GMP Regulated Production

GMP Regulated Production

Our route to your compliance.

Connect 2 Cleanrooms provide manufacturing environments for activities regulated under GMP. Applications range from Aseptic Processing, Medical Device Manufacturing, Advanced Therapy Medicinal Products (e.g. Cell and Gene therapy), to medicinal cannabis and many more.

The environment is a core component of a Quality Management System and ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use.

Our GMP manufacturing environments are designed to diminish the risks inherent to (bio)pharmaceutical production, such as viable and non-viable particulates, as well as cross-contamination.

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    Full Design Package

    It is a GMP requirement that manufacturers control the critical aspects of their particular operations through qualification and validation over the life cycle of the product and process. Our qualification process is not an independent activity but an integrated application of GxP practices.

    Based on the User Requirement Specification, Design Qualification is the documented verification that the proposed design of the facilities, systems and equipment, is suitable for the intended purpose. It starts right from the conceptual design phase of the project. We integrate current regulations and guarantee the performance of the rooms, in accordance with the parameters as stipulated in your URS.

    Our 2D and 3D design package, along with our virtual tour, offers you a unique preview of your entire facility before it is built. This enables us and your end users to optimise the layout, simulate work and materials flow, and also check maintenance related activities upfront. This approach avoids delays and modification costs at later stages of the project.

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    The success of a GMP cleanroom design is dependent on a clear and concise User Requirement Specification (URS) to take through a successful Design Qualification.

    Design Qualification (DQ) is the documented verification that the proposed design of the facilities, systems and equipment is suitable for the intended purpose.

    In the DQ process, we will go through your URS line by line and prove how each requirement is met. This could be through design drawings, by technical data sheets and meeting regulatory rules and guidance.

    Then, at a DQ execution meeting, we will confirm with your key stakeholders, that all URS requirements are met and, if not, raise any nonconformances against the URS. We work to close any nonconformances in a timely manner, to allow unconditional approval of the DQ.

    An initial User Requirement Specification (URS) defines the processes, equipment, operations, capacities and the environmental criteria for a cleanroom design. In a URS, designers need to review the flow of people and products through the facility to assess the optimum layout for regulatory compliance, efficient operation and the minimisation of cross contamination opportunities.

    It is vital that relevant personnel from production, quality, logistics, maintenance and engineering are involved in the early stages of the design. This avoids reworking of design layouts and minimises costly errors by overlooking or misinterpreting practical issues.

    Leading design principles keep cleanroom entry, exit and the flow of personnel and materials separated. Sufficient space needs to be allowed in the layout for incorporating transfer hatches, material airlocks and multiple garment changes, especially when designing cleanroom suites of multiple grades, B, C and CNC. If available space is not sufficient, and waste, people, starting materials and finished goods are sharing transfer hatches and corridors, procedures may have to be put in place to avoid cross contamination.

    The URS for a facility will define which equipment is to be used and what services are required. It should stipulate whether equipment is to be flush-built into walls, fixed at a certain location on the floor, or used “skid-mounted”, as this will have a significant impact on the design layouts. For instance, CMOs may require modular, “skid-mounted”, or freestanding equipment, to retain a level of flexibility. In those situations, it is also important to think of the internal movement of temporary equipment. Door and corridor widths, along with general storage and access requirements need to be considered.

    Locating process equipment outside the main room with an interface to the controlled environment can maximise on footprint space and may benefit the overall workflow. It also allows maintenance access from a non-cleanroom or lower grade area which could improve operational maintenance efficiency.

    For modern (bio)pharmaceutical facilities, our design will integrate process needs with cleanroom architecture to provide an appropriate solution for product, process and people.

    Digital Modelling

    The time to embed performance and sustainability to a cleanroom design is at the front end of the process. 

    C2C use digital modelling to assess the interrelationship between process, plant and equipment, verifying the accuracy of a technical solution, before we manufacture and install the room. Every cleanroom, whether it is being retrofit or as part of a complete new build, needs a seamless interface with its surrounding facility.

    A 3D building information model helps optimise a cleanroom design solution. 3D laser surveys enable our design engineers to ensure that the design solution provided is fully optimised to accommodate any existing mechanical and electrical interfaces or existing building layout requirements.

