ISSUES INCLUDE MOLD GROWTH AT STERILE MANUFACTURING ENTRY AND DEAD AND DECAYING FROGS NEAR THE PRODUCT EXIT DOCK
Between October 29 and November 1, 2013, the FDA inspected Marck Biosciences Ltd., Kheda, India. As a consequence of this audit, the FDA issued six extensive Observations. This Blog only reviews Observation 5 (a) and 5 (b).
- “Your firm failed to maintain the buildings used in the manufacture, processing, packing, or holding of a drug product in a clean and sanitary condition and keep them free of infestation by rodents, birds, insects, and other vermin (21 CFR 211.56(a)).
Other sections of 21 CFR 211.56 are included below. These sections continue to amplify the issues found within the facilities.
21 CFR 211.56(b) states that “there shall be written procedures assigning responsibility for sanitation and describing in sufficient detail the cleaning schedules, methods, equipment, and materials to be used…
21 CFR 211.56(c) states there shall be written procedures for use of suitable rodenticides, insecticides, fungicides, fumigating agents, and cleaning and sanitizing agents. Such written procedures shall be designed to prevent the contamination of equipment, components, drug product, containers, closures, packaging, labeling materials or drug products and shall be followed….”
- During the inspection, investigators noted significant mold growth in the washroom located at the entry to the sterile manufacturing area. The ceiling of this room had been allowed to deteriorate to such an extent that it caved in. This room shares a common mezzanine with the adjacent sterile processing rooms.
Your response does not identify any efforts to identify the mold growth or relate it to environmental monitoring data from the neighboring sterile suite, nor does it discuss the potential effect on the microbial quality of products made in your facility. Your response also does not discuss why this deterioration was permitted by your management until our inspection of the facility. In response to this letter, describe your investigation into the extent of mold within your facility, including within your HVAC system. Describe any additional findings of mold, corrective measures, and your investigation into the effect of any findings on product quality.
It appears that the facilities’ management chose not to perform any remediation of the area containing mold until the FDA arrived. When mold becomes visible to the naked eye, and no one automatically performs remediation, this suggests significant neglection of responsibilities. Also, the FDA Guidance for Industry (2004) Sterile Drug Products, requires any microorganisms isolated from such areas to be identified.
We note that a recent MHRA report of a December 2013 audit conducted at your facility discussed the findings of fungus growth within a large volume parenteral product manufactured at your facility. Please provide a full accounting of this incident and a copy of your investigation into the matter, along with corrective and preventive actions taken.
Because the various regulatory agencies interact with one another and share information, it is not surprising that this event became available to others. Finding fungal growth within LVP (large volume parenterals) within the ISO 5 environment begs the question as to the root source of the fungal masses. Fungal masses within LVP often are obvious to the naked eye.
- The investigators noted numerous dead insects in the “Sample Pass Through” Room, located approximately (b)(4) from the Sterile Filling Line #(b)(4) of the small volume parenterals facility. In addition, dead and decaying frogs were found next to the product exit dock. Your response states that these pest infestation issues would be corrected. It also includes a commitment to remove the manufacturing waste near the entrance to the facility and to fill in the swamp-like perimeter that appeared to be serving as a harborage for vermin. Your response does not address why the observed conditions were permitted to exist in and around the manufacturing facility. In response to this letter, discuss this issue and provide details of your pest prevention program.
The presence of “numerous dead insects in the “Sample Pass Through” Room, located approximately (b)(4) from the Sterile Filling Line #(b)(4) of the small volume parenterals facility” again questions why management was not aware of this condition. Similarly, the presence of “dead and decaying frogs” gives pause as to why this firm was not immediately placed on “Import Alert”.