185406445 b103-syringe-filler-072709

Eli Lilly and CompanyTechnical Specifications Revision 0.2

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Technical Specifications

B103 Commercialization Launch Filling Facility

Syringe Filling Line

Revision Date: 27-Jul-09 B103-SYRFLL-TS-0.2 of 72

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Revision: 0.2Revision date: 27 July 2009

Eli Lilly and Company



Revision History

Revision Date Changes0.2 DRAFT

Any difference between this document and any previous document must be resolved in favor of the current version.

This document contains confidential material of the company to be used exclusively by Eli Lilly & Co., its associated companies and contract personnel.



Prepared by:

Justin Svec B103 Senior Process Engineer Printed Name Title Signature Date

Your signature indicates the user requirements were accurately developed for this system and are in compliance with Eli Lilly and Company procedures.

Review and Approval

Reviewed by:

Justin Farrell Engineering. Consultant, ETC Printed Name Title Signature Date

Printed Name Title Signature Date

Lyle FaitB103 Senior Process Automation Engineer

Printed Name Title Signature Date

Printed Name Title Signature DateYour signature indicates that the requirements pertaining to your area of expertise were included.

Approved by:

Engineering / Operations Representative

Ken Weerts Manager – B103 Parenteral Eng/Ops

Printed Name Title Signature DateYour signature indicates that the requirements with product quality impact accurately reflect current process knowledge.

Quality Representative

Anne Renton Assoc Quality ConsultantPrinted Name Title Signature Date

Your signature indicates that individuals with the appropriate expertise reviewed and approved this document..



1.0 TABLE OF CONTENTSTable of Contents

2.0 Introduction........................................................................................................................................5

2.1 Purpose.................................................................................................................................52.2 Scope....................................................................................................................................52.3 System Description………………………………………………………………………...52.4 Assumptions.........................................................................................................................52.5 Proposal Submittals..............................................................................................................5

3.0 Technical Specifications Matrix..................................................................................................63.1 General Design.....................................................................................................................6

3.1.20 Outer Bag Removal Station……………………………………………… …103.1.34 Inner Bag Stretching Conveyor, Tub Accumulation Conveyor, and Debagger……………………………………………………………………………..123.1.67 Delidder……………………………………………………………………….143.1.90 Syringe Filler…………………………………………… …………………..153.1.143 RABS Enclosure………………………………………………………… ….20

3.2 Mechanical.........................................................................................................................213.3 Materials of Construction………………………………………………………………...253.4 Safety..................................................................................................................................283.5 Electrical.............................................................................................................................313.6 Enclosures..........................................................................................................................333.7 Auxiliary Controls..............................................................................................................343.8 Automation, Instrumentation and Controls........................................................................34

4.0 Documentation and Data...........................................................................................................404.1 Documentation...................................................................................................................404.2 Data....................................................................................................................................41

5.0 Commissioning And Qualification............................................................................................415.1 Commissioning..................................................................................................................415.2 Factory Acceptance Test (FAT).........................................................................................435.3 Shipping and Installation....................................................................................................445.4 Site Acceptance Test (SAT)...............................................................................................455.5 Installation Qualification (IQ) and Operational Qualification (OQ)……………………..45

6.0 General Options.........................................................................................................................467.0 Appendices................................................................................................................................47

7.1 Appendix A - Syringe and Plunger Reference Document.................................................477.2 Appendix B - Product Defect Criticality............................................................................497.3 Appendix C – Detailed Description of FAT Testing.........................................................507.4 Appendix D – Vendor Documentation Requirements.......................................................517.5 Appendix E – Right Information (Component) Data Requirements..................................517.6 Appendix F – Submission Transmittal Form.....................................................................517.7 Appendix G – Good Documentation Practices..................................................................52



2.0 INTRODUCTION

2.1 Purpose

This document identifies and describes the Technical Specifications for the design and operation of a Syringe Filling Line to be installed at the Eli Lilly and Company, Lilly Technology Center, Building103 site. The Vendor shall provide a design, cost, and schedule proposal for a Syringe Filling Line in accordance with this specification. The Vendor shall be completely responsible and liable for all equipment supplied, whether manufactured or subcontracted to a third party supplier.

2.2 Scope

This document is limited to the Syringe Filling Line to be installed at the Eli Lilly and Company, Lilly Technology Center, Building103 site.

2.3 System Description

The Syringe Filling Line to be located in the B103 Commercialization Launch Facility is a direct impact system that receives 0.5ml or 1mL Long glass syringes or 3mL polymer cartridges in a pre-sterilized nested tub format. The line debags, delids, and aseptically fills the syringes (fill volumes between 0.20 mL and 3 mL) using either rotary piston pumps or peristaltic pumps, inserts a plunger, and sends the filled and plungered syringes to an outfeed conveyer. The filler will perform checkweighing at a variable, user-defined frequency. On the outfeed conveyor, the tubs are detained until released by the filler when passing checkweigh results are obtained. The tubs are coded with an ink jet printer, manually closed with a plastic snap-on lid, and staged for palletization. The Syringe Filler will be designed to operate up to a maximum rate of 600 units per minute using up to 10 filling needles. This filling line will be used to produce clinical trial material and approved pharmaceutical products that meet USFDA, EU and JP cGMPs.

2.4 Assumptions

Key project assumptions are given below:

All components designed to run on the filler or used for FAT testing are as listed in Section 7.1 Appendix A - Syringe and Plunger Reference Document and meet specifications.

The product fluid to be tested during FAT will be water or buffer. Active Pharmaceutical Ingredient (API) will not be used for FAT testing. Eli Lilly (Buyer) will provide Material Safety Data Sheets (MSDS) for all ingredients and an approximate composition for the buffer/placebo.

2.5 Proposal Submittals

Any Exceptions to the technical requirements in the specifications must be noted within the Submittal. Failure to note exceptions will be regarded as confirmation that the Vendor’s Submittal complies with the specification.

Vendor may be contacted for technical questions or clarifications during the review period. Vendor shall provide contact information for such questions and clarifications.

With Purchase Order award, Submittals will either be “Approved as Noted”, using the clarifications and RFIs as support for any modifications to the submittals, or “Approved”.



3.0 TECHNICAL SPECIFICATIONS MATRIX

3.1 General Design

ID# Description ER Reference

3.1.1This Specification, together with attachments to it, and with referenced Owner’s SECTIONS, codes and standards, covers the scope of work and the minimum requirements for the design, fabrication, inspection, testing and delivery of a fully integrated syringe filling line for use in a sterile parenteral pharmaceutical cGMP environment. This Specification covers the following:

Tag Number

Description/Size

Outer bag removal stationInner bag stretching and tub accumulation conveyorsDebaggerDelidderFiller including in-process checkweighRABS enclosure for debagger, delidder and filler

3.1.2 The post-fill process equipment is currently covered in the XXX Specification No. XXX.

3.1.3 Omissions in this Specification or in the design of Supplier drawings shall in no way relieve the Supplier from its responsibility for furnishing equipment within the obvious intent of this Specification.

3.1.4 Other work performed may include the following:Equipment receiving and unloading

1. Equipment installation and connections to process and utility servicesUtility lines, conduits and wiring routed to the equipment tie-in pointsSupport foundation for equipmentConnection to Owner’s network

3.1.5 The syringe filling line shall be delivered to the site as a fully functional line. The Owner need only connect piping, power wiring, and controls wiring for a fully functioning system, prepared for start up, commissioning, and qualification.

3.1.6 The related Owner Specifications sections referenced in this document and to be attached as part of the Specification package at a later date include: 1. SECTION 01040, ADMINISTRATIVE PROVISIONS2. SECTION 01340, SUBMITTALS3. SECTION 01910, COMMISSIONING REQUIREMENTS FOR CONTRACTORS4. SECTION 16154, MOTORS THROUGH 250 HP5. SECTION 16995, ELECTRICAL REQUIREMENTS FOR

PACKAGED EQUIPMENT



ID# Description ER Reference 6. SECTION 15981, CONTROL PANELS 7. SECTION 16155, AC ADJUSTABLE DRIVES 8. SECTION 16918, INSTRUMENT AIR SUPPLY9.SECTION 16910, INSTRUMENTATION FOR PACKAGED

EQUIPMENT10.SECTION 15200, HYGIENIC PIPING11.SECTION 15200 700, PIPING SCHEDULE12.SECTION 15200 8.1, PIPING SCHEDULE

3.1.7 References: Abbreviations and AcronymsAISC American Institute of Steel ConstructionANSI American National Standard InstituteASME American Society of Mechanical EngineersASTM ASTM InternationalAWS American Welding SocietyCFR Code of Federal RegulationsCGMP Current Good Manufacturing Practices of the Food and Drug Administration, United States Department of Health and Human Services, Title 21 U.S. Code of Federal Regulations (CFR), Parts 11, 210, 211 and 600

GAMP Good Automated Manufacturing Practices published by the International Society for Pharmaceutical Engineering

IEST Institute of Environmental Sciences and TechnologyISA Instrumentation Systems and Automation SocietyISO International Standards OrganizationISPE International Society for Pharmaceutical EngineeringNEMA National Electrical Manufacturer’s AssociationNEC National Electrical CodeNFPA National Fire Protection AssociationNIST National Institute of Standards and TechnologyOSHA Occupational Safety and Health AdministrationUL Underwriter’s LaboratoriesUSP United States Pharmacopoeia

3.1.8 The following industry, association, and government codes and standards shall be followed, as applicable to the design, fabrication, assembly, and testing of all equipment furnished under this Specification:

ANSI B11.TR3-2000 <referenced below>ANSI B46.1 “Surface Texture (Surface Roughness, Waviness,

and Lay)”ANSI B155.1 “Packaging Machinery and Packaging-Related

Converting Machinery - Safety Requirements for Construction, Care, and

Use”ANSI Z535.1 “Safety Colors”ANSI Z535.2 “Environmental and Facility Safety Signs”ANSI Z535.3 “Criteria for Safety Symbols”ANSI Z535.4 “Product Safety Signs and Labels”ANSI Z535.5 “Safety Tags and Barricade Tapes (for Temporary



ID# Description ER ReferenceHazards)”

ASSE Z244.1 “Control of Hazardous Energy Lockout/Tagout and

Alternative Methods”ASME-BPE GuidelinesASME B15.1 “Safety Standard for Mechanical Power

Transmission Apparatus”ASME Form U-1 “Manufacturer’s Data Report for Pressure

Vessels”ASTM C795 “Standard Specification for Thermal Insulation for

Use in Contact with Austenitic Stainless Steel”CFR Title 21 Part 11 “Electronic Records; Electronic

Signatures”CFR Title 21 Part 177 “Indirect Food Additives: Polymers”CFR Title 21 Part 178 “Indirect Food Additives: Adjuvants,

Production Aids and Sanitizers”EN779 “Particulate Air Filters for General Ventilation”EN1822 “High Efficiency Particulate Air Filters (HEPA and

ULPA)”GAMP Version 5 “Guideline for Validation of Computer

Systems”GAMP Supplier Guide for the Validation of Automated Systems

for Pharmaceutical ManufacturingIEST-RP-CC 001.3 “HEPA and ULPA Filters”ISO 3864-1:2004 “Graphical Symbols - Safety Colors and Safety

Signs - Part 1: Design Principles for Safety Signs in Workplaces and

Public Areas” MCA Rules and Guidance for Pharmaceutical Manufacturers

and Distributors, latest edition. (EMEA guidelines)NFPA 79 “Electrical Standard for Industrial Machinery”OSHA 1910.212 “Machinery and Machine Guarding: General

requirements for all machines” UNI EN 292 (general principles for design)UNI EN 1088 (guards)The issues and revisions of these codes and standards that apply shall be effective from the date of Supplier’s proposal.

3.1.9 The construction of the equipment shall be in full compliance with FDA, EU and JP current GMPs. Vendor shall verify that a similar filling line has been successfully commissioned and inspected by FDA, EU or JP inspectors.

3.1.10 Regarding equipment safety, supplier shall provide an executed Equipment Risk Assessment (operator safety risk analysis) in compliance with ANSI B11.TR3-2000 (for US and Puerto Rico installations) or EN 1050 (for European installations).

3.1.11 Supplier shall either perform or provide a quantitative ergonomic analysis using industry accepted calculation tools, (e.g. NIOSH




Lifting equation) to determine the need for material handling equipment during lifting, pushing or pulling of machine components.

The Syringe Filling system shall be designed such that an operator will not be required to lift more than 30.8 lbs (14 kgs) in any single operation, and such that all parts will have appropriate lifting surfaces (e.g., handles on plunger bowl) for the service and size of part.

3.1.12 Warranty: Refer to SECTION XXX

3.1.13 The syringe filling line is being purchased for installation in a renovated sterile parenteral products pharmaceutical manufacturing building. The equipment shall provide consistent and validatable filling of pharmaceutical solutions into empty, presterilized syringes. The equipment shall have the capability of running different recipes that are configurable when they are created but are version controlled and secured after creation. A minimum of three access levels shall be provided (e.g. operator, supervisor, and maintenance), with the ability to modify recipes being limited to a single access level. The syringe filling line shall require no manual intervention during operation under normal circumstances, with the exceptions of the manual outer bag removal system and inner bag stretching conveyor upstream of the automated inner bag removal system (hereafter referred to as the “debagger”) and the addition of pre-sterilized plungers from an RTP ported bag. The debagger, delidder and filler operational data shall be capable of being accessed by the Owner’s Process Control System via Ethernet for remote monitoring and archiving of data.

