee break
..................................................................................

10.45 - 11.45
European Centralised Procedure at the EMA

1. Essentials on regulation and procedures

  • Review process

o Procedure
o Validation of the MAA
o Time lines
o Assessment report
o CHMP Peer Review
o Oral explanation
o CHMP Opinion
o Withdrawal
o Re-examination
o Commission decision

  • Life-cycle of European Marketing Authorisations o Actual marketing

o Cessation of placing a product on the market o Suspension
o Revocation
o Withdrawal
o “Renewal”
o Sunset clause
o Annual re-assessment
o Time lines, procedures, documents, exemptions

 
..................................................................................

11.45 - 12.45 Lunch 
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12.45 - 13.45 continued
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13.45 - 14.30 
European Centralised Procedure at the EMA 

2. Strategic aspects to be considered in the interaction with the EMA

  • Success factors of the centralized procedure
  • From pre-submission to approval – what is essential to take care of
  • Best practice for the communication with the EMA
  • How to prepare and perform at oral explanations at the CHMP and expert group meetings such as SAG meetings
  • Good behavior practice for EMA meetings
  • Best slide practice for a successful oral explanation


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14.30 - 15.00 Coffee break 
..................................................................................

15.00 – 17.00 
The EMA concept of Adaptive Pathways

  • What is the concept
  • What does it mean for regulatory strategy
 
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17.00 End of Day 1
18.30 Get-together with food and wine 


Day 2

..................................................................................

08.30 - 10.30 
USA

  • Legal basis for medicinal products and medical devices
  • Types and procedures of regulatory submissions
  • Role and function of and interaction with the FDA
  • The FDA’s review process
  • The Investigational New Drug Application (IND)
  • The New Drug Application (NDA)
  • The Biological License Application (BLA)
  • Accelerated development options
  • FDA’s approach to the CTD
  • Supplements and post-marketing obligations
  • Regulations for biopharmaceuticals, biosimilars and advanced therapies
  • Orphan drugs 
 
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10.30 – 11.00 Coffee break 
..................................................................................

11.00 - 12.30 
The PDUFA process at FDA 

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12.00 – 13.30 Lunch
..................................................................................

13.30 - 15.30 
Japan
  • Pharmaceutical legislation in Japan
  • Organisation of and interaction with the MHLW
  • Types and procedures of regulatory submissions
  • Pre-submission procedures
  • Relevance of clinical bridging studies
  • KIKO consultation – Clinical Trial Notification (CTN)
  • Regulations for biopharmaceuticals, biosimilars and advanced therapies
  • Orphan Drugs 
 
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15:30 – 16:00 Lunch
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16:00 - 18:00
The regulatory system in China 
  • Pharmaceutical legislation
  • Organisation of the S-FDA
  • Types and procedures of regulatory submissions
  • Pre-submission procedures
  • Clinical Trials
  • Regulations for biopharmaceuticals, biosimilars and advanced therapies
  • Orphan Drugs 

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18:00 End of Day 2
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For whole course attendees: 
17:30 - 17:45
Introduction to the homework



Day 3

..................................................................................

08.30 - 10.30 
European National Mutual recognition (MRP) and Decentralised Procedure (DCP) 

  • Network and resources of the agencies: role and activities of the RMS, CMS, CMD(h)
  • Filing, validation, time lines, process management, fees
  • Review process
  • Assessment report
  • CMD(h) and CHMP referrals
  • Referral
 
..................................................................................

10.30 – 11.00 Coffee break 
..................................................................................

11:00 - 13:00
Clinical Trial Application (CTA) in Europe: legal basis and relevant procedure 

  • The Clinical Trials Directive
  • European and national guidelines and publications
  • National authorisation procedures and their particulars
    • Content and format
    • Procedures, timelines, submission to regulatory authorities and ethic committees
    • EUDRACT and EUDRACT tracking number o Notification of amendments
    • Safety reporting requirements
    • Annual Safety Report
    • End of Trial Notification
    • Summary Clinical Trial Report
    • “Grounds for Non---approval”(GNA) letter and appeal procedure
  • Interventional and non---interventional trials
  • Voluntary Harmonisation Procedure
  • The new Regulation on Clinical trials 
 
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13:00 - 14:00 Lunch  
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14:00 - 15:00 continued
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17:00 End of Day 3


Day 4

..................................................................................

08.30 - 10.30 
Variations-European Regulations and national legal provisions for changes to the CTD 

  • Classifications, documentation
  • Procedures and time lines
  • Contact points
  • Downgrading, pooling and consequential changes
  • Multiple agency submissions
  • Appeals
 
..................................................................................

10.30 – 11.00 Coffee break 
..................................................................................

11:00 - 13:00
Changes to the Biotech CTD 

  • Data and documentation requirements
  • Typical changes and their evaluation
  • New approaches and challenges for changes and their handling 
 
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13:00 - 14:00 Lunch  
..................................................................................

14:00 - 14:30 
Discussion on variations


..................................................................................

14:30 - 15:30
Changes to the SmPC / Product Information

  • Post-approval procedures
  • Efficacy and safety (pharmacovigilance)
  • Quality changes
  • SmPC Harmonisation
  • Issues and Challenges
..................................................................................

15:30 - 16:00 Coffee break 
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16:00 - 17:30 continued
..................................................................................

17:30 End of Seminar 2
..................................................................................

