Biopharmaceutical GMP clean room

Project overview

• Project name： Biopharmaceutical GMP clean room
• Project location： Tokyo, Japan
• Project background/requirement analysis： The client is a pharmaceutical company dedicated to the production of tablets. In order to meet the requirements of the Japanese Pharmaceuticals and Medical Devices Act (PMD Act) and GMP related requirements, it needs to build a clean room that meets the standards for the production of tablets.The project emphasises economy, practicality and safety, and needs to be integrated with the client’s existing intelligent management system (ERP, quality and safety monitoring, barcode management).
• Cleanliness Level Requirements：Class 1000 , meet the requirements of the production process of tablets and comply with GMP related specifications.

Design proposal

• Design basis/criteria： Japanese Pharmaceuticals and Medical Devices Act (PMD Act), Japanese GMP-related guidelines, ISO 14644 series standards, EU GMP guidelines (as a reference), WHO GMP guidelines (as a reference).

• Process flow/layout：
  • The total area of the project is 3380 ㎡, including offices, testing workshops, production workshops, warehouses, laboratories and business management administrative areas and other functional areas.
  • Personnel flow line: set up a strict personnel in and out of the management system, including changing rooms (one shift, two shifts), hand-washing and disinfection area, air shower room, etc., to ensure that the personnel enter the clean area before the purification.Material flow line: set up independent material channel and transfer window/shower room to avoid direct transfer of materials between non-clean and clean areas and prevent cross contamination.According to the requirements of different cleanliness levels of materials, set up different levels of transfer channels.
  • The interior of the production plant is rationally partitioned according to the production process of the tablets, for example：

Feedstock area： Weighing and mixing of raw materials etc.

Preparation area: Tabletting and coating operations.

Inner packaging area: tablet dispensing, bottling and other operations.

Outer packaging area: Product packaging, labelling and other operations.

Buffer rooms are provided between areas to reduce the risk of cross-contamination.

• Air purification system：
  • Air supply: The core area of the production workshop adopts unidirectional flow (laminar flow) air supply, while other areas adopt mixed flow air supply to maximise pollution control.
  • Filtration system: A multi-stage filtration system is used, including: 
    • Primary filter: Filter particles ≥5μm in the air.
    • Intermediate filter: Filter particles ≥1μm in the air.
    • High-efficiency filter (HEPA): HEPA filter is adopted in the core area of the production workshop, with a filtration efficiency of ≥99.99% @ 0.3μm, which meets the requirement of 1,000-level cleanliness.
  • Air conditioning system： An independent air-conditioning system is adopted to precisely control the temperature, humidity, differential pressure and fresh air volume in the workshop.According to the requirements of the production process of the tablets, the appropriate temperature and humidity control range is set, and a high-precision control system is adopted to ensure the stability of the environmental parameters.Considering the geographical location of Japan, the air-conditioning system needs to have strong dehumidification capability.
  • Other purification equipment: According to the need may be configured FFU (fan filtration unit), clean workbench and other auxiliary purification equipment, in order to improve the cleanliness of the local area, such as in the aseptic operation area.

• Other systems：
  • Personnel purification system: Set up locker rooms, hand-washing and disinfection facilities, air shower rooms, etc. in accordance with GMP requirements.
  • Material purification system: Set up transfer window/shower room, and classify and manage the materials according to their cleanliness level.
  • Monitoring system: Adopting online monitoring system in line with GMP requirements, real-time monitoring, recording and alarming of various parameters in the workshop, and docking with the customer’s intelligent management system to achieve data sharing and remote monitoring.
  • Other auxiliary systems: Including lighting system, fire-fighting system, electrical system, pure water system, compressed air system, etc., all of which are designed and constructed in accordance with relevant specifications.

• Main materials and equipment：
  • Enclosure structure: 0.6mm thick rock wool sandwich colour steel plate, class A fireproof, rock wool density ≥120kg/m³.
  • Doors and windows: steel/aluminium alloy purification doors and windows, good airtightness.
  • Ground: 2mm thick epoxy self-levelling ground, anti-static.
  • High-efficiency air supply outlet: made of aluminium alloy/stainless steel, built-in HEPA filter, efficiency ≥ 99.99% @ 0.3μm.
  • Purification lamps and lanterns: LED purification lamps and lanterns.
  • Air shower room: SUS304 stainless steel, double blowing air shower room, nozzle wind speed ≥ 25m/s.
  • Pass box: SUS304 stainless steel, mechanical interlocking transfer window.
  • Air-conditioning unit: Adopt high efficiency and energy saving air-conditioning unit, with precise temperature and humidity control capability.

Construction process

• Construction Organisation and Management： The OUDELONG project team carries out comprehensive project management, including schedule management, quality management, safety management, etc., to ensure that the project is completed on time and in good quality.
• Construction process and technology： Professional cleanroom construction techniques and technologies are adopted, such as splicing and sealing of colour steel sheets, welding and installation of pipelines, installation and debugging of filters, etc., to ensure the quality of the project.
• Quality control measures： Strictly implement quality control standards for material inspection, process inspection, concealed works acceptance, completion acceptance, etc., and keep relevant records and reports.

Challenges and solutions

·Challenge 1: Compliance with Japanese PMD Act and GMP requirements. 

Solution： The OUDELONG team is familiar with the relevant Japanese laws and regulations and GMP guidelines, and strictly follows the relevant requirements during the design and construction process, as well as communicating and coordinating with the local Japanese accreditation body to ensure the project passes the accreditation successfully.

·Challenge 2：Interfacing with the customer’s intelligent management system. 

Solution： OUDELONG’s technical team worked closely with the customer’s IT department to develop a detailed data interface solution to ensure that the cleanroom monitoring data could be seamlessly integrated into the customer’s ERP, quality and safety monitoring and barcode management systems.

·Challenge 3：Transnational project communication and coordination. 

Solution： The OUDELONG project team uses effective communication tools and methods to communicate and co-ordinate with the client in a timely manner, overcoming barriers brought about by language and cultural differences to ensure the smooth running of the project.

Completion and testing

·Receiving and Inspection Criteria： Acceptance is based on the Japanese PMD Act and GMP related requirements, ISO 14644 series standards.

·Test Items and Methods： Including dust particle counting, wind speed test, differential pressure test, temperature and humidity test, airflow pattern test, microbiological monitoring, etc., and issue detailed test reports.

·Test results： All test results comply with Class 1000 cleanliness and GMP related requirements.

Project results/client testimonials

·Operating Result： After the cleanroom was put into use, it effectively improved the quality and efficiency of the customer’s Chinese medicine tablet production and fully complied with the relevant Japanese laws and regulations and GMP requirements.

·Testimonials： The OUDELONG team is very professional and familiar with Japanese regulations and GMP requirements, and we are very satisfied with the successful construction of a compliant cleanroom for us.

Summary and outlook

·Project Summary： With rich experience and professional technology, OUDELONG team successfully completed a GMP cleanroom project for biopharmaceuticals in Tokyo, Japan, providing a safe, efficient and compliant production environment.·

Future outlook： OUDELONG will continue to pay attention to the latest development trend of the international pharmaceutical industry, and constantly improve its technology and service level to provide better cleanroom solutions for global customers.