3.1.14 The scope of work is to build, commission and support qualification of an integrated syringe filling system. The system shall include associated equipment and controls. It shall be supplied ready for connection to services (i.e. power, compressed air, etc).

3.1.15 The equipment included in the scope of this Specification is as follows:

1. Outer bag removal station2. Inner bag stretching conveyor, tub accumulation

conveyor, and debagger3. Delidder4. Filler including in-process checkweigh5. RABS enclosure for debagger, delidder and filler

3.1.16 The Syringe Filling Line shall be designed such that no more than six (6) operators are required to effectively operate the system, with no more than the following number of operators for each subcomponent of the line:Tub feeding: 1Outer bag removal: 1Inner bag stretching and removal: 1Filling : 2Post-fill palletization: 1

3.1.17 The syringe filling line shall be used to process any one or more of the following items:

1. 1ml long syringe with staked needle, packaged in 160 syringe tub

2. 1ml long plunger, gray, packaged in bulk RTP bags



ID# Description ER Reference3. 1ml long plunger, gray Fluorotec-coated, packaged in

bulk RTP bags4. 0.5ml syringe with staked needle, packaged in 160

syringe tub5. 0.5ml plunger, gray Fluorotec-coated(?), packaged in bulk

RTP bags6. 3ml flanged cartridge, packaged in 64 unit tub7. 3ml plunger, gray Fluorotec-coated, packaged in bulk

RTP bags

(Refer to Section 7.1 Appendix A - Syringe and Plunger Reference Document for additional detail)

3.1.18 Each unit shall be pre-piped and pre-wired such that the Owner needs only to provide a single connection, per utility, to form a complete functional and integrated system. Utility connections shall be clearly identified, with connection size and type, by the Supplier to insure ease of installation at Owners facility.

1. Vendor shall be responsible for all piping and wiring interconnections (cables but not cable trays) between equipment components and control panels. Wiring interconnections distances from remote mounted control panels to the equipment shall be per the Data Sheets. All piping connections to owner’s utility systems will be piped to the exterior of the machine base/frame and fitted with an ASME standard dimension S-line sanitary pipe coupling fitting. S-Line connections consist of two matching ferrules, a gasket, and a clamp to compete this union (standard tri-clamp fitting).

2. Owner will provide a single 480V/60Hz/3phase power supply to vendor’s main control panel. Vendor is responsible for all power and instrumentation voltage interconnections and distribution from this main feed. The interconnection wiring shall be labeled, both cables and individual wires, and used during the equipment vendor’s check-out/testing phase and the FAT. The same wiring will be shipped complete, labels intact, with the equipment to owner’s site following FAT approval.

3.1.19 The Supplier shall fabricate, finish, clean, examine, acceptance test, treat, insulate, and package for shipment the equipment components, piping, instrumentation, and electrical components integral to the equipment.

Outer Bag Removal Station

ID# Description ER Reference3.1.20 The outer bag removal station shall be of pharmaceutical grade

and shall allow for manual removal of outer bags from tubs without additional tools and without operator contact of or other source of contamination of the inner bag.

3.1.21 Presterilized syringe tubs in bags shall be conveyed into and out of the station without being damaged in the process. Penetration of the outer or inner bag during infeed, or of the inner bag or tub during outfeed to the debag room, shall not occur during operation



ID# Description ER Referencein accordance with vendor’s guidelines. Defect generation caused solely by the equipment shall not exceed 0.1 percent during a given manufacturing run.

3.1.22 The outer bag removal station shall not experience more than 1/2 percent downtime annually during operation (24 hours per day; seven days per week; 50 weeks per year available time at 80 percent utilization).

3.1.23 The outer bag removal station shall meet applicable tub protection requirements during operation, decontamination/cleaning and servicing.

3.1.24The unidirectional airflow enclosure shall maintain ISO 7 (Class 10,000) internal conditions, with the machine sitting in an external CNC environment.

3.1.25The laminar flow unit shall have user adjustable alarm limits for differential pressure across the HEPA filters. Alarms shall be audible, and will be captured electronically.

3.1.26 A powered roller conveyor shall be provided at the right-hand side infeed of the station. A cursory inspection of the outer bag will be performed by one operator prior to placing the tub on this conveyor. No special lighting is required. A second operator will depress a foot pedal to index the tubs into the station.

3.1.27 The bag removal station shall include an enclosure with 3/8” min. (10mm) thick clear safety glass guarding with open base. A partial front wall will be used to separate the second operator’s face and chest from the manual bag removal process but will allow reach in with arms. The wall shall be positioned to prevent glove reach to the powered outfeed conveyor.

3.1.28 A vertical unidirectional airflow unit shall be provided with single pass airflow to minimize the likelihood of contamination of the outer or inner bag surfaces. HEPA filters must be of type Class H14 to EN1822 (99.995% collection efficiency) with Flanders Blu-Jel Seal system, and prefilters must be of type Class G4 to EN779. The system shall include validation connections for the supply and measurement of raw gas concentration of HEPA filter integrity test aerosol (e.g. PAO (polyalphaolefin)). Differential pressure across the filters will be monitored but not controlled.

3.1.29 A powered outfeed roller conveyor shall be included to transport the tubs towards an inner bag stretching conveyor housed in the Grade C debag room; the outfeed conveyor shall not extend into the debag room. An operator in the debag room will call for a tub by depressing a button or footswitch, thereby activating the outfeed conveyor.

3.1.30 A mousehole plus deadplate shall be employed to separate the outer bag removal station conveyor from the inner bag stretching conveyor. Facility differential pressure from the debag room to the outer bag removal room will ensure continuous outward airflow through the mousehole. A gate will be considered for isolation of the debag room from the outer bag removal room.

3.1.31 A waste receptacle on wheels shall be provided for accumulation of outer bags, with a minimum bag capacity equivalent to 10 minutes of run time at 600 syringes per minute. The bin shall be easily reachable from the left-hand side of the enclosure, through an opening, for loading without the operator having to remove gloved hands from under the unidirectional airflow. Removal of the bin for emptying shall be from outside the enclosure.



ID# Description ER Reference3.1.32 Means of removing rejected tubs prior to transport into the debag

room shall be provided at the left side of the bag removal station. This may be in the form of a short roller conveyor.

3.1.33 Conveyors associated with the Outer Bag removal station shall have an integral e-stop button, protected mushroom button style. Mounting locations to be shown on submittal drawings.

Inner Bag Stretching Conveyor, Tub Accumulation Conveyor and Debagger

ID# Description ER Reference3.1.34 The inner bag stretching conveyor shall be of pharmaceutical

grade and shall allow an operator to easily access a tub below unidirectional airflow and extend the tab of the inner bag to permit subsequent capture and slitting of the bag on the debagger machine.

3.1.35 The tub accumulation conveyor shall provide adequate accumulation of tubs upstream of the debagger, under unidirectional airflow protection, and shall be of hinged style to permit access to the rear of the line for tank transport and line maintenance.

3.1.36 The debagger shall be of pharmaceutical grade and shall consistently automatically remove inner bags from tubs without damaging the tubs or lids.

3.1.37 Tubs and lids shall not be contaminated during removal of the inner bag. Machine components contacting the bag shall avoid contacting the tub or lid to the greatest extent possible.

3.1.38 Lid integrity shall not be compromised.3.1.39 Incomplete bag opening and tub removal shall not exceed 1%

frequency, provided that the end of the bag has been properly oriented and smoothed by the operator on the conveyor upstream of the debagger.

3.1.40 Failure to transfer the bag to the waste bin shall not exceed 1%.3.1.41 Limits for damage to tub, nest and syringe can be found in the

Debagger datasheet.3.1.42 The slitting knife shall be capable of cutting open a minimum of

5000 bags before requiring replacement.3.1.43 The debagger shall not experience more than five percent

downtime annually during operation (24 hours per day; seven days per week; 50 weeks per year available time at 80 percent utilization).

3.1.44 The debagger shall not compromise the sterility of the syringes within the tubs during operation.

3.1.45 The unidirectional airflow RABS enclosure shall maintain Grade B internal conditions, with the machine sitting in an external Grade C environment.

3.1.46 Each Process Operating Parameter, including laminar flow unit differential pressure, shall have user programmable alarm limits that are recipe driven. Alarms shall be captured electronically.

3.1.47 Engineering parameters shall be configurable within recipes. 3.1.48 The control system furnished shall provide a means for physical

and logical security.



ID# Description ER Reference3.1.49 The computer system furnished shall be 21CFR Part 11 compliant3.1.50 The inner bag stretching conveyor shall be provided with

dedicated unidirectional airflow, full guarding on the back side along its length, and partial guarding along the front side, allowing an operator to reach in with gloved hands and manually extend the inner bag surrounding the tub in the proper orientation for automatic removal. (See Debagger details below for filter and guarding requirements)

3.1.51 A second section of conveyor, adjacent to the debagger and used for tub accumulation, shall be a hinged, swing-type to permit transport of the product fill tank to the opposite side of the debag room, and to allow maintenance from the other side of the debagger. Unidirectional airflow shall be provided along its length, plus full guarding on both front and back sides, with hinged doors to be opened to allow the tank to pass through. (See Debagger details below for filter and guarding requirements)

3.1.52 An automatic gate shall be provided separating the tub accumulation conveyor from the debagger infeed. When the swing conveyor is opened for passage of the product tank, the gate shall automatically close to isolate the debagger.

3.1.53 The debagger unit shall include an automatic slitting system for opening the bag, and automatic waste collection system, including a main waste bin for bags and a separate drawer for bag tabs. An audible alarm shall be provided indicating a full main waste bin, based on a machine cycle count. The machine shall continue operating for a period of up to one minute while the waste bin is moved out of its storage location and is replaced by a spare bin. Up to four bags shall be accumulated during this period and not dropped on the floor.

3.1.54 The debagger unit shall be housed within a RABS enclosure with integral unidirectional airflow and 10mm minimum thickness safety glass panels. HEPA filters must be of type Class H14 to EN1822 (99.995% collection efficiency) with Flanders Blu-Jel Seal system, and prefilters must be of type Class G4 to EN779. A CG-manifold shall not be used on the downstream side of the HEPA filters.

3.1.55 The system shall include validation connections for the supply and measurement of raw gas concentration of HEPA filter integrity test aerosol (e.g. PAO (polyalphaolefin)).

3.1.56 The status of each individual RABS door shall be monitored and alarmed (audible and visual). In order to open a door, the operator must first release the door at the HMI.

3.1.57 The enclosure shall be provided with automatic differential pressure control, achieved via variable frequency fan speed control. In the event of a leak, for example from a glove failure, fan speed will increase to compensate and reestablish the differential pressure setpoint. When a RABS door is opened, fan speed will be frozen at the last controlled speed and will not be able to reach the original differential pressure setpoint. After a short duration of the door being open, the internal pressure will equilibrate with the surrounding room pressure.

3.1.58 Lighting within the enclosure shall be to >500 Lux.3.1.59 The debagger shall operate at up to 225 tubs per hour.3.1.60 The main waste bin shall be provided with wheels, designed to

accommodate a liner bag, and a minimum capacity of 40 bags (equivalent to 11 minutes of run time at 600 syringes per minute). Removal of the bin for emptying shall be from below the



ID# Description ER Referenceenclosure, without having to open the enclosure guarding. A spare bin shall be provided to ensure uninterrupted processing.

3.1.61 Incomplete removal of the inner bag or incomplete disposal into the main waste bin shall be automatically detected and cause a machine stoppage and audible alarm.

3.1.62 Gloves (to be provided by the customer) will be used to clear incompletely opened bags, disposal jams and other faults. Glove mounting ports shall be provided by the vendor with the enclosure, and shall be designed to accommodate in-place integrity-testing of the gloves. However, integrity testing may be performed off-line. Materials of construction and dimensions shall be equivalent to those used for the gloveports on the RABS surrounding the delidder and filler.

3.1.63 Light barriers shall be provided to cause immediate machine stoppage upon extension of gloves, to ensure safety. Restart of machine operation must be done at the HMI.

3.1.64 Tubs requiring removal from the line will be accessed by opening one of the RABS doors and removal by a gloved operator. As noted above, in order to open a door, the door must first be unlocked using the HMI. Subsequent machine restart must be initiated at the HMI.

3.1.65 Properly debagged tubs will be automatically discharged via conveyor, past an automatically acting gate separating the debagger from the delidder in the adjacent room, and onto the delidder. The outfeed conveyor shall not extend into the delidder/filling room. A positive differential pressure of at least 7.5 Pa shall be maintained at all times between the delidder and debagger enclosures. With a delidder RABS door open and debagger doors closed, a positive differential pressure shall still be maintained, by virtue of the elevated pressure in the fill room versus the debag room.

3.1.66 Each side of the Debagger shall have an integral e-stop button, protected mushroom button style. Mounting locations to be shown on submittal drawings.