For Full Course Students: 

9:00 - 11:30 
Questions and answers

11:30 - 12:15 Lunch

12:15 - 13:15 Written Exam

13.15 End of Seminar 2 for Full Course Students 

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Seminar 3: Particulars of specific product classes: monoclonal antibodies, vaccines, ATMPs and blood products

Content

  • Essentials of the development of monoclonal antibodies – case study

     o Milestones and typical pitfalls in the development of mAbs

  • Registration of vaccines

     o Overview on the product class
     o Underlying immunology of the mode of action and clinical efficacy of vaccines
     o Current and new adjuvants
     o Manufacture and quality control requirements
     o Special characteristics of the pre-clinical and clinical development of vaccines
     o Pre- and post-authorisation documentation requirements for pandemic vaccines

  • Case study: Approval of HPV vaccines in the EU
  • Overview on ATMPs

     o Regulation and relevant procedures
     o Successfully authorised and failed products
     o Case studies illustrating the particulars of ATMP development and registration

  • Registration of blood products

     o Manufacturing methods and quality control approach
     o Requirements for the selection of the starting material
     o Pre-clinical and clinical data requirements
     o Certification scheme on Plasma Master File (PMF)

Four unique product classes are introduced with respect to their regulation, the essential requirements for their development, their unique characteristics. Blood products stand for classical biologicals as they are manufactured from a biological source, i.e. human plasma. Their use is still required for many life-threatening and chronic diseases despite the progress recombinant technology made. Vaccines are mostly recombinant proteins and an increasing number of newly developed products is available which are all of special importance for the health systems. Both, blood products and vaccines, require special considerations in their manufacture, selection of starting material, testing and characterization and clinical development. The product class of monoclonal antibodies delivers an increasing number of novel medicines. Their development requires understanding of their special issues such as manufacturing technology options, species specificity for non-clinical development, pleiotropy, limitations of dose-finding approaches etc. Advanced therapy medicinal products are also unique as they are based on gene therapy, somatic cell or tissue engineering approaches. For these products the conventional requirements for biopharmaceuticals often do not apply as they are developed and manufactured for individual patients.

The development process of a biopharmaceutical has principle features in common with conventional drugs but is special in various aspects since their protein nature requires specific considerations. The four featured product classes illustrate how the current regulatory system ensures that a holistic approach of interaction between the manufacturing/testing, non-clinical and clinical team is followed during development.

Learning Objectives

  • Get an detailed introduction into the product classes of monoclonal antibodies (mAbs), blood products, vaccines and ATMPs
  • Understand why mAbs, blood products, vaccines and ATMPS require a particular development programme
  • Understand the underlying principle of the Plasma Master File
  • Learn the specific requirements applicable for vaccines
  • Get an insight into a special case of a vaccine presented by a regulatory and a company representative
  • Learn the specific regulation of ATMPs and the practical requirements for development

Agenda


Day 1

09.00 - 09.15 
Welcome and introduction

09.30 - 10.30
The product class of blood products: The special nature determines the quality, pre-clinical and clinical requirements // Certification scheme on Plasma Master File (PMF)

10.30 - 11.00
Coffee break

11.00 - 12.00
continued

12.00 - 13.00
Lunch

13.00 - 15.00
Overview on ATMPs: Regulation and relevant procedures // Successfully authorised and failed products

15.00 - 15.30
Coffee break

15.30 - 17.30 
Case studies to illustrate the challenges in the development of ATMPs: Quality data // Pre-clinical data // Clinical data

17.30
End of Day 1

19.00
Get together with food & wine

For Full Course students:
17.30 - 17.45 
Introduction to the homework
 


Day 2

08.30 - 10.30
Vaccines: History of vaccine development and currently approved products // Vaccination impact and challenges for new developments // Underlying immunology of the mode of action and clinical efficacy of vaccines // Continuing evolution of vaccine antigens // The role of adjuvants in current and new vaccines // Special characteristics of clinical development of vaccines

10.30 - 11.00
Coffee break

11.00 - 13.00
continued

13.00 - 14.00
Lunch

14.00 - 15.30  
The product class of monoclonal antibodies (mAb): Technologies used to express mAb // Principle quality requirements // Outsourcing and partnering // Non-clinical and clinical development
 

15.30 - 16.00
Coffee break

16.00 - 17.00
continued 
 

17.00
End of Day 2


Day 3 

08.30 - 10.30
Registration of vaccines: Manufacture and quality control requirements // Pre-clinical package // Benefit/Risk assessment // Pre- and post-authorisation requirements for pandemic vaccines // Special case: Ebola

10.30 - 11.00
Coffee break

11.00 - 12.30
continued

12.30 - 13.30
Lunch

13.30 – 15.30
Cervarix as an example for successful authorisation of a HPV vaccine: Introduction // Regulatory history // Clinical development - primary authorization and life cycle of the clinical indication // Success factors

15.30 - 16.00
Coffee break

16.00 - 17.30
Continued

17.30
End of Seminar 3


For Full Course students:

Day 4

09.00 - 14.00
Exam Seminar 3: Case study with group work

14.00
End of Seminar 3 for Full Course students

Seminar 4.1: The Module 3 (CMC Dossier) of biopharmaceuticals

Content

The Module 3 (CMC Dossier) of biopharmaceuticals

  •   The Module 3 of the CTD of biopharmaceuticals
  •   CMC data requirements of biopharmaceuticals
  •   Module 3 dossier and data requirements for biopharmaceuticals in the USA and Japan
  •   Relevant EMA and ICH CMC-related guidelines
  •   Special areas to be considered for biopharmaceuticals

o Formulation and stability
o Critical process and quality attributes
o Characterisation and testing of biopharmaceuticals o Comparability
o Virus and TSE safety

  •   CMC data requirement for biosimilars
  •   Typical pitfalls in regulatory submissions 

Biopharmaceuticals are special since they stem from a biological source, or the protein structure is transcribed from genetic information and is expressed by a living cell. They are usually complex and large and the quality is determined by the manufacturing process, where consistency and stability need particular attention. This has implications on the way biopharmaceuticals are developed and regulated and particular guidelines are available which are covered in this seminar. The manufacturing process determines the quality of these products and the requirements for the key quality (CMC) issues are complex accordingly. Issues specific to biopharmaceuticals such as the manufacturing process definition, consistency, stability, definition of specifications, infectious agents' safety, comparability, bioassay are covered in this seminar as well as specific topics such as how changes of the process can impact the quality of these products. In addition to the European requirements on biopharmaceuticals the specific requirements of other global regions are dealt with in detail. Furthermore, the specific requirements for IMPs, investigational medicinal products are covered.

