Operator Specific GMP Training

Operator Specific GMP Training

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Training Objectives

The purpose of this training is to provide operator specific information about GMP (Good Manufacturing Practices) and to focus on the required forms and procedures found in the GMP manual, located in Sharepoint. This training will be followed by a short test to verify your understanding of the covered materials.

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Introduction to GMP

GMP (Good Manufacturing Practices) is a system to ensure that products meet food safety, quality and legal requirements for products that come into intimate contact with the human body, and which must be free of any harmful contaminant.

After the events of September 11, 2001, the United States enacted the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (the Bioterrorism Act) to protect the public from terrorist attacks on the U.S. food supply. The Food and Drug Administration (FDA) tightened its regulations on manufacturers, including those of excipients, or processing aids used in many food and pharmaceutical products.

One common excipient is glycerine, which now faces stricter regulations.

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Introduction to GMP

Emery sells refined glycerin to customers for use in pharmaceutical applications; therefore, the site needs to ensure full compliance with excipient GMPs. According to IPEC & PQG, (IPEC-PQG 2006, 3). To support this objective, the excipient manufacturers must maintain quality systems that meet the intent and help deliver GMP requirements.

The GMP principles applied are based on the 2006 International Pharmaceutical Excipients Council (IPEC) Guide.

To comply with GMP, Emery will maintain the facilities, controls, resources, and quality management systems necessary to ensure the resultant excipients possess the quality and purity which they claim to possess and are suitable for their intended use.

QMS General Requirements

The principles identified in the GMP Manual provide a comprehensive basis for the quality management system required for the manufacture of bulk pharmaceutical excipients. The Manual further identifies the quality management processes, policies, and procedures required to assure excipient quality.

Where manufacturing, testing, packaging, or other outsourced operations could affect excipient quality, the responsibility for quality remains with the excipient manufacturer and appropriate control measures need to be defined and documented.

QMS Documentation Requirements

The excipient manufacturer shall have a system in place to control documents and data that relate to the requirements of the defined quality management system (QMS).

The GMP Manual fulfills the requirement for a documented quality manual. It defines the scope of the excipient quality management system, references supporting procedures, and describes the interaction between the quality management processes.

The Oleochemicals GMP Manual is located in Sharepoint at: North America/Document Management System/US Manufacturing/Site Manuals/Good Manufacturing Practices (GMP) Manual.

All controlled documents are maintained in Sharepoint.

QMS Document Control

All controlled documents are subject to an approval process, are authorized and issued, and are made available at the point of use.

CONTROLLED INTERNAL DOCUMENTSPREPARATIONREVISIONDOCUMENTAPPROVALDOCUMENT FILE MAINTENANCEDOCUMENT RETENTIONGMP ManualGMP Mgmt RepGMP Mgmt RepGMP Mgmt Rep3 yearsAdministrative ManualTech StaffPlant MgrTech Staff3 yearsFA SOPs Tech StaffProduction Area MgrTech Staff3 yearsFA PWIs Tech StaffProduction Area MgrTech Staff3 yearsProduction Log SheetsProduction Area MgrProduction Area MgrManufacturing Mgr3 yearsNight NotesProduction Area MgrProduction Area MgrManufacturing Mgr3 yearsSpurs, Glyc., E3124 ScheduleFinite PlannerFinite PlannerFinite Planner3 yearsFatty Acid Production ScheduleFinite PlannerFinite PlannerFinite Planner3 yearsQC SOPs & PWIsQC StaffQC MgrQC Staff3 yearsMaintenance SOPs & PWIsMtce StaffMtce MgrMtce Staff3 yearsUtilities SOPs & PWIsUtilities StaffUtilities MgrUtilities Staff3 yearsPurchasing SOPs & PWIsPurchase StaffPurchase MgrPurchase Staff3 yearsLogistics/Dist SOPs & PWIsL & D StaffL & D MgrL & D Staff3 yearsEngineering SOPs & PWIs Engineering StaffEngineering MgrEngineering Staff3 yearsCustomer Service SOP/PWIsC S StaffC S MgrC S Staff3 yearsWarehouse/Tolling SOP/PWIsW/T Staff W/T MgrW/T Staff3 yearsHuman Resource SOP/PWIsHR StaffHR MgrHR Staff3 years

