Facility design and layout
1) Location and Surroundings
1.1) Preferred Location:
The premises should ideally be situated in an industrial area and, under no circumstances, in residential or commercial zones.
1.2) Surrounding Environment:
The premises should be located in an environment that poses minimal risk of contamination to materials or products. It should be away from unsanitary surroundings and should not be adjacent to:
- Open sewers
- Public lavatories
- Factories emitting unpleasant odors or fumes
- Areas with excessive amounts of soot, dust, or smoke could contaminate the manufactured drugs or affect their quality. Existing facilities should maintain clean surroundings under their control.
The plot should have a minimum area of 2000 square yards.
2) Building Layout and Pre-Approval
The building should be of adequate size, appropriate design, and construction, considering the requirements for drug manufacturing and related operations. The site and layout plan of the building should be approved by the Central Licensing Board or an authorized person before commencing construction. Any minor changes to the layout plan should be communicated and a revised updated layout plan should be submitted during the renewal of the Drug Manufacturing License.
3) Building Design and Construction (General)
3.1) General Design:
The layout and design should aim to minimize the risk of errors, promote good sanitation, and enable effective cleaning and maintenance. This includes avoiding cross-contamination, accumulation of dust or dirt, and any other factors that could adversely affect product quality.
Electrical supply, lighting, temperature and humidity controls, and ventilation systems should be appropriate and not have any direct or indirect adverse effects on pharmaceutical products during manufacturing and storage, or the proper functioning of equipment.
3.3) Protection against Insects:
The premises should be designed and equipped to provide maximum protection against the entry of insects or other animals.
In pharmaceutical Good Manufacturing Practice (GMP) areas, maintaining a clean and hygienic environment is crucial to ensure product quality and safety. To prevent the entry of insects and rodents, as well as to promote air cleanliness, various tools, and equipment are employed, including air curtains, insect repellants, and rodent repellant tools.
Air curtains are commonly used in pharmaceutical GMP areas to create a barrier of high-velocity air at doorways and openings. These curtains work by generating a consistent flow of air that acts as a physical barrier, preventing outside air, insects, and airborne contaminants from entering the controlled environment. Air curtains also help to maintain temperature differentials between different areas, ensuring that the appropriate environmental conditions are maintained.
Insects pose a significant risk in pharmaceutical manufacturing areas as they can contaminate products and compromise the integrity of the manufacturing process. To address this concern, various insect repellants are employed in GMP areas. These repellants include insect screens on windows and ventilation openings, sticky traps, and ultraviolet light traps. Insect screens act as a physical barrier, preventing insects from entering the facility, while sticky traps and ultraviolet light traps attract and capture flying insects, ensuring they are effectively controlled.
Rodent Repellant Tools:
Rodents, such as mice and rats, can introduce serious contamination risks in pharmaceutical manufacturing areas. To deter rodents and prevent their entry, several tools and strategies are utilized. This includes the installation of rodent-proof doors and windows, sealing of gaps and cracks in walls and floors, and the use of rodent-repellant devices. Ultrasonic-repellant devices emit high-frequency sound waves that are unpleasant to rodents, deterring them from the area. Additionally, bait stations and traps may be strategically placed to capture and control any rodent activity.
3.4) Surfaces In GMP Area:
In areas where raw materials, in-process materials, or drugs are exposed, the following conditions should be met to prevent contamination:
a) Floors, walls, and ceilings should allow easy cleaning, and porous materials like brick and cement blocks should be sealed.
b) Surfaces should be hard, smooth, and free of sharp corners where foreign materials can accumulate.
c) Joints between walls, ceilings, and floors should be sealed.
d) Pipes, light fixtures, ventilation points, and other services should not create surfaces that are difficult to clean.
e) Screened and trapped floor drains should be provided if necessary.
3.5) Selection of Material for surfaces in GMP area.
