1. CONFIDENTIAL ©2014 PAREXEL INTERNATIONAL CORP. ALL RIGHTS RESERVED. THE PRACTICE OF REGULATORY INTELLIGENCE: CASE STUDIES OMICS 5 th International Pharmaceutical Regulatory Affairs 3 - 5 August 2015, Orlando, Florida, USA Presented by: Mariam Aslam

2. CONFIDENTIAL ©2014 PAREXEL INTERNATIONAL CORP. ALL RIGHTS RESERVED. / AGENDA Introduction Case Study 1 Case Study 2 Case Study 3 Summary 2

3. CONFIDENTIAL ©2014 PAREXEL INTERNATIONAL CORP. ALL RIGHTS RESERVED. / INTRODUCTION Regulatory Intelligence (RI) process 3

4. CONFIDENTIAL ©2014 PAREXEL INTERNATIONAL CORP. ALL RIGHTS RESERVED. / INTRODUCTION Regulatory Affairs Professionals will either execute all or specific steps of the RI process depending on their role & responsibility The following case studies will be illustrated to demonstrate the importance of gathering RI and how the process steps are delivered: 1.Company A updating their pack design and identified that SPCs need to be updated to align to current guidelines 2.Company B changing manufacturer of drug product, manufacturing method and also reformulating the excipients. The current manufacturer cannot meet Company B’s current demand 3.Company C changing the legal entity name of manufacturing sites on a global scale 4

5. CONFIDENTIAL ©2014 PAREXEL INTERNATIONAL CORP. ALL RIGHTS RESERVED. / CASE STUDY 1 Company A updating their pack design and identified that SPCs need to be updated to align to current guidelines Case study 1 will demonstrate where only the following RI segments were executed: Data Collection Data Analysis Regulatory Strategy Communication Application 5

6. CONFIDENTIAL ©2014 PAREXEL INTERNATIONAL CORP. ALL RIGHTS RESERVED. / CASE STUDY 1 – DATA COLLECTION Company A updating their pack design and identified that SPCs need to be updated to align to current guidelines Sources of Date Collection: - Company marketing function - Product History -MHRA, EU websites, current regulations and guidelines -MHRA assessors 6

7. CONFIDENTIAL ©2014 PAREXEL INTERNATIONAL CORP. ALL RIGHTS RESERVED. / CASE STUDY 1 – DATA ANALYSIS Company A updating their pack design and identified that SPCs need to be updated to align to current guidelines Data Analysis: - Data collection from sources - Current and proposed pack design comparison - Impact on SPC - How many products will need a pack design and amended SPC - PIL required for many existing products 7

8. CONFIDENTIAL ©2014 PAREXEL INTERNATIONAL CORP. ALL RIGHTS RESERVED. / CASE STUDY 1 – REGULATORY STRATEGY Company A updating their pack design and identified that SPCs need to be updated to align to current guidelines Regulatory Strategy based on: -Data collection and analysis -Business priority needs -Conditions to be fulfilled for SPC regulatory submission approval -Procedure type for update to artwork design -Documentation & fees required for submission package -Timelines for preparing submission package, approval, grace periods & new pack design launch 8

9. CONFIDENTIAL ©2014 PAREXEL INTERNATIONAL CORP. ALL RIGHTS RESERVED. / CASE STUDY 1 – COMMUNICATION Company A updating their pack design and identified that SPCs need to be updated to align to current guidelines Communicated regulatory strategy with: - Senior management for green light -Marketing -Supply Chain -Artwork Coordinators/designers 9

10. CONFIDENTIAL ©2014 PAREXEL INTERNATIONAL CORP. ALL RIGHTS RESERVED. / CASE STUDY 1 – APPLICATION Company A updating their pack design and identified that SPCs need to be updated to align to current guidelines Steps for Application: - Preparation of proposed artwork, SPCs -Internal review and approval of proposed regulatory documentation -Preparation of submission package -Submission to Regulatory Authority (MHRA) 10

11. CONFIDENTIAL ©2014 PAREXEL INTERNATIONAL CORP. ALL RIGHTS RESERVED. / CASE STUDY 1 – CONCLUSION Company A updating their pack design and identified that SPCs need to be updated to align to current guidelines The updated pack designs and SPCs were approved after a delay of 3 months. This was due to MHRA questions and non acceptance of the initial proposal during the assessment of the submission package. Risks such as the non acceptance of the pack design could have been controlled by having a preliminary dialogue with the MHRA. The execution of a risk assessment to highlight the risks and control of them would have most likely reduced the approval timeline. 11

12. CONFIDENTIAL ©2014 PAREXEL INTERNATIONAL CORP. ALL RIGHTS RESERVED. / CASE STUDY 2 Company B changing manufacturer of drug product, manufacturing method and also reformulating the excipients. The current manufacturer cannot meet Company B’s current demand Case study 2 will demonstrate where all RI segments were executed: Data Collection Data Analysis Risk Assessment Regulatory Strategy Communication Application 12