QMS Record Control

Extensive quality related records are maintained that demonstrate the effective operation and application of the excipient QMS. Each process owner is responsible to document the following:

identification of quality records for their respective process

specifying quality record retention times

establishing and maintaining a controlled, documented procedure for identification, collection, indexing, access, filing, storage, maintenance, and disposition of quality records

ensuring that records are legible and identifiable

ensuring that records are readily retrievable and available for review by the customer

ensuring that records are maintained in a suitable environment

ensuring that records are kept for the required retention period

ensuring hand-written quality records are completed in blue or black ink only

ensuring incorrect entries are voided by a single strikethrough, initialed, and dated

ensuring all required fields are completed

ensuring no whiteout or similar is used on quality records

ensuring records are original copies, not photocopies

Personal Hygiene Requirements

To protect excipients from contamination, the following requirements shall apply to personnel that come in direct contact with the product or packaging or are working in an area where the process or product is exposed:

Personnel with any illness that may adversely affect the safety or quality of the excipient must be restricted from excipient processing and handling activities.

Any open wounds, sores, or lesions must be bandaged and taped with a water proof covering.

Personnel must wash hands thoroughly with germicidal hand soap.

Clean, cotton or nitrile gloves should be worn. If direct hand contact with the excipient must occur, then clean, nitrile gloves must be worn.

Personal Hygiene Requirements

A clean hard hat must be worn. Hair nets and beard nets must be worn during packaging.

All outer garments, protective equipment, and boots should be kept clean. Disposable white cover-alls (or blue lab coat) and boot covers must be worn during packaging

Personnel must ensure jewelry and other loose items, are removed or covered.

No food or drink products, personal property, personal medication, or tobacco products are permitted to be taken into excipient manufacturing or packaging areas.

Only authorized personnel shall enter buildings and facilities designated as limited access. Signage shall be posted where applicable.

Infrastructure Requirements

All buildings and facilities are managed, operated, cleaned, and maintained in accordance to Plant safety and housekeeping standards.

Building 70 and its associated facilities, is subject to full IPEC guideline compliance.

Equipment shall be maintained in a good state of repair and be suited to facilitate cleaning, maintenance, and correct operation.

The maintenance department and production operators are responsible for maintenance and cleaning of the equipment.

The manufacturing process is a closed, continuous operation utilizing dedicated equipment, facilities, and personnel. No cross-contamination potential exists.

Sanitizing Procedure shall be used to prevent contamination

No highly sensitizing or toxic chemicals are used in or stored near the process.

Finished bulk glycerine storage tanks are located outdoors. The tanks are kept closed and are temperature controlled to protect the integrity of product.

Cleaning of equipment occurs at scheduled shutdowns, or as necessary.

Quality critical instruments are specified and calibrated per the Maintenance Quality Procedures Manual located in Sharepoint.

Preventative Maintenance (PMs) schedules, standard shutdown work orders, and individual work order histories are maintained indefinitely in SAP.

Sanitizing Procedure

Sanitizing solution is provided and intended for use as a disinfectant against bacteria and viruses.

Responsibilities:

Production personnel will prepare the Sanitizing Solution for use in Building 70 as required.

Production and Maintenance personnel are responsible for using the sanitizing solution as required.

To prepare the Sanitizing Solution as an effective disinfectant :

Mix approximately 1 liquid ounce of the concentrated Sani-T-10 with 1 gallon of water.

Transfer diluted solution into spray bottles. Make sure bottles are labeled as Sani-T-10 Sanitizing Solution.

Apply a course spray of Sanitizing Solution to surfaces during any of these activities:

Glycerine-contact equipment or piping is removed from the process and is being put back into service.

Tools or other equipment are placed into glycerine-contact equipment or piping components.

Equipment or materials used for loading Tank Trucks or Railcars that come into contact with the glycerine.

Bottom piping for Tank Truck discharge line has been opened and inspected for moisture or contamination.

After spraying the sanitizing solution, allow the material to dry (~ 10 minutes) before allowing any potential contact with glycerine.

Critical Equipment and Instruments

Critical Equipment : For a detailed description of Normal Operations for E-916 production, refer to the following Standard Operating Procedures (SOPs)

Caustic Addition System to CL-1 (RG39.070)

Vacuum System (RG22.070)

CL-1 Crude Still (RG31.070)

CL-2 Fractionator (RG33.070)

Carbon Bleachers G-1, G-2, and G-4 (RG34.070)

Filter Press FP-4 (RG34.070)

Bulk Finished Tanks Y-192, Y-193, Y-194, and Y-195 (RG38.070)

E-916 dilution to E-912 (RG37.070)

Quality Critical Instruments: Maintenance and calibration procedures and records are maintained by the Maintenance Department.

