Bid for the design and upgrade of p2000 production facility to cgmp-compliant grade b radiopharmaceutical manufacturing facility

Scope of work:

• Upgrade the P2000 Production Facility and HVAC System at NECSA Complex, Pelindaba, North-West Province.
• Modify the existing layout to establish a Grade B environment in the Radiochemistry room (front of synthesis and dispensing hot cells).
• Improve personnel and material flow, including cascading into/from Grade B areas.
• Upgrade or replace the HVAC system to provide clean and conditioned air to all areas.
• Improve facility surface finishes to meet cGMP, ISO 14644, WHO, PIC/S, and SAHPRA standards.
• Exclusions: Cyclotron technical area and hall are not part of this upgrade.

Facility requirements:

• Must comply with current Good Manufacturing Practice (cGMP), ISO 14644 (cleanrooms), WHO, PIC/S, and SAHPRA standards.
• The Radiochemistry room must achieve Grade B classification (ISO 14644-1 Class 5 at rest, Class 7 in operation).
• Temperature control: 22 °C ± 3 °C (range: 19–25 °C) in all areas.
• Relative humidity control: 30–60 % RH in specified areas.
• Air cleanliness: Compliance with PIC/S Annex 1 (total particle and microbial contamination levels) for "at-rest" and "in operation" states.
• Pressure cascade: Minimum 10 Pa differential between adjacent rooms of different GMP classifications. Design must prevent reverse flow and radiological contamination.
• Air change rate (ACPH): Must support a clean-up period of <20 minutes from "in operation" to "at-rest" state.
• HEPA filter integrity: Must comply with ISO 14644 Part 3 leakage/penetration criteria.

Layout and design:

• Effective and logical material and personnel flow to avoid cross-contamination and errors.
• Separation of material and personnel flows where possible.
• Safe and easy removal/storage of solid and liquid waste.
• Transfer of materials between classifications via ventilated pass-through hatches or Material Airlocks (MAL).
• Unidirectional process for materials entering Grade A/B areas.
• Prevention of dust, insects, rodents, and other contaminants.
• Surface finishes: Smooth, impermeable, non-porous, and free from open joints. Materials must resist cleaning agents, disinfectants, and sporicides. Stainless steel is preferred; wood is prohibited in cleanrooms.
• Doors: No sliding doors; must be self-closing, open to high-pressure side, and fitted with flush-mounted viewing panels.
• Ceilings/walls: Modular sandwich panels, non-combustible fill, coved and sealed junctions.

Process and capacity:

• Facility must support aseptic preparation of F-18 FDG radiopharmaceuticals (sterile, injectable, time-sensitive).
• Required areas: Preparation Area, Radiochemistry Room, Decontamination/Clearance Area, Packaging/Dispatch Area, Street Clothes Change Rooms, GMP Grade D/C/B Change Rooms, Radiological Change Rooms, Emergency Shower Area, Material Transfer Systems.
• Adequate space for equipment, storage (chemicals, flammables, consumables), safety equipment, and personnel movement.
• Conveyor/roller systems for lead pots and radioactive materials (space allowance required; installation by NTP).

Supplier responsibilities:

• Perform an assessment of the existing facility to determine the upgrade scope.
• Ensure all legal, compliance, safety, and regulatory requirements are met in the proposed scope.
• Identify omissions or additional cGMP/regulatory requirements not listed in the URS.
• Use the URS as a reference for design, QRM, and C&Q activities.

Regulatory and standards compliance:

• Mandatory compliance with ISO 14644 series (cleanrooms: Part 1, 3, 4), ISO 17873 (nuclear ventilation), and ISO 9001:2015 (QMS).
• PIC/S GMP: Part I, Annex 1 (sterile medicinal products), Annex 3 (radiopharmaceuticals), Annex 15 (qualification and validation).
• SAHPRA: Guideline on Good Manufacturing Practice for Medicines (SAHPGL-INSP-02_v9, August 2025).
• WHO Technical Report Series: TRS No. 957 (hazardous substances), TRS No. 1010/1019 (HVAC for non-sterile products), TRS No. 1025 (radiopharmaceuticals), TRS No. 1044 (sterile products).
• SANS standards: SANS 10400 (building regulations), SANS 10142 (wiring), SANS 10114-1 (interior lighting).
• NECSA SHEQ instructions: SHEQ-INS-0234 (QMS for external design), SHEQ-INS-1110 (housekeeping), SHEQ-INS-1120 (lighting), SHEQ-INS-7010 (hazardous chemical zoning), SHEQ-INS-7030 (surveillance), SHEQ-INS-7132 (ventilation design), SHEQ-INS-7140 (hazardous waste), SHEQ-INS-8030 (radiological area classification), SHEQ-INS-8050 (radiological surveillance), SHEQ-INS-8180 (ALARA programme), SHEQ-INS-8310 (ventilation for nuclear facilities).
• Occupational Health and Safety Act (OHSA).
• ISPE Baseline Guide: Commissioning and Qualification (Volume 5, 2nd Edition, 2019) and HVAC Good Practice Guide (2009).

Classification and validation:

• The P2000 Production Facility and HVAC System are classified as Direct Impact (quality-critical) systems.
• Full commissioning and qualification required: Design Qualification (DQ), Installation Qualification (IQ), Operational Qualification (OQ), Performance Qualification (PQ).
• Risk-based approach: Scope of qualification determined by risk to product quality and other relevant risks.

Supplier obligations:

• Must comply with all South African laws and municipal by-laws, even if not explicitly listed in the URS.
• Responsible for identifying and addressing any additional compliance requirements.