13. CONFIDENTIAL ©2014 PAREXEL INTERNATIONAL CORP. ALL RIGHTS RESERVED. / CASE STUDY 2 – DATA COLLECTION Company B are changing manufacturer of drug product, manufacturing method and also reformulating the excipients. The current manufacturer cannot meet Company B’s current demand Sources of date collection: - Company marketing, supply chain and quality function - Product History -MHRA, EU websites, current regulations and guidelines -MHRA assessors 13

14. CONFIDENTIAL ©2014 PAREXEL INTERNATIONAL CORP. ALL RIGHTS RESERVED. / CASE STUDY 2 – DATA ANALYSIS Company B changing manufacturer of drug product, manufacturing method and also reformulating the excipients. The current manufacturer cannot meet Company B’s current demand Data Analysis: - Data collection from sources -Impact on SPC and packaging -Availability of documentation required for submission package such valid GMP Certificate, QP declaration, stability studies 14

15. CONFIDENTIAL ©2014 PAREXEL INTERNATIONAL CORP. ALL RIGHTS RESERVED. / CASE STUDY 2 – RISK ASSESSMENT Company B changing manufacturer of drug product, manufacturing method and also reformulating the excipients. The current manufacturer cannot meet Company B’s current demand Risk Assessment: - Incomplete submission, such as insufficient data -Incorrect variation procedure type and change code resulting in non- acceptance -Grouping of variations submitted to the MHRA has not been pre- approved -Pre-approval notification of grouping of variations has not been included in the submission package -Disruption in supply of drug due to current manufacturer no longer meeting company’s current demand 15

16. CONFIDENTIAL ©2014 PAREXEL INTERNATIONAL CORP. ALL RIGHTS RESERVED. / CASE STUDY 2 – REGULATORY STRATEGY Company B changing manufacturer of drug product, manufacturing method and also reformulating the excipients. The current manufacturer cannot meet Company B’s current demand Regulatory Strategy based on: -Data collection and analysis including submission procedure type -Business priority needs -Conditions to be fulfilled for regulatory submission approval -Documentation & fees required for submission package -Timelines for preparing submission package, approval, grace periods 16

17. CONFIDENTIAL ©2014 PAREXEL INTERNATIONAL CORP. ALL RIGHTS RESERVED. / CASE STUDY 2 – COMMUNICATION Company B changing manufacturer of drug product, manufacturing method and also reformulating the excipients. The current manufacturer cannot meet Company B’s current demand Communication with: MHRA for pre-submission dialogue - Senior management, Quality, Manufacturing, Supply Chain and Marketing for green light -Artwork Coordinators/designers 17

18. CONFIDENTIAL ©2014 PAREXEL INTERNATIONAL CORP. ALL RIGHTS RESERVED. / CASE STUDY 2 – APPLICATION Company B changing manufacturer of drug product, manufacturing method and also reformulating the excipients. The current manufacturer cannot meet Company B’s current demand Steps for Application: - Preparation of proposed artwork, SPCs -Internal review and approval of proposed regulatory documentation -Preparation of submission package -Submission to Regulatory Authority (MHRA) 18

19. CONFIDENTIAL ©2014 PAREXEL INTERNATIONAL CORP. ALL RIGHTS RESERVED. / CASE STUDY 2 – CONCLUSION Company B changing manufacturer of drug product, manufacturing method and also reformulating the excipients. The current manufacturer cannot meet Company B’s current demand Although the submission package had a long than anticipated approval timeline, the pre-submission dialogue/communication and control of risks ensured continuation of drug supply. 19

20. CONFIDENTIAL ©2014 PAREXEL INTERNATIONAL CORP. ALL RIGHTS RESERVED. / CASE STUDY 3 Company C changing the legal entity name of manufacturing sites on a global scale Case study 3 demonstrates where the following RI segments were executed: Data Collection & Data Analysis: - Executing a gap analysis (what data is available, what is missing) - Conducting Regulatory surveys (asking a serious of regulatory implication questions) in all impacted countries Conclusion: Due to the complexity of this change, executing the above RI steps is imperative prior to proceeding to the steps of the RI process. 20

21. CONFIDENTIAL ©2014 PAREXEL INTERNATIONAL CORP. ALL RIGHTS RESERVED. / SUMMARY RI should be executed at an early stage to identify and manage risks. Regulatory strategy is driven by the implementation of RI. These case studies demonstrate that RI is an important task to execute when a company is making changes to it medicines and at the same time ensuring the continuation of supply. One final point - I was practicing RI on a daily basis about ten years ago in my first RA role. To conclude, Regulatory Intelligence (RI) has always been an industry practice. It is gradually being acknowledged in its own right and gaining it’s long awaited recognition. 21

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23. CONFIDENTIAL ©2014 PAREXEL INTERNATIONAL CORP. ALL RIGHTS RESERVED. / THANK YOU CONFIDENTIAL ©2014 PAREXEL INTERNATIONAL CORP. ALL RIGHTS RESERVED. / 23