Delidder

ID# Description ER Reference3.1.67

The delidder shall be of pharmaceutical grade and shall accurately remove lids and liners from tubs without damaging the tubs or damaging or contaminating the syringes and nests residing therein. Satisfactory performance is defined by the following criteria:

3.1.68 Incomplete lid removal shall not exceed 1% frequency.3.1.69 Failure to transfer the lid to the waste bin shall not exceed 1%.3.1.70 Incomplete liner removal shall not exceed 0.5%.3.1.71 Failure to transfer the liner to the waste bin shall not exceed 1%.3.1.72 Limits for damage to tub, nest and syringe can be found in the

Delidder data sheet.3.1.73 The delidder shall not experience more than three percent

downtime annually during operation (24 hours per day; seven days per week; 50 weeks per year available time at 80 percent utilization).

3.1.74 The delidder shall not compromise the sterility of the syringes within the tubs during operation.




The RABS enclosure, shared with the filling machine, shall maintain Grade A internal conditions, with the machine sitting in an external Grade A environment.

3.1.76 Each Process Operating Parameter shall have user programmable alarm limits that are recipe driven. Alarms shall be captured electronically.

3.1.77 Engineering parameters shall be configurable within recipes. Supplier shall describe the impact of engineering parameters on the process.

3.1.78 The control system furnished shall provide a means for physical and logical security.

3.1.79The computer system furnished shall be 21CFR Part 11 compliant.

3.1.80 Unit shall include automatic lid removal and liner removal stations. A mechanical gripper will be used for lid removal. A separate vacuum gripper will be incorporated for liner removal.

3.1.81 Lids and liners will be collected in a common waste bin. An audible alarm shall be provided indicating a full waste bin, based on a machine cycle count.

3.1.82The machine shall continue operating for a period of up to one minute while the waste bin is moved out of its storage location and is replaced by a spare bin. Lids and liners shall be accumulated during this period and not dropped on the floor.

3.1.83 The delidder unit shall be housed within a RABS enclosure with integral unidirectional airflow and hardened glass panels. The RABS is part of an overall RABS shared with the filler, but with a physical separation panel in between. Detailed requirements for the RABS can be found beginning in Sec. 3.1.129.

3.1.84 The delidder shall operate at up to 225 tubs per hour.3.1.85 Incomplete removal of the lid or liner or incomplete disposal into

the waste bin shall be automatically detected and cause a machine stoppage and audible alarm. Supplier shall quote, as an option, sensors or a vision system to detect incomplete disposal. Tubs with incompletely removed lids or liners will automatically be conveyed through the filling machine without filling or plunger assembly, and will be rejected at the exit of the filler.

3.1.86 Gloves (provided by the customer) will be used to clear jams but are not currently planned as backup for lid/liner removal (subject to performance reliability studies during machine qualification). Gloveports shall be provided by the vendor. Other types of interventions possible via gloves to be defined by the equipment vendor. All gloveports shall be supplied with a light safety curtain to prevent operator injury.

3.1.87 The waste bin shall be of perforated construction for optimal airflow, and shall be provided with wheels and a minimum capacity of 100 total lids and liners (equivalent to 13 minutes of run time at 600 syringes per minute). Removal of the bin for emptying shall be from below the enclosure, without having to open the RABS guarding. A spare bin shall be provided to ensure uninterrupted processing.

3.1.88 Tubs will be automatically discharged via conveyor to the filler.3.1.89

Each side of the Delidder shall have an integral e-stop button, protected mushroom button style. Mounting locations to be shown




on submittal drawings.

Syringe Filler


The syringe filler shall be of pharmaceutical grade and shall accurately dose liquids into presterilized 0.5ml or 1ml long syringes or 3ml polymer cartridges. Satisfactory performance is defined by the following criteria:

3.1.91 Filling rates and bottom-up fill profiles shall be adjustable to prevent excessive shearing, splashing or foaming of pharmaceutical solutions.

3.1.92 The exterior of the syringe shall remain completely free of product. The exterior of the filling needles shall remain substantially free of product during filling. Filling needles shall not contact syringes during filling.

3.1.93 The system shall monitor fill weight and calculate a weighted average of current and last dose per filling needle, alarming if the average exceeds an upper or lower limit (user-configurable).

3.1.94 Mean fill weights shall be within 95 – 105% of label claim for fill volumes of 0.2 – 3.0ml.

3.1.95 System shall have the ability to signal the tub buffer system in the post-fill room to hold tubs and not release them until the next successful dose check.

3.1.96 Filling shall be achieved using either rotary piston pump or peristaltic techniques. Overall fill accuracy shall be such that one standard deviation of fill weight is within plus or minus 1.5 percent of target set point, for both filling methods, for fill volumes ranging from 0.2 – 0.6ml, plus or minus 1.0% for 0.6 – 1.0ml, and plus or minus 0.5% for 1.0-3.0ml ?? as measured over a fill period no less than 15 minutes and no more than 30 minutes (N = 100 minimum *)

3.1.97 The average dose weight will meet the stated dosing accuracy when using rotary pumps when filling up to an 8 hour period. Peristaltic pumps will meet stated accuracy when filling over a 30-minute period and maintain stated accuracy over an 8 hour period or longer.

3.1.98 The Syringe Filler system shall be able to complete the "dose-in" phase with minimal product loss (achieve acceptance limits within 3 cycles and target fill weight ± 1 SD in no more than 10 line cycles after line purging).

Vendor to quote dose-in and down-dose 100% weigh dosing (move needles over scale) for peristaltic dosing system only (optional).

3.1.99 The absolute accuracy for the checkweigh load cells running at line speed under unidirectional air flow shall be as below. For testing purposes, syringes weighed by the IPC system will be checked on a calibrated analytical balance.

± 0.006 g tare or gross weight stations for fill weight ≤ 5 g

± 0.004 g for calculated net weight for fill weight ≤ 5 g

Note: Lilly defines accuracy as:



ID# Description ER Reference the accuracy of each scale individually on the

operational machine (0.006 g on the bullet above) against a lab balance.

accuracy of the entire system operationally (comparing the net fill weight from IPC against the fill weight per lab balance).

Note: Vendor to provide IPC FAT check-out procedure.(Previous version said: IPC checkweighing accuracy for an 0.2 gram fill shall be plus or minus 2mg, with reproducibility of plus or minus 1 mg, and linearity of plus or minus 1 mg.)

3.1.100 The Syringe Filler shall be capable of the addition of a future nitrogen gassing station (optional) that is able to achieve a syringe oxygen content of less than 7.0%.

3.1.101 Vendor shall provide a sanitary lift device that enables interchangeable filling modules to be changed out.

3.1.102 For a specific filling module, changeover time from one syringe size to another shall not exceed one hour. All adjustments must be performed aseptically (??).

3.1.103 The syringe filler shall be capable of placing a plunger using one of three methods: standard vent tube, vacuum-assisted vent tube, or vacuum bell method (the latter associated with the 3ml polymer cartridge). The three systems shall be interchangeable on the machine, with a time required for changeover not to exceed two hours.

3.1.104 Plunger shall be placed in a target range of 3-5 mm above the liquid surface with a tolerance of ± 1.0 mm regardless of the method employed. Reference for the syringe insertion depth for vent tube mechanical insertion method is the flange of the syringe. For vacuum-assisted or vacuum bell plunger insertion, the distance between the liquid surface and final plunger location will be measured. Typically, this requirement is 3 mm or less for vacuum-assist and X mm or less for vacuum bell.

3.1.105 Filler should be able to feed and properly insert plungers of size 0.5ml, 1ml long, or 3ml made from standard rubber compounds or plungers with a laminated fluoropolymer film.

3.1.106 Limits for damage to syringe, nest and tub can be found in the attached Filler datasheet. (?)

3.1.107 The Syringe Filler shall not exceed 5% downtime (at least 95% efficiency) as tested in an 8 hour performance run at maximum machine speed. Efficiency is defined as: number of accepted syringes produced/ theoretical number produced at maximum speed. Mean time between failure (mean time between line stoppages due to machine fault) shall be no less than 15 minutes for each syringe size.

3.1.108A RABS enclosure with dedicated laminar flow, shall maintain Grade A internal conditions, with the machine sitting in an external Grade A environment. A positive differential pressure shall be maintained between the filler and delidder at a minimum of 5 Pa at all times. See Section 3.1.1XX for additional performance requirements for the RABS enclosure.

3.1.109Each Process Operating Parameter shall have user programmable alarm limits that are recipe driven. Alarms shall be captured electronically.

3.1.110 Engineering parameters shall be configurable within recipes.



ID# Description ER Reference3.1.111 The control system furnished shall provide a means for physical

and logical security.3.1.112 The computer system furnished shall be 21CFR Part 11 compliant.3.1.113 Product fluids will be supplied to the filler from a small, 316L

stainless steel surge tank (by Vendor) fed by either a pressurized formulation tank or a disposable bulk-fluid bag (both by Buyer).

3.1.114 Level control shall be provided on the surge tank. Surge tank fluid level will be controlled by on/off control of product supply from the formulation tank or disposable bag, via a pinch valve.

3.1.115 The surge tank will function with two liquid product filters on the tank inlet and two gas filters on the tank compressed air supply. Filters provided by Buyer.

3.1.116 A slight tank headspace pressure is desirable for sterility maintenance purposes. For rotary piston filling, this headpressure can be maintained by the control system during filling operations. For peristaltic filling, this headpressure will be used prior to filling operations or during prolonged machine stoppages, but must be vented to atmospheric pressure for filling. (correct?)

3.1.117 The surge tank shall be capable of receiving drug product at a flow rate of at least 1.8 liters per minute.

3.1.118 The surge tank shall be designed for cleanability out-of-place to a standard of visually clean.

3.1.119 The surge tank outlet will feed a filling manifold that will be able to be directed to either the rotary pumps or the peristaltic pump dosing system, whichever is installed.

3.1.120 The manifold shall include product temperature measurement means, but not temperature control.

3.1.121 The product filters shall be sterilizable off-line in an autoclave, preassembled to the pumps/tubing and needles, and later aseptically installed. The filters, provided by the Owner, shall be of Opticap 4” XL type.

3.1.122 The product filters shall be located below the height of the sterile holding tank bottom outlet and above the base of the surge tank, and the surge tank shall have a bottom drain, to minimize line holdup and maximize product yield.

3.1.123 The piston pumps shall be provided on the machine plate, and peristaltic apparatus on a separate cart. The interchangeable filling systems shall be designed such that the alternate filling module can be connected to the machine table and be mechanically complete within a two hour time period.

3.1.124 Filling and plunger handling components shall be capable of being installed using aseptic techniques, using locating pins and minimal tools, and zero aseptic connections. Final assembly and adjustment steps shall be feasible through gloveport rather than via open RABS doors.

3.1.125 The filler shall include automatic weight adjustment based on feedback from an IPC checkweighing system. Peristaltic filling pumps shall be controlled individually, while rotary piston pumps will be adjusted as a group.

3.1.126 The checkweighing system shall be unaffected by machine vibrations and fluctuations in airflow within the RABS enclosure, through the use of an extra weigh cell and independent mounting from the machine frame.

3.1.127 Fill weight data, as well as all operating parameters and alarms, shall be sent to the Process Data Historian.



ID# Description ER Reference3.1.128 Checkweighing frequency shall be adjustable in a range of 1% to

100% of syringes. The 100% rate shall be employed at the start of the dose-in phase, which shall require no more than one hour to complete. The system will be programmable with dose-in limits, adjust limits and segregation limits.

3.1.129 The Syringe Filler will operate at the following maximum speeds, when using the various plunger placement methods:

Syringe Size (ml)

Vent tube (syr/ min)

Vac-assist(syr/ min)

Vac-bell(syr/ min)

Fill Volume

0.5ml 600 480 N/A 0.5 mL

1ml Long 600 480 N/A 1.0 mL

3ml cartridge

N/A N/A 160 3.0 mL

3.1.130 For the 0.5ml and 1ml long syringes, with standard vent tube plunger insertion, checkweighing line speed should be a minimum of 25 syringes per minute during 100% checking, 490 syringes/minute for 2% checking and 540 syringes/minute for 1% checking.

3.1.131 The Syringe Filler shall have an adjustable speed range of 25-100% of maximum line speed for any syringe size. Machine speed is defined as 100% = max speed for syringe size/fill volume.

3.1.132 Syringe filling parameters shall be configurable and set independently of machine speed.

3.1.133 Installation of individual load cells or scale electronics shall allow for “bolt-on and connect” replacement should a cell fail during filling operations.

3.1.134 The system shall be designed to accept presiliconized, presterilized plungers delivered in bulk bags with alpha/beta connection port.

Note to Vendor: Please quote both Biosafe and LaCalhene RTP ports.

3.1.135 The plunger chute and hopper shall be designed to accept an entire bag of plungers at one time, without requiring an operator to repeatedly raise the plunger bag to resupply the hopper.

3.1.136 The Syringe Filler system’s plungering operation shall operate at line speed despite twinned or clumped plungers. This can be achieved by a mechanism which sorts and discards clumps or twins.

3.1.137 Improperly filled or plungered syringes shall be automatically detected and rejected as an entire tub at a reject station on the filler. Improperly plungered syringes include those missing a plunger and those with plungers in a high position. All syringes must be plungered before rejection. The Syringe Filler will maintain a correct count of plunger faults over the course of a batch filling operation. Missing and improperly positioned plunger rejects shall not exceed 2% of total units filled. Tubs continuing on to the outfeed conveyor will be automatically counted.

