Premises Design Principles & GMP

• This lesson covers premises design principles - process, material, people flow - as well as requirements for site choice.

GMP and Premises

• Design, location, and maintenance of premises are crucial for preventing cross-contamination and product deterioration in manufacturing.
• GMP guidelines state premises must be located, designed, constructed, adapted, and maintained to ensure minimal risks of errors and cross-contamination.
• Maintain hygiene standards through effective cleaning and operational reliability via effective maintenance.
• Ensure minimization of dirt and dust build-up to reduce contamination risks, and elimination of adverse effects on product quality.

Supporting Principles for Premises Design

• Premises should be in an environment minimizing external contamination risks like direct sunlight or heating.
• Logical layout enables proper material and process segregation.
• Materials used must be durable, non-reactive, and easy to clean.
• Premises should be adaptable to accommodate process changes without compromising quality.
• A maintenance schedule is necessary to prevent equipment failure and contamination, ensuring GMP compliance, product quality, and consumer safety.

Location

• Pharmaceutical manufacturing facilities should not be located near sources of contamination, e.g., a malting factory.
• Important location factors include geography, climate, neighbours, noise, economic factors, and pollution control.

Design Principles for GMP Premises

• Sanitation-oriented design principles need to be followed for GMP premises.
• Cleaning methods and materials must be considered when selection surfaces
• Surfaces need to be smooth, impervious finishes and allow for easy cleaning.
• Windows should be designed to fit flush with frames, window ledges avoided
• Coving between floors and walls, and ceilings and walls is essential.
• Materials should be durable and non-porous to resist contamination; wood should be avoided because it absorbs odors and is not impervious
• Prevent insects and animals from entering; sliding doors are unsuitable for sterile areas because they are difficult to clean

Facility Design and Flow Control

• Careful planning of material, process, and people flows is vital to prevent cross-contamination.
• Map out sequence of events in each process and summarize the flow in a room data sheet.
• Show material routing through the facility, indicating material status (quarantined, approved, or rejected), volume, weight, frequency, and mode of movement (e.g., forklift, pipeline, or manual).
• Create a factory plan showing staff and visitor routes which should prevent product or material contamination; restrict visitor access to sensitive areas.

Building Design Actions to Prevent Cross-Contamination

• Key design and operational measures prevent cross-contamination for GMP compliance.
• Segregated areas: Designate dedicated production areas for each product to minimise contamination risks.
• Airlocks and pressure differentials: Implement airlocks and maintain correct pressure differentials; use dust extraction systems to manage airborne contaminants.
• Air treatment: Treat recirculated air using properly designed and maintained filtration systems.
• Protective clothing: Provide dedicated protective clothing in specific areas as required.
• Validated cleaning procedures: Cleaning protocols needs to be developed and validated for each compound and piece of equipment to ensure complete removal of residues.
• Closed production systems: Adopt closed systems to prevent material escape and contamination by technicians.
• Residue testing: Conduct residue testing to confirm that areas and equipment meet cleaning standards.
• Status labels: Use accurate status labels to indicate the current status of areas, equipment, or materials, reducing confusion and potential risks.

Ancillary Areas

• Ancillary areas should be placed strategically to ensure staff convenience without increasing contamination risks.
• Rest and refreshment rooms: Accessible but separate from production areas.
• Changing, washing and toilet areas: Provide adequate facilities to maintain hygiene standards.
• Maintenance workshops: Locate maintenance workshops to avoid contamination risks during repairs and maintenance.
• Animal houses: Ensure animal houses are isolated from production and storage areas to prevent cross-contamination.

Key Areas and Their Special Considerations

• Warehouses: Must have adequate storage capacity, protect materials from heat, dirt, and weather, and limit access to authorized personnel.
• Mark areas clearly for materials under different statuses, including quarantined goods, rejected/recalled materials, hazardous substances, printed materials, and Schedule 5/6 medicines.
• A dedicated QC sampling area must be located near the warehouse and adhere to GMP standards.
• Weighing areas must ensure correct materials are weighed and dispensed accurately.
• Environmental controls should maintain proper air handling, pressure differentials, airflow, and dust extraction.
• Ensure segregation from the main warehouse to prevent contamination.
• Surface quality should have rounded corners and be smooth, impervious, and durable for easy cleaning
• Cleaning validation include frequent product changes which require validated cleaning methods and logbooks for process tracking/compliance.
• Provide intermediate storage to accommodate intermediate storage while ensuring separation and efficient movement of orders.

Manufacturing and Packaging Areas

• Facility layout requires the building to have dedicated, self-contained areas with logical flows of materials and personnel, adequate working space, and orderly equipment placement.
• Interior surfaces need to be smooth, crack-free, and easy to clean.
• Sufficient lighting is required to reduce eye strain and aid in issue detection.
• Pipework and drains: Avoid recesses and open channels; ensure drains are equipped to prevent backflow.
• Air handling systems should control temperature, humidity, and filtration as per product requirements and monitor air quality.

Quality Control (QC) Laboratories

• These laboratories require a specialised design, tailored to specific QC operations with suitable storage space.
• Equipment placement separate from manufacturing areas to prevent electrical interference, vibration, moisture exposure, and contamination is required.
• Need to have dedicated rooms for biological, microbiological, or radio isotopic testing to adhere to safety regulations and ensure compliance with legal requirements for high-risk operations.
• Legal requirements for high-risk operations needs to be complied with.