Parenteral Fill Suite

Functional Management Outline

Department Responsibilities

Three major departments are listed here, followed by break outs showing where their areas of authority are and how they interact.

Other business units (not included in this Outline) :

· human resources,

· finance,

· project management,

· sales & marketing

· safety

· information technology

· R & D

Included Business Units:

1. Operations

2. Quality Assurance

3. Engineering

1. Operations

1.1. Production of Sterile Products

1.1.1. Washing/ Wrapping of Materials for Sterilization – Time Critical Function.

1.1.2. Sterilization of Materials - Time Critical Function.

1.1.3. Filtration of Products/Media - Time Critical Function.

1.1.4. Filling of Liquid into Vials - Time Critical Function.

1.1.5. Training of Production personnel – routine training program

1.1.6. Visual Inspection - Time Critical Function.

1.1.7. Labeling & Packaging - Time Critical Function.

1.1.8. Counting and Accountability – Calculation of Yield

1.1.9. Conduct filter integrity testing pre and post use. - Time critical function.

1.2. Disinfection / Decontamination / Sanitization Program

1.2.1. Room cleaning and disinfection - Time Critical Function.

1.2.2. Preparation of materials for decontamination (compounding / filtration).

1.2.3. Activity Logs

1.2.4. Refuse collection and removal from clean suites

1.2.5. Restocking of gowning supplies, refuse bags.

1.2.6. Sanitization of equipment for entry into suite.

1.3. Planning

1.3.1. Writing Fill Batch Records

1.3.1.1. Media Fill Records

1.3.1.2. Product Fill Records (Master Batch Record)

1.3.1.3. Test Batch Record

1.3.2. Scheduling

1.3.2.1. Fill Schedule (Product / Media / Fill Volume / etc.)

1.3.2.2. Sterile Suite Equipment Validation Schedule

1.3.2.3. Sterile Suite Personnel Schedule – all entries

1.4. Purchasing (Usually requires computerized system)

1.4.1. Coordinate with Planning and Testing departments

1.4.2. Maintain list of approved vendors

1.4.3. Maintain Inventory from ‘critical supply’ list.

1.5. Warehousing

1.5.1. Receiving and Quarantine

1.5.2. Release

1.5.3. Reject

1.5.4. Shipping

1.5.5. Assure Stock Rotation

1.5.6. Assist purchasing with inventory management

1.6. Compounding

1.6.1. Creation of Compounding Batch Record

1.6.2. Execution of Test Batch Records

1.6.3. Execution of Batch Record until post filtration. Time Critical Function.

1.6.4. Preparation of growth media for validation testing.

1.6.5. Preparation of product simulants for validation testing.

1.7. Sample Collection and Distribution

1.7.1. Product samples on filling days

1.7.2. Water samples per schedule

1.7.3. Environmental samples

1.7.4. Steam samples

1.7.5. Stability samples

1.7.6. Reserve samples

2. Quality Assurance

2.1. Analytical Laboratory – identity, strength, quality, and purity

2.1.1. Component Release Testing

2.1.2. Validation

2.1.2.1. Local Area SOP writing

2.1.2.2. Local Area Equipment Validation (e.g. HPLC)

2.1.2.3. Test Validation (Write & Execute)

2.1.2.4. Test Method Development / Validation

2.1.3. Analytical Product Testing

2.1.3.1. In Process Testing – Time critical function.

2.1.3.2. Release Testing

2.1.3.3. Stability Testing – Time critical function.

2.2. Microbiology Laboratory

2.2.1. Environmental Monitoring Program - Time critical function.

2.2.1.1. Room Pressure Logs

2.2.1.2. Room Humidity Logs

2.2.1.3. RODAC sample sites / schedule / performance

2.2.1.4. Settling plates / sites / schedule / performance

2.2.1.5. Swabs / sites / schedule / performance

