6-MONTH STABILITY REPORT

LIEN:    OCTALIA_STABILITE_2013_115

0.05%ML7 AND PLACEBO EYE-DROPS CONTAINING

0.3%HPMC (BATCHES E728-1’ AND E728-2’)

OR 0.1%HEC (BATCHES E728-3 AND E728-4)

6-MONTH STABILITY REPORT

NEUROPTIS

Issued date: February 07th, 2014

TABLE OF CONTENTS

1. Introduction ........................................................................................................................ 3

2. Batch Characteristics .......................................................................................................... 4

3. Stability Protocol ................................................................................................................ 4

4. Operating Procedure ........................................................................................................... 5

4.1. Macroscopic Appearance ............................................................................................ 5

4.2. pH ................................................................................................................................ 5

4.3. Osmolality ................................................................................................................... 5

4.4. Viscosity ...................................................................................................................... 5

4.5. Active Assay ................................................................................................................ 5

5. Stability Results .................................................................................................................. 7

6. Discussion ........................................................................................................................ 12

6.1. Macroscopic Appearance .......................................................................................... 12

6.2. pH .............................................................................................................................. 12

6.3. Osmolality ................................................................................................................. 12

6.4. Viscosity .................................................................................................................... 12

6.5. Active Assay .............................................................................................................. 12

7. Conclusion ........................................................................................................................ 15

8. References ........................................................................................................................ 16

9. Appendices ....................................................................................................................... 16

TABLE OF TABLES

Table 1: Batch characteristics .................................................................................................... 4

Table 2: Testing schedule for the formal stability study ............................................................ 4

Table 3: Testing schedule for the stressed stability study .......................................................... 5

Table 4: ICH threshold for impurities in New Drug Product ..................................................... 6

Table 5: Stability data for batch # E728-1' (0.3% HPMC eye-drop placebo) ............................ 8

Table 6: Stability data for batch # E728-2' (0.3% HPMC-0.05% ML7 eye-drop) .................... 9

Table 7: Stability data for batch # E728-3 (0.1% HEC eye-drop placebo) .............................. 10

Table 8: Stability data for batch # E728-4 (0.1% HEC-0.05% ML7 eye-drop)....................... 11

Table 9: Additional peaks ........................................................................................................ 14

1. INTRODUCTION

This report presents the 6-month stability data generated on 0.05% ML7 and placebo eyedrops

containing 0.25% HPCxD and 0.3% hydroxypropylmethyl cellulose (HPMC) or 0.1%

hydroxyethylcellulose (HEC) as viscosing agent.

7. CONCLUSION

This report presents the 6-month stability data generated on 0.05% ML7 and placebo eyedrops

containing 0.25% HPCxD and 0.3% hydroxypropylmethyl cellulose (HPMC) (E728-

1’ and E728-2’) or 0.1% hydroxyethylcellulose (HEC) (E728-3 and E72-4) as viscosing

agent.

The two active batches were prepared using the second batch of ML7 raw material provided

by Provence Technologies.

Batches E728-1’ and E728-2’ (HPMC) were manufactured in accordance with a final

sterilization process.

Batches E728-3 and E728-4 (HEC) were manufactured using a manufacturing process

incorporating heat sterilization and sterile filtration.

No significant modification of the parameters studied was reported for both type of

formulations (HPMC and HEC) after 6 months storage at 4°C, RT and 40°C.

A special attention needs to be paid to the viscosity as stressed study at 70°C showed

downward trends while not correlated by the current 6-month data generated at 40°C or RT.

Additional peaks were thoroughly investigated and were observed close to the reporting

threshold from 6 months/40°C as anticipated under stressed condition (70°C).

Based on these data, it can be concluded that the stability behaviors of the four batches

studied remained satisfying at 4°C, RT and 40°C after 6-month storage.