    Airflow Modelling

    CFD Airflow Modelling is used to demonstrate that air-flow patterns do not present a contamination risk. Cleanroom materials, leakage rates, oxygen requirements, exhaust volume and speed as well as air inflow are calculated and balanced to ensure exact requirements are delivered

    The example on the right shows the calculations and modelling to determine the quantity of fan filter units (FFU) required in a GMP facility: 45 FFUs against 60 FFUs.

    Functional Systems & Advanced Control

    UltraTech Precision's wall and ceiling panels are specifically designed for use in the most stringently regulated cleanrooms. The system is fully flush and available with a variety of CLEANsafe coatings.

    Over the years, we have developed proven envelope solutions and reliable HVAC concepts for many applications. Our systems meet the required ISO classification as well as qualification to international cGMP.

    Functional and mechanical system design is essential to achieve GMP regulatory compliance. Our cleanrooms deliver the highest quality with controlled running costs. Each one features an air handling system that is optimised for the intended application and operates with redundancy to improve reliability.

    Our ECO2 control system helps simplify all aspects of cleanroom management. It allows control of the full range of cleanroom auxiliary items to achieve optimum conditions for lighting, temperature, humidity and particle counts. Users can remotely control and monitor multiple rooms, and it can be integrated with existing facilities management systems and business management systems.

    The UltraTech Precision Flush panel system creates a fully-flush, ledge-free and impervious cleanroom envelope, making it an excellent solution for GMP facilities. Each insulated panel is pre-engineered off site to the correct size and then interlocked and sealed during assembly for a clean and efficient installation on site.

    The wall and ceiling panels integrate with the UltraTech Precision range of fully flush doors, windows, lighting and profiles to create the perfect custom design for your cleanroom.

    The system offers a range of accessories including integrated air return panels, which take up a much lower amount of space than traditional low-level ducted extract routes.

    The panels are 100% inspected for quality and utilise CLEANsafe 55 coating to give a fully smooth finish that is tested to withstand rigorous cleanroom cleaning procedures and products.

    When combined with C2C’s advanced cleanroom design and efficient air handling, the panel envelope system creates a market-leading and regulatory-compliant cleanroom environment.

    The HVAC system is a vital component to deliver the level of compliance required in a controlled environment.

    An effective cleanroom must deliver a high-volume of air through filter media to remove particulate and, where applicable, microbial contamination. The supply air may also need to be temperature and humidity-controlled to support the process needs and the ventilation requirements of all cleanroom staff.

    What is decentralised air handling?

    Decentralised air handling requires no central air handling unit (AHU). Instead, it features the constituent parts of an AHU, broken down into separate pieces of plant. Fan filter units (FFUs), temperature control units and dehumidification modules are distributed locally.

    Once seen as the prerequisite plant for compliance, the AHU is ever more frequently being replaced with this decentralised approach. Benefits range from reduced construction costs and complexity, to an increase in usable footprint and flexibility.

    Benefits include:

    • Energy Efficiency
    • Modularity
    • Individual Controls
    • Plant space
    • Lead time
    • Flexibility to change specification

    The ECO2 cleanroom control system was developed by Connect 2 Cleanrooms to provide optimised automatic cleanroom control and monitoring.

    The flexible system can be incorporated during the cleanroom design phase, but can also be quickly and easily retro-fitted or scaled up if the size of a cleanroom needs to be increased.

    The system is designed to minimise energy use, extend filter life and allow the simple control of modular cleanrooms, creating a culture of continuous improvement.

    Real-time visibility

    Our ECO2 control system gives real-time visibility on a cleanroom’s performance by monitoring pressure differentials, temperature, relative humidity, particle counts and other requirements.

    Complete cleanroom control

    The digital, touch-screen panel – which can be operated while wearing lab gloves – allows control of the full range of cleanroom auxiliary items, including fans, lighting, temperature, humidity and more.

    Control access is set using predetermined access levels to prevent unauthorised access to critical controls. The system can be operated on a timed setup allowing power saving outside operational hours.

    Continuous monitoring with alarm function

    Continuous monitoring is provided through remote sensors that are located in the critical points of operation. The system is set up to alarm if any monitored parameters vary outside of a user-specified threshold. This enables set limits to be continuously monitored and flagged if there is an excursion.

    SMS or email alerts can be sent when an issue is detected, for example if an element of the cleanroom is in need of service or falls outside defined operating parameters. This is accompanied by a visual on-screen warning for added peace of mind.