DEPT.MCWI #FIELD IDFREQ. DESCRIPTIONRefined Glycerine970470-TIC1256 Months CL-1 Reboiler Outlet TICRefined Glycerine970670-TIC2196 Months CL-2 Reboiler Outlet TICRefined Glycerine971170-TIC2496 Months Bleacher Inlet TIC

Hazard Analysis and Critical Control Points (HACCP)

A scientific and rational systematic approach for the identification, assessment, and control of chemical, biological, and physical contaminants has been conducted to ensure the quality of excipient grade glycerine.

The following table summarizes the Critical Control Points (CCP) identified from this study.

The following CCPs are recognized:

Filter located between check tank and storage tanks, F1: replaced every three months.

Filters used for loading glycerine into bulk container, F2 & F3: replaced every 3 months.

Utilities

The following utilities are employed in the production, storage, or transfer of bulk excipients. These have been assessed and are effectively managed to control the risk of contamination and cross-contamination of the excipient quality and integrity.

Low Pressure Steam (300, 125, 90, 30#) generated internally.

High Pressure Steam (1500, 800#) generated internally.

Electricity purchased externally from Duke Energy.

Plant & Instrument Air generated internally.

Nitrogen purchased externally from Air Products.

City Water purchased externally from Greater Cincinnati Water Works (GCWW).

Industrial grade, non-potable, high quality groundwater purchased externally from Southwestern Ohio Water (SWOW) Company.

Process Water generated internally (city water/soft water/steam condensate/ evaporation water from Bldg 18 Crude Glycerine).

Deionized (DI) Water internally generated with equipment leased from Seimens.

Cooling Tower Water generated internally from city water; treatment service provided by Chemtreat.

Tempered Water generated internally from steam condensate.

Chemicals

The following are direct contact chemicals and process aids employed in the production of bulk glycerine excipients. These have been assessed and are effectively managed to control the risk of contamination and cross-contamination of the excipient quality and integrity. Where possible, only USDA, FFC, or FDA approved food-grade process chemicals or aids are utilized.

Sodium Hydroxide, 25% soln., membrane grade, purchased from KA Steel Chemicals, Inc. (CL-1)

Granular Activated Carbon, CAL TR, purchased from Calgon. CAL TR is kosher, FCC approved and is considered GRAS for use in food processing application (carbon bleachers).

Antifoam 1510FG (Kosher, USDA approved) added to CL-1.

For direct or non-direct contact chemicals, additives, processing aids, and substances, regulatory compliance information obtained from the supplier is reviewed and documented as part of the Material/Supplier Approval process.

The following chemicals are used to treat cooling tower water. Tower water quality is monitored weekly and records are retained by ChemTreat:

Chemtreat CL-3857 (USDA approval G5 and G7)

Chemtreat CL-40 (USDA approval G7)

Sodium hypochlorite, 12% soln. (EP, UL, USDA approved, Chemicals Inc. )

Water

Water shall be demonstrated to be of suitable quality and unless otherwise justified should meet WHO guidelines for drinking (potable) water quality. Water that comes into direct contact with the excipient should be supplied under continuous positive pressure in a system free of defects to control the risk of excipient contamination.

GCWW water used in the manufacture of excipients is certified to be potable based on an annual certification.

GCWW water is tested bi-annually for elemental analysis by Chemtreat .

The backflow preventers installed to protect the city water from any potential contamination are tested on an annual basis. Maintenance maintains backflow preventer testing records.

GCWW water exclusively feeds make-up water to the Bldg 70 Cooling Tower.

GCWW water used for back-flushing carbon beds is additionally filtered.

GCWW water feeds the DI water system used in the E912 process. The deionized water is filtered, purified through a series of ionic beds, and passed through an ultra-violet (UV) sterilizer to prevent microbiological contamination. Monthly audits of E-912 and the dilution water are conducted for microbial analysis to verify the effectiveness of the UV sterilizer. Records are maintained by QC.

SWOW water is industrial grade, non-potable water used in the Boiler House and cooling towers outside Bldg 70. SWOW water quality is assessed by the Ohio EPA

SWOW is tested bi-annually for elemental analysis by Chemtreat.

Steam

Boiler feed water comes from South West Ohio Water (SWOW) and is treated and tested daily at the Demineralization Plant.

