Radiopharmaceutical Cleanroom Design?

USP standards are developed by the United