At Angstrom Technology, we get asked a lot what the equivalent ISO class for a cGMP area is. Particularly from organizations at the start of a cleanroom project. Here, we answer that question for you.

The International Standard for cleanrooms and associated controlled environments is ISO 14644. To be classified as a cleanroom, zones must meet air cleanliness levels that are classified by particle concentration limits detailed in ISO 14644-1. While ISO 14644 governs all cleanrooms, the FDA Current Good Manufacturing Practice (cGMP) is specifically for medicines manufacturers. It describes the minimum standard they must meet in their production processes.

What are the different cGMP areas?

Two clean areas are of particular importance to sterile drug product quality in cGMP. These are the critical area and the supporting clean areas associated with it. Each area has a minimum recommended ISO class. Although, with ISO validation two particle sizes are usually considered, whereas cGMP standards dictate that only particles ≥ 0.5 μm should be controlled.

EU GMP takes a slightly different approach. Four grades (A-D) are detailed. Since each grade has particle concentration limits, there is an equivalent ISO class for each cGMP grade. Although they are not mentioned in cGMP guidance, these grades are becoming part of the common cGMP language in the US.

• EU GMP Grade A is approximately equivalent to ISO Class 5
• EU GMP Grade B is approximately equivalent to ISO Class 5
• EU GMP Grade C is approximately equivalent to ISO Class 7
• EU GMP Grade D is approximately equivalent to ISO Class 8

Need more information on the ISO particulate concentration limits? We have a table that breaks them down on our cleanroom classifications page.

What ISO Class Should Critical Areas Meet?

Critical areas must meet particle concentration limits according to ISO Class 5. These areas are equivalent to EU GMP grades A/B.

A critical area is one where the sterilized drug product is exposed to environmental conditions that must maintain product sterility. Activities conducted in such areas include aseptic processes. This can include manipulations of sterile materials before and during filling and closing operations.

Because an exposed product is vulnerable to contamination and will not be subsequently sterilized in its immediate container, this area is critical.

What ISO Class Should Supporting Clean Areas Meet?

Supporting clean areas must meet a minimum of ISO 7 (equivalent to EU GMP grade C). Depending on the activity in these areas, manufacturers can also classify them as ISO 6 or maintain the entire aseptic filling room at ISO 5.

Supporting clean areas can have various classifications and functions. Many support areas function as zones in which nonsterile components, formulated products, in-process materials, equipment, and container/closures are prepared, held, or transferred. These environments are soundly designed when they minimize the level of particle contaminants in the final product and control the microbiological content (bioburden) of articles and components that are subsequently sterilized.

Build a cGMP-Compliant Cleanroom with Angstrom Technology

At Angstrom Technology, we’re proud to have delivered high-quality, high-performance cleanrooms across North America for over 30 years.

If you’re interested in building an ISO or GMP-compliant cleanroom in your facility, contact Angstrom’s Life Sciences group for information on how to get started.

CONTACT A LIFE SCIENCE CLEANROOM EXPERT

On August 9, 2022, President Biden passed the CHIPS Act.

What’s that? We’re here to fill you in. 

The CHIPS Act

CHIPS stands for Creating Helpful Incentives to Produce Semiconductors for America Act. The investment promises $50 billion to domestic R&D and manufacturing, marking a seminal moment for US semiconductor manufacturing.

This article looks at how organizations can use the funding to create a cleanroom space that supports the semiconductor supply chain.

What does the CHIPS Act mean for OEMs?

The CHIPS Act presents an opportunity for semiconductor R&D companies and manufacturers—along with their supply chain—to upgrade or extend facilities.

The program also intends to incentivize new participants to the semiconductor industry, allowing companies in vertical industries, such as electronics manufacturers, to diversify with reduced risk.

Funding will be available for a range of purposes, including the following:

• Construction or expansion of facilities for the fabrication, packaging, assembly, and testing of legacy and current-generation semiconductors
• Facilities to produce new or specialty technologies or emerging technologies
• Facilities that manufacture equipment and materials for semiconductor manufacturing, potentially co-located in regional clusters

Entering the semiconductor market

The cost of semiconductor fabrication plants—often termed semiconductor fabs—can run into the billions of dollars. This creates a significant barrier that has obstructed new entrants into the market. But to be part of the supply chain, a semiconductor fab is not essential.