Demineralization Plant uses the following chemicals:

Sodium hypochlorite, 12% soln., EP, UL, USDA approved, Chemicals Inc.

Chemtreat BL124, Dechlorinating Agent - FDA approved

Sulfuric Acid 93%, diluted to 3%, used during resin bed regeneration.

Sodium Hydroxide, 50% soln., diluted to 2%, during resin bed regeneration.

Low Pressure Steam Boiler uses the following chemicals:

Chemtreat BL1324, Deposit Control Treatment - FDA approved

Chemtreat BL1255, Corrosion Inhibitor (Oxygen Scavenger) - FDA approved

Chemtreat BL1544, Steam Corrosion Inhibitor - FDA APPROVED

Sodium Hydroxide, 50% soln., purchased from Univar. Meets chemical requirements of Food Chemical Codex (FCC).

High Pressure Steam Boiler uses the following chemicals:

Chemtreat BL1792, Deposit Control Treatment - FDA approved

Chemtreat BL1255, Corrosion Inhibitor (Oxygen Scavenger) - FDA approved

Chemtreat BL1790, Deposit Control Treatment - FDA approved

Chemtreat BL1544, Steam Corrosion Inhibitor - FDA approved

Work Environment

Where the excipient is exposed during manufacturing, storage, and packaging, an appropriate environment to minimize contamination shall be maintained.

Air Handling: There are no special air handling systems required or installed for the bulk glycerine process. Air filters used in the general ventilation system for Bldg 70 are replaced regularly per the preventive maintenance schedule. Where the excipient may be exposed, protective devices are procedurally applied to minimize potential contamination.

Controlled Environment: The application of a controlled environment for the bulk glycerine process exists only during final product storage. The bulk tanks are normally closed, nitrogen-blanketed, temperature-regulated and vent to a closed vent header system. An additional vent seal pot servicing Y-192, Y-193, and Y-195 entrains water present in the vent header. A dedicated vent tank dryer services Y-194, typically used for E-912 storage.

Cleaning and Sanitary Conditions: Adequate cleanliness and sanitary conditions shall be applied to all facilities, equipment, and materials involved in the manufacture, storage, and packaging of the excipient.

Work Environment

Pest Control: Buildings and facilities shall be free from infestation by rodents, birds, insects, and other vermin.

Lighting: Adequate lighting is provided and maintained throughout excipient processing, storage, and packaging areas.

Drainage: Areas where the excipient is open to the environment , drains shall be of adequate size, and where directly connected to a sewer should be provided with an air break or other mechanical device to prevent back-siphoning.

Wash and Toilet Facilities: Adequate, accessible wash and toilet facilities, including hot and cold water, soap, and single service towels are maintained throughout the excipient production and packaging areas. Adequate facilities for showering and/or changing clothes are additionally provided.

Housekeeping

Building 70, Refined Glycerine, and its associated facilities, will be managed, operated, cleaned, and maintained in accordance to Plant safety and housekeeping standards.

Production Operators are responsible for ensuring proper housekeeping standards are applied, conducting audits, documenting deficiencies, initiating corrective actions, and issuing audit reports to management.

GMP Coordinator is responsible for ensuring audits are conducted at prescribed frequencies, corrective actions are complete and effective, and maintaining records as specified in this procedure.

The buildings, process areas, equipment, transfer centers, tank farms, and loading facilities shall be maintained in a clean and orderly manner at all times. To that end, weekly audits will be conducted, documented, and remediated by the production operators in conjunction with the requirements defined on the GMP Areas Inspection Checklist.

Completed GMP Areas Inspection Checklists will be retained by the GMP Coordinator for 3 years minimum.

GMP Housekeeping Checklist

Is the process area clean and orderly?Is the equipment and piping in good condition without any signs of visible leakage?Is the area free of non-GMP materials (glass, chemicals, personal items, rags, food, drink, etc)?Is the area free of chemical spills, standing water, and waste materials?Are process and floor drains covered, open and flowing?Are all lights functional with protective covers in place?Are hoses and jumpers in use in good condition, clean, and properly secured?Are all windows and doors closed, clean, and in good operational condition?Are hand washing stations accessible and in good working condition?Is the Control Room clean and orderly?Are wash and toilet facilities clean, operational, and adequately stocked?Is there 18" minimum between walls and stored process chemicals?Are process chemicals stored in their designated locations, properly labelled, and protected?Are pest control devices and equipment in place and in working order? Are LOTO supplies, documentation and lockboxes properly maintained and kept current?Are trash cans throughout the building maintained (in proper location, not overflowing, etc)?Are drums and other containers stored in designated location?Are hoses and jumpers not being used properly stored in designated areas?Are tools, ladders, equipment, and supplies properly stored?Are filters and other supplies stored in designated location?