Learning Objectives

  • Understand the key quality (CMC) issues specific to biopharmaceuticals such as the manufacturing process definition, consistency, stability, definition of specifications, infectious agents' safety, comparability, bioassay use and apply them in the regulatory strategy
  • Understand and adapt the implications of the introduction of changes in the manufacturing process on the quality of the product, i.e. apply the comparability concept
  • Allows to conduct and steer the relevant regulatory strategy for CTA and MAA submissions for biopharmaceuticals due to knowing the rules and required data for Module 3
  • Understand the CMC essentials of an IMPD/CTA, CTD and MAA submission
  • Understand the regional differences in the scientific requirements for regulatory submissions for biopharmaceuticals and to utilize this in global submissions

Agenda


Day 1

09.15 - 09.30
Welcome and introduction

09.30 - 10.30
The structure of the Quality Module 3 of the CTD for biopharmaceuticals and the relevant guidelines
This session provides an introduction into Module 3 structure first which is used throughout the seminar as a kind of frame, in which the individual headings of the structure are embedded either as interactive sessions or as presentations.

10.30 - 11.00
Coffee break

11.00 - 11.30 
First interactive session of the dossier and data requirements for the individual sections of the Module 3.

For all interactive sessions, Beatrix Metzner and Heike Volkmer develop with the audience the content related to biopharmaceuticals and will summarise at the end of the session the essentials. 

To start with: General information (3.2.S.1 and 3.2.P.1) 

11.30 - 12.15
Manufacture (3.2.S.2 and 3.2.P.3) (Interactive session)

12.15 - 13.00
Control of Materials (3.2.S.2.3.) (Interactive session)

13.00 - 14.00
Lunch

14.00 - 16.00 
How do ICH Q 8, 9, 10 and 11 determine the Module 3 structure and content: 
Controls of critical steps and intermediates (3.2.S.2.4 and 3.2.P.3.4.) // Process validation (3.2.S.2.5. and 3.2.P.3.5.) // Manufacturing process development (3.2.S.2.6. and 3.2.P.2.)

16.00 - 16.30
Coffee break

16.30 - 17.30
Continued

Time for discussion until 18.15

18.30
End of Day 1

19.00 

Get-together with food and wine


Day 2

09.15 – 11.15 
Characterisation of biopharmaceuticals (3.2.S.3)
Importance of product characterisation // Examples of parameters investigated and their impact on process and product consistency: Heterogeneity and isoforms, Glycosylation, Undesired modifications of molecules, Potency determination, Impurities, 

11.15 – 11.45
Coffee break

11.45 – 13.00
Control of Drug Substance / Drug Product (3.2.S.4. and 3.2.P.5.) (Interactive session)

13.00 – 14.00
Lunch

14.00 – 15.00 
Continued

15.00 – 15.45 
Virus and TSE-safety of biopharmaceuticals
Overview on the risks of transmission of infectious agents // General principles of ensuring virus and TSE safety //   Principles of virus validation of the manufacturing process capacity to inactivate and remove viruses and TSE //   Requirements for early stage products (IMPs) versus late stage and commercial products (Phase 3 and MAA)

15.45 – 16.15
Coffee break

16.15 – 18.30 
Continued

18.30
End of Day 2


Day 3

09.00 – 10.30
Interactive session: Reference Standards (3.2.S.5. and 3.2.P.6.) // Container Closure System (3.2.S.6. and 3.2.P.7.) // Stability (3.2.S.7. and 3.2.P.8.) 

10.30 – 11.00
Coffee break

11.00 – 13.00
Interactive session: Pre- and post-authorization changes // The comparability exercise – what to do and what to present in the dossier when the manufacturing process is changed 

13.00 – 14.00
Lunch

14.00 – 16.00 
Formulation and drug product manufacturing of biopharmaceuticals: Formulation development // Process development // Routes of administration // Special developments to modify proteins and formulations

16.00 – 16.30
Coffee break

16.30 – 18.30
Consideration for the CMC development and submission requirements for a drug-device combination product

18.30
End of Day 3



Day 4

09.00 – 10.30
CMC particulars of biosimilars

10.30 - 10.45
Coffee break

10.45 - 12.45 
Experience with the CMC review procedure by EMA and FDA of Gazyva, a global dossier with approved design space

12.45 – 13.45
Lunch

13.45 – 14.30  
What is special in other regions on Module 3 requirements?  USA // Japan // Other regions

14.30 – 14.45
Coffee Break

14:45 - 16.30
Regulatory CMC concerns and issues from an agency perspective

16.30
End of Seminar 4.1

Seminar 4.2: Non-clinical and clinical development of biopharmaceuticals including biosimilars and the Module 4 and 5 requirements

Content

  • Principles of the non-clinical development
    • What is special in the pre-clinical development of biopharmaceuticals
    • Which investigations are required at which stage of development
    • The non-clinical dossier of biopharmaceuticals (Module 4)
    • What did change after the TeGenero Case
  • Principles of the clinical development
    • The clinical dossier of biopharmaceuticals
    • Development and use of biomarkers and companion diagnostic
    • Key elements of the benefit-risk assessment
    • The clinical dossier of biopharmaceuticals (Module 5)
  • Immunogenicity
  • Development and registration of biosimilars
  • Case studies on a biosimilar mAb and on benefit-risk assessment

Biopharmaceuticals play an important role in the pharmaceutical industry since they deliver an increasing number of candidates for new product developments. They are however special and require certain considerations in their pre-clinical and clinical development. They are pleiotrop and immunogenic and their non-clinical pharmacodynamic and safety characterisation is often hampered by insufficiently relevant animal models. Biosimilars are developed following a special regulation and expanded programme as compared to conventional generics. This all has implications on the way biopharmaceuticals are developed and regulated. The particulars of the non-clinical and clinical requirements of biopharmaceuticals are covered and the specific considerations on the development of biosimilar medicinal products are part of this seminar as well. In this seminar case studies will also be presented on successfully authorized products, such as on a tri-functional monoclonal antibody and on a biosimilar. The seminar also introduces how to perform a benefit-risk assessment at the authorization stage and how to update it during life-cycle of the product.

