This specific module includes the necessary elements to store the oral liquid product already produced, and before filling process.

• Aqueous based products.

• Oil based products.

• Suspensions.

  
  

Module’s general characteristics as per Base Clean Room Module: 

1. Clean room level:

   • Dimensions:

     • External: 5,84 m x 2’35 m x 2’6 m (Length x Width x Height).

     • Internal: 5,72 m x 2’23 m x 2’5 m (Length x Width x Height).

   • Classified ISO 8 as per ISO 14644 (Class D GMP).

   • Clean room panels and finishing as per SAMPU standards.

     
     

2. Technical level:

   • Technical area installed above including HVAC ducts, cables and piping. 

     
     

3. Total combined height of clean room level + technical level is 4,5 m.

Manufacturing elements

1. Reactor 1000 l:

   1. Cooling jacket using Chilled Water. 

   2. Heating jacket using electricity.

      1. OPTIONAL: if there is an existing network of Industrial Steam, the heating jacket can be adapted to this utility instead.

   3. Manhole with lighting.

   4. Safety valve.

   5. Radar level transmitter.

   6. Pressure transmitter.

   7. Loading cells under the reactors legs.

   8. Sterile filtration for venting and air inlet.

   9. Sampling Point of Use.

      
      

2. Clean utilities manifold:

   1. Purified Water (PW) Point of Use.

   2. Pharmaceutical Compressed Air (PCA) Point of Use.

   3. Cleaning In Place (CIP) Point of Use using two rotative sprayball.

   4. OPTIONAL: N2 or CO2 Point of Use.

      
      

3. Control panel:

   1. SCADA.

   2. 15” touchscreen.

      
      

4. OPTIONAL: Filtration skid: 

   1. Product filtration using cartridge and removable filter.

   2. Pressure control before and after filtration.

   3. Sampling point of use after filtration.

Manufacturing process

1. Receive the product from the manufacturing reactor.

2. Jacket fill: the jacket will be filled during the selected time.

3. Jacket empty: the jacket will be emptied during the selected time.

4. Agitation: agitation will run during the selected time and the selected rotation speed.

5. Temperature control: the jacket pump will start running and the temperature will be controlled in order to reach the desired set point.

   1. Chilling water will be added to cool, and the heating resistance will be started in case of need of heating.

6. Transfer: product is transferred to the filling machine by means of compressed gas or other gas as optional. Transfer can be made through an additional filtration skid.

7. Solid loading / mixing: the blender will start during a certain parameter of time, recirculating through the reactor during a certain time parameter.

8. Transfer between equipment.

9. CIP cycle phases:

   1. First rinse.

   b. Washing with detergent.

   c. Final rinse.

HMI

• Information retained with data integrity complying with CFR 21 Part 11.

• Prepared to generate:

  • Batch report.

  • Alarms report.

  • Audit trail report.

• Remote connection for aftersales services.

Design and Manufacturing criteria

• For all surfaces in contact with the product (applies to pipes, tanks and instruments):

  • Made of stainless steel 316L with Roughness < 0,8μm. 

  • Pressure tested + Passivated.

  • Only tri-clamp or welded connections.

  • Orbital welding, with GMP standard documentation package.

  • Welding inspection with borescopy and/or radiography.

  • For those elements that must be flexible (such as seals or membranes), PTFE approved by GMPs will be used.

  • All valves are of diaphragm type.

    
    

• According to regulations:

  • European Commission Vol. 4 EU Guidelines to Good Manufacturing Practice. Medicinal Products for Human and Veterinary Use. 

  • Good Manufacturing Practices of the Food and Drug Administration (FDA).

  • 21 CFR Part 11 “Electronic Records, Electronic Signatures”. Food and Drug Administration Title 21 of the Code of Federal Regulations. 

  • Equipment Directive 2006/42/EC.

  • EN ISO 14122: Safety of machinery - Permanent means of access to machinery, part 1 till 4. 

  • EN ISO 13849: Safety of machinery - Safety-related parts of control systems.

    
    

• Operable by maximum 2 people.

Documentation

• Design documentation.

• DQ protocol + report.

• As-built documentation:

  • CE Declaration of Conformity.

  • Layouts.

  • Electrical diagram.

  • Pneumatic diagram.

  • Datasheet of valves and/or instrumentation and components.

  • Calibration Certificates.

  • Operation manual:

    • Start-up procedure.

    • Format changeover procedure.

    • Cleaning procedure.

    • Alarms list with every troubleshooting.

  • Maintenance manual.

  • Spare parts list and fungible assets.

• FAT & SAT protocols + report.

• IQ & OQ protocols + report.

• PQ protocol + report.

  
  

The standard language of all documentation will be English.