Before they are scaled up to industrial production, there are pre-commercial activities that need to be conducted to research, develop, and learn about new products. A semiconductor pilot plant can produce small volumes of chips for R&D purposes.

Since chips are highly susceptible to damage, even the smallest particle could cause a defect. This is why the specification for semiconductor chip fabrication cleanrooms typically ranges from ISO class 4 to 6. A HardWall cleanroom would be able to achieve this level of particulate control for a pilot plant. Zones can provide segregated spaces with control of environmental parameters—such as temperature, humidity, and UV—to be optimized for various steps of the production process.

The packaging, assembly, and testing of circuits or chips could be performed in ISO class 7 or ISO class 8 cleanrooms, with all considerations handled on a project-by-project basis. Equipment can be enclosed in a modular cleanroom, either RigidWall or SoftWall construction.

Over the years, Angstrom Technology has served the semiconductor industry with a wide range of cleanrooms. We’ve put together a simple guide to help you understand more about what type of cleanroom is suitable for your process.

Whether you are an existing semiconductor specialist or looking to diversify — the Angstrom Technology team can support your organization.

Contact Angstrom Technology to discuss your semiconductor cleanroom

Our cleanrooms are proudly made in America. We have the expertise to support organizations looking to build domestic capacity in line with the principles of the CHIPS program.

Are you thinking about investing in a semiconductor cleanroom? Request a semiconductor cleanroom quote today, or contact our team of experts for more information.

What’s that? We’re here to fill you in. 

What Is Cleanroom Commissioning & Why Is It Important?

Cleanroom commissioning is the practice of verifying that a cleanroom functions in alignment with its design intent and the user’s operational requirements. It’s a systematic process that involves thorough evaluation and documentation of designs, systems, and procedures. 

Cleanroom commissioning is important because it helps to ensure a cleanroom operates as it’s intended and that all stakeholder expectations are met. It also ensures that components, machinery, and equipment within the cleanroom are approved by regulatory authorities and function appropriately. 

Who Is Responsible for Cleanroom Commissioning?

Depending on the extensivity of the commissioning needed, commissioning can start at different points during the cleanroom build process. In most cases, it’s largely the responsibility of the customer/user to complete the commissioning process. The cleanroom provider can help provide necessary documentation, but is not involved much more than that. 

However, a reputable cleanroom provider can help make the commissioning process successful by listening closely to customer specifications and delivering a high-quality solution that meets them. 

5 Stages of the Cleanroom Commissioning Process

The cleanroom commissioning process can vary tremendously. It can be abbreviated and include just a few stages or types of commissioning, or it can be very in-depth and take longer than the entire cleanroom project. It’s all set forth by the customer, their specific commissioning requirements, and documentation needed for their project. 

To give you a general sense of what the commissioning process could look like, we’ll outline five of the most common stages below. 

1. Design

One step of the commissioning process happens before a cleanroom is constructed: design. The design stage is important because this is where project expectations are set. 

Here are a few examples of expectations that are established during the design stage:

• Vision and requirements for the cleanroom
• Project and design goals
• Measurable performance criteria
• Budget
• Schedule

From there, a cleanroom provider steps in to create the preliminary cleanroom designs, keeping applicable standards, codes, and regulations in mind. Once drawn, stakeholders are given multiple chances to review and approve designs before installation begins. 

2. Installation Verification

For modular cleanrooms with prefabricated components, installation verification is a two-part process. It begins offsite in the controlled environment where various modular components are engineered and manufactured. Here, the following tasks are performed: 

• Verification that materials and equipment meet the original design intent
• Verification that materials and equipment meet industry standards
• Factory acceptance testing

Then, once the modular components are manufactured, they’re shipped to the site where they’ll be installed. Onsite, a few more tasks are performed: 

• Site acceptance testing
• Verification that equipment and system start-up meet protocol requirements
• Verification of the test and balance report
• Assembly of the cleanroom in accordance with established protocols
• Creation of cleanroom maintenance manuals

3. Operational Verification

Operational verification is completed during three separate installation stages:

• As-built – The cleanroom structure, mechanical systems, and electrical systems are built, but the cleanroom is empty. There are no machines, equipment, or pieces of furniture in it yet.
• At-rest – All cleanroom components are in place, but nothing is running. No operators have started and run process systems.
• Operational: All cleanroom components are in place and operating with operators. 

