CRED Project Management for Regulatory Affairs Professionals

Project Management for Regulatory Affairs

Professionals 5 March 2019

*Course presentations

* ©The Organisation for Professionals in Regulatory Affairs 2018 Presentations are supplied to delegates for their personal reference and are the copyright of the speaker and The Organisation for Professionals in Regulatory Affairs. The presentations must not be copied, stored in a retrieval system or transmitted in any form without prior permission from TOPRA. Agreement must be reached with TOPRA before any part of this material is reproduced, abstracted, stored in a retrieval system or transmitted in any form by any means – that is, electronic, mechanical, photocopying, recording or otherwise.

CRED Project Management for Regulatory Affairs Professionals 5-6 March 2019 Presenters: • Dipesh Mistry, Pfizer Ltd • Gurdeep Bhangra , IQVIA Limited • Joe Cheal, Imaginarium Learning & Development • Sinéad Usher, Smart Regulatory Services Ltd Day 1 Programme Time Presentation 09.15 Registration and coffee 09.30 Welcome from TOPRA 09.40 Introduction • Welcome & domestics • Introduction to the speakers • Course overview/objectives • Your aims/objectives? • Your introduction (including personal aims) 10.10 What is Project Management • What is a project? • Life cycle: The four-stage project o Define (what/why), Plan (how), Implement, Final Review o The Fantasy – Reality Gap • The Time Cost Quality Triangle… plus the missing piece! • Qualities of effective project managers 11.10 Tea/ Coffee break 11.30 Project Management and how it fits with Regulatory Affairs • Definitions of Regulatory Affairs and Project Management • What are regulatory projects? o Roles of RA pre and post Marketing Authorisation Approval o Other RA projects • Regulatory Affairs (RA) professionals as Project Managers 12.15 Stage 1: Defining • What is the defining stage? • The Pre- Project ‘P’s • Identifying stakeholders o Governance (Internal and External) • Project kick-off meeting o Scope • Risk o Contingency planning 12.45 Lunch 13.30 Stage 1: Defining (Cont.) 14.30 Tea/ Coffee break 14.50 Stage 2: Planning • Work Breakdown Structure

Time

Presentation

o Roles & responsibilities o Creating and reading charts o Milestones Communication & reporting Plans Gantt/Timeline Charts

•

•

16.20 16.40

Review of the day

Close

Day Two Programme

Time 09.10 09.30

Presentation Introduction

Stage 3: Implementation •

Project delivery: Staying on track and within budget (time-cost- quality) • Handling change and handovers • Key skills: o Juggling projects and everyday work o Delegation o Chairing project review meetings & how to maintain control o Dealing with ‘difficult’ people (with different priorities) o Maintaining motivation

Tea/ Coffee break

10.40 11.00 12.00

Stage 3: Implementation Cont’d

Stage 4: Final Review •

Why review the project (and why does it not always happen)? • Making the reviews useful • Key questions to ask, e.g.: o What to do differently next time? o What to do now – follow up? o How to celebrate? • Recording & sharing information/ lessons learnt

Lunch

12.30 13.15

Case Study: A Regulatory Project Tea/ coffee to be taken during case study

15.00 16.15 16.45

Case Study Feedback Review and discussion

Close of Meeting

CRED Project Management for Regulatory Affairs Professionals

Speaker biographies

Dipesh Mistry Dipesh Mistry started his regulatory journey after a brief encounter in Pharmacokinetics and has worked in departments such as CMC, Submission Management, Project Management and more recently working in the Oncology space within Pfizer’s Established Health business. He has worked in a variety of organisations including big pharma, generics, CROs and consultancies. Dipesh is a big supporter of education of science, and volunteers as a STEM ambassador for London and the South East of England. Gurdeep Bhangra Gurdeep has more than 15 years’ experience in global Regulatory Affairs. She began her career in the Pharma Industry supporting Marketing Applications and move into the CRO field as Regulatory Project Manager. Responsibilities include provision of strategic regulatory support to plan, build an delivery high quality regulatory clinical trial applications globally to support product development plans for the pharma industry. Joe Cheal Joe Cheal, from Imaginarium Learning and Development, has been training, consulting and coaching since 1993, working with thousands of people from a diverse range of companies over the past 25 years. He is a highly interactive and engaging speaker who focusses on practical solutions for ‘real-world’ implementation.” Sinéad Usher Sinéad Usher has almost 20 years of regulatory experience. She is currently the director of SMART Regulatory Services Limited which provides regulatory expertise to both large Pharma and CRO’s. Assignments have included Regulatory Project Manager roles with responsibility for a range of portfolios such as vaccines (biological), oncology, respiratory and more recently HIV. Other regulatory assignments have included: Labelling Audit Project, Regulatory Intelligence, Common Technical Document conversions and auditing dossiers for submission. Sinéad is a registered pharmacist and has a post graduate diploma in regulatory affairs with distinction.