3.1.138 Tubs containing out-of-spec fill weight syringes shall be tracked while conveying out of the filling room and accumulating on the



ID# Description ER Referencebuffer conveyor in the post-fill room. These tubs will then be inkjet marked as rejects by the tub coder, plus the nest will be marked with a dot alongside the appropriate row of syringes by a second inkjet head operated by the same controller. The tubs will be automatically rejected onto the reject spur, and manually removed from this spur.

3.1.139 A swing conveyor shall be provided at the outfeed of the filler to provide access to the rear of the filling machine. The clear opening of this conveyor shall be a minimum of 57” to allow an autoclave rack or interchangeable dosing cart of width 45” to pass with 6” clearance on each side.

3.1.140 The conveyors exiting the filler shall be covered with clear polycarbonate guarding to prevent disruption of tub order and particulate deposition on the outside of syringes prior to automated inspection.

3.1.141 An automatic airlock shall be supplied on the outfeed of the line, near the shared wall with the post-fill room, with interlocked gates to prevent area contaminants from entering the filling room. The filling line roller conveyor shall not extend into the airlock, nor shall the post-fill room conveyor. The airlock will have its own conveyor. Continuous, active airflow will be provided.

3.1.142 Each side of the Filler shall have two integral e-stop buttons, protected mushroom button style. Each side of the outfeed conveyor between the filler and the post-fill room air lock shall have two integral e-stop buttons, protected mushroom button style. Mounting locations to be shown on submittal drawings.

RABS Enclosure


The RABS enclosures for the line shall accept air from the Buyer’s HVAC system. The air will be exhausted into the surrounding room and directed downward toward the floor to prevent impact on surrounding area’s airflow pattern.

3.1.144The RABS enclosure for the syringe filler and delidder shall be of pharmaceutical grade and shall control the environment within the enclosure to Grade A. The RABS enclosure for the debagger shall control the internal environment to Grade B.

3.1.145 Satisfactory performance is defined by the following criteria: The RABS enclosure shall not experience more than 0.5% percent downtime annually during operation (24 hours per day; seven days per week; 50 weeks per year available time at 80 percent utilization).

3.1.146 Each Process Operating Parameter shall have user programmable alarm limits that are recipe driven. Alarms shall be captured electronically.

3.1.147Engineering parameters shall be configurable within recipes. Supplier shall describe the impact of engineering parameters on the process.

3.1.148 The control system furnished shall provide a means for physical



ID# Description ER Referenceand logical security.

3.1.149The computer system furnished shall be 21CFR Part 11 compliant.

3.1.150 The status of each individual RABS door shall be monitored and alarmed (audible and visual). In order to open a door, the operator must first release the door at the HMI.

3.1.151 Unit shall include dedicated unidirectional airflow supply with automatic differential pressure control, achieved via variable frequency fan speed control. Overpressure from the filler RABS to the filling room shall be maintained at a minimum of 15 Pa (0.06” WG) when the doors are closed, and alarmed both audibly and visually. Overpressure from the delidder RABS to the fill room shall be maintained at a minimum of 10Pa (0.04” WG). The fill room pressurization is anticipated to be at 60 or 65Pa (0.24” or 0.26” WG). Average air velocity within the RABS, continuously monitored, shall be 90 feet per minute.

3.1.152 HEPA filters must be of type Class H14 to EN1822 (99.995% collection efficiency) with Flanders Blu-Jel Seal system, and prefilters must be of type Class G4 to EN779. A CG-manifold will not be used on the downstream side of the HEPA filters.

3.1.153 Differential pressure across the HEPA filters and air velocity shall be monitored and alarmed.

3.1.154 The system shall include validation connections for the supply and measurement of raw gas concentration of HEPA filter integrity test aerosol (e.g. PAO (polyalphaolefin))

3.1.155 Air temperature within the enclosure shall be continuously monitored but not controlled.

3.1.156 Lighting within the enclosure shall be to >500 Lux.3.1.157 Gloveports shall be oval in shape, with opening size of major

diameter 364 mm and minor diameter 236 mm. Height of the ports off the floor and horizontal locations will be determined by Lilly at the vendor’s location during fabrication, using temporary clear plastic wall panels. Ports will be positioned to provide glove accessibility for all critical machine manipulations, to be confirmed at FAT. The gloveport used for opening the RTP plunger transfer door will be raised higher off of the floor in order to reach the RTP port, and will be accessed via a portable platform of height 21” off the floor.

3.1.158 Gloveports shall be designed to mate with Piercan or North Safety Products Hypalon ambidextrous isolator gloves and sleeves provided by the Owner. Gloves of 0.4mm thickness, 330mm length, sizes 5-10.

3.1.159 Light barriers shall be provided to cause immediate filling machine or delidder stoppage upon extension of gloves, to ensure safety. Machine restart must be done at the HMI.

3.1.160 Unit shall include necessary hardware for continuous, nonviable particulate monitoring. Supplier to include isokinetic funnels and 316L stainless steel tubing on the interior of the machine, the tubing penetrating the RABS enclosure, with a sanitary Triclamp connection and endcap on the exterior. 110 VAC electrical outlets to be provided on the exterior, for connection of the portable particle monitoring machine. Six monitoring points shall be supplied with the line, with locations to be determined during detailed design (e.g. two at filler, one at lid removal, one at liner removal, one at debagger, and one on tub accumulation conveyor).

3.1.161 Unit shall include necessary hardware for viable particulate monitoring, including stands for Rodac plates and tubing plus


ga30558, 07/21/09,

Should we specify expectations for when the doors are open during setup? Should we state that air flow pattern testing must be acceptable for door open and door closed conditions? And how are we able to hold Inova to that?


ID# Description ER Referencestands for SMA plates. Owner to provide SMA units and plates. Six monitoring points shall be supplied with the line, with locations to be determined during detailed design (e.g. three at filler, one at lid removal, one at liner removal, and one at debagger).

3.1.162 An alpha-beta port shall be provided for IDC plunger bag attachment, along with a gloveport 90 degrees from this port, to facilitate opening of the port, extension of the bag, and delivery of the plungers to the plunger chute.

3.1.163 Introduction and removal of environmental monitoring materials, filler changeparts, and waste materials will be done by opening a RABS door (???)

3.1.164 RABS door status shall be monitored and each access sent to the Process Data Historian.

3.2 Mechanical


3.2.1

The Outer Bag Removal station shall be operated within a surrounding CNC (controlled nonclassified) space. The Vendor will ensure that the unidirectional airflow enclosure is adequately designed to achieve ISO 7 (Class 10,000) within the enclosure.

3.2.2

The inner bag stretching conveyor, tub accumulation conveyor, and Debagger shall be operated within a surrounding ISO 8 (Class 100,000 or Grade C) space. Vendor shall ensure that the unidirectional airflow enclosures surrounding these operations are designed to achieve ISO 7 (Class 10,000 or Grade B) within the enclosures.

3.2.3

The Delidder and Syringe Filler shall be operated within ISO 5 (Class 100 or Grade A) surrounding area. The Vendor will ensure that the delidder and filler are designed to operate in a Class 100 area without introducing particles or impeding downward unidirectional airflow, and that their enclosures are designed to maintain Class 100 within their interior.

3.2.4

Equipment shall be of sanitary design and shall include provisions for ease of maintenance and cleaning of all components. All conveyance mechanisms and tray tables shall be of sanitary design (raised, clean) and shall be constructed to permit easy cleaning and inspection.

3.2.5

Syringe tubs and syringes shall be transported and handled throughout the line in a seamless and controlled manner, throughout the entire operating range, without causing more than:

a) 0.1% critical and major syringe defects

b) 0.5% minor syringe defects

Reference Section 7.2 for description and classification of defects.

3.2.6

Each component of the Syringe Filling Line shall be pre-piped and pre-wired such that the Buyer only needs to connect utilities to form a completely functional and integrated system. All utility connections are to be clearly identified by the Vendor to insure ease of installation at the Buyer’s facility.




3.2.7

Product path connections shall be Buyer approved sanitary fittings (U.S. tri-clamp style). This applies to all product path (or compressed gas) fittings, not only surge tank connections, excluding the rotary piston pump inlet and outlet connection.

3.2.8

Surge tank (fed from Buyer-provided product tank) shall be designed for full vacuum to 1 bar (gauge) internal pressure and shall be completely drainable. If this vessel is fabricated from tubing, weld acceptance criteria shall be per American Society of Mechanical Engineers (ASME) Biopharmaceutical Engineering (BPE) International Standard 2005 Table MJ-3. Vendor to quote price difference between EU and ASME standard.

3.2.9

Welding shall be performed using the following processes: gas metal arc welding (GMAW), and/or gas tungsten arc welding (GTAW). Full penetration is required for all welds. Weld metal thickness shall be equal or greater than adjacent base metal. Completed welds shall be free of cracks, pores and spatter. Final weld surface shall be visibly uniform and comply with component surface specification. Vendor shall have available for review Welding Performance Qualifications for each welder and/or operator performing production welds on the vessel. Vendor should verify that the particular batch of metal can be successfully electropolished prior to fabrication.

3.2.10

Presiliconized, presterilized plungers shall be delivered in bulk bags with an attached alpha/beta connection port (BioSafe port or LaCalhene port preferred). The plunger chute and hopper shall be designed to accept an entire bag of plungers at one time without requiring an operator to repeatedly manipulate the plunger bag to resupply the hopper.

Vendor to advise Buyer of plunger capacity for all plungers referenced in section 7.1 below.

3.2.11The Delidder and Syringe Filler RABS will draw air from the building HVAC system via enclosed fans and pass air through gel-sealed HEPA filters (99.99% retention at 0.3 μm).

3.2.12

The RABS enclosures will direct uniform air flow (UAF) downward to below the syringe height before exhausting into the surrounding room. Enclosure panels and doors will provide the maximum possible view of conveying, debagging, delidding, filling and plungering operations.

3.2.13Every location within the RABS-enclosed Syringe Filling line requiring access during normal operations shall be reachable from a gloveport.

3.2.14

Gloveports shall be oval in shape. Gloveports shall be designed to mate with Piercan or North Safety Products gloves. Ambidextrous isolator gloves and sleeves. Gloves of 0.4 mm thickness. Gloves shall be able to be changed out in no more than 10 minutes.

3.2.15Gloveports shall be suitable for use with Buyer furnished Glove Integrity Tester and will allow for testing of gloves in place.




3.2.16RABS enclosure doors will be lockable and individually alarmed. Light curtains will be used to interrupt machine operation if an operator attempts to use gloves.

3.2.17

All product and plunger contact equipment shall be designed to be removable and cleaned to a visually clean standard (defined as not more than 100µg of active material per swab of 25cm²) in a parts washer and sterilized in an autoclave. All parts to be autoclaved must be compatible with a maximum 130°C steam sterilization temperature. The compatibility requirement will be considered to be met if said parts are constructed of 316L SS as a minimum alloy requirement.

3.2.18Any parts (plunger presence sensors, hold down bars, etc…) located above plunger feeding tracks must be able to be sterilized out of place.

3.2.19Pump pistons and cylinders must be autoclaved separately. Vendor to propose fixtures that allow Buyer to join pistons and cylinders after autoclaving without directly touching sterile parts.

3.2.20All mounted parts on tabletops shall be bolted from the bottom with no exposed bolt heads on any table surface. Bolting for format parts are an allowed exception to this requirement.

3.2.21The Syringe Filling Line shall be constructed so as to prevent syringes and other debris from falling inside of the machine or into outer mechanisms.

3.2.22

The Syringe Filler shall be constructed to prevent liquids from running into the inside of the machine through the machine table, and to allow the area inside the RABS to be manually spray wetted and wiped for cleaning and sanitization on a twice daily frequency.

3.2.23

All vertical shafts on the filling line shall be sealed by bellows or an equivalent engineering solution (such as dual lip seals) to prevent contamination by the vertical motion of the shafts between the mechanical drive system/mechanisms below the machine plate and the syringe filling area above the machine plate. Wiper use should be minimized where possible. All machine penetrations must have dual sealing or bellows to keep sanitization agents above the table, and keep materials from underneath the machine below. Buyer preference is bellows.

3.2.24

The Syringe Filling Line shall allow servo control of key machine motions. The Vendor shall provide a matrix after the order is placed to show all possible configurable machine settings and their allowed ranges. Known servo controlled machine motions consist at a minimum of: lid removal, rotary pumping (rotation and up/down rate), and needle up/down motion.

3.2.25 The Vendor shall statically and dynamically balance all rotating equipment (e.g., unidirectional airflow fans).

3.2.26 No lubrication points shall be above the machine table.




3.2.27All bearings shall be pre-lubricated and sealed. No leakage of lubricant is permitted. Lubricants shall be FDA accepted food grade lubricants (ref. 21 CFR 178.3570).

3.2.28

All equipment requiring routine servicing and calibration must be easily accessible and readily removable without major disassembly. The Supplier shall clearly identify required “pull spaces” necessary to facilitate the removal of machine parts or components.

3.2.29

For the following pieces of equipment, service utilities shall be accessible from the following spaces: Outer bag removal station: surrounding CNC space Debagger, delidder, and filler: mechanical areaVacuum pump, if required, shall be provided by the vendor located remotely in the mechanical space.

