Ben Venue Laboratories, Inc. — FDA 483 Findings

The firm contracted the validation of disinfectants and received the results in November 2009 for a disinfection efficacy study performed by the contactor.

There is no record to document that the air pressure readings (inches per water column) for the aseptic filling areas (Class 100 and 1 0,000} and the surrounding manufacturing areas are reviewed by the Physical Monitoring Department and/or the Quality Unit.

The I Hot Air Oven is used to depyrogenate vials and glassware for the manufacture of finished products.

According to the Supervisor of Physica ring, the firm has defined the limits of non- viable particulates to be not more that micron and not more than micron particulates in 1 cubic meter of air, as defined in Annex 1 and ISO 14644.

The 11 Facility and Equipment Qualification Master Plan", document #030..SOP-OP-13, effective date 30 Dec 2009, "applies to all Facilities, Utilities, and Process Equipment involved in the manufacture, packaging or holding of raw materials or drug products at BVL.

The "Clearance Procedure for Filling Interventions in Buildi cument #030-SOP-D-80, effective date 22 Mar 2011, "outlines the steps to be followed for line clearances performed after interventions in sterile filling", which are also performed during aseptic media fill processing.

The 2010 and 2011 quarterly environmental monitoring (EM) data document the percent of microbial identification for gram-positive rods (i.e.

Document 030-SOP-J-204, Dynamic and Static Environmental Monitoring Using Portable Non-Viable Particulate Counters, states that NVP monitoring during dynamic filling operations will be performed according to 030-LST-00033, Dynamic Non-Viable Particulate Sampling Locations.

The Sterility Test Isolators were qualified and validated on 3/26/07 and 4/2/07.

The 1/25/93 ilization/Depyrogenation Cycle Validatio ious Glass Carboys in Hot Air O Study document the time and temperature ( of the depyrogenation of glass ware.

According to SOP #030-SOP-J-36 (effective 12/30/08), entitled "Training of Quality Control Analysts" al sts and technicians in the Quality Control Laboratory must successfulfy complete er evaluation of knowledge.

The Manager Quality Assurance and Supervisor Physical Monitoring confirmed that the temperature a.nd relative humidity of the sterile storage area in building as not monitored in response to a rain water leakage from the ceiling on 4/23/11 as required per SOP "Contingency Plan", Document #030-SQP...

Per SOP 030-.SOP-E-1 0 (7.0), "Operating the Exterior Vial Washer", your firm uses a vial washer on packaging lines n build f the south complex, to ensure that the exterior of vials are clean of any foreign material.

We observed various mobile carts that are used to transfer material or equipment into the Class 10,000 manufacturing fill rooms with what appears to be rust-like, non-smooth, uncleanable surfaces on the wheel supports.

We observed that three tools maintained in aseptic fill room 4165 of the Phase IV facility had rust-like material inside th ockets.

On 04/02/11, an Environmental Control technician collected a water sample from a valve in the Water for Injection Loop I, which is use in the manufacture of aseptically filled parenteral drug products.

The I CCTV System can be used to observe the production and/or personnel activities, independently or collectively, by the Production, Physical Monitoring and Compliance Departments.

On 08/08/10, the parenteral finished drug product l -failed sterility testing, which was determined to be caused by the us sed during the transfer of pre-chilled glass vials from the lyophilizer to the infeed fill table.

The Quality Unit lacks the responsibility and authority to review and approve BVL Engineering or ContractorNendor CAD drawings.

Failure to identify the root cause of foreign material, identified as stainless steel particles in two products, and which are contract manufactured by your firm.

Document 03Q..SOP-K-46, Personnel Monitoring Program, states that every employee who participates in the set up for the active filling portion of the aseptic filting operation is required to contact Environmental Control (EC) for glove and gown testing.