In GMP (Good Manufacturing Practice) areas, where cleanliness, durability, and resistance to chemicals are essential, epoxy coatings are often used to create seamless and easy-to-clean surfaces. There are different types of epoxy coatings available for surfaces in GMP areas, each with specific properties and advantages. Here are some common types:
- Epoxy Mortar Coatings: These coatings are a combination of epoxy resin and quartz sand or other aggregates. Epoxy mortar coatings provide excellent impact resistance, chemical resistance, and durability. They are often used in areas where heavy equipment or machinery is present.
- Self-Leveling Epoxy Coatings: Self-leveling epoxy coatings are fluid and flow easily to create a smooth, level surface. They are ideal for large, open areas where a seamless and aesthetically pleasing finish is desired. Self-leveling epoxy coatings offer high chemical resistance, durability, and easy maintenance.
- High-Build Epoxy Coatings: High-build epoxy coatings are applied in multiple layers to achieve a thicker coating system. They provide increased durability, impact resistance, and protection against chemicals. High-build epoxy coatings are often used in areas subject to heavy traffic or where a more robust surface is required.
- Conductive or Anti-Static Epoxy Coatings: These specialized epoxy coatings are designed to dissipate static electricity and prevent the buildup of electrostatic charges. Conductive or anti-static epoxy coatings are commonly used in areas where sensitive electronic equipment or flammable materials are present.
- Chemical-Resistant Epoxy Coatings: As the name suggests, these epoxy coatings are formulated to resist the effects of various chemicals, acids, and solvents. They provide protection against chemical spills and exposure, ensuring the longevity and integrity of the coated surface.
- UV-Stable Epoxy Coatings: UV-stable epoxy coatings are designed to withstand prolonged exposure to sunlight without yellowing or degrading. They are commonly used in outdoor GMP areas or areas with significant natural light exposure.
It’s important to select the appropriate epoxy coating based on the specific requirements of the GMP area, such as the level of chemical exposure, desired finish, and durability needed. Consulting with epoxy coating manufacturers or specialists can help determine the most suitable type of epoxy coating for a particular GMP environment.
4) Storage Areas
The storage area should be clearly defined and have sufficient capacity to accommodate various categories of materials and products, including starting and packaging materials, intermediates, bulk and finished products, products in quarantine, and released, rejected, returned, or recalled products separately.
Storage areas should be designed or adapted to maintain good storage conditions. They should be clean, dry, adequately lit, and maintained within acceptable temperature limits based on the storage requirements of the drugs. Special storage conditions, such as controlled temperature and humidity, should be provided, checked, and monitored when necessary.
4.3) Types of Material Storage Area
- Receiving and Dispatch Bays: Bays for receiving and dispatching materials should protect them from the weather. Reception areas should be designed and equipped to allow for the cleaning of incoming material containers, if required, before storage.
- Quarantine Area: Well-defined quarantine areas should be allocated for incoming materials, in-process materials, and finished drugs. If separate areas are used to ensure quarantine status, they should be clearly marked and access should be restricted to authorized personnel. Any alternative systems replacing physical quarantine should provide equivalent security.
- Sampling Area: Ideally, there should be a separate sampling area for starting materials. If sampling is conducted in the storage area, it should be done in a way that prevents contamination or cross-contamination.
- Rejected Area: A segregated area should be designated for the storage of rejected, recalled, or returned materials or products.
- Special Material Area: Highly active materials, narcotics, other dangerous drugs, and substances presenting special risks of abuse, fire, or explosion should be stored in secure and safe areas.
- Packing Material Area: Printed packaging materials play a critical role in ensuring the conformity of pharmaceutical products to their labeling. Therefore, special attention should be given to the safe and secure storage of these materials.
5) Weighing Area/Dispensing:
Separate weighing areas should be provided for estimating the yield of starting materials, with provisions for dust control. Additional arrangements should be made for materials that pose a high risk of contamination, such as steroids and antibiotics, particularly penicillin.