Throughout each of these sub-stages, tests are run to verify that cleanroom equipment and systems are operating in accordance with the design intent and sequence of operations. Staff also receive some training on how to operate certain machinery and systems.

4. Functional Verification

The functional verification stage is similar to the operational verification stage, but it focuses more on how the cleanroom and its systems function together. The following verifications are completed: 

• Verification that all cleanroom equipment and systems operate per design intent and sequence of operations when integrated with each other
• Verification that all cleanroom equipment and systems fail as intended in the user’s established “failure cascade”

5. Post-Occupancy

Once the cleanroom has completed the first four stages, it’s ready to be used for its intended purpose. But the commissioning work isn’t entirely done. After the cleanroom is up and running, a few more tasks need to be completed by the user. 

• Ongoing tests and maintenance (usually in alternate seasons)
• End of warranty inspections
• End of warranty interviews with cleanroom operators
• Creation of a recommissioning plan

10 Types of Cleanroom Commissioning

There are many different “types” of cleanroom commissioning — or in other words, many different tests and verifications that can happen during the commissioning process. Most of these tests and verifications are completed during the operational verification stage, but some are also completed again during the functional verification and post-occupancy stages. 

Some of these commissioning tests and verifications are: 

• HVAC
• Temperature
• Humidity
• Static pressure
• Differential/cascading pressure
• Vibration & noise
• Utilities
• Automation
• Alarms & interlocks
• Finishes (e.g. floors, walls, ceiling, doors, airlocks, lighting, etc.)

Again, the commissioning process often differs from one cleanroom to the next and one end user to the next. So while some cleanrooms may only undergo one or two of these tests, others may require much more.

Ready to Start Your Cleanroom Project? Contact Angstrom Technology. 

Commissioning is an important process that ensures quality control within your cleanroom. While you’re responsible for completing the commissioning process, we’ll do our part by manufacturing, building, and installing a high-quality, per-spec cleanroom that sets you up for success. To learn more about our turnkey cleanroom design-build services, contact us online. 

Understanding cleanroom quality standards can be tricky. There are various systems, all of which have different themes, criteria, guidelines, and regulations.

One distinction that can be particularly challenging is the difference between GMP and cGMP standards. These standard sets sound similar, and they both work to ensure safety, quality, and repeatability in cleanroom environments. However, there are some key differences between the two. 

Let’s take a closer look at GMP vs. cGMP standards below. 

GMP vs. cGMP Standards for Cleanrooms

We’ll first note that GMP and cGMP standards may differ, but neither is “better” or “more effective” than the other. Often, the two systems work hand in hand to ensure a cleanroom is operating at peak performance and is in continuous compliance. In fact, the terms are frequently used interchangeably, even though they technically shouldn’t be. 

Let’s dive into some definitions. 

What Are GMP Standards for Cleanrooms?

GMP stands for “Good Manufacturing Practices.” It’s a quality management system used mainly by medical and pharmaceutical manufacturers. Its main goal is to “minimize the risks of microbiological, particulate, and pyrogen contamination during preparation and sterilization of medicines or medical devices.”

GMP standards focus largely on production and quality control. When applied specifically to cleanrooms, they address issues like:

• Sanitation and cleanliness
• Record keeping and documentation
• Personnel qualification
• Process validation
• Equipment verification

In the United States, GMP standards are created and enforced by the Food and Drug Administration (FDA). In other countries, they’re created and enforced by other regulatory agencies. But while GMP standards may have minor differences across the globe, their main goal is the same. 

Learn more about GMP standards for cleanrooms in this blog post. 

What Are cGMP Standards for Cleanrooms?

cGMP stands for “Current Good Manufacturing Practices.” It’s a quality management system incredibly similar to GMP but with small yet important differences. 

With cGMP standards, every production stage is done using GMP guidelines but in the most “current” manner available. In a broad sense, “current” means a cleanroom and its operators must employ technologies and systems that are up to date and comply with GMP requirements. 

