3Rs Working Group Meeting Agenda and Updates August 24th, 2022

3Rs WG Q3 Meeting August 24th, 2022 1

1. Agenda 1. Agenda Wednesday 24 August 2022 Time Topic Speaker Chair & co- chair 13:00-13:05 Brief introduction of all participants & agenda DCVMN Updates on ATT, PSPT and other opportunities 13:05-13:20 DCVMN 13:20-13:30 Single Dilution Survey Project Timelines and External Experts WG Members Your 3Rs Goals Share your companies 3Rs objectives 13:30-13:45 WG Members 13:45-13:55 Monocyte Activation Test - We want to hear from you! WG Members 13:55-14:05 Recombinant Factor C - We want to hear from you! DCVMN 3Rs Manuscript Volunteers to contribute & review DCVMN 14:05-14:15 AOB & Wrap up Next call is planned on November 30th at 1 PM CEST. Chair & co- chair 14:15-14:30 2

1. Updates Deletion of ATT South Korea has fully deleted ATT from its requirements on August 12th, 2022 both manufacturers and NCLs are not requested to perform it anymore! Link: https://www.mfds.go.kr/brd/m_99/view.do?seq=46610&srchFr=&srchTo=& srchWord=&srchTp=&itm_seq_1=0&itm_seq_2=0&multi_itm_seq=0&comp any_cd=&company_nm=&page=3 IFPMA is checking on whether its members have been experiencing waiver and deletion opportunities and challenges. Feedback will be shared once available. India (ATT is deleted for almost all human vaccines and antisera), but it is still part of the Indian Pharmacopoeia. IPC is willing to consider the full deletion previous risk assessment. 3

1. Updates Deletion of ATT India Impact of full deletion: the test is completely deleted, new products authorization won t include ATT; no safety risks due to in-process controls and other specific tests for contaminants. Indonesia product specific waiver(s) Mexico and Turkey any experience? 4

1. Updates PSPT Project 2 Publications are in preparation Review of all the material ongoing (SOPs, Spreadsheets, Reports) Everything will be available on the project webpage by end of September Webinars and workshops NC3Rs PanAmerican Workshop September 26th (online): https://nc3rs.org.uk/events/nc3rs-workshop-implementing-3rs-who-guidelines- understanding-impact-quality-control-and-0 IABS 3rd Next General Sequencing Conference September 27th-28th: https://3rd- ngs-rockville-2022.iabs.org/ DCVMN webinar on Rabies ELISA October (Date to be defined) DCVMN workshop on in vitro potency test for TDP (date to be defined in Q4 or Q1, 2023 - single dilution project workshop(s) prioritized) 5

2. Single Dilution Assay Project Objective: Support the members participating to the project to create implementation plans (one per each company) of the single dilution assay for their D or T (or both) components for the in vivo challenge or the serology potency assay. Participating members (and interested DCVMN members) can familiarize with the theoretical part of the single dilution principles and the experience of other members and external experts 6

2. Single Dilution Assay Project Execution Members will receive dedicated support from external experts which will provide theoretical knowledge and common form for the creation of the implementation plans. MoU with ISS/Italy, Sciensano/Belgium and PEI/Germany under discussion DCVMN members that has successfully implemented the assay are welcome to join the external experts and share their feedback, but they won t be able to access the other members implementation plans. 7

2. Single Dilution Assay Project Timelines MoU signature by mid-October Opening meeting by end of October Official start of the project and first workshop end of November or early December Members Engagement and questionnaire External Experts Agreements Opening workshop Working groups (members & experts) Workshops Members working on their plans Review of the plans Feedback to members M0 M1 M2 M3 M4 M5 M6 8

3. Your company 3Rs Goals 3. Your company 3Rs Goals DCVMN 3Rs WG focus is on vaccines and methods with the highest animal use Tetanus, Diphtheria, whole-cell/acellular Pertussis In vivo -> in vitro potency Rabies In vivo -> in vitro potency International collaborative study ongoing interested in a webinar as update? Hepatitis B/A In vivo -> in vitro potency IPV In vivo -> D-antigen Adventitious/extraneous agents In vivo -> Next Generation Sequencing What are your company 3Rs Goals? Possibility to align them with DCVMN 3Rs WG or viceversa? 9

4. Monocyte Activation Test EDQM (European Pharmacopoeia) is replacing Rabbit Pyrogenicity Test by 2026 with MAT (based on risk assessment approach of pyrogenic contaminants during the production process (incl. raw materials). EDQM is planning a 3 days conference on this topic in Q1 2023. NC3Rs Project on revision of WHO TRS has a dedicated WG on pyrogenicity and specific recommendations will be proposed on when and how to replace RPT. MAT included already in Eur Ph, Indian Pharmacopoeia, Chinese pharmacopoeia, included into FDA Industry Recommendation on Pyrogenicity, Brazilian Pharmacopoeia is initiating the work on a chapter. 10

4. Monocyte Activation Test Technical challenges Procurement challenges Regulatory challenges What is your company experience? Have you checked which MAT kit/method would be the best for your product? Do you have access to the material? Is it affordable? You have already switched to BET based on your product s type of pyrogenic contaminant, so MAT is not the best choice for your company. Other comments? Could DCVMN do anything more to support you on MAT implementation? 11

5. Recombinant Factor C EDQM (European Pharmacopoeia) included a chapter on the recombinant Factor C as a method to detect Bacteria Endotoxins. NC3Rs Project on revision of WHO TRS has a dedicated WG on pyrogenicity and specific recommendations will be proposed on when and how to use rFC rFC is also included into the Chinese Pharmacopoeia; USP is considering its inclusion while US FDA is approving products with rFC in their specifications; it has been assessed positively by Korean authorities; the Japanese are performing an assessment study and there is interest from the Indian Pharmacopoeia Committee to learn more about it. 12

5. Recombinant Factor C What is your company interest, knowledge and experience? Have you checked if and which rFC kit is available in your country? Do you have access to the material? Is it affordable? Could DCVMN do anything more to support you on considering the rFC implementation? 13

6. DCVMN 3Rs Manuscript Introduction 3Rs Principle (+4th R removal) Advancement in the field 4Rs Drivers and Benefits DCVMN s rationale for the engagement in the promotion for the 4Rs implementation Animal Use in DCVMN (Internal survey results anonymized) Opportunities for DCVMN PSPT Single Dilution Assay MAT 14

6. DCVMN 3Rs Manuscript DCVMN 4Rs Strategy Conclusion Small working group to review and finalize the manuscript volunteers? Authors? 15

Thank you! Next Call Q4 November 30th, 2022 16