Learning Objectives

  • Understand the specific challenges in the pre-clinical development of biopharmaceuticals
  • Understand the essential clinical development approach
  • Learn to assess the benefit-risk ratio during the whole life cycle of a product
  • Understand the data requirements specific to biosimilars
  • Learn why immunogenicity is a typical issue for biopharmaceuticals and how it is investigated and handled appropriately
  • Allows to conduct and steer the relevant regulatory strategy for CTA and MAA submissions for biopharmaceuticals due to knowing the rules and required data for Modules 4 and 5 of biopharmaceuticals

Agenda

 

Day 1

09.15 - 09.45 Welcome and Introduction

09.45 - 10.45 The principle of clinical development of biopharmaceuticals

  • Target rationale definition
  • Dose-finding justification
  • Proof of Concept and confirmatory studies
  • Relevant efficacy and safety studies – pivotal trials
  • Principles of the clinical review and decision on the benefit-risk conclusion
  • Module 2 sections 2.5 and 2.7.
  • Presentation of clinical data in Module 5 of the CTD

10.45 - 11.15 Coffee Break

11.15 - 12.45 continued

12.45 - 13.45 Lunch

13.45 - 15.45 Research to early development: a clinical pharmacology perspective

  • Future clinical Proof-of-Concept strategies
  • Validity of biomarkers in drug development
  • Why large trials fail - although effects (efficiency) have been seen in small studies

15.45 - 16.15 Coffee Break

16.15 – 17.45 Case study (TBC)

17.45 End of Day 1

Day 2

09.15 - 11.00 Case study for group work: How to define the clinical development programme of a new monoclonal antibody – from Phase I to Phase III towards a positive benefit-risk assessment

11.00 - 11.30 Coffee break

11.30 – 13.00 Immunogenicity

  • What is immunogenicity?
  • How is immunogenicity caused?
  • How is immunogenicity tested ?
  • Risk-based approach

13.00 - 14.00 Lunch

14.00 - 15.00 Case study: Erythropoietin and PRCA

15.00 - 15.30 Coffee break

15.30 - 18.00 Regulatory principles of development of biosimilar medicinal products in the various regions

  • EU
  • FDA
  • WHO

Global development, experience with submissions in different regions

Experience with Sandoz biosimilars

18.15 End of Day 2

19.00 Get-together with food and wine

Day 3

09.15 - 10.45 Current considerations on regulatory requirements for monoclonal antibodies developed as biosimilars

10.45 - 11.15 Coffee break

11.15 - 13.00 Case Study for group work: Development of a biosimilar monoclonal antibody

13.00 - 14.00 Lunch

14.00 - 15.00 Continued

15.00 - 15.30 Coffee break

15.30 - 17.00 Case study: Molybdenum Cofactor deficiency: Bench to bedside and Beyond

17.00 End of Day 3

Day 4

09.15 - 11.00 Principles of non-clinical development

The non-clinical CTD

What is special in the non-clinical development of biopharmaceuticals

  • Unique characteristics of biotech products to be considered when designing a preclinical programme
  • Pharmacodynamic studies and disease models considerations for pharmaco- and toxicokinetic studies
  • Immunogenicity in non-clinical models

11.00 – 11.30 Coffee break

11.30 - 13.00 The TeGenero case and its implications for the development of new biopharmaceuticals

13.00 - 14.00 Lunch

14.00 End of Seminar 4.2.

For Full Course students:

14.00 - 15.30 Exam: case study. Introduction, group work, presentations

15.30 - 16.00 Coffee break

16.00 - 18.00 continued

18.00 End of Seminar 4.2. for Full Course students

Seminar 5: Specific considerations for the development and authorization of medicinal products for children

Content

  • Background of development and content of the Paediatric Regulation No 1901/2006 EC
  • The role of the EMA and of the Paediatric Committee (PDCO)
  • The Paediatric Investigational Plan (PIP) (Scope, legal aspects, considerations for developing and executing the PIP, Preparation of the PIP)
  • Requirements on paediatric drug formulations
  • Juvenile Animal Studies
  • Implications of the EU legislation for the pharmaceutical industry: perspectives, challenges and opportunities
  • Other regions, focus on US

The new legislation on the development and authorization of medicines for use in children aged 0 to 17 years was introduced in the European Union in January 2007. The Paediatric Regulation (Regulation/EC No 1901/2006 as amended) affects the regulatory environment for pharmaceutical companies and agencies enormously since it required many new tasks and responsibilities for the authorities, mainly the EMEA, and remarkable new requirements for the overall development plans of medicinal products for all types of pharmaceutical companies. Seminar 5 is designed to provide comprehensive information on the new European requirements for medicines for children, the legislation, regulatory bodies and procedures and their practical implementation in the daily work of a pharmaceutical company. In addition to the European requirements on the development of medicines in children the regulations of the FDA and of other regions are dealt with in detail.