3.2.30

All equipment should be designed such that minimal tool use is required for disassembly and reassembly during cleaning or maintenance. If standard tools are required, the Vendor should indicate what tools are required. If non-standard tools are required, the Vendor shall provide them in appropriate quantities.

3.2.31

Format parts must be constructed to prevent incorrect mounting and/or mixed types. Known format parts are: syringe guides for each diameter syringe, plunger bowl, tracks, and pick and place system for plunger size/type, rotary piston pumps (depending on fill volume needed).

3.2.32All unique format parts shall be permanently labeled and easily identifiable via color coding and text descriptions.

3.2.33

All subcomponents that are labeled with a tag number identifier on Vendor P&IDs shall have a permanent physical tag with the same tag number placed on the component on the machine. Tags for components that are present in the aseptic area will be 316 stainless steel.

3.2.34

Syringe Filler shall include necessary hardware for three (3) continuous, nonviable particulate monitoring stations. Supplier to include isokinetic funnels and 316L stainless steel tubing on the interior of the machine (optional), the tubing penetrating the RABS enclosure, with a sanitary Triclamp connection and endcap on the exterior. 110 VAC electrical outlets to be provided on the exterior, for connection of the portable particle monitoring machine.

3.2.35

Syringe Filler shall include necessary hardware for three (3) viable particulate monitoring stations, including stands for Rodac plates and tubing plus stands for SMA plates (optional). Buyer to provide SMA units and plates.

3.2.36

The Syringe Filler System's panels which need to be accessed for maintenance (sensor adjustments, mechanical adjustments) shall be external to the RABS (i.e., accessed from below the machine table). Components with adjustments (sensitivity, pressure switches, etc.) on the filling machine must be accessible and not sealed within secondary under-machine control cabinets.



ID# Description ER Reference3.2.37 Instrument air piping shall include a filter/pressure regulator and

pressure indicating transmitter. Pressure indicating transmitter shall be suitable for calibration.

Each valve shall have a visual indicator showing the open or closed position of the valve.

Piping connections shall be accessible without removal of major components.

3.3 Materials of Construction

ID# Description ER Reference3.3.1 Equipment, components, and subassemblies shall be thoroughly

cleaned of water, dust, sand, grit, weld spatter, grease, oil and other foreign materials prior to surface polishing.The use of polishing compounds on part of the equipment that has product contact is prohibited and will be cause for automatic rejection of the unit.Surfaces shall be free of pits. Previous pass grit marks, due to previous mechanical polishing steps with coarser grit, shall be removed. There shall be no blemishes and the surface shall be aesthetically acceptable.Internal corners shall have radii of not less then 0.250 inches (6 mm), for adequate cleanability. Supplier to confirm versus its standard.Liquid product contact surfaces shall be sloped, smooth, and free draining

3.3.2 The mechanical surface finishing procedure shall incorporate the use of progressively finer grit to generate the final surface finish. The first pass shall be course enough to remove weld porosity and surface imperfections such as mandrel marks and surface voids. The final pass shall be fine enough to produce the specified surface finish.Interior product contact welds shall be smooth, flush and polished.Final inspection and acceptance of the surface finish shall be per ANSI B46.1.

3.3.3 The fabrication and assembly of this equipment shall be performed in an area used exclusively for fabrication of stainless steel materials. Tools used in the assembly of this unit shall be exclusively for fabrication of stainless steel equipment. The Supplier shall demonstrate that this and other practices within the fabrication area ensure that no particles of carbon steel can be deposited on the stainless steel material during fabrication. During fabrication, deviations in satisfying these practices are cause for rejection of parts.

3.3.4 Supplier shall furnish nameplates that are permanently attached to the equipment. The nameplates shall be easily accessible, stainless steel plate with embossed letters at least 0.250 inches (6 mm) high and containing the following information:

Purchase Order NumberDate of manufactureModel number Serial number



ID# Description ER ReferenceOwner’s Equipment NumberOwner’s Name

3.3.5 Materials shall be new, free from defects and completely suitable for cGMP pharmaceutical use.

3.3.6 Non-metallic contact surfaces, such as gaskets and elastomers, shall be 21CFR177 and 178 compliant. Supplier shall provide certificate of compliance to these requirements. The Supplier shall also demonstrate that these materials do not shed particles or fibers that may contaminate the Owner’s product or premises. Acceptable non-metallic product contact surfaces include but are not limited to pharmaceutical-grade silicone and PTFE.

3.3.7 Metallic surfaces in contact with bagged syringe tubs, tubs, lids, liners, liquid solution, syringes, and nests shall be 316 or 316L stainless steel. Supplier to notify Owner of exceptions. For the required materials of construction and surface finishes for various parts of the machine, refer to the respective equipment data sheets.

3.3.8 All components of the equipment, including the electrical and communications systems, shall be compatible with repeated treatment using the following cleaning and sanitizing agents: Steris CIP100, Steris CIP200, and sporicidal agents pH-adjusted bleach 1%, 70% IPA, 4% hydrogen peroxide, Spor-Klenz RTU, and Steris LPHSE (aqueous acid phenolic disinfectant consisting of 15% phosphoric acid, 7.7% 2-phenylphenol, 7.6% pentaphen, 7.5% isopropyl alcohol, <5% dodecyl sulfonic acid, and water). Equipment supplier to provide documentation verifying such compatibility.Components with surfaces that cannot be directly sanitized must be completely sealed in cladding or an enclosure that can be sanitized.

3.3.9 Materials of construction shall not contain asbestos, chloride, lead, cadmium, mercury or chromate.

3.3.10 All metal liquid-product-contact parts and plunger contact parts, will be electropolished (EP) and passivated. Interior surfaces of rotary piston pumps are allowed to be chrome plated. Known exceptions to the EP requirement are the filling needles (due to their thin walls). Product contact surface finish shall be 25 Ra max (0.63 μm max).

3.3.11 Unless otherwise specified, materials of construction shall be theVendor's standard. Materials for tubing shall be as indicated below:

Service Material* Internal Surface FinishProduct tubing 316L SS Ra 0.63 m max w/ EPProduct tubing (alternate)

Teflon or Pt-cured Si

standard

Instrument Air SS or PVC standardProcess Air or vacuum 316L SS Ra 0.63 m max No EP

* Mill test reports are required for metallic product contact parts. Material certificates are required for nonmetallic product contact parts. Exceptions to this must be approved by the Buyer.

3.3.12 All non-metallic product contact tubing shall be Teflon or Buyer approved silicone.



ID# Description ER Reference3.3.13 Product contact surge-tank pinch valve tubing shall be European

Pharmacopoeia and USP compliant. Vendor to provide certification for this. Tubing shall have suitable durability for 100,000 pinch cycles. Vendor shall provide testing data supporting this. Vendor to provide Buyer with list of all tubing types available meeting these criteria and provide tubing manufacturer’s data.

3.3.14 All product- or plunger-contact nonmetallic materials other than tubing (e.g., gaskets, valve diaphragms, etc.) shall be Teflon or platinum-cured silicone, and meet CFR and USP Class VI standards. Materials of construction and surface finish for the machine cover plate and flanges shall be solid 316L SS and finish of 35 μin Ra max. (0.89 μm) as determined by profilometer.

3.3.15 Materials of construction and surface finish for major metallic components exposed to ambient conditions on the exterior of the filler shall be 304 SS (minimum) and mill finish. For nonmetallic materials, supplier shall submit to the Buyer the list for approval before filler fabrication is started. Vendor to quote upcharge for stainless materials on interior and exterior of machine and RABS to 316LSS for Sporklenz resistance (optional).

3.3.16 Materials of construction not specified by the Buyer shall be the Vendor’s standard for pharmaceutical services.

3.3.17 All permanent joints and seams shall be continuous welded, ground smooth, pit-free construction.

3.3.18 No materials or components used in the filling machine shall expose product material to excessive heat or temperatures exceeding 25°C.

3.3.19 Vendor shall submit for Buyer pre-approval a list and composition of polishing compounds that might be used in the course of filler fabrication. Vendor shall certify that no animal source or ferrous-based surface polishing compounds (e.g., jeweler’s rouge), lubricants, or materials were used. Use of unapproved polishing compounds is cause for rejection of equipment.

3.3.20 No ferrous, brass, copper, or plated materials (piston pumps excepted) shall be used where they would be exposed and subject to daily cleaning or sanitization.

3.3.21 All fiber optic or electric cable should be armored (smooth surfaces only) and protected from sanitizing agent contact.

3.3.22 Materials used for the RABS shall be new, free from defects and completely suitable for cGMP pharmaceutical use.

3.3.23 Metallic surfaces on the interior of the enclosure shall be 316 or 316L (or both) stainless steel. Supplier to notify Owner of exceptions.

3.3.24 Windows and see-through doors shall be hardened safety glass. Positioning of gloveports shall be determined during pre-FAT through the use of disposable panels prior to the installation of windows and doors. Glass load-bearing hardware shall be used.

3.3.25 For the required materials of construction and surface finishes for various parts of the enclosure, refer to the RABS equipment data sheet. Supplier shall provide material certificates.

3.3.26 Service utilities shall be accessible from the mechanical area (if appropriate).



3.4 Safety

ID# Description ER Reference3.4.1 All machine safeguarding shall be based on the executed

Equipment Risk Assessment generated by the Supplier in order to meet EN requirements. All machine safeguarding shall be consistent with ANSI B11.19.

3.4.2 All moving parts shall be enclosed with OSHA and CFR 1910.22 and 1910.219 approved safety guards. In compliance with CEE 89/392 CEE 91/368 CEE 93/68 EN 292 EN 414, guarding shall minimize the use of special tools for removal and reinstallation.

3.4.3 Feed screws, worm gears, star wheels, and conveyor head and tail sprocket assemblies shall be completely guarded unless the mechanism is completely smooth, has no protrusions or indentations, rotation shall not cause entrapment, and can be removed with minimum force.

3.4.4 Belt return, idlers and drive components shall be fully enclosed.

3.4.5 All guards that need to provide access for normal operation and/or maintenance shall be fabricated from polycarbonate, safety glass, or acrylic material. This guarding shall protect personnel from moving or heated parts.

3.4.6 All guards covering moving parts that need to provide access for normal operation shall be electrically interlocked to interrupt equipment operation immediately when opened. This interlock is a distinct and different circuit than the emergency stop circuit. All interlocks shall be OSHA approved, or adhere to EN 60204-1, mechanically actuated devices appropriate for the specified application. Stationary components/devices shall be accessible without machine interruption.

3.4.7 Interlock safety switches shall fail in the fail-safe position and shall be classified as safety switches.

3.4.8 If an interlocked door is opened during operation, the equipment shall require manual restart after closing the door.

3.4.9 The Vendor shall provide emergency stops for the entire system. The emergency stop sequence will be designed in accordance with NFPA 79 (for US and Puerto Rico installations) or EN 418 (for European installations). Compliance with SECTION 16995, ELECTRICAL REQUIREMENTS FOR PACKAGED EQUIPMENT is required. Pressing an E-stop button shall disrupt input power, de-energize all valves and stop the system in a safe condition. Emergency stops should be located and designed for easy access and to prevent inadvertent operation.

3.4.10 If the risk assessment requires a control reliable circuit, then either a multiple channel programmable logic control (safety PAC) or a safety circuit is permitted. The choice must be based on the Risk Assessment.

3.4.11 Energy isolating devices on machines must be designed to accept a lockout device. Disconnect must not be more than 1.83 m (6.0 ft.) or less than 0.5 m (1.5 ft.) above the operating floor line. Disconnect must clearly indicate the ON and OFF positions. All disconnects must be designed so to be capable of being locked in the open (OFF) position. Lockout points for equipment and machines must be accessible. Disconnect must be located in proximity or in sight of the motor.



ID# Description ER Reference3.4.12 Machine piping systems must be designed to allow for the

dissipation of residual pressure.

3.4.13 A Maintenance mode shall be provided which allows operation of the machine with the access doors open.

3.4.14 Noise from the equipment, as installed and operated, shall not contribute to ambient exposure noise levels over 80 dBA [8 hour time weighted average (TWA)] or 78 dBA (12 hr TWA).

3.4.15 Equipment must be designed and positioned to allow easy access for routine maintenance, cleaning and operation. The interface between equipment and the worker must be within an 18” (45 cm) reach, and between the knee height for a 95th percentile American male and shoulder height for a 5th percentile American female (i.e. 24” to 54”). One exception is for equipment which can only be accessed from below the machine enclosure. Supplier to list operations outside of this range.

3.4.16 Proper allowances must be made for the use of tools and maintenance equipment. Four inch (100mm) gap to be provided between machine bottom and floor to allow for cleaning under the machine. Alternatively, Owner to consider having machine skirted to the floor with sealant to prevent contaminant ingress below machine.

3.4.17 All Human Machine Interfaces (HMIs) or Display Screens must be ergonomically designed to accommodate the workstation. Screen tilt or inclination from the horizontal must range between -10° and +15°. Supplier to quote, as an option, an adjustable screen height such that the top of the screen adjusts between 56” and 74”.