2.2.1.6. Viable air contamination (Reuter centrifugal air sampler (RCS))

2.2.1.7. Non-Viable particulate in air – static and dynamic data – ongoing.

2.2.1.7.1. Electronic air particle counters. Sites / schedule / performance.

2.2.1.8. Conduct disinfectant effectiveness studies.

2.2.1.9. Maintain ‘gridding’ study for common flora

2.2.1.10. Trending of Micro-organism results

2.2.2. Water System Monitoring

2.2.2.1. Microbial Quality and Endotoxin

2.2.2.2. TOC and Conductivity

2.2.2.3. Trending of Water Quality and Water Use

2.2.2.4. Condensed steam WFI testing.

2.2.3. Air and Nitrogen bioburden testing

2.2.4. Product Release Testing

2.2.4.1. Direct Transfer Sterility Testing

2.2.4.2. Membrane Filtration Technique

2.2.4.3. Test validation

2.2.4.4. Testing environment validation (ongoing requirement)

2.3. Stability Laboratory

2.3.1. Schedule of Testing and Results

2.3.2. Maintenance by validation and trending of Stability Chambers

2.3.3. Performance of Testing – Time critical function.

2.3.4. Validation of Testing Methods

2.4. Audit (Sometimes called ‘Quality Control’)

2.4.1. Document Control (usually requires computerized system)

2.4.1.1. Library Function

2.4.1.1.1. Training Records

2.4.1.1.2. Production Records

2.4.1.1.3. SOP Review, Distribution, Maintenance

2.4.1.1.4. Historical Logs – all Departments

2.4.1.1.4.1. Cleaning and Use Logs

2.4.1.1.4.2. Room entry and use Logs

2.4.1.1.4.3. Maintenance Logs for all Equipment / Utilities

2.4.1.1.4.4. Validation Records

2.4.1.1.4.5. Testing Results

2.4.1.1.4.5.1. Components

2.4.1.1.4.5.2. Products

2.4.1.1.4.5.3. Environmental

2.4.1.1.4.5.4. Certificates of analysis from outside the company

2.4.1.2. Batch Record Issuance - Time critical function.

2.4.1.3. Internal Audits (usually a team function).

2.4.1.4. Review / Signature

2.4.1.4.1. All controlled Records. (including Logs)

2.4.2. CAPA administration (Corrective Action / Preventive Action)

2.4.2.1. Variances / Deviations / Investigations

2.4.3. Training Coordination

2.4.4. Schedule and perform vendor audits

2.4.5. Issuance of Labels - Time critical function.

2.4.6. MIL standard testing of finished products.

2.4.7. Bar Code control on all labels.

2.5. Sample Receipt / Storage / Distribution / Testing / Result storage.

3. Engineering

3.1. Validation

3.1.1. Internal – schedule (through Planning) and performance

3.1.2. External – schedule and coordinate

3.1.3. Write & Perform Validation Protocols

3.2. Calibration

3.2.1. Maintain schedule (coordinate with Planning) and perform calibrations.

3.3. Maintenance

3.3.1. Facility

3.3.1.1. Electrical and Lighting and Back-Up Power

3.3.1.2. HVAC

3.3.1.2.1. Filter replacement at equipment

3.3.1.2.2. Filter replacement in Suites

3.3.1.3. Water (USP Waters)

3.3.1.4. Steam

3.3.1.5. Gasses

3.3.1.6. Chilled Water

3.3.1.7. Sewage and Refuse

3.3.1.8. Bio-waste

3.3.1.9. Floors, Walls, Ceilings and painting

3.3.2. Equipment (include microbial or HEPA filter integrity testing for all)

3.3.2.1. Oven

3.3.2.2. Autoclave

3.3.2.3. Lyophilizer

3.3.2.4. Filler / Plugger / Capper

3.3.2.5. Tanks

3.3.2.6. CIP systems

3.3.3. External Maintenance Contracts

3.3.3.1. Janitorial

3.3.3.2. Roof maintenance.

3.3.3.3. Snow Removal

3.3.3.4. Lawn management

3.3.3.5. Make maintain and install ‘Signs’

3.3.3.6. Shutdown Operations

3.3.3.6.1. HEPA re-qualification

3.3.3.6.2. Internal Suite maintenance

3.3.3.6.3. Passivation

3.3.3.6.4. Special Projects

3.4. Design Projects

3.4.1. Integrate new facilities and equipment into an ongoing system.

3.4.2. Create new SOP’s / Validations / Operation plans.