CRED Project Management for Regulatory Affairs Professionals

Project Management and how it fits with Regulatory Affairs

5-6 March 2019

Sinéad Usher, Director, SMART Regulatory Services Limited

ENABLING AND PROMOTING EXCELLENCE IN THE HEALTHCARE REGULATORY PROFESSION

Learning objectives

• Definitions of Regulatory Affairs and Project Management • What are Regulatory Projects? ● Rôles of RA pre and post Marketing Authorisation approval ● Other RA projects • Regulatory Affairs (RA) professionals as Project Managers

DEFINITION of a Regulatory Affairs Professional

A regulatory profess ional is responsible for keeping track of the ever- changing legislation in all the regions in which a company wishes to distribute its prod ucts, advise on the legal and scientific restraints and requirements, and collect, collate and evaluate scientific data. They are responsible for the presentation of registration documents to regulatory agencies, and carry out all the subsequent negotiations necessary to obtain and maintain marketing authorisation for the products concerned. They give strategic and technical advice at the highest level in their companies, right from the beginning of the development of a product, making an important contribution both commercially and scientifically to the success of a development programme and the company as a whole.” https://www.topra.org/TOPRA_Member/About_Us/What_is_regulatory_affairs_/TOPRA/TOPRA_Member/What_is_regulatory_affairs.aspx?h key=d6c99cd1-dcb4-4e9f-9a6a-2fed902b2b00

TOPRA webpage, downloaded 16 June 2018

DEFINITION of a Regulatory Affairs Professional

A regulatory professional is responsible for keeping track of the ever-changing legislation in all the regions in which a company wishes to distribute its products, advise on the legal and scientific restraints and requirements , and collect, collate and evaluate scientific data . They are responsible for the presentation of registration documents to regulatory agencies , and carry out all the subsequent negotiations necessary to obtain and maintain marketing authorisation for the products concerned. They give strategic and technical advice at the highest level in their companies, right from the beginning of the development of a product, making an important contribution both commercially and scientifically to the success of a development programme and the company as a whole.” https://www.topra.org/TOPRA_Member/About_Us/What_is_regulatory_affairs_/TOPRA/TOPRA_Member/What_is_regulatory_affairs.aspx?h key=d6c99cd1-dcb4-4e9f-9a6a-2fed902b2b00

TOPRA webpage, downloaded 16 June 2018

DEFINITION of Project Management, what is a project?

It's a temporary endeavor undertaken to create a unique product, service or result. And a project is unique in that it is not a routine operation, but a specific set of operations designed to accomplish a singular goal. Project management, then, is the application of knowledge, skills, tools, and techniques to project activities to meet the project requirements.”

https://www.pmi.org/about/learn-about-pmi/what-is-project-management Project Management Institute, downloaded 16 June 2018

DEFINITION of Project Management, what is a project?

It's a temporary endeavor undertaken to create a unique product, service or result. And a project is unique in that it is not a routine operation , but a specific set of operations designed to accomplish a singular goal. Project management, then, is the application of knowledge, skills, tools, and techniques to project activities to meet the project requirements.”

https://www.pmi.org/about/learn-about-pmi/what-is-project-management Project Management Institute, downloaded 16 June 2018

RA and Lifecycle of a medicinal product

RA involvement

Pre-MA Approval

Time

MAA Approval

Start of Clinical Trials

Divestment or Cancellation

Market expansion

MA submission

MAA= Marketing Authorisation Application

Pre-Marketing Authorisation approval

• High profile, high resource • Is there a dedicated Professional Project Manager?