Learning Objectives

  • Understand the requirements and principles of authorization of medicinal products for use in children
  • Learn the key strategic considerations and their implications on the general strategy of a company followed in their development programme
  • Understand the details of the regulatory procedures to follow and the stake holders involved
  • Understand the issues to be considered in the planning of the paediatric development programme
  • Develop the appropriate regulatory strategy for the Paediatric Investigation Plan (PIP)
  • Prepare a PIP successfully

Agenda

Day 1

09.00 - 09.15 Welcome and introduction

09.15 - 10.15 EMA and the Paediatric Committee (PDCO)

  • Role, function, procedures and decision-making
  • Interactions with other EMA’s committees and working parties

The scope of the Paediatric Investigation Plan (PIP)

  • Waivers (incl. class waivers), deferrals
  • Indications and conditions
  • Regulator’s experience with Articles 7 & 8
  • Opinions and decisions on PIP applications
  • Considerations for obtaining scientific advice

List of paediatric needs and priority list of off-patent medicines

Publication of clinical trial results

Development of regulatory guidelines on considerations of drug development in children

10.15 - 10.45 Coffee Break

10.45 - 12.15 continued

12.15 - 13.15 Lunch

13.15 - 15.15 Preparation of the Paediatric Investigation Plan (PIP)

  • Format
  • Application - incl. Application for PUMA (Paediatric Use Marketing Authorisation)
  • Regulatory procedure for the PIP assessment by the PDCO
  • EMA Paediatric Team: roles and responsibilities during the assessment vs. PDCO

15.15 - 15.45 Coffee Break

15.45 - 17.30 Considerations for developing and executing the PIP

  • Clinical trials (Criteria and decision-making on First in Child studies, EudraCT)
  • PK modelling and extrapolation

Paediatric Networks

17.30 – 18.30 Requirements on paediatric drug formulations

18.30 End of Day 1

19.00 Get-together with food and wine

Day 2

09.00 - 11.00 PIP-related legal aspects

  • Legal aspects related to Article 7 & 8 under the global marketing authorisation concept
  • Compliance checks
  • Rewards for paediatric data
  • National Patent Offices

11.00 - 11.30 Coffee Break

11.30 - 13.00 Juvenile animal studies

13.00 - 14.00 Lunch

14.00 - 14.45 The EU Regulation No 1901/2006 on medicinal products for paediatric use – the Paediatric Regulation

  • Implementation of the Paediatric Regulation and Commission PIP guideline

14.45 - 15.45 Regulation for medicines in children in other regions with focus on the US

15.45 - 16.15 Coffee Break

16.15 - 17.00 Implications of the EU legislation for the pharmaceutical industry: Perspectives, challenges and opportunities

17.00 - 18.00 Case illustrating PIP practice with discussion

18.00 End of Seminar 5

For Full Course students:

Day 3

09.00 - 10.30 Debriefing & discussion of the homework

10.30 - 11.00 Coffee break

11.00 - 12.00 Written exam

12.00 End of Seminar 5 for Full Course students

Seminar 6: Pharmacovigilance – Post-authorisation surveillance standards to meet regulatory requirements for product safety

Content

  • Pharmacovigilance concepts and specific aspects relevant to biologicals
  • Legal requirements and safety deliverables
  • Regulatory expectations
  • Risk management approach
  • Operational aspects:PhV system, business processes, project managment, quality oversight, saftey governance models, audits and inspections

Pharmacovigilance, i.e. the standard of constant monitoring of the safety of medicinal products after authorisation, is an important obligation of the marketing authorisation holder (MAH) and authorities. It requires constant exchange between companies and health authorities.

The EU legislation requires MAHs to provide the competent authorities with a description of their pharmacovigilance, risk management and quality system. Collecting, monitoring, assessing and evaluating information from healthcare professionals and patients on the adverse effects of medicinal products is conducted to identify new information about hazards associated with medicinal products and preventing harm to patients. Periodic Safety Reports (PSURs/PBRERs) and Risk Management Plans need to be generated and communicated regularly.

Depending on the signals observed, the MAH may have to implement actions for risk mitigation, for example changes to the SmPC or even measures on the marketing authorisation such as suspension or restriction of authorised therapeutic indications. The product information has to be kept up-to-date and communicated to health care professionals, patients and consumers in an effective and timely manner.

Learning Objectives

  • Explain the basis of the regulatory environment and processes to be followed related to pharmacovigilance
  • Discuss the principles and core activities involved in pharmacovigilance of medicinal products and the methods of pharmacoepidemiological studies
  • Understand and support the pre- and post-approval obligations to keep marketing authorisations valid in the EU
  • Provide the knowledge on the appropriate preparation of a Periodic Safety Report (PSUR/PBRER), Risk Management Plan (RMP) and in the implementation of risk minimisation
  • Learn to handle regulatory measures and processes such as an urgent safety restriction, a dear doctor letter, changes to the Safety Part of the SmPC, measures on the marketing authorization
  • Identify the relationship between PV systems, their quality systems and the regulatory frame work

Agenda

Day 1

09.00-10.00 Introduction to the pharmacovigilance

  • Are authorised products safe?
  • What do patients/consumers and physicians expect?
  • Biologicals: from vaccines to immunotherapy
  • Benefit/risk concept at the individual and the population level
  • Principles of surveillance
  • The legal framework conceptually: national legislation, EU legislation, CIOMS, ICH

10.00-10.45 Case Study

10.45-11.15 Coffee break

11.15-11.45 Pharmacovigilance System and core PV processes I

  • PSMF
  • ICSR

11.45-12.00 Questions and Answers

12.00-13.00 EU Regulatory requirements at time of authorisation

  • How is the safety information presented in the relevant sections of the CTD submitted with the MAA
  • The PhV system and the role of the EU QPPV
  • Agreement on the labeling text, the SmPC
  • Post-authorisation commitments
  • Risk Management Plans

13.00-14.00 Lunch

14.00-14.30 Case Study

14.30-15.30 EU Regulatory requirements post-authorisation

  • Expedited reporting of safety information
  • Periodic Safety Reports (DSURs/PSURs/PBRERs)
  • Company Core Safety Information
  • Type II variations related to safety aspects
  • Urgent safety restrictions
  • Interaction of the company with agencies on safety aspects
  • Communication with the public