3.4.18 All controls and gauges, used in the normal course of daily operation and/or routine basis, must be ergonomically designed and positioned. Controls must be positioned to allow operation with the upper limb joints in neutral position. Hand operated devices (such as toggles, switches, knobs, etc.), used in the normal course of daily operation and/or routine basis, must be ergonomically designed and positioned. Controls and enclosures must not obstruct the operator’s normal line of vision necessary to perform the task or machine operation.

3.4.19 Any equipment that is going to be routinely manually lifted, carried, pushed or pulled must be equipped with appropriate handles or hand holds.a. Handles must be approximately 1.5 inch (38cm) in

diameter, 5 inch (13cm) in length, and provide at least 2.5 inch (6cm) of hand clearance, where possible. Supplier to provide list of exceptions.

b. Handle designs that require the use of a pinch grip shall not be allowed.

c. Handles must be oriented either vertically between waist and shoulder or horizontally at waist height.

d. Carts shall be equipped with roller bearings and large casters to minimize transport force.

e. Carts shall be transported in the push mode instead of the pull mode.

3.4.20 Supplier shall identify syringe filling line equipment and any component, instrument, valve or piping assembly which is greater than 15 pounds (7 kg). Items over 25 pounds (12.5 kg) shall be




provided with suitable lifting points or appendages, and documentation of the appropriate lifting method. Supplier shall provide lift assist devices for covers or lids that weigh 15 pounds (7.5 kg) or more, for example spring assist on hinges.

3.4.21 Equipment must be designed with enough clearance to minimize the potential for injury. Locate routinely accessed openings so that they do not expose operators to hot surfaces, electrical currents, sharp edges or other safety hazards.

3.4.22 Fasteners for access panels must be easy to operate with gloved hands. Ensure that access panel doors are positioned so that personnel will not pinch their fingers. Access panels shall be easy to open (hinged is preferred).

3.4.23 The Supplier is responsible to meet structural and seismic Zone 2 design requirements as applicable for the project site location and type of equipment supplied.

3.4.24 Supplier shall provide static and dynamic equipment load calculations along with anchor point details.

3.4.25 Proper signs should be included on equipment warning personnel of danger from moving parts, voltage, heat, etc.

3.4.26 All equipment with pneumatic or hydraulic utility sources shall be supplied through a fixed and pad-lockable disconnect device. The devices shall also be capable of relieving all sources of stored pressure or potential. The pressure on the surge tank will be isolated (not vented) in an emergency stop event.

3.4.27 If there are OSHA requirements that are not previously met by the CE/UL label, these additional requirements will be implemented at no cost to the Buyer.

3.5 Electrical


3.5.1

The Buyer shall provide a single point electrical supply (480 V / 3 ph / 60 Hz) for each major piece of equipment (e.g. one for debagger, one for filler/delidder combination). The Vendor shall provide all electrical components necessary for the operation of the machines, including but not limited to: motor starters, transformers and all power distribution and control wiring.

3.5.2

All electrical components must be labeled with UL or other nationally recognized testing laboratory. The machine and electrical cabinet do not require a separate UL inspection. Electrical equipment and components that are not UL labeled (or other equivalent listings) must have documentation that asserts that the equipment is safe for its intended use on the basis of test data. Copies of test data shall be sent to the Owner. Exceptions must be approved by Lilly.




3.5.3 The electrical area classification of the Buyer’s equipment location shall be Non-Hazardous per NEC.

3.5.4

Wiring:a. Wiring standards shall be per NEC / UL / NFPA 79.b. Exposed wiring above the machine plate shall be enclosed in

silicone tubing or equivalent for protection and to facilitate cleaning.

c. Wiring exposed outside of the RABS shall be enclosed in armored sheathing for protection.

3.5.5

Labeling and nameplates: a. All electrical cables and wires shall be uniquely identified in

English per NEC / UL.b. Provide permanent nameplates for each instrument,

component, terminal block, bulkhead connector, field connector or device that are mounted on the face of the panel or within the panel enclosure. Devices such as disconnect switches, relays, fuses, etc., are to be identified.

c. Nameplates shall be legible, substantial and permanent, suitable for the environmental conditions specified.

d. Self adhesive types are not acceptable above the machine plate.

3.5.6

Transformers and Power Supplies:a. The Vendor shall supply all transformers or power supplies

required by the equipment and its components. b. All transformers and power supplies shall be sized with a

minimum of 20% spare capacity.c. Control power shall be obtained from the Vendor’s

furnished transformer or power supply. All control power shall be 24V. Exceptions must be approved by Lilly.

d. Transformers shall be mounted in control panels where size and heat dissipation requirements permit.

e. Switching power supplies shall not be used. Exceptions must be approved by Lilly.

3.5.7

Disconnects and Fuses:

a. The Supplier shall provide disconnects for each electrical point of contact.

The main power disconnect shall be either a fused disconnect or circuit breaker, switch rated for the total load of the packaged system, and shall be capable of being padlocked ONLY in the open position.

b. Disconnects for voltages in excess of 120VAC shall be interlocked with all enclosure doors so that the disconnect must be an open circuit for the enclosure door to open. A method for defeating the interlock using a maintenance tool shall be provided. These disconnects shall also be capable of being padlocked in the open position only.

c. Power supply circuits to control components shall be individually fused. Exceptions must be approved by Lilly.

d. Fuse holders for 120 Volts and lesser service shall be lighted indicating type.




3.5.8

Motors and VFDs:a. Motors shall be Energy Efficient, Severe Duty and Inverter

Duty rated.b. VFDs shall be Allen Bradley / Rockwell. Exceptions must

be approved by Lilly.c. VFD power leads to motors shall be shielded cable to

minimize EMI.d. Motors that are 5 hp and above without VFDs shall have

soft starts.

3.5.9

The Vendor shall provide control voltage UPS backup for the PLC, HMI and control voltage components. The UPS will be sized to provide power for 10 minutes, and will provide an orderly system shutdown.

3.5.10

The systems shall be electrically grounded and isolated to ensure personnel and equipment safety and signal integrity.a. A copper bus equipped with compression lugs shall be

provided for Owner’s ground conductor connection.1. The Vendor shall supply one set of terminals for

Isolated Instrument Ground and an additional set of terminals for Electrical Equipment Ground. Each grounding source shall be dropped to one location within the Supplier’s package.

2. The Vendor shall separate Instrument Ground from Electrical Equipment Ground in order to minimize electrical interference within the system. Isolated instrument ground terminals shall be electrically isolated from skid, panel, and electrical equipment ground.

b. Ground conductors shall be sized per NEC Article 250, green or green w/yellow stripe and appropriately insulated.

c. All enclosures and raceways shall be properly bonded together and connected to the metal skid frame. Equipment grounding conductors shall be installed within the raceways. Utilizing raceways as grounding conductors is unacceptable.

d. Transformers supplied for 120VAC circuits shall have a common grounding point for transformer secondary by grounding one leg of each circuit. Other than overload circuits no contact shall be wired between coils and the grounded leg. The ungrounded leg of the transformer secondary shall be properly fused

3.6 Enclosures


3.6.1

Enclosures to be located in process areas shall be NEMA 4X / IP56 stainless steel at a minimum. Enclosures to be located in mechanical areas shall be NEMA 3 / IP54 at a minimum. Enclosure doors shall be gasketed. Exceptions must be approved by Lilly.




3.6.2

Each freestanding, stationary enclosure shall be provided with the following:

a. Interior fluorescent type lighting to illuminate the interior of the enclosure. Lighting shall be controlled by switches inside the enclosure.

b. Hasps or other mechanisms to allow the enclosure to be padlocked to manage physical access to the automation system components.

c. Grounding mechanism.

3.6.3Enclosures shall be suitable for cable entry from above and below. The Vendor shall provide drawings showing locations for cable entrance including dimensions.

3.7 Auxiliary Controls


3.7.1The Vendor shall select controls (pushbuttons, selector switches, indicating lights, etc.) suitable for the environment in which they will be located.

3.7.2

The following color scheme shall be used, where applicable:a. RED shall be used for Stop, Emergency Stop, or Off

operations only.b. GREEN shall be used for Start or On operations.c. Pushbuttons that cause movement when pressed and stop

movement when they are released (e.g., jogging) shall be BLACK.

d. Reset pushbuttons shall be BLUE, BLACK, WHITE, or GRAY except when they also act as a Stop or Off button, in which case they shall be RED.

3.7.3Pushbuttons shall be constructed or mounted to minimize inadvertent operation.

3.7.4Indicating lights shall be push-to-test type suitable for operation on 24V DC. Lamps and caps shall be replaceable from the front.

3.8 Automation, Instrumentation and Controls

ID# Description ER Reference3.8.1 The Supplier shall furnish a fully functional control system,

including but not limited to designing, documenting, procuring, configuring, installing and testing all components, software and wiring as required for complete operation of the Supplier-provided equipment.

3.8.2 The Supplier shall be responsible for providing components required for the complete fabrication of the packaged control




system except as noted in this Specification. Component level receipt verification (RV) and installation verification (IV) shall be required in order to meet the standards of pharmaceutical industry commissioning and qualification.

3.8.3 The Owner shall provide a single point instrument air supply per machine and the Supplier shall provide all air distribution components within the individual machine. In the post-fill room, a single air supply shall be provided. The Owner’s air supply is 90 psig.

3.8.4 All devices shall be individually wired to the control system. Switches and other discrete inputs should not be wired in series or be monitored by a single status bit. Exceptions require approval by Lilly.

3.8.5 The system shall be controlled by a Rockwell ControlLogix PAC (Programmable Automation Controller), model 1756-L63 / B. The Process Control System controller code shall be created using Rockwell Automation's RSLogix™ programming software (Latest Version).

3.8.6 The control system shall have an HMI to allow authorized personnel to operate the machine (logical access shall be provided at an individual level). The HMI shall be configured with Ethernet connectivity for integration into Lilly’s network, and all software applications will be capable of being integrated with the Lilly Domain.

3.8.7 The HMI hardware shall be one of the following (to be identified as separate line item costs). Rockwell PanelView Plus terminal, model 2711P-T10C15D7, utilizing a Rockwell RSView ME application created using Rockwell Automation's RSView™ Studio programming software (Latest Version).Rockwell VersaView industrial PC, model 6181F-15TPXPHSS, utilizing a Rockwell RSView ME application created using Rockwell Automation's RSView™ Studio programming software (Latest Version).Thin client terminal with a Citrix published Rockwell RSView SE application using Rockwell Automation's RSView™ Studio Distributed programming software (Latest Version).

3.8.8 The Supplier shall furnish a control system that presents all data in the English language.

3.8.9 The Supplier shall provide manual on/off control for all motors for maintenance and testing purposes. This control can be either field-based or a software switch, with access via HMI. Exceptions require Lilly approval.

3.8.10 The control system shall generate an alarm and communicate the alarm information to the operator via the HMI in the event of a system failure. All system failures are to be identified by the Supplier, but must include process parameter excursions, safety events and machine faults.

3.8.11 The control system shall provide functionality to adjust control setpoints via parameters. The parameters shall be displayed and adjusted via the HMI. All system parameters to be identified by the system supplier. The control system shall provide




functionality to store, edit and select sets of parameters grouped as recipes (formats).

3.8.12 The Supplier shall furnish a control system that is Electronic Record/Electronic Signature (ER/ES) capable. Electronic records are not required to be maintained by the control system as long as all process information is available for collection by an external Data Historian via an OPC data connection.

3.8.13 Measurement instruments and gauges shall be easily accessible and readily removable for calibration purposes. All instruments and gauges shall be capable of being calibrated. Exceptions require Lilly approval.

3.8.14 The Supplier shall provide calibration certificates for every piece of calibrated equipment.

3.8.15 Instrument and Control Systems shall be designed fail-safe, so that upon failure, instrument readings fail to an alarm state and devices will revert to their safest state.

3.8.16 All instruments shall have a sufficient accuracy and range for the designated process. Instruments will utilize a 4-20 mA convention or use bus technology. Exceptions must be approved by Lilly. Smart instruments shall be used if possible.

3.8.17 The Instrumentation Tagging strategy shall be one of the following (to be identified as separate line item costs).

a. The Vendor’s standard tagging methodology.b. The Vendor’s standard tagging methodology, with the

requirement that tagging must be consistent for all software and documentation. Individual components shall only have one tag identifier, which is used throughout the software, electrical drawings, P&ID drawings, IOM manual, etc.

The Buyer’s tagging methodology, with the requirement that tagging must be consistent for all software and documentation. Buyer will not specify tagging for every component, but will emphasize P&ID tags.

3.8.18 The Supplier shall provide a completely wired and tested electrical control cabinet. Equipment or piping connections, which require service, shall not be located behind the cabinet. The cabinet shall be at a minimum NEMA 4 or IP54, and shall provide functionality to physically apply a lock to prevent access.

3.8.19 Any electrical supply (and/or air isolation valves) shall be fitted with isolation locks to control hazardous energy that meets the requirements of ANSI Z244.1-2003.