Waterfall

Waterfall

Black belt

PRINCE2

RA and Lifecycle of a medicinal product

RA involvement

Pre-MA Approval

Time

MAA Approval

Start of Clinical Trials

Divestment or Cancellation

Market expansion

MA submission

MAA= Marketing Authorisation Application

RA and Lifecycle of a medicinal product

RA involvement

Post-MA approval

Pre-MA Approval

Time

MAA Approval

Start of Clinical Trials

Divestment or Cancellation

Market expansion

MAA submission

Post-Marketing Authorisation approval

• Market expansion • Lifecycle management e.g. variations for specification change or label extension • Majority of regulatory professionals work in post-MAA • Less money resource • Less likely to have a dedicated R&D project manager • Therefore, more likely that Regulatory function takes a lead in project management

RA and Lifecycle of a medicinal product

RA involvement

Advocacy, Regulatory Intelligence and other projects

Post-MA Approval

Pre-MA Approval

Product Incident and process gaps

Time

MAA Approval

Start of Clinical Trials

Divestment or Cancellation

Market expansion

MAA submission

Regulatory Affairs professionals as Project Managers

Regulatory Affairs professionals as Project Managers

Competent Authority e.g. EMA

Supply Chain

Safety (PVG)

CMC

Clinical

Regulatory

Non- Clinical

Marketing

Project Managem ent

Labelling

Publishing

Regulatory Affairs professionals as Project Managers

Patient/ HCP

Competent Authority e.g. EMA

Supply Chain

Safety (PVG)

CMC

Clinical

Regulatory

Non- Clinical

Marketing

Project Managem ent

Labelling

Publishing

Regulatory Affairs professionals as Project Managers

Patient/ HCP

Competent Authority e.g. EMA

Supply Chain

Safety (PVG)

CMC

Clinical

External

Regulatory

Non- Clinical

Marketing

Project Managem ent

Labelling

Publishing

Your Objective…

• Think of a regulatory project • The project can be past or present that you have personally worked on • Take 5 minutes to think about your project at the end of each of the 4 stages: • Defining • Planning • Implementation • Review • What will you do? Or what would you do different?

Learning Outcomes Recap

Definitions of Regulatory Affairs and Project Management ● RA profession is diverse and likewise projects are diverse and unique What are Regulatory Projects? ● Rôles of RA pre and post MAA – often differs, but principles overlap ● Other RA projects- never to be overlooked Why are Regulatory Affairs professional chosen as Project Managers? ● Key link to many functions

Abbreviations

 CPP – Certificate of Pharmaceutical Product  HCP – Healthcare Professional  MA – Marketing Authorisation  MAA – Marketing Authorisation Application  PIP - Paediatric Investigation Plan (EU terminology)  PM – Project Management  PSP - Pediatric Study Plan (US terminology)

 PV – Pharmacovigilance  RA - Regulatory Affairs  R&D – Research and Development

Thank you for your time. Questions?

CRED Project Management for Regulatory Affairs Professionals

STAGE 3. IMPLEMENTATION Practical Examples

2-3 August 2018

ENABLING AND PROMOTING EXCELLENCE IN THE HEALTHCARE REGULATORY PROFESSION

Dashboard?

What is a Dashboard?

A Dashboard is a visual to show KPIs They can be used during regulatory team meetings to show:

– Key submission milestones – Submission, Approval dates – Planned vs Actuals – Align your strategies and goals – Metrics

Regulatory Response

Safety Response

Efficacy Response Clinical Lead/Pharm Sci

Responsible Person

GRL

SRL

Final Draft

DD-MMM-YY DD-MMM-YY DD-MMM-YY

Document Status

Or as complex as this…

Image Reference: https://docs.losant.com/dashboards/overview/

Global Working

Benefit of Global Working

Access to regulatory knowledge for that market Interfacing with regulatory authorities in nature

language 24 hours

Networking Cost Saving

Best Practices

Be mindful of language barriers Time zone differences – consult your stakeholders Public Holidays – how will this impact you project? Meeting Minutes – keep them simple Cultural differences (do not get offended)

CRED Project Management for Regulatory Affairs Professionals

Stage 4: Final Review

5-6 March 2019

Gurdeep Bhangra, Regulatory Affairs Manager, IQVIA Limited

ENABLING AND PROMOTING EXCELLENCE IN THE HEALTHCARE REGULATORY PROFESSION

Learning Outcomes

 Stage 4: Final Review  Why review the project (and why does it not always happen)?

 Making the reviews useful  Key questions to ask, e.g.: ● What to do differently next time?

● What to do now – follow up? ● How to celebrate the successes ● Constructive Feedback  Recording & sharing information/ lessons learnt

Operational Challenges.. And Solutions..

Why review the project (and why does it not always happen)? Making the reviews useful Key questions to ask, e.g.: What to do differently next time? What to do now – follow up? How to celebrate? Recording & sharing information/ continual assessment Internal &/or External risk factors

Operational Challenges.. And Solutions..