15.30-16.00 Coffee break

16.00-17.00 Pharmacovigilance concepts and core processes II

  • Brief introduction into epidemiology
  • Methods of studying benefits and risks
  • Weighting evidence
  • Signal detection and investigation

17.00-17.45 Case Study

17.45-18.00 Wrap-up

18.00 End of Day1

19.00 Get-together with food and wine

Day 2

09.00-09.30 Rehearsal Key Messages Day 1

09.30-10.30 Pharmacovigilance concepts and core processes III

10.30-11.00 Coffee break

11.00-11.45 Case Study

11.45-12.15 Differences between EU and non-EU requirements with respect to PSMF, ICSR, periodic reports, RMP, product information

12.15-13.00 Case Study

13.00-14.00 Lunch

14.00-15.00 Implications of the EU PV legislation - Questions & Answers

15.00-15.45 Benefit Risk Management in Practice

  • Benefit - Risk frame work
  • Risk management planning
  • Risk mitigation
  • Effectiveness of risk minimisation
  • Progress reports

15.45-16.15 Coffee break

16.15-17.00 Case Study (Students)

17.00-17.15 Case Study (Plenary)

17.15-18.00 Rehearsal Key Messages Day 1 and 2

18.00 End of Day 2

Day 3

09.00-09.45 Safety Communication and Transparency

  • Risk communication to HCPs, patients/consumers and public at large
  • Erice Declaration
  • PRAC minutes
  • RMP summaries

09.45-10.45 Case Study

10.45-11.15 Coffee break

11.15-12.00 PV Quality Management

  • PV system performance
  • Quality control
  • Audits and inspections
  • CAPA management
  • Quality oversight

12.00-12.30 Case Study

12.30-13.00 Rehearsal Day 3

13.00-14.00 Lunch

13.00 End of Seminar 6

For Full Course students (Afternoon Day 3)

14.00-15.30 Introduction of homework; Questions & answers – Preparation for the exam

15.30-16.00 Coffee break

16.00-17.00 Exam

17.00 End of Seminar 6 for Full Course students

Seminar 7: The roles of the supervising authorities and the essential characteristics of quality systems

Content

  • Principles and underlying legislation for the establishment of GMP, GLP, GCP
  • GMP authorization - procedures in the EU and requirements for third countries
  • The supervising authorities - role of national inspectorates and EMA
  • Experience with GMP - inspections by inspectorates from USA, EU, Japan
  • Compliance and steady optimization of production and processes
  • Role of EDQM and OMCLs
  • Certificates of suitability
  • The Rapid Alert System

Companies manufacturing, testing or distributing active ingredients or medicinal products, clinical centres conducting clinical trials and research organisations performing studies need to follow common standards of quality system requirements. The quality system is supervised by national inspectorates who increasingly co-operate globally. If the establishment inspected is found to be compliant with the relevant requirements a license is issued as an authorisation to manufacture, test or distribute the medicinal product or active ingredient.

With the introduction of ICH Q 8, 9 and 10 principles, and with the increasing global trade of active ingredients and products, quality systems become more and more important in ensuring their quality.

The primary purpose of a quality system is to ensure that adequate quality standards are used and maintained. The Good Manufacturing Practice (GMP) applies to the manufacture and control of active ingredients and final dose forms of pharmaceuticals and their clinical supply, the Good Laboratory Practice (GLP) to non-clinical investigations of new compounds, the Good Clinical Practice (GCP) to the conduct of clinical studies, the Good Distribution Practice (GDP) to the storage and distribution of medicinal products.

Learning Objectives

  • Understand the characteristics of a quality system and the particulars of the different types of GxP
  • Understand how regulatory affairs is connected to the Quality System
  • Become familiar with the legislation and guidelines defining the rules for GxP
  • Learn how national inspectorates including those from different regions collaborate on facility inspections and which role play the individual stake holders
  • Understand how supervision is executed and inspections are conducted
  • Understand the function and responsibilities of the Qualified Person
  • Recognise what is special with GMP and GDP for biopharmaceuticals
  • Understand ICH guidelines Q 8, 9 and 10

Agenda

European Directorate for the Quality of Medicine & HealthCare (EDQM)

Council of Europe

Day 1

09.00 - 09.15 Welcome and introduction

09.15 - 11.00 European Directorate for the Quality of Medicines and Healthcare (EDQM)

  • Role
  • Structure
  • Activities
  • Certificate of suitability

11.00 – 11.30 Coffee break

11.30 – 12.45 Characteristics of quality management systems – an introduction

  • Which quality management systems apply in the EU and how they are regulated and executed
  • Who supervises the companies in the EU and in third countries and how this supervision is authorized and documented

12.45 - 13.45 Lunch

13.45 - 15.00 The principles of GMP

  • Legal requirements for obtaining a manufacturing authorisation or an authorisation for importation
  • Obligations of a holder of a manufacturing authorisation or an authorisation for importation

Company’s responsibility in batch release and The Qualified Person

  • The Qualified Person for marketed products or Investigational Medicinal Products (IMPs)

Special GMP considerations for biopharmaceuticals including advanced therapies

  • What is special for biopharmaceuticals
  • GMP for starting materials
  • GMP of blood products and blood components
  • Are biopharmaceuticals subject to counterfeits

15.00 – 15.30 Coffee break

15.30 - 16.30 continued

16.30 - 18.00 The Regulatory Affairs department at the interphase

  • Which role the Regulatory Affairs department has at the interface of GMP authorization of manufacture and testing, GLP compliance of pre-clinical testing and GCP compliance of clinical trials
  • How supervision works – when an inspection is required – who performs the inspections – which authorization documents are required and how they are maintained – when and how the documents are submitted to agencies for CTA and marketing authorization

