Eli Lilly and Company — FDA 483 Findings

SOP #0027777-018 ‘Viable Monitoring of Aseptic Manufacturing Areas” describes the frequency of monitoring, sampling methods, recording and analysis of data.

SOP #009138 “GMP Computer Systems and Purchased Automated Systems in Quality Control Laboratories (FDA-Regulated)” establish validation requirements for GMP computer systems.

There is no record to document that the AHU diagrams or As-build drawings have .

The firm uses aRE Forge: Tester to determine that the finished product yials, rubber stoppers, and aluminum closures meet the predefined torque specifications.

There is no diagrams or system description for the Pressure Test Equipment that is used to leak test the In addition: .

There is no established written procedure to describe restrictions to prevent cross ; contamination of other aseptic filling lines and/or products when employees have a lyophilized powder on their aseptic gown attire.

SOP #001-001757 “Process Control System Security” is used as a global document to , describe the guidelines for maintaining the security oftheprocess control systems and related documents for Parenteral Products Operations.

The 1999 and 2000 Deviation Audit Reports do not document the reasons why the .

There are a number of ceiling panels above the personnel corridors that are adjacent to oo _ the manufacturing rooms that appeared to be either ajar or positioned in a manner which provide for small openings in the ceiling.

In the event that aseptic fill room operators leave the filling areas they are required to re-gown into the appropriate clean room attire prior to returning to the aseptic filling areas.

The yellow color shoe covers are required to be don by personzel prior to entering into the manufacturing area pre-gowning room.

Conceming coor ain 20-25° C incubator that is used to incubate the media .

There are a number of non-approved documents or instructions that are used by personnel, for example: a.

Concerning the HEPA filters in the depyrogenationI The HEPA filters in the bot zone are not jntegrity tested on a periodic base in order to assure that the HEPA filters are not compromised.

The Air Handling Unit(AHU) As-Build drawings document specific pre-filter forthe =| air tbat supplies the various xooms and ultimately theHEPA filters.

The firm’s procedure (or any associated document) for the transfer of“Ready To Use” stoppers sterilization does not contain provisions for requirements of transfer conditions.

Non-viable particle measurements are taken with the use ofaPParticie Counter.

There is an inventory logbook that contains a ATCC culture index, Seed Culture List ATCC Lyophilized Cultures in Stock, Department Lyo’s in Stock, and Nitrogen Tank | ; Inventory list.

The Differential Pressure System (DPS) that is used to monitor the differential air pressures within the manufacturing ateas provide audio and visual alarms ifthere is a .

There is no established written procedure to describe the set-up of the capper.

The media fill batch records do not document the names or initials ofthe aseptic filling operators who actually perform some of the aseptic filling steps.

SOP “001-00243 ° “Operation of Capping Machine” provide instructions for the .

SOP #001-001754 “Air Pressure Differential Monitoring” instructs that individual critical alarm report suzomary will be reviewed and signed by the building engineer and ; by a Quality Control representative.

Conceming the acceptance ofmedia that is used in the laboratory for various analyses there is no established written procedure to describe the practice that is used to identify and label approved and non-approved media.

During a review of the media i io fill; cess operators were observed opening and closing the , zones, by the door bottom and side edges.

The 1999 and 2000 HEPA filter integrity tests for the Isolators document that there a were “no leaks detected”.

The following observations concern the 12/19/ tocol for Heat Profile of Incubators for the walk-in 30-35° C incubator, room .

During the recent airflow pattern.

The aseptic fill operators areallowed toperform the Quality ControlEM sampling,that is, self-sampling of self-monitoring prior to exiting the aseptic filling area.

The Environmental Monitoring (EM) Program does not include the use of microbial growth media that is optimum for the propagation of yeast or mold contaminates.

There are a number of observations conceming theBE testy Test Isolators He Validation and Qualification documents.

There is a CAD Standards Manual that describe the various processes that are to be , .

Room Ais used by personnel that are required to change from their street clothes and shoes into the requisite blue or white color work “scrub” suits.