Specifically,

(A) Investigations are not always performed for environmental / personnel monitoring excursions within the ISO-5 and ISO-7 (action limits of *** and ***, respectively) areas as required by SOP 3.030, Environmental Monitoring, Version: 10, Date Effective: 09/22/2023. The following are examples where investigations were not performed to determine a root cause, product impact, and the need to implement a CAPA to prevent recurrence:

Date of sampling – Location – ISO-Result – Organism – Associated Product and lot number

09/26/2022 – *** – ISO5 – 1 cfu-Fungal (Unable to ID) – Cyclosporine 0.2% in Cornn Oil 15mL Lot#***

03/10/2022 – *** – ISO5 – 1 cfu – Kocuria rhizophilla – Demecarium Bromide 0.125% Ophthalmic Solution, Lot#***

03/10/2023 –  *** – ISO5- 1 cfu – Micrococcus luteus – Tacrolimus 0.02% in Corn Oil 15 mL Lot#***

04/14/2023 – *** – ISO5 – 1 cfu – Baccillus altitudinis – Cyclosporine 2% Ophthalmic Suspension 15mL lot#***

05/01/2023 – *** – ISO5 – 1 cfu – Kocuria palustris – Buprenorphine 0.6 mg/mL Injection Solution, Lot#***

11/03/2023 – *** – ISO7 – 13 cfu – Staphylococcus aureus and Staphylococcus epidermidis – Tacrolimus 0.03% in Corn Oil, 15mL Lot#***, Tacrolimus 0.03% in Corn Oil 5mL Lot#***, Tacrolimus 0.02% in MCT Oil 10mL Lot#***

07/06/2023 – *** – ISO7 – TNTC – Unable to ID – No production in this room

08/04/2023 – *** – ISO7 – 13 cfu – Rhizobium species – Tacrolimus 0.03% Ophthalmic Suspension 15mL Lot#*** and Tacrolimus 0.02% ini MCT Oil, 5mL Lot#***

(B) Investigation into the turbid media fill 15ml bottle under OOS00041, for lot#*** did not include identification of the microorganism recovered. Additionally, the operator who performed this media fill was not requalified through performance of an additional media fill, and to date, this operator has filled approximately *** batches of sterile human and animal drug products.