While cGMP standards have rules and regulations, they’re still somewhat flexible. They allow each manufacturer to choose which controls, systems, and technologies to use and how they want to implement them — as long as they remain compliant. This enables manufacturers to take innovative approaches and to constantly work on improving their processes. 

Learn more about cGMP standards in this article from the FDA.

Other Differences Between GMP and cGMP Standards for Cleanrooms

Besides the main distinction of “current,” there are a few other differences to note between GMP and cGMP standards for cleanrooms. The most pertinent ones to many manufacturers are cost and requirements for certification and testing. 

Cost

cGMP cleanrooms use new, innovative systems and technologies. This often makes their overall manufacturing, installation, and operating costs higher than those of GMP cleanrooms. 

Of course, cleanroom costs can vary depending on the overall project size and scope. This is just a common trend we’ve noticed and something to consider while you’re determining a project budget. For many manufacturers, the additional cost is well worth it for modern systems.

Certification & Testing

In most cases, cGMP cleanrooms are subject to a longer, more rigorous certification process before they’re ready for operation. They also tend to undergo more frequent, thorough tests year after year to verify ongoing compliance. This is to ensure that all controls, technologies, and systems are current, operable, and compliant. 

Questions? Contact Angstrom Technology.

Have more questions about cGMP and GMP standards and how they may fit into your cleanroom manufacturing, installation, and operation processes? Contact our Life Sciences team at Angstrom Technology. We have the experience and an extensive portfolio of cGMP and GMP cleanroom projects under our belt, and we’d be happy to help design and build yours. 

CONTACT A LIFE SCIENCE CLEANROOM EXPERT

Cell and gene therapies have become more recognized as viable forms of treatment for serious, life-threatening illnesses. However, there’s still quite a bit of information to learn about them — including the controlled environments in which they’re tested, produced, and administered. 

If you’re hoping to learn more about cell and gene therapy cleanrooms, you’ve come to the right place. 

10 Frequently Asked Questions About Cell and Gene Therapy Cleanrooms

Below is a list of 10 of our most frequently asked questions about cell and gene therapy cleanrooms, along with their respective answers. 

1. What Is Cell and Gene Therapy?

Cell and gene therapies are two forms of regenerative medicine. They both have similar goals of lessening or curing a serious illness or disease, but there are some differences in how they’re implemented. 

• Cell therapy involves injecting live, intact cells into a patient to lessen or cure their illness. These cells may be from the patient themself (autologous) or from a donor (allogeneic). 
• Gene therapy involves injecting genetic material into a patient to change how a single protein or group of proteins is produced by the cell, ultimately lessening or curing their illness. 

Cell and gene therapies are gaining recognition in the field of medicine as safer, more personalized, less invasive, and potentially more effective ways to treat life-threatening diseases. 

2. What Are the Unique Risks Associated with Cell and Gene Therapy?

Cell and gene therapies are highly sensitive applications – more so than many other medical or medicinal functions. The many processes that go into testing, producing, and applying them can be manipulated easily if not completed with extreme caution.

Think of tasks like cellular and genetic engineering, growth, and purification. It’s critical that the results of those tasks are safe, effective, and reproducible to ensure treatment viability and patient safety. 

3. What Is a Cell and Gene Therapy Cleanroom?

Since cell and gene therapy applications are so high-risk, a controlled operating environment is necessary. A specially designed cleanroom can offer specialized control, cleanliness, equipment, and whatever else is needed to ensure treatment viability and patient safety. 

Cell and gene therapy cleanrooms have unique features compared to other types of cleanrooms. Many of these unique features are described in the answers to the questions below. 

4. What ISO Classification Do Cell and Gene Therapy Cleanrooms Require?

Typically, cell and gene therapy cleanrooms need to meet ISO Class 5-7 standards. However, this can vary depending on what particular task is being performed and how much environmental control it requires.

ISO classification can change from cleanroom to cleanroom, or from one of a cleanroom’s zones to another, or within a designated work chamber inside of the cleanroom. It can change to a level of less or more control. 

5. What Other Quality Standards Do Cell and Gene Therapy Cleanrooms Need to Meet?

ISO standards aren’t the only set of quality standards that cell and gene therapy cleanrooms require. In many cases, they need to comply with GMP (or cGMP) standards as well. 