Building 70:

GMP Housekeeping Checklist

Is the bulk-loading equipment, platform, boom, piping, in good condition and void of leakage?Are the bulk-loading dome covers clean, dry, and properly stored?Are tools used for bulk-loading properly stored?Are bulk-loading booms capped?

Are the tanks, pumps, filters, piping and hoses clean, orderly, and labelled for use as GMP only?Is the area free of chemical spills, standing water, waste materials and other non GMP-materials?Is the Nitrogen purge to the storage tanks maintained at a flow above 10 SCFM?

Is the GMP storage area clean, orderly and labelled for use as GMP only?Is the GMP area free of non-GMP materials (chemicals, personal items, rags, food, drink, etc)?Is the GMP area free of chemical spills, standing water, and waste materials?Are all lights functional with protective covers in place?Are pest control devices and equipment in place?

GMP Bulk Loading Area

Glycerine Bulk Storage Tanks

Bldg 65 GMP Storage Area

Pest Control

Pest control services are conducted, at a minimum of monthly, throughout the entire Cincinnati plant using a contract service provider, Pest-All Services, Inc.

These treatments are performed as preventative pest management measures to eliminate potential insect and rodent infestations from occurring.

The pest control program is managed in the most professionally and environmentally effective manner possible.

All potentially applied chemical agents within the defined GMP area(s) have been reviewed and approved for use. Where possible, pesticides approved for use in food/feed applications, are applied exclusively at the minimum usage required.

Bait boxes and insect lights must:

Be inspected according to the established service schedule

Be clean, numbered, positioned as identified, and operational

Contain adequate unused bait (bait box only)

Be free of carcasses and droppings (Pest-All to dispose of carcasses/insects)

Be replaced immediately if damaged or missing

Be dated in accordance to each inspection

Be on a 6 month bulb replacement PM (insect lights only)

Pest Control

Under normal operating conditions, doors and windows must remain closed at all times. The integrity of doors, windows, and the building structure must be maintained to prevent potential external contamination or infestation. These requirements will be audited and documented.

During the high insect activity months (May to October), two external perimeter treatments will be applied to the base of the building, the adjacent 3 foot strip of ground, all ground level doors, overhead doors, and windows.

Within the critical GMP defined process area, Building 70 Refined Glycerine, the Pest-All service person is required to complete and sign the Pest Control Service Report, as a record of the service visit, findings, and applicable corrective actions.

On completion of the Pest Control Service Report, the service person must obtain a signature, from a qualified manufacturing representative, constituting acknowledgement of services and actions rendered.

The GMP Coordinator will review and sign the completed Service Reports.

Pest Control Map

Pest Control Map

Glass Replacement

To ensure an acceptable glass substitute is used when replacing any glass windows within the defined GMP manufacturing areas

The Maintenance Contractor coordinator will be responsible for assuring that glass repairs are made with an acceptable glass substitute material.

The Maintenance Contractor coordinator will train contractors in this procedure.

The Maintenance Planner will maintain a supply of an approved glass substitute for repairs.

1/4" QUE Clear Lexan will be used for all glass pane replacements. NOTE: Plexiglas has proven to be unacceptable due to clouding and warping.

SAP Maintenance work orders will be retained in SAP for 3 years minimum.

Filters

The loading filters used in the finish product lines consist of materials, all of which are FDA listed for contact with food or bulk pharmaceutical excipient usage.

The filter press pads contain materials that are FDA listed for contact with food or bulk pharmaceutical excipient usage.

The city water filter used when back-flushing the carbon beds contain materials that are FDA listed for use in the food/bulk pharmaceutical excipient applications.

All filters are to be checked regularly and changed if they are dirty.

New, unused filters will be properly stored in a clean, dedicated cabinet, free from contaminates.

The carbon bed & filter for the De-ionized Water (used in 912) are replaced as needed or every 6 months by Siemens Industry.

