1. Assigned Protection Factors (APFs) A Need for Harmonization ----- Merck’s Experience International Society for Respiratory Protection (ISRP) York, UK - April 11, 2013 Prepared By: Theresa Lane, CIH, CSP, Global Director of IH Erik Kateman, Site IH Oss, NL Presented By: Chris Cooper, Site IH Cramlington, UK 1

2. AGENDA Background Problem Statement Case Studies Summary Conclusions Recommendations Q & As

3. BACKGROUND – ABOUT MERCK Merck (MSD) is a global healthcare leader that discovers, manufactures, and supplies innovative human health and animal health medicines, including vaccines Merck operates in more than 140 countries Workers must be protected by the hierarchy of IH controls during our development and manufacturing processes

4. BACKGROUND – ABOUT PROTECTION FACTORS Assigned Protection Factor (APF) - the level of protection that a respirator/class of respirators is expected to provide where an effective respiratory protection program is in place – Established by regulation, consensus groups, and / or suppliers Nominal Protection Factor (NPF) – minimum level of protection needed to gain “approval” for respirators

5. PROBLEM STATEMENT NPFs are indicative of laboratory performance; actual performance expected to be less APFs for same respirator / respirator class are not consistent Respiratory protection study methods are not consistent, easy to conduct, or transparent – Simulated Workplace Protection Factor Studies (SWPF) – Workplace Protection Factor (WPF) Studies Results in confusion and wasted resources

6. PROBLEMS With CURRENT STUDY PROTOCOLS Determining the “Real” APF Merck confirms: – Site has implemented an effective Respiratory Protection Program – Respirator’s established APF is founded on scientifically valid and defensible studies Evaluate SWPF studies against “ORC-like” study protocol sponsored by the pharmaceutical industry Inconsistencies with study protocols & interpretations WPF studies extremely difficult to perform within pharmaceutical industry

7. Exercises & Equipment Interpretation Data Evaluation PROBLEMS with Study Design & Data Interpretation

8. Exercises & Equipment Interpretations Data Evaluation Test subjects Type & # of exercises Individual PFs Average PF Non-detects Application of Results Safety Factors SWPF WPF EXAMPLES of INCONSISTENCIES Sensitivity Time

9. * APF of 1000 only where scientifically valid study Respirator TypeUS-OSHA* APF UK-HSE APF Germany APF` Finland APF Manufacturer’s (APF / NPF) Independent (ORC-like - APF) A - PAPR25/1000*401002001000 (APF)825 B - PAPR25/1000*401002001000 (APF)715 C - PAPR25/1000*401002001000 (APF)670 D - SAR25/1000*-100-1000 (APF)1000 E - SAR25/1000*-100-1000 (APF)1000 F - SARNA-100-200 (NPF)1000 G – SAR with blouseNA-100-200 (NPF)170 9 Determining the “Real” APF CASE STUDIES - SUMMARY Same respirator, different protection? Who is to decipher & decide? EMPLOYERS are left trying to define proper protection

10. Establishing APF Values: CONCLUSIONS Employers must ensure effective RPE program Regulators & Manufacturers need to identify consistent criteria: – Study type & design Robust, representative, and transferrable SWPF studies – Data handling & interpretations – Pre-approval / endorsement by regulatory bodies – Management of Change Users need simplicity and transparency Currently, Employers need to understand how APFs are established to ensure adequate protection

11. Establishing an APF Value: RECOMMENDATIONS Need consistent, robust and representative criteria – Study design, execution, data evaluation and interpretation – Harmonization – Involvement & approval from regulatory bodies Need improved transparancy from suppliers Need easy-to-understand & interpret APFs Need to identify the “real” APFs Differences in APFs for a given respirator / class, must reflect actual differences in protection and not differences in study protocols or geographical region. Let’s start the dialogue and begin to harmonize!

12. Q & A

13. ACKNOWLEDGMENTS Erik Kateman – Oss, NE Chris Cooper – Cramlington, UK Merck’s Independent Testing Lab Respirator manufacturers Merck’s Independent Consultant

14. BACKUP SLIDES 14

15. References HSG53 Respiratory protective equipement at work, HSE, 2005. Selectie en gebruik van adembeschermingsmiddelen, NVvA, 2001. Simulated Workplace Protection Factor Study of Powered Air-Purifing and Supplied Air Respirators, AIHAH (62) 2001. NEN-EN 529:2005 Respiratory protective devices –recommandations for selection, use, care and maintanance NEN-EN 14594 Respiratory Protective Equipement, R.M. Howie, OEM 2005 (62) 423-428 Workplace Protection Factors – Supplied Air Hoods, T.J. Nelsen, AIHAJ (62) 2001 Assigned Protection Factors for the Revised Respiratory Protection standard, OSHA 3352-02 2009. NIOSH Respirator Selection Logic, N.Bollinger, DHHS Publication No. 2005- 100 AIHAJ 62:595–604 (2001) Merck-sponsored SWPF studies & consultant reviews Respirator manufacturers’ sponsored SWPF studies