Good Manufacturing Practice (GMP) and Current Good Manufacturing Practice (cGMP) are two quality management systems that are enforced by the U.S. Food and Drug Administration. They’re used by medical and pharmaceutical manufacturers to help minimize the chances of microbiological, particulate, and pyrogen contamination during the preparation and sterilization of medical devices and medicines. 

We have a few blogs that provide more specifics on GMP standards. You can check them out through these links: 

• What Are GMP Standards for Cleanrooms?
• GMP Cleanroom Requirements for Safe and Effective Workflow
• What Do the GMP Qualification & Validation Processes Look Like?
• What Industries Require GMP Cleanrooms?

6. What Types of Special Equipment Do Cell and Gene Therapy Cleanrooms Require?

All cleanrooms require specialized equipment to meet the demands of their particular industry and application. Cell and gene therapy cleanrooms are no different. Some of their unique pieces of equipment include: 

• Biosafety cabinets: enclosed workspaces that utilize laminar airflow to filter out contaminants and fumes. 
• Incubators: devices that create the ideal environment for growing and maintaining cell and gene cultures. 
• Refrigerators: devices used to store cell and gene cultures in the cold temperatures they need to survive for short periods of time. 
• Freezers: devices used to store cell and gene cultures in the freezing temperatures they need to survive for extended periods of time. 
• Centrifuges: machines that isolate strains of DNA or cells from body fluid. 

You can learn more about these types of equipment, as well as the risks that are associated with them, in this blog article. 

7. What Type of Cleanroom Is Best for Cell and Gene Therapy Applications?

Since cell and gene therapy cleanrooms need a lot of environmental control, a HardWall cleanroom solution is usually the best option. They offer a level of control against contamination, temperature, humidity, and more that other types of cleanrooms just aren’t designed for. 

8. What Type of Pressure Is Needed In Cell and Gene Therapy Cleanrooms?

It’s common for cell and gene therapy cleanrooms to be designed and installed as cell and gene therapy cleanroom suites. This means that the larger cleanroom facility contains multiple separate cleanroom zones. 

Within these zones, a cascading (or differential) pressure effect is employed. This means that the most stringent cleanroom zone has the highest level of pressure, and that the least stringent cleanroom zone has the lowest level of pressure. This pressure design is highly intentional, so that contaminant particles cannot flow into the cleanest, most controlled cleanroom zone.

9. Are HEPA or ULPA Filters Best for Cell and Gene Therapy Cleanrooms?

ULPA and HEPA filters are both effective at removing airborne particles from the cleanroom environment. However, ULPA filters provide the best filtration for most cell and gene therapy processes. 

ULPA filters are 99.999% efficient at removing particles 0.12μm or larger, while HEPA filters are 99.999% efficient at removing particles .3μm or larger. ULPA filters’ ability to filter out those smaller particles gives them the upper hand. However, some cell and gene therapy cleanrooms do just fine with a HEPA filter. 

10. Can You Provide an Example of a Cell and Gene Therapy Cleanroom Project?

Sure thing! In 2021, our UK division – Connect 2 Cleanrooms – designed, built, and installed a cleanroom suite for RoslinCT — a leading cell therapy contract development and manufacturing organization in the UK. 

The cell and gene therapy cleanroom suite was installed within a two-story building and included 33 internal rooms. It now operates with high performance and control on a day-to-day basis to help healthcare professionals test and manufacture life-saving treatments. 

Some special features of the cleanroom include: 

• ISO 5 classification (equivalent to EU GMP Grade B)
• HEPA filtration with 79no. air changes per hour
• Vaporized hydrogen peroxide (VHP) cabinets
• Integrated medical gas systems
• Cryostorage
• Fire-rated active pass-through chambers

To learn more about this project and see photos and video of the finished result, visit this project page. 

Have More Questions? Contact Angstrom Technology

If you have more questions about cell and gene therapy cleanrooms, or you’re ready to design and install one of your own, don’t hesitate to reach out. We’d be happy to provide you with the answers or solutions you need. 

CONTACT A LIFE SCIENCE CLEANROOM EXPERT