Protection from contamination during a filter change is accomplished by administrative controls using a Filter Changing Checklist

Filters

Location/ServiceNumberMaterial of ConstructionRating (microns)PM FrequencyTallow Unloading Filter 1 stainless steel25As requiredFat Feed to SplitterFilter 2stainless steel600 (30 mesh)As requiredCrude Glycerine to CL-1 Filter 3 stainless steel600 (30 mesh)As requiredFilter Press (direct contact)FP-4cellulose paper< 5 QuarterlyCheck Tank (direct contact)F-1polypropylene10QuarterlyBulk Loading (direct contact)F-2, F-3polypropylene10QuarterlyCity Water @ BleachersF-4polypropylene5AnnualN2 to Y-192, 193, & 195F-5polypropylene5AnnualCompressed Air to Y-194F-6polypropylene5AnnualCity Water to DI TanksF-7polypropylene5AnnualNitrogen to P-33 line blowF-8polypropylene5AnnualCity Water @ DI TanksSiemensactivated carbonNAAs requiredRecovered Water to Splitter stainless steel600 (30 mesh)As required

GMP Filter Changing Checklist

Prior to Changing FilterOperator is in good health and is not aware of having any health condition that could adversely affect the safety or quality of the glycerine being manufactured.Operator has washed hands thoroughly with germicidal hand sanitizerOperator has put on new, clean blue nitrile gloves prior to changing filterOperator has put on clean hard hat and hair net or beard net (if long hair or facial hair is present) Operator has put on clean lab coat (or disposable white coveralls)Operator has ensured that jewellery and other loose items have been removed Operator has ensured that the new filter element is clean and dry.Operator has ensured that any tools needed to change the filter are clean and dry. During the Filter ChangeOperator has ensured that the filter inlet and outlet are isolated. Operator has opened the filter housing and removed the spent filter element. Operator has inspected the empty filter housing and found NO presence of foreign objects inside the container.Operator has cleaned the empty filter housing with sanitizing solution.Operator has replaced the filter element.Operator has secured the filter housing with bleeder valves and vent valves closed.After Filter Change Operator has re-opened flow access through the filter and confirmed there are no leaks.Operator has insured that any unused filters are clean and properly stored in its cabinet.

Bleachers

The Carbon Bleachers used in the process consist of materials, all of which are FDA listed for contact with food or bulk pharmaceutical excipient usage.

The activated carbon is listed for contact with food or bulk pharmaceutical excipient usage.

The three bleachers are set up so that two remain in operation while the third is having its spent carbon removed and refilled with new carbon.

New, activated carbon is stored in a clean area free from contaminates.

Equipment to remove the spent carbon is stored in dedicated area and kept free from contaminates..

Protection from contamination during a carbon change is accomplished by administrative controls using a Bleacher Change Checklist.

GMP Bleacher Change Checklist Page 1

Prior to Removing Spent Carbon (to be completed by personnel removing the spent carbon)Personnel have received authorization from Operators to begin removing the spent carbonPersonnel are NOT aware of any illness that may adversely affect the safety or quality of the glycerine Personnel have washed hands thoroughly with germicidal hand sanitizerPersonnel have put on new, clean cotton gloves Personnel have put on clean hard hat, with a hair net or beard net (if long hair or facial hair is present) Personnel have put on clean, disposable white cover-alls and boot covers Personnel have ensured that jewelry and other loose items outside the coveralls have been removed Personnel have ensured that vacuum hose and other tools/items to be placed inside the bleacher are clean. Personnel have confirmed that the bleacher hatch has been closed until ready to have its carbon removed.Removing Spent Carbon (to be completed by personnel removing the spent carbon)Personnel have used only the approved equipment and tools for removing spent carbon.Personnel have ensured that no foreign materials have contaminated the bleacher while removing the carbon.Personnel have ensured that the bleacher hatch has been closed when not supervised.After Spent Carbon has been removed (to be completed by personnel removing the spent carbon)Personnel have ensured that the bleacher hatch is closed.Personnel have cleaned the dedicated equipment for removing spent carbon..Personnel have properly stored the dedicated equipment for removing spent carbon.