18.00 End of Day 1

19.00 Get-together with food and wine

Day 2

09.00 - 10.30 Experience with inspections conducted by the different inspectorates from Europe, U.S. and Japan

How an inspection is performed

10.30 – 11.00 Coffee break

11.00 – 12.30 continued

12.30 – 13.30 Lunch

13.30 – 15.00 Surveillance of medicines through testing in the EU/Europe

  • OMCL Network
  • CAP testing program and Market Surveillance
  • Official Control Authority Batch Release (OCABR)

15.00 – 15.30 Coffee break

15.30 – 16.30 The principles of GLP

  • Recording, archiving, reporting investigations
  • Global Implementation and mutual recognition
  • The competent authorities

16.30 - 17.30 The principles of GDP (Ralf Hess, Parexel)

  • Maintenance of the level of quality throughout the distribution chain

The Rapid Alert System

Product defects

Recalls

17.30 End of Day 2

For Full Course students:

Introduction of Homework Seminar 7

Day 3

09.00 – 10.30 The principles of GCP

  • Introduction

o Why we have GCP

o Declaration of Helsinki

o The ICH GCP process

o Ethical and scientific principles in clinical trials to ensure protection of trial subjects and integrity of trial results

  • The responsibilities of sponsors, e.g.

o Quality Control and Quality Assurance
(Monitoring and Auditing)

o The interface to service providers

o GCP information flow and reporting requirements

  • The responsibilities of investigators, e.g.

o How to delegate trial tasks within a team

o Protocol adherence

o Informed Consent Procedure

o Source Data and Case Report Forms (CRFs)

o GCP information flow and reporting requirements

  • Typical GCP Inspection Findings

10.30 - 11.00 Coffee break

11.00 - 12.30 continued

12.30 - 13.15 Lunch

13.15 - 14.30 continued

14.30 End of Seminar 7

For Full Course students:

14.30 - 14.45 Coffee Break

14.45 - 15.30 Questions & Answers – Group work as preparation for the exam

15.30 - 16.30 Written exam

17.00 End of Seminar 7 for Full Course students

Seminar 8: Scientific advice, regulatory strategy and health technology assessment

Content

  • Regulatory strategy and global positioning of newly developed and existing products
  • Pre-marketing interactions with regulatory agencies: scientific advice and pre-IND
  • Concepts and tools to support regulatory processes
  • Regulatory strategy for the introduction of changes in the manufacturing process
  • Intellectual Property Rights
  • Health Technology Assessment

According to the records of the EMA, constantly 25% of newly developed medicinal products submitted to the centralised authorisation procedure in Europe fail. This high failure rate is remarkable taking into account all the efforts installed in Europe within the 15 years from the time the EMA had been inaugurated. Numerous incentives are in place to stimulate regular pre-submission interactions with agencies to discuss the compliance of development programs with regulatory principles. Regulatory guidelines for all areas of drug development are available describing the regulatory standards. In order to translate these efforts into higher success rates of marketing authorisations an essential component of the overall regulatory strategy is the establishment of regular cross-functional interactions between teams of drug discovery and development, pharmaceutical development, marketing. Regulatory affairs should play an important role in this process. Health technology assessment is another increasingly important aspect of drug development, which requires earlier consideration in development concepts in the future. The seminar addresses concepts and tools by which strategic bridging is established and conducted efficiently in practice throughout the life cycle of the medicinal product.

Learning Objectives

  • Reduce critical set backs in registration procedures by a successful scientific advice strategy and anticipating questions from regulators
  • Lead and conduct appropriate scientific advice activities
  • Understand how to plan and organize pre-authorisation interactions with regulatory authorities
  • Understand the scientific advice process at the EMA and the pre-IND process at the FDA and the relevant dossier requirements
  • Learn to plan, establish and conduct regular cross-functional regulatory forums from the early stage of development on
  • Understand the principles of Health Technology Assessment and its implications on development programms and regulatory strategy

Agenda

Day 1

09.15 - 09.30 Welcome and introduction

09.30 - 11.00 Regulatory Strategy

  • What is a regulatory stategy and when is it needed?
  • Which implication a global development has for a company and for the agencies involved?
  • Stakeholder and liaison functions
  • Active participation in development of new requirements
  • Choice of submission type and procedure
  • Management of product life cycle
  • Regulatory risk evaluation

11.00 - 11.30 Coffee break

11.30 - 12.45 continued

12.45 - 13.45 Lunch

13.45 - 15.30 A cross-functional strategic forum to support decision-making for regulatory processes

  • Life cycle of development projects
  • Regular interactions of regulatory affairs, clinical development, marketing, pharmaceutical development, pharmacovigilance
  • Tools, teams and deliverables
  • Preparation, briefing book, questions, discussions, minutes, internal communication
  • Gap analysis of data packages available for regulatory submissions
  • Involvement of external experts

15.30 - 16.00 Coffee break

16.00 - 17.30 Regulatory strategy for the introduction of changes in the manufacturing process

  • What important is in the manufacturing process
  • Planning changes of manufacture and comparability projects
  • When to demonstrate consistency
  • When to introduce a pre-clinical and clinical bridging study
  • Change control processes in practice

17.30 End of Day 1

18.45 Get-together with food and wine

Day 2

09.15 - 10.30 HTA as a new element of the regulatory strategy - national requirements and European initiatives

  • Reimbursement in Europe
  • Considerations on how to design clinical development programmes to be used for approval and HTA

10.30 - 11.00 Coffee break

11.00 - 11.30 continued

11.30 - 12.30 The regulatory affairs department at the interphase – cooperation with the market access department and its role in HTA

12.30 - 13.00 Discussion round on HTA

13.00 - 14.00 Lunch

14.00 - 15.30 An introduction about patenting biopharmaceuticals and freedom-to-operate studies