• Why review the project (and why does it not always happen)? • Typically projects are driven by timelines and financial targets. During the intensive periods of the project deliverables, it is not always possible to “take a pause” and review, what is working and where areas can be improved. • Sometimes a “sticking plaster” approach is taken as issues are arising.. rather than a holistic one to meet the timelines and objectives of the project • Making the reviews useful/ Key questions to ask, e.g.: • Don’t be afraid – if you are unclear of your role/responsibilities vs. the project scope, it is possible that other team members may need clarity, but are not sure who to ask. • Remember – There are no “stupid questions”

Operational Challenges.. And Solutions..

 What to do differently next time? ● Review, Assess, discuss and revise ● Change for the sake of change does not always fly… ● Propose suggestions that management can relate to – Impact on costs reduction, reaching goals in a timely manner will engage with key stakeholders to  Follow up ● Feedback to key stakeholders. ● Positive constructive feedback is always a win-win. – For e.g. ” Team A didn’t deliver and messed up the timelines ” may lead to resistance from teams and management.. – Whereas changing the tone to “ Though Team A delivered output was delayed, it was of high quality and no rework was required. Inevitably, this did impact Team B and C deliverables and the final project output-timelines. In the future allowing for additional reviews and management oversight may be worth considering to ensure timely and seamless output …”

Operational Challenges.. And Solutions.

 How to celebrate: ● Objectives Achieved – ● On time and within budget ● Feedback and encouragement to teams from Project team and Senior Management ● Positive team work  Recording & sharing information/ continual assessment ● Purpose of the exercise is not to blame anyone or team, but to learn and strive to continually improve.  Internal &/or External risk factors ● Matters outside of our control – change of regulations, requirements, company SOPs/Processes..

Transferring the Knowledge – Real life example

 Project Review [PROCESS]: Regulatory Strategy and Delivery on a Phase III Global Clinical Development for Alzheimer's Disease Programme. [Study included use of tracers]  Challenges – What did not go well [Development] ● Clinical Trial Applications – Received More than 50% Validation Queries ● Every Clinical Trial Application received Regulatory Questions: – Questions on IMPD, Protocol Design, Application Forms. ● Resulted in more than 50% Country-Specific Protocol Amendment’ – Impact: Study Result Analysis, as this was intended to be the pivotal study for Marketing Authorisation Application.

Global Study Impact vs. Marketing Authorisation/Registration Goals

• Clinical Programme Start-Up timelines significantly increased • Clinical Research Investigators time is of essence. Delays with obtaining Regulatory and Ethics approvals impacts their availability to recruit patients and support the study. • Outreach to Sites and Patients delays • Patients miss the opportunity to take part in ground-breaking research • Perception of Sponsor (and CRO) at ECs/RAs • Pharmaceutical Companies – Retain a positive, responsible perception with the authorities [Broader Aspects – Impact on future projects]

Why (?) – Operational Planning

 Learning Points/Future recommendations  Sponsor [Pharmaceutical Company] – Typically seeks Scientific Advice from US FDA and EMA for Protocol Design and CMC (Quality) and Pre-Clinical product Development strategy. ● If Sponsor decision is to not include all of the SA recommendations – Justifications for deviation from guidance obtained/protocol study design should be carefully considered. [People]  Country Specific Regulations & Guidelines ● Knowledge and Application of Regulatory requirements at Local Office/Affiliate level [People]  Adhering to Requests from Local Affiliates ● Sponsor accommodating requests to support accurate clinical trial applications – some resistance [Denmark PGx], affected delays [People]  Communication

Meeting the Project Objective –

Outcome –

 Study was started up – Delays of 6-12 months  Patient recruitment slow –  Interim analysis - indicated no additional benefit from the study drug  Start Up/Regulatory Delays – Significant impact on budgets

CRED Project Management for Regulatory Affairs Professionals

Article 30(1) Case Study Introduction

6 March 2019

ENABLING AND PROMOTING EXCELLENCE IN THE HEALTHCARE REGULATORY PROFESSION

Purpose of Article 30(1) of Directive 2001/83/EC

Article 30

MRP

Harmonisation of dossier strategy

Indication(s)

ADRs

Quality

Clinical Study Report(s)

Safety Databases/PSURs/RMP/ Literature Searches

Module 3 Drug Product

SmPC and PIL

Clinical Overview/Tabulated Summaries

Clinical Overview/Tabulated Summaries

SmPC and PIL

SmPC and PIL

CRED Project Management for Regulatory Affairs Professionals

Article 30(1) Case Study Introduction

6 March 2019

ENABLING AND PROMOTING EXCELLENCE IN THE HEALTHCARE REGULATORY PROFESSION

Purpose of Article 30(1) of Directive 2001/83/EC

Article 30(1)

MRP

Harmonisation of dossier strategy

Indication(s)