GMP Bleacher Change Checklist Page 2

Prior to Packing the Bleacher with Carbon Operator is NOT aware of any illness that may adversely affect the safety or quality of the glycerine Operator has washed hands thoroughly with germicidal hand sanitizerOperator has put on new, clean cotton gloves Operator has put on clean hard hat, with a hair net or beard net (if long hair or facial hair is present) Operator has put on clean, disposable white cover-alls and boot covers Operator has ensured that jewellery and other loose items outside the coveralls have been removed Operator has ensured that any dedicated tools to be when packing the bleacher are clean. Operator has ensured the bleacher hatch has been closed until ready to pack the carbon.While Packing the Bleacher with Carbon Operator has used only the approved equipment and tools for packing the bleacher with carbon.Operator has ensured that no foreign materials have contaminated the bleacher while adding the carbon.Operator has ensured that the bleacher hatch has been closed when not supervised.After Packing the Bleacher with Carbon Operator has ensured that the bleacher hatch is closed.Operator has cleaned the equipment and tools for packing the bleacher with carbon.Operator has properly stored the equipment and tools for packing the bleacher with carbon.Operator has initiated backflush sequence to wash the bleachers with water before putting into use.

Finished Product Storage

The operator is responsible for properly storing all finished bulk pharmaceutical excipient grade glycerine.

Storage Tanks

Finished product tank openings are kept closed and free from debris at all times.

Finished product tank vents are screened to eliminate the possibility of contamination.

Finished product tank temperatures are routinely monitored. Tank temperatures are recorded in the PI Historian database.

Finished product tanks are nitrogen blanketed. Nitrogen flow to finished tanks is recorded weekly on the GMP Housekeeping Inspection Sheet.

Blending/Mixing

Blending batches that individually do not conform to specifications with other conforming material in an attempt to salvage or hide adulterated material is prohibited.

Sampling

Prior to loading, the operator must submit a representative sample from the storage vessel to the Quality Control Lab for a New Batch/OK to Load analysis. The sample must be at least 16 ounces and collected in a plastic container.

Upon completion of the analyses, the Quality Control Lab will log the sample identification and analytical results onto the department log sheet. Quality Control will advise product disposition and has exclusive authority for material release.

Upon completion of a bulk loading, the operator must obtain a representative sample from the loaded container and submit it to the Quality Control Lab for an OK to Ship analysis. The sample must be taken using a dedicated go-devil sampler.

An 8 ounce sample of the New Batch and OK to Ship samples are to be labeled by Quality Control specifying the product number, date, batch number, J file number (OK to Ship samples only), and the type of sample (New Batch or OK to Ship). These reserve samples are to be securely retained by the Quality Control Department:

New Batch samples are retained for a minimum of 3 years

Shipment samples are retained for a minimum of 6 months

Bulk Loading Product Identification

The Finite Planner issues the shipping information to the operator. This includes: customer name, delivery number, product name, product number, loading and transportation means, and quantity requested.

The operator is to also complete a Tank Wagon Loading Inspection Checklist or Tank Car Loading Inspection Checklist (Forms 8300 and 8301, respectively).

After loading is complete, the operator is to collect a sample out of the tank wagon or tank car and take it to the Quality Control Lab for an OK to Ship analysis.

After completion of the Loading Inspection Checklist,

The operator is to give the form to the driver of the tank truck

The driver will submit it to the Traffic Department.

A Certificate of Analysis, issued from the Quality Control Lab, is submitted to the Traffic Department

The Traffic Department will, in turn, provide the C of A it to the driver. This will identify information such as product name, product number, batch number, and complete OK to Ship analysis.

NOTE: for the case of a Tank Car, the operator is to fax the Loading Inspection Checklist to the Traffic Department.

Bulk Loading Procedure

The operator is responsible for properly loading all tank cars and tank trucks.

At the Cincinnati Plant, dedicated fleets of tank cars and trucks are primarily used for all bulk packaged glycerine. However, if circumstances do arise and a dedicated car is not available, then the following actions must take place:

A finished goods car is sent to D&H, where it is inspected for appropriate lining.

The car is then cleaned, which includes removing the outlet valve.

Cleaning certificate is to be retained in the Building 70 Control Room.

The operator will complete a GMP Bulk Loading Inspection checklist (in addition to the Tank Wagon or Tank Car Loading Inspection Checklist) to ensure GMP requirements are followed during the loading. If any requirement cannot be met, then the operator must stop the loading and notify Supervisor or GMP Coordinator.

Upon completion of loading, the operator will retain the GMP Bulk Loading Inspection Checklist along with a copy of the cleaning certificate in the Building 70 Control Room. This will be retained for a period of at least one month.