  • What can be patented? The patentability criteria
  • For what purposes? What would by the scope of my patent exclusivity? Differences with data exclusivity?
  • The consequence of third party existing patent rights for my drug development
  • Patenting mAb as a case

15.30 - 16.00 Coffee break

16.00 - 17.15 Regulatory protection of medicinal products

  • Regulatory data exclusivity and lifecyle management
  • PIP compliance and SPC extension
  • Market exclusivity for orphan drugs

17.15 End of Day 2

For Full Course students:

17.15 - 18.00 Introduction of Homework

Day 3

09.15 - 10.15 Strategic considerations on interactions with regulatory agencies

  • Introduction
  • Examples of how to plan national and EMA scientific advice activities

10.15 - 11.00 Scientific advice from national competent authorities

  • Experience and process followed at the German competent authority, the Paul-Ehrlich-Institut

11.00 - 11.30 Coffee break

11.30 - 13.00 Interactions with regulatory agencies in the EU to receive scientific advice

  • The procedure of the European scientific advice at the EMA
  • Process and experience
  • Documentation, discussion meeting
  • Follow-up and clarification
  • EU/US paralell Scientific Advice
  • The EMA´s Innovation Task Force

13.00 - 14.00 Lunch

14.00 - 15.30 Interactions with FDA in the pre-IND process

  • Pre-phase I and post-phase II meetings
  • Preparation, documentation, meeting, telephone conference, written procedure

15.30 - 16.00 Coffee break

16.00 - 17.00 Interactive panel discussion: Interactions of companies and agencies in the development of biopharaceuticals

17.00 End of Seminar 8

For Full Course students:

09.15 - 10.45 Preparation for the exam

10.45 - 11.15 Working lunch

11.15 - 12.15 Exam

12. 15 End of Seminar 8 for Full Course students

Seminar 9: Good Regulatory Affairs practice: communication skills, project management and tools for the daily practise

Content

  • Good regulatory practice
  • Function, skills and performance of a regulatory affairs professional
  • Cross-functional communication and interaction
  • Agency meetings in practice
  • Project management, time lines
  • Data and document management
  • Tools for daily practice and conferences to attend

Knowledge of the subject matter is required to understand the science of the product under development, to facilitate the adoption of regulatory principles and to integrate teams involved and information gained in this process. Regulatory affairs is thus determined by its interdisciplinary character requiring individuals committed to processes which are deadline-determined. Scientific and administrative requirements need to be integrated into the development concept, gap analysis of data packages as compared to regulatory requirements are conducted, teams need to be integrated internally and the interphase between the company and health authorities needs to be handled appropriately. The conduct of an agency meeting is trained at this seminar. Particular capabilities in preparing regulatory documents are required since style and content are special due to the orientation along regulatory requirements. Project management skills, time line awareness, interaction and communication skills are essential. Strategic planning, the ability to anticipate problems, to analyse complex situations and to offer the optimal strategy to achieve a certain strategic goal in a timely manner become important as the career progresses. These skills are necessary to communicate adequately with partners internally and externally. Certain tools for daily work are presented and ways to exchange with colleagues are discussed.

Learning Objectives

  • Understand the role and responsibility of the regulatory affairs’ professional
  • Understand the essential features of Good Regulatory Practice (GRP)
  • Understand the importance of interactions and interfaces for the overall success of a project – cross-regional, cross-functional, company-agency
  • Learn how to develop negotiation skills, to solve conflicts and to compromise adequately
  • Understand and conduct data and project management in regulatory affairs
  • Understand the important media tools to be regularly applied
  • Gain presentation skills for internal and external meetings, inclusive agency meetings
  • Get knowledge of the essential websites, media tools, industry associations and conferences relevant for regulatory affairs

Agenda

Day 1

09.15 - 09.30 Welcome and introduction

09.30 - 10.30 Conducting effective meetings

  • Processes of preparation, conduct, rehearse and debriefing
  • Selection of attendees
  • Scenario preparation
  • Mandates for decision making

10.30 - 10.45 Coffee Break

10.45 - 11.45 Agency Code of conduct

  • The Code of Conduct of agencies
  • Conflict of Interest
  • Transparency (EU), the Freedom of Information Act (USA)
  • Disclosure of data
  • Exchange of information with agencies

11.45 - 12.45 Regulatory intelligence and document management

  • Regulatory intelligence and knowledge management
  • The Master Dossier
  • Data repository
  • Dossier compilation and submission
  • TIGes - e-submissions practilaties
  • The EU Telematics Strategy

12.45 - 13.30 Lunch

13.30 - 14.30 continued

14.30 - 14.45 Coffee break

14.45 - 16.15 Interaction of central project management with regulatory affairs

  • Goals of typical project managements
  • Tools
  • Types of time lines
  • Data collection
  • Interaction with external service providers

16.15 End of Day 1

16.15 Start of Sightseeing and Pre-Graduation Party of the fifth EUCRAF Course

Day 2

09.15 - 11.15 The regulatory affairs professional

  • Function and tasks
  • Skills
  • Performance

11.15 - 11.45 Coffee break

11.45 - 13.15 The Regulatory Professional at the interface

  • Effective interpersonal communication
  • Intercultural communication
  • Collaborative communication

Good practices for virtual and global communication

13.15 - 14.15 Lunch

14.15 - 16.15 continued

16.15 - 16.45 Coffee break

16.45 - 18.45 Psychological aspects of project management

18.45 End of Seminar 9

After 18.45 for Full Course students: rehearsal of agency meeting

For Full Course students:

Agency Meeting with video recording and analysis

08.30 - 10.00 Preparation

10.00 - 10.30 Coffee Break

10.30 - 12.30 Agency Meeting

12.30 - 14.00 Lunch

14.00 - 17.30 Debriefing - Analysis of the performance at the agency meeting

17.30 End of Seminar 9 for Full Course students