    Data

    Fully auditable data, with trends as well as real time data that can be extracted in as little as two minutes.

    Batch control

    Clients can record batch ID against datasets, making it suitable for full audit trail requirements for traceability of data.

    Digital, touch-screen control

    The Human Machine Interface (HMI) is a full colour Touchscreen, displaying cleanroom status. The HMI allows clients to monitor and control all environmental parameters within the cleanroom environment.

    • Touch-screen has IP54 rating
    • Icon-based, intuitive interface
    • Password protected
    • Program reminders for service
    • Provides remote diagnostics
    • Integrate with existing facilities management systems and business management systems (BMS)

    Commissioning, Qualification, Validation

    Qualification is a method of systematically demonstrating and documenting that facilities, systems and equipment perform as intended.

    • Installation Qualification (IQ) is a documented process that ensures the facility and equipment provide what is required.
    • Operational Qualification (OQ) verifies and documents that the as built facility and equipment operate in accordance with the design specifications.
    • Performance Qualification (PQ) or Process Validation verifies that the loaded facility and equipment perform as intended. Performance Qualification is also an ongoing process, meeting annual qualification and validation requirements for GMP facilities.

    As an essential part of GMP, Qualification and Validation should be part of an ongoing programme, specified in your Quality Manual and Validation Master Plan.

    Our commissioning process verifies that what was specified was installed, that it functions properly, and that the installation can be handed over to be qualified. Typical activities in this phase may include design reviews, factory acceptance testing, site acceptance testing, and functional testing. The results are documented, and any deviations encountered during testing are logged, corrected and retested.

    FAT (Factory Acceptance Test)

    A Factory Acceptance Test (FAT) is a process that evaluates any bespoke or customised equipment during and after the assembly process, by verifying that it is built and operating in accordance with design specifications.

    SAT (Site Acceptance Test)

    A Site Acceptance Test (SAT) is a tool to determine the functionality of the equipment at site before installation.

    IQ (Installation Qualification)

    Installation Qualification (IQ) is a documented process that ensures your facility and equipment provide what is required.

    Examples of what may be included are:

    • Checking room sizes and room finishes
    • Checking floor colours in different graded areas
    • Checking presence of vision panels into rooms

    IQ also includes the examination of equipment, to check it corresponds with documentation. We will perform a check, which is then verified by you to ensure both parties are confident that the key architectural and functional components of the system are present and satisfactory.

    OQ (Operational Qualification)

    Operational Qualification (OQ) is a documented program to demonstrate that the Cleanroom, when operating within the defined parameters, can consistently perform and maintain the specified conditions.

    In action, this means identifying and inspecting facility and equipment features that can impact final product quality.

    The OQ should cover worst case scenarios. For example, if the cleanroom still operates correctly at the minimum and maximum temperature and humidity limits specified in the URS.

    During OQ, each test must be carried out individually. For example, if the same sensor is used for temperature and humidity, our test engineers will test these functions separately.

    The output of this phase of qualification is an OQ report detailing how the functional requirements of the cleanroom meet what is specified in the URS.

    PQ (Performance Qualification)

    Performance Qualification (PQ) is usually the final step in initial qualification.

    For the initial Performance Qualification our test engineers will repeat what has been done at OQ but now under load, rather than as built.

    For a cleanroom particle count, this would be Operational, as opposed to At Rest. For a piece of equipment, e.g. a freezer or incubator, it would be working with its typical load, rather than being empty.

    Ongoing Performance Qualification requires a repeat of the initial testing on the cleanroom to ensure that its operation continues to meet initial requirements as the facility ages. This is also described as Requalification.

    This is usually on an annual basis, however the revision of Annex 1 looks to change the requirement to every 6 months for Grade B rooms and Grade A equipment.

    It provides an ongoing assurance that facilities and equipment can continue to meet their original specifications.

    Tests may include but not be limited to:

    • As built/At rest Particle Counts
    • Air Volumes and Air Change Rates
    • Filter Integrity Testing
    • Pressure Differentials
    • Temperature and Humidity Levels
    • Recovery Rate Testing
    • Smoke Visualisation Airflows
    • Containment Leak Testing
    • Light (Lux) Level Testing
    • Sound Level Testing
    • Door interlocks Testing

    Are you about to start a GMP Cleanroom project?

    Get us involved and we will guide you through your project step by step.