GMP Bulk Loading Checklist

Operator is in good health and not aware of having any health condition that could adversely affect the safety or quality of the glycerineOperator has washed hands thoroughly with germicidal hand sanitizerOperator has put on new, clean blue nitrile gloves prior to loading glycerineOperator has put on clean hard hat and hair net or beard net (if long hair or facial hair is present)Operator has put on clean lab coat (or disposable white coveralls) and boot coversOperator has ensured that jewellery and other loose items have been removedOperator has ensured that the loading platform, applicable tools, and protective equipment are clean and dryOperator has found the end of the loading line to be covered and free of contaminationOperator has inspected the container and found NO presence of water, dirt, foreign or sharp odors, rags, or any other foreign objects inside the containerOperator has inspected the piping between the Tank-wagons inner and outer discharge valve to make sure it is clean and dry. This section of pipe has been cleaned with Sanitizing Solution prior to fillingOperator has inspected the protective dome cover and the loading boom inlet pipe to ensure they are clean. These have been cleaned with Sanitizing Solution prior to use

Prior to Loading

Operator has ensured that no food or drink products, personal property, personal medication, or tobacco products are present in the loading area.Operator has placed the manhole cover over the dome once the loading boom is inserted into the container.Operator has ensured that unauthorized personnel are kept out of the loading area during loading.Operator has loaded the container in accordance to G03.070 or G04.070Operator has ensured that any sampling device placed into the container is clean and sealed prior to use.

During Loading

Operator has insured that the loading boom has been cleaned and properly stored.Operator has covered the end of the loading line so that it is not exposed and is free of contamination Operator has insured that the manhole cover is clean and properly stored in its cabinet.Operator has attached a copy of the Tank Truck cleaning certificate to this checklist.

After Loading

GRATITUDE!!

Thank you for having reviewed this presentation covering the Operator Specific, GMP Training. Hopefully you now have a better understanding of what GMP is and why management has made the decision to move forward with the implementation plans. By implementing and complying with GMP, Emery will maintain the facilities, controls, resources, and quality management systems necessary to continue producing top quality excipient materials suitable for use in pharmaceutical applications .

Component Potential

Hazard?

(Y/N)

Rationale Hazard

Analysis

Significant

Hazard?

(Y/N)

Control Measures Decision Tree

(Y/N)

CCP?

(Y/N)

L S T Q1 Q2 Q3

Emery 916

from Check

Tanks

a) Biological - N

b) Chemical N

c) Physical - Y

a) Free Water < 0.35%

b) Dedicated process.

c) Foreign matter particulates

(carbon fines)

1

1

5

1

5

3

1

5

15

a) No

b) No

c) Yes

a) Routine QC.

b) Routine QC.

c) Filtration, 10 . Filter #5.

CCP RG01

a) N

b) N

c) Y

a)

b)

c) Y

a)

b)

c)

No

No

Yes

Emery 916 or

Emery 912

Bulk Loading

(TT/TC)

a) Biological - N

b) Chemical N

c) Physical - Y

a) Free Water < 0.35%

b) Dedicated process.

c) Foreign matter particulates

(carbon fines)

1

1

5

1

5

3

1

5

15

a) No

b) No

c) Yes

a) Routine QC.

b) Routine QC.

c) Filtration, 10 . Filter #6.

CCP RG02

a) N

b) N

c) Y

a)

b)

c) Y

a)

b)

c)

No

No

Yes

Component

Potential Hazard?

(Y/N)

Rationale

Hazard Analysis

Significant Hazard?

(Y/N)

Control Measures

Decision Tree

(Y/N)

CCP?

(Y/N)

L

S

T

Q1

Q2

Q3

Emery 916 from Check Tanks

a) Biological - N

b) Chemical N

c) Physical - Y

a) Free Water < 0.35%

b) Dedicated process.

c) Foreign matter particulates (carbon fines)

1

1

5

1

5

3

1

5

15

a) No

b) No

c) Yes

a) Routine QC.

b) Routine QC.

c) Filtration, 10 . Filter #5.

CCP RG01

a) N

b) N

c) Y

a)

b)

c) Y

a)

b)

c)

No

No

Yes

Emery 916 or Emery 912 Bulk Loading (TT/TC)

a) Biological - N

b) Chemical N

c) Physical - Y

a) Free Water < 0.35%

b) Dedicated process.

c) Foreign matter particulates (carbon fines)

1

1

5

1

5

3

1

5

15

a) No

b) No

c) Yes

a) Routine QC.

b) Routine QC.

c) Filtration, 10 . Filter #6.

CCP RG02

a) N

b) N

c) Y

a)

b)

c) Y

a)

b)

c)

No

No

Yes