3.8.20 All logic, including scaling to engineering units, shall be performed in the PLC, not the HMI.

3.8.21 The Vendor shall furnish a control system using the following Units of Measure:

Process Variable Acceptable UnitsTemperature degrees C, CPressure, differential PaPressure, above atmospheric bar Pressure, below atmospheric mbar Level percent range, %



ID# Description ER ReferenceProcess Variable Acceptable UnitsWeight gVolume LitersDensity g/ccSpeed, revolutions RPMSpeed, air velocity m/sSpeed, machine SPM

3.8.22 The system shall include the following external interfaces:a. The system shall be configured to receive a hardwired signal

from the Buyer’s Viable Monitoring System. This signal will create an alarm and function as an interlock to notify the Syringe Filler when the Viable Monitoring System is out of service.

b. The system shall be configured to receive a hardwired signal from the Buyer’s Non-Viable Particulate Monitoring System. This signal will create an alarm and function as an interlock to notify the Syringe Filler when the NVPM System is out of service.

3.8.23 The control system on the debagger shall include the following controls, with alarming for each:

(to be completed)a. Minimum tub accumulation detection at the infeed.b. Tub counting at the infeed and outfeed [100% accuracy via

physical sensor – not shift register].c. Incomplete bag removald. Tub conveying jame. High level in empty bag waste container

3.8.24 The control system on the delidder shall include the following controls, with alarming for each:

(to be completed)a. Minimum tub accumulation detection at the

infeed.b. Tub counting at the infeed and outfeed [100%

accuracy via physical sensor – not shift register].c. Incomplete lid removald. Tub conveying jame. High level in lid waste container

3.8.25 The control system on the filling machine shall be capable of controlling (where applicable) the surge tank level, plungering vacuum level, fill weight and other parameters within defined limits.

3.8.26 The control system on the filling machine shall include the following controls, with alarming for each:

a. Minimum tub accumulation detection at the infeed.b. Tub counting at the infeed and outfeed [100% accuracy via

physical sensor – not shift register].c. Tub detection and counting at the reject station [100%

accuracy]. The system shall verify that all rejected tubs correctly enter the reject station.

d. Raised syringe detection.e. Raised filling needle detection.



ID# Description ER Referencef. Syringe weight outside of predetermined product based

limits.g. Minimum plunger accumulation detection in the sorting

bowl.h. Minimum plunger accumulation detection in the feed

lane(s).i. Missing plunger detection on all syringes processed.j. Raised plunger detection on all syringes processed.k. Overtorque / following detection on all syringe or plunger

handling shafts. l. Low vacuum level for starwheels or plungering.

3.8.27 The system shall require the following safety controls:a. Emergency Stop buttons (large, red mushroom-type) on

each machine which stop the machine immediately and de-energize all devices via a hardwired safety rated relay. At a minimum, restarting after an emergency stop shall require manual release of the Emergency Stop button, acknowledgment of the alarm on the HMI, and initiation of a restart on the HMI.

b. An Emergency Stop shall release all pneumatic pressure to the machine. Machine mechanisms that will retain potential energy in the event of an air pressure loss must be designed to be in a safe condition when the air is released. Venting of air should be done exterior to the classified filler room or be vented into the room through a sterilizing filter. Vacuum maintaining products should never be released.

c. Process Stop button, which performs a soft stop of the machine in a manner that does not jeopardize product in the machine.

d. Interlocked doors and/or light curtains, which stop the machine immediately via the safety circuit.

e. A multi-color, machine function-indicating light tower. Color scheme to be approved by Lilly.

f. No single point of failure shall expose personnel to a hazard (i.e. pinch point, rotating parts, and lacerations). All safeguards must be interlocked with a hardwired safety circuit.

Hardwired interlocks shall only be used for safety purposes and all other interlocks shall be generated by the control system. The control system shall indicate when any hardwired interlocks (including E-stops) are active.

3.8.28 The system shall require the following maintenance controls via a Maintenance Operating mode:

a. Manual control of all motors. Exceptions must be approved by Lilly.

b. Bypass of the door interlocks and/or light curtains via keyswitch. If this cannot be executed due to code compliance, Vendor to provide mechanism or procedure by which door safety switches and light curtains can be bypassed.

c. Operation of the machine via hand-held control unit. d. The ability to enable or disable stations of the machine.e. The ability to specify the machine operation speed during

Maintenance.The ability to specify the output destination of syringes/tubs



ID# Description ER Referenceprocessed during Maintenance.

3.8.29 The system shall require the following power loss controls:a. The machine shall be designed fail-safe, so that upon failure,

instrument readings fail to an alarm state and devices will revert to their safest state.

b. The machine shall not auto-restart upon restoration of electrical power.

3.8.30 The control system shall be prepared for a minimum future expansion of 20%, in program size, I/O connections and electrical cabinet space.

3.8.31 All client and server platforms that are connected to the Lilly network will allow the installation of Lilly standard antivirus and operating system patches.

3.8.32 The system shall provide counters for the following data. The counters shall be automatically cleared when starting a batch and can also be reset manually.

a. Number of tubs at infeed of filler.b. Number of tubs accepted.c. Number of tubs rejected due to each rejection reason

(individual counter for each rejection reason). d. Total number of tubs rejected.

3.8.33 The control system shall reject syringes based on monitored process conditions. All rejection reasons are to be identified by the Vendor and approved by Lilly, but must include the following:

a. Filling weight outside acceptance limits.b. Missing plunger.

c. Raised plunger.3.8.34 The system shall alarm and stop the syringe filling process if the

following conditions occur:a. A consecutive number of syringes from the same plungering

station have missing plungers during continuous filling. The number of consecutive syringes that triggers this alarm shall be an adjustable parameter.

b. A consecutive number of syringes from all plungering stations have missing plungers during continuous filling. The number of consecutive syringes that triggers this alarm shall be an adjustable parameter.

3.8.35 The system shall alarm and stop the syringe filling process if the following conditions occur:a. A consecutive number of syringes from the same plungering

station have raised plungers during continuous filling. The number of consecutive syringes that triggers this alarm shall be an adjustable parameter.

b. A consecutive number of syringes from all plungering stations have raised plungers during continuous filling. The number of consecutive syringes that triggers this alarm shall be an adjustable parameter.

3.8.36 The system shall provide a “line clearance” mode, which can be manually initiated via a button on the HMI. This mode will inhibit tubs from entering the infeed and transport all syringes/tubs currently in the machine to the appropriate location, clearing the line.

3.8.37 The system shall display at least XX sets of fill weight data on the HMI (format to be agreed upon). The information displayed for each syringe shall include the following:

a. Gross weightb. Tare weight



ID# Description ER Referencec. Net weight

For weight values displayed on the HMI, the display shall use background color animation to indicate the weight value with respect to the following limits, which are adjustable parameters.

a. Within adjustment (alert) limits: Greenb. Within acceptance limits and outside adjustment limits:

Yellowc. Outside acceptance limits: Red

The Vendor shall also provide a proposal for trending the weight values.

3.8.38 The system shall provide functionality to enter data for batch identification, product identification, and process order number via the HMI.

3.8.39 The system shall alarm and stop the syringe filling process if the following conditions occur:

a. A consecutive number of fill weights from the same filling station are outside of the predetermined limits, during continuous filling. The number of consecutive measurements that triggers this alarm shall be an adjustable parameter.

b. A consecutive number of fill weights from all filling stations are outside of the predetermined limits, during continuous filling. The number of consecutive measurements that triggers this alarm shall be an adjustable parameter.

3.8.40 The Syringe Filler System must have the capability to reject a configurable number of tubs after it has been inactive for a configurable time period, by product.

3.8.41 The Syringe Filler control system shall function in an environment of 59-86 F and 10-80% RH.

3.8.42 The Syringe Filler System shall alarm and stop the line if an expected reject is not present.

4.0 DOCUMENTATION AND DATA

4.1 Documentation

ID# Description ER Reference4.1.1 The Vendor shall supply, at a minimum, the documents listed in

the Vendor Documentation Requirements table, in the English language. (Appendix D)

4.1.2 Documents are supplied in hard copy and electronic format.

a. Draft versions of documents for Lilly review shall be provided in electronic format whenever possible.

b. The turnover package, comprised of finalized versions of all documents, shall be provided as one <1> hard copy and one <1> electronic copy of all documents.

c. Acceptable electronic formats are listed in the Vendor Documentation Requirements table in Appendix D.

d. Electronic files shall be provided on CD or DVD media. Media shall be labeled to identify the system and the contents of the media.

e. Media will be provided in a three ring binder in a protective sleeve(s).

4.1.3 Hard copy documentation shall be provided in a three-ring hard cover binder(s) that is clearly labeled to designate the system.



ID# Description ER ReferenceWhen more than one binder is required, all binders associated with the same system shall be labeled “Binder X of Y” where “X” is the particular binder number and “Y” is the total number of binders.

a. All hard copy documentation shall comply with Attachment F – Good Documentation Practices.

4.1.4 A title page and table of contents shall be provided at the beginning of each volume. The title page shall include the following information:

a. Project Nameb. System name and numberc. Version number, starting with version 1.0d. Document Date – Date the document was completed or

revisede. Issuer Identification: Name and Company Affiliation

4.1.5 All documentation submissions should include a Submittal Transmittal (See Appendix F). The form should be completely filled out and provided by the contractor to signify that the submission is complete and accurate.

4.1.6 All documentation submission materials shall be directed to the Lilly designated primary contact for the project.

4.1.7 Equipment as-built(s), detailed control panel and instrument/control circuit drawings, instrument location plans, process and instrumentation diagrams shall be provided within four weeks after completion of factory acceptance test (FAT). Refer to separate Lilly FAT job specification number XXXX.

4.2 Data

ID# Description ER Reference4.2.1 Right Information (Component) Data shall be provided for all PID

tagged components (at a minimum) for the system.

The Right Information (Component) data fields required to be provided are identified in Appendix E. Data shall be submitted in a template supplied by the Buyer (refer to Appendix E).

Right Information (Component) Data will be verified by the Buyer prior to closure of the FAT.

4.2.2 Corrections to submitted component data shall require a change notification to assure communication of the correction.

5.0 COMMISSIONING AND QUALIFICATION

5.1 Commissioning

ID# Description ER Reference5.1.1 Commissioning activities will be conducted by the Buyer.5.1.2 The Vendor shall be responsible for supporting commissioning

activities and assisting with technical support and troubleshooting



ID# Description ER Referenceefforts during commissioning.

5.1.3 The Owner may visit or be in residence at the Supplier’s shop to ensure that quality control is being properly maintained. A minimum of 48 hours notice of these visits shall be given.

5.1.4 The Supplier shall notify the Owner at least ten working days prior to anticipated factory acceptance or witness test dates.

5.1.5 The system shall be fully inspected and functionally tested prior to Owner witness testing. This testing shall be completed, prior to scheduling the factory acceptance test (FAT).

5.1.6 The Owner’s representatives witnessing the FAT shall have free entry to the areas, where activities related to the testing are to take place.

5.1.7 The Supplier shall provide labor, general materials and utilities used in tests witnessed.

5.1.8 Inspection of units shall include, but not be limited to, the following:Visually inspect equipment, piping and accessories for conformance to Specifications.

5.1.9 The assembly shall be inspected for signs of wear or damage after each test run.

5.1.10 Control switches; alarms, safety interlocks and instruments shall be checked prior to test and during testing.

5.1.11 Instruments shall be calibrated before testing begins.

5.1.12 The Owner may waive shop inspection or equipment inspection. Inspection by Owner, or waiver of inspection, shall not relieve the Supplier of their responsibility to meet the requirements of this Specification.

5.2 Factory Acceptance Test (FAT)

ID# Description ER Reference5.2.1 The Syringe Filler shall be subjected to an FAT (Factory

Acceptance Test), which will be carried out at the Vendor’s premises.

5.2.2 The Vendor shall perform preliminary FAT testing prior to the FAT. The Buyer representatives shall be allowed to be present during pre-FAT testing.

5.2.3 The FAT protocol is to be generated by the Vendor for Buyer’s review, edit, and approval. The Buyer reserves the right to utilize its own FAT protocol. Vendor (with Buyer participation) shall be responsible for executing the FAT. Buyer and Vendor will agree in advance what tests will be performed and/or witnessed by the Buyer.

5.2.4 FAT protocols shall contain:a. cover page that identifies the equipment or subsystem tag

name b. approver’s signature page c. signature log that documents signature, printed name,

initials and company identification d. test pages with test steps initialed and dated by executore. test equipment calibration log f. FAT acceptance letter summarizing test results and any

open punch list itemsg. a revision number and document date



ID# Description ER Reference5.2.5 The FAT shall consist of the following:

a. Documentation Verificationb. Data Verificationc. Mechanical / Installation Verificationd. P&ID and Pneumatic Drawing Verificatione. Utility Verificationf. Power Verificationg. Wiring Verificationh. Programmable Device Configuration Verificationi. Instrumentation Calibration Verificationj. Test Instrumentation Verificationk. Source Code Verificationl. Maintenance Verificationm. Operational / Functional Testingn. Performance Testingo. Component Verification

See Appendix C for detailed descriptions.

5.2.6 FAT Timing Requirements:a. The Vendor shall inform the Buyer not less than twelve (12)

weeks in advance of the quantities of product and packaging materials required to carry out the requirements of this specification.

b. The Vendor shall submit the FAT protocol to the Owner or Owner’s representative at least (6) weeks before the scheduled FAT for pre-approval. Pre-approval of FAT protocols shall be required to use the FAT protocol for testing.

c. The Vendor shall inform the Buyer of the equipment’s readiness for the FAT not less than four (4) weeks in advance for appropriate resource planning.