ADRs

Quality

Clinical Study Report(s)

Safety Databases/PSURs/RMP/ Literature Searches

Module 3 Drug Product

SmPC and PIL

Clinical Overview/Tabulated Summaries

Clinical Overview/Tabulated Summaries

SmPC and PIL

SmPC and PIL

CRED Project Management for Regulatory Affairs Professionals

Article 30(1) Case Study Example Answer

6 March 2019

ENABLING AND PROMOTING EXCELLENCE IN THE HEALTHCARE REGULATORY PROFESSION

Stage 1: Define the Project

Project P’s Problem

Divergencies in the registered indications and shelf-life across several EU markets. TOPREXA – aiming for identical indications, ADRs and shelf- life across the 12 Member States (MS) Safety and confidence in the product through harmonised labelling. Increase in shelf life, patient exposure

Product/service/outcome

Purpose

Process

Comparison of SmPC/Module 2.3 and 3 Current tenders and pricing Available stability data

People

Refer to Stakeholder Slide

Politics

Company position, Commercial, Local requirements, Tenders, Pricing CHMP, National Competent Authorities, Company Senior Management Resource (people and subsequent submissions), Impact on other markets (labelling dependencies)

Power

Pounds

Priorities

Supply to patients, Timelines, Label

Stage 1: Define the Project

Scope • Harmonise SmPC indications, ADRs and shelf-life for 12 MSs.

Scope Creep (Avoid) • Other EU national authorised products for TOPREXA • Impact to labelling where EU National SmPC is a reference label for Emerging Markets. • Pricing and reimbursement nationally.

Stakeholders – Roles and Engagement

Clinical

Senior Mgmt

Commercial

Regulatory Operations

Medical Writing

Regulatory Affairs

Labelling / Artworks

Pharmaco- vigilance

– ‘Spanner’ Holders – Team Members – Service Providers – End Users

Pharma-Sci

CMC

Stakeholders

Spanner Holder

Team Members

Service Providers

End User

CHMP

CMC

IT

Patient

TOPRAPharm Pharmcoviligan -ce

Information Management (IM) Document Management System

Research and Institutions

Patient Advocacy Groups

Regulatory

Healthcare Professionals

Labelling Manufacturing Site(s)

Pharmaceutical Sciences

Artworks

Medical Writing Publishing Clinical

Identify Risk and Contingency Planning

Missing submission Date

Delays of issuing CPPs

Labelling worst case scenario

Loss of market share

Team members leaving

Risks

Different Timezones /Language barriers

Poor Handovers

Annual Leave/ Public Holidays

Validation Issues

Work Breakdown Structure

Medical Writing Provide Support CSRs

Clinical Sub Team Meeting

Senior Mgmt Approval

Author CO Addendum

Safety Conducts SB and Literature Search

Author Safety Report to support ADRs

Safety Sub Team Meeting

Update EU Nat Labels

Senior Mgmt Approval

Update EN Labels

KO Meeting to discuss CHMP Q’s

Publishing

CMC Assess Current Available Stability Data

Update Relevant M3 Sections

Author Cover Letter

Author Response Document to CHMP Questions

Example GANTT Chart

Task No. Activity

Duration (Days)

DPB

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34

1 KO Meeting

1 1 2

2 Clinical Sub Team Meeting 3 Medical Writing Provide CSRs 4 Author CO Addendum 6 Safety Sub Team Meeting 7 SB and Literature Search 8 Author Safety Report 9 Senior Management Approval 10 CMC Assess Current Data 11 Update Relevant M3 Sections

1 3 4 1 6 8

10

1 5

10

2 1 5

4,8

1

10

12 Author Response Document to CHMP Questions

12 3,7,11

13 Update EN Labels 14 Update EU Nat Labels 15 Author Cover Letter

2 5 5

9,12

13 12

16 Publishing

20 4,8,12,13,14,15

Communication Plan

Executive Summary

Frequency of distribution

Lessons Learnt

Key Messages

Content

Schedule

Roles and Responsibilit -ies

Target Audience

Communicat ion Media

Stage 3: Implementation

1.What can change and how do you handle it?

2.How do you maintain motivation?

Stage 4: Final Review

Reviewing and Closing out activities: • How does your company perform reviews? • How do you or would you record and share the knowledge gained?

Acknowledgements here if required (16pt)

Onsecuptatur? Ximus, cumquam eatae volorror sequatus ata quis elis accae. Nequia seritia sum sequam es as estorum quodis con cuptate niendae. Nam, consequid expeliciae. (14pt)