5.1) Specifications of Weighing Area/Dispensing Area in Pharma GMP
The weighing area or dispensing area in pharmaceutical Good Manufacturing Practice (GMP) plays a critical role in ensuring accurate and precise measurement of materials for formulation and manufacturing processes. Here are some key specifications for a weighing area/dispensing area in Pharma GMP:
- Dedicated Space: The weighing area should be a designated, dedicated space separate from other manufacturing or processing areas to minimize the risk of cross-contamination.
- Environmental Controls: The weighing area should have appropriate environmental controls to maintain suitable temperature, humidity, and lighting conditions. These controls help ensure the stability and integrity of the materials being weighed.
- Equipment: The area should be equipped with calibrated and validated weighing scales, balances, and other necessary equipment suitable for the specific weighing requirements. The equipment should be regularly maintained and calibrated to ensure accurate measurements.
- Containment Measures: The weighing area should have appropriate containment measures, such as laminar airflow systems, glove boxes, or containment enclosures, to prevent cross-contamination and protect operators from exposure to hazardous materials.
- Cleanliness and Hygiene: The weighing area should adhere to high cleanliness and hygiene standards. Regular cleaning and disinfection should be performed to maintain a clean environment, minimizing the risk of product contamination.
- Adequate Work Surface: Sufficient workspace, including a clean and flat countertop, should be available for weighing activities. The surface should be resistant to chemicals and easy to clean.
- Standard Operating Procedures (SOPs): Standard operating procedures should be in place for all weighing activities, including guidelines for equipment usage, material handling, cleaning protocols, and documentation practices. These SOPs ensure consistency, accuracy, and traceability of weighing operations.
- Material Segregation: Clear segregation measures, such as separate storage or designated areas, should be implemented to prevent cross-contamination between different materials, especially potent or hazardous substances.
- Personnel Training: Personnel working in the weighing area should receive appropriate training on GMP practices, equipment operation, and safety procedures. Training ensures that employees understand the importance of accuracy, cleanliness, and compliance with GMP regulations.
- Documentation and Record-Keeping: Accurate documentation and record-keeping should be maintained for all weighing activities, including batch records, material reconciliation, and any deviations or adjustments made during the weighing process.
Adhering to these specifications helps to ensure that weighing activities in the pharmaceutical GMP environment are carried out accurately, safely, and in compliance with regulatory requirements.
5.2) Area Boundary Color Differentiation in GMP storage areas:
Color differentiation in GMP storage areas is a common practice to visually distinguish different categories of materials and products. While specific color-coding schemes may vary between facilities, the following are general recommendations for color differentiations:
- Starting and Packaging Materials: It is often beneficial to use a distinct color, such as green, to designate storage areas for starting materials and packaging materials. Green can represent the initial stages of the production process and highlight areas where these essential components are stored.
- Intermediates: To differentiate storage areas for intermediates, which are materials in the process of being transformed into finished products, a color like yellow or orange can be used. This color choice signifies the transitional nature of intermediates.
- Bulk and Finished Products: Blue is commonly used to represent storage areas for bulk and finished products. Blue color coding indicates the final stages of production and serves as a clear indicator of areas containing fully processed and ready-to-use products.
- Products in Quarantine: Products that are in quarantine, awaiting approval or release, are typically assigned a distinctive color such as red. This color coding helps prevent the unintentional use or movement of products that have not yet undergone necessary quality control measures.
- Released Products: Storage areas for released products, those that have successfully passed quality control and are ready for distribution, can be designated with a color such as white or transparent. This color coding signifies that these products have met all requirements and are authorized for use.
- Rejected, Returned, or Recalled Products: To differentiate storage areas for rejected, returned, or recalled products, a color like black or gray can be employed. These colors represent caution and indicate that these products require special attention or appropriate disposal procedures.
It’s important to note that color differentiation should be complemented by clear labeling, signage, and documentation to ensure accurate identification and prevent confusion. Additionally, adherence to industry guidelines and local regulatory requirements is essential when implementing color-coded storage systems in GMP areas.