5.2.7 FAT Materials and Components:a. The Buyer shall provide raw materials (e.g., approved

packaging materials, active or placebo test syringes, etc), and dispose of hazardous materials necessary to meet the requirements of this specification for factory and on-site testing.

b. The Vendor shall provide utility services similar in quality and quantity to those available at the Buyer’s site.

c. The Vendor shall provide any peripheral equipment required to perform FAT.

5.2.8 All test data recorded during FAT shall follow Good Documentation Practices (GDP) per Appendix G.

5.2.9 At the conclusion of the FAT, the Vendor shall provide an FAT summary report containing the results of the FAT and all punch list items from the testing. The summary report shall be provided to Lilly for review and approval.

5.2.10 Successful completion of the FAT does not relieve the Vendor of it obligations relating to the specifications and contractual documents; it authorizes the Vendor to send the equipment to the Lilly Site.



ID# Description ER Reference5.2.11 If the FAT fails due to gross neglect on the part of the Vendor (i.e.

insufficient pre-testing), the Vendor will be liable for expenses related to the failed FAT. These costs will include two people’s travel expenses should an additional trip be required.

5.2.12 After the completion of the FAT and prior to SAT, any changes or updates noted during FAT (or due to issue resolution thereafter) shall be incorporated into the appropriate documentation. The Buyer shall receive an updated electronic copy of all documentation prior to SAT.

5.3 Shipping and Installation

ID# Description ER Reference5.3.1 Only after receiving written approval from Lilly, the Vendor shall

crate, box, and seal equipment for shipping as required to prevent damage during shipment. All FAT action items must be resolved prior to shipment, if possible. The Buyer shall arrange shipment of the filler.

5.3.2 Prior to packing, exterior surfaces shall be cleaned to remove grease, rust inhibitors, metal flakes, chips, residues from manufacturing and assembly processes and other foreign materials.

5.3.3 Equipment shall be shipped completely assembled, whenever possible; unless doing so could damage the equipment during shipment. Those items shall then be disconnected and shipped separately. Parts shipped separately shall be clearly match marked for easy reassembly at the site.

5.3.4 Accessories and parts shipped separately shall be boxed and properly identified with durable, waterproof shipping tags attached with stainless steel wire or plastic tie strips and marked with the information required in shipping instructions.

5.3.5 Openings to the equipment, piping or vessels will be sealed for shipment. Seals must be weather tight and compatible to the material being sealed.

5.3.6 Supplier shall pack, crate and protect equipment to prevent damage from handling, weather, shock, vibration, water and corrosion during shipment. Packaged or crated assemblies shall be wrapped in weatherproof plastic sheeting prior to shipment. Supplier shall install shock and tilt indicators on the skid for assessment of shipping conditions made when the unit arrives at the job site.

5.3.7 Supplier shall include complete handling, reassemble of disconnected parts and system installation data with the equipment shipped to the jobsite.

5.3.8 Supplier shall coordinate shipments with Owner’s Traffic Operations and additionally, international shipments with Owner’s Customs Operations.

5.3.9 Damaged equipment shall not be accepted at the jobsite. Receipt of delivery does not remove liability for undiscovered shipping damage.

5.3.10 The Buyer shall be responsible for moving the machine into the room of intended operation. The Vendor shall be responsible for moving the machine into the final location within that room, as well as mechanical integration with neighboring equipment.

5.3.11 The Buyer shall be responsible for providing utility supply lines to the machine, as well as routing all cabling and wiring to the machine. The Vendor shall be responsible for making all utility connections to the machine, as well as all wiring termination at the machine and at the control panel.



5.4 Site Acceptance Test (SAT)



ID# Description ER Reference5.4.1 The Syringe Filler shall be subjected to an SAT (Site Acceptance

Test), which will be carried out at the Buyer’s premises with representation from the Buyer and Vendor.

5.4.2 The SAT protocol is to be generated by the Vendor for Buyer’s review, edit, and approval. The Buyer reserves the right to utilize its own SAT protocol. Vendor (with Buyer participation) shall be responsible for executing the SAT. Buyer and Vendor will agree in advance what tests will be performed and/or witnessed by the Buyer.

5.4.3 Supplier shall submit the SAT protocol to the Owner or Owner’s representative at least 6 weeks before the scheduled SAT for pre-approval. Pre-approval of SAT protocols shall be required to use the SAT protocol for testing.

5.4.4 All test data recorded during SAT shall follow Good Documentation Practices (GDP) per Appendix G.

5.4.5 The results and any punch list item from the tests will be submitted in an SAT acceptance report written by the Vendor and approved by the Buyer.

5.4.6 The Buyer shall provide raw materials (e.g., approved packaging materials, active or placebo test syringes, etc), and dispose of hazardous materials necessary to meet the requirements of this specification for on-site testing.

5.4.7 SAT protocols shall contain:a. cover page that identifies the equipment or subsystem tag


initials and company identification d. test pages with test steps initialed and dated by executore. test equipment calibration log f. SAT acceptance letter summarizing test results and any


5.4.8 The SAT (or equivalent) protocol may consist of any testing described in the FAT section. SAT testing shall be sufficient to verify to the Owner that the equipment as installed at site performs in accordance with Lilly specifications. At a minimum, the SAT (or equivalent) protocol shall include the following:

a. Inspection for damage.b. Repeat testing or verification of any items with the potential

to have been impacted by breakdown and/or shipment.c. Testing of any functionality not able to be verified at FAT

(site utility connections/interfaces, site utility failure testing, data interfaces, etc.).

d. Performance testing to verify equipment performs in accordance with performance criteria in the equipment specifications (e.g., line speed, throughput, efficiency, runtime).

e. Verification that all FAT open issues have been adequately addressed.

f. Verification of final turnover package completeness

5.4.9 The Vendor shall be present at system start-up to verify that the





















energized system is operating in a controlled and stabilized manner





















prior to functional testing. In particular:





















a. Verify that the utilities are connected to the system and comply with specifications.





















b. Allow the system to run for an extended time and note any





















aberrant trends in performance.





















c. Verify the reaction of the machine to utilities failures.





















d. Document configurable parameters and settings. It is





















understood that the Vendor will provide an electronic





















download.





















e. Perform safety test (e.g. Interlocks, soft and hard stops due





















to opening of machine enclosures/doors, E-stops, etc) and





















verify safety documentation.





















5.4.10 Operational Testing similar to testing completed at FAT





















a. Reliability testing





















b. Random alarm and interlock testing





















c. Documented evidence for the completion of the FAT





















punch list items (as required).



5.5 Installation Qualification (IQ) and Operational Qualification (OQ)

ID# Description ER Reference5.5.1 IQ and OQ will be performed by the Buyer with the option to

purchase from the Vendor services for protocol development and execution.

If IQ and OQ services and protocols are purchased, the protocols shall be generated by the Vendor for Buyer’s review, edit, and approval.

5.5.2 The Vendor shall be available to support the Buyer during these activities.

6.0 GENERAL OPTIONS

The Vendor shall provide separate costs for each of the following services in the proposal:

ID# Description ER Reference6.1.1 Right Information (Component) Data.6.1.2 Operator/Maintenance Training for Lilly Technicians (at Supplier

and Vendor sites).6.1.3 All necessary spare parts to allow commissioning and one year’s

operation of the machine.6.1.4 On-Site start up and acceptance test (SAT) execution (Daily Rate).6.1.5 IQ Protocol Development.6.1.6 OQ Protocol Development.6.1.7 Cost per day for continued development and optimization work

following successful completion of all requirements and Buyer acceptance of the equipment.



7.0 APPENDICES

7.1 Appendix A - Syringe and Plunger Reference Document

PROPOSED B103 LIQUID FILLING LINE: SYRINGE DATA

MATERIALNUMBER

NOMINALSYRINGEVOLUME

SYRINGE DIAMETER

SYRINGE HEIGHT

SYRINGEWEIGHT

MANUFACTURERMFR

DRAWINGNUMBER

NOMINAL PLUNGER

SIZE

LIQUIDFILL

VOLUME NOTES

milliliters millimeter ± millimeter ± grams millimeter milliliters

0.5

1

3



PROPOSED B103 LIQUID FILLING LINE: PLUNGER DATA

MATERIALNUMBER

NOMINALPLUNGER

SIZE ELASTOMERFORMULATION COATING MANUFACTURER

MFRDRAWINGNUMBER

NOTES

millimeters



7.2 Appendix B - Product Defect Criticality

Syringe Subsystem Defect Category

Plunger Missing plunger Critical

High plunger (X mm) Critical

Inverted plunger Critical

Product under plunger flange Critical

Plunger slanted (not perpendicular to syringe body)

Critical

Syringe Body Visible scratches Major or minor depending on severity

Broken syringe Critical

Crack that affects container integrity Critical

Product on exterior of syringe Critical

Chip greater than 2 mm length on outer finish of syringe

Major

Foreign material or particles shown to be introduced to the syringe by the filler (through root cause investigation and evidence acceptable to buyer and vendor)

Major

Syringe Liquid No fill Critical

Gross over-fill Critical

Gross under-fill Critical



7.3 Appendix C – Detailed Description of FAT Testing

Documentation Verification – Verify that all documentation is available and meets the requirements of the VDR (Refer to Appendices D). Data Verification – Verify that all data is available and meets the requirements of the VDR (Refer to Appendices E). Mechanical / Installation Verification – Verify that the general arrangement drawings for overall system and critical installation items properly reflect as-built dimensions.P&ID and Pneumatic Drawing Verification – Verify that process relevant P&ID and Pneumatic drawings represent as-built conditions.Utility Verification – Verify that utility connections and capacities properly reflect design specifications and are representative of final conditions at Lilly.Power Verification – Verify that no short circuits exist, power is present and at the appropriate voltage and frequency for UPS and normal power. All equipment with control systems shall be subject to a power outage recovery test and simulated UPS operation.Wiring Verification – Verify instrumentation and electrical wiring is installed as per specifications/drawings. Verify that all components are tagged adequately using good engineering practices and match documentation. Verify 100% point-to-point continuity wiring checks are complete. Inspect electrical panels to verify proper grounding techniques, voltage segregation, etc.Programmable Device Configuration Verification – Verify that the configuration of all programmable devices is recorded and reflects the design specifications, system drawings, and manufacturer’s manuals. Instrumentation Calibration Verification – Verify that all instrumentation has been calibrated prior to FAT testing. Instruments shall be calibrated to national or international reference standards and calibration reports shall be provided to the Buyer.Test Instrumentation Verification – Verify that each test instrument has been calibrated for FAT test execution. The seller shall provide the correspondent calibration certificates. Source Code Verification – Verify that the versions of all software used at FAT are recorded. The seller shall provide an electronic copy of all software (the versions must match those used at FAT). Maintenance Verification – Verify equipment change parts and start-up spare parts are available per design/specifications and change parts can be assembled and disassembled efficiently. Verify that all equipment is easily accessible and designed for execution of maintenance and/or calibration.Operational / Functional Testing – Verify equipment functions in accordance with Lilly approved specifications. Operational testing may include testing of the following, as applicable: operating modes, alarms, interlocks, safety features, emergency stops, pushbuttons, switches, sensors, physical security, logical security, format / recipe configuration, and other equipment controls.Performance Testing – Verify equipment performs in accordance with performance criteria in the equipment specifications (e.g., line speed, throughput, efficiency, runtime).Component Verification – Verify components are installed against specifications, materials of construction and surface finish for product contact parts are as specified, proper elastomeric materials are as specified, and that components are free of obvious defects. Verify that specified component model numbers match the actual model numbers.



7.4 Appendix D – Vendor Documentation Requirements

7.5 Appendix E – Right Information (Component) Data Requirements

7.6 Appendix F – Submission Transmittal Form



7.7 Appendix G – Good Documentation Practices

1. All entries must be made on official forms.

2. Document entries must be readable, accurate, complete, and done in blue or black permanent ink.

3. All handwritten entries must be recorded as close to the event occurrence as possible. Entries can only be

dated with the current date. Entries can not be made before the event has occurred.

4. Entries to document completion of a task must be initialed and dated instead of using a check mark or an

‘X’.

5. Date and time formats must be defined and consistently followed when a date or time entry is required.

(e.g. 01 Jan 2009)

6. If there are data print outs which support a form being filled out, attach that print out to the form. Data

that has been entered into a computer must still be printed out, signed and dated.

7. Making up data or leaving off actual data is unacceptable.

8. Destroying all or part of any forms is unacceptable.

9. Ditto marks ( “ “ ) and continuation lines ( … ) through a series of entries are unacceptable.

10. How to make corrections:

a. Draw a single line through the entry so the original entry is still readable (i.e., correction). Do not

use correction fluids or tapes, erasers or solvents to remove or obscure original entries.

b. Enter the correct entry as close to the original as possible.

c. Initial and date the correction using the format listed above.

d. If there is not enough room to make your correction, attach a blank sheet of paper to the form and

write correction there. Number the mistake and the correction with the same number.

e. Every correction must be briefly explained. The explanation can include: wrong number, wrong

date, entry error, calculation error, spelling error.

11. Blanks are not acceptable unless the instructions allow them. Where areas do not apply, cross out the

area, initial/date, and provide an explanation for why the area should be blank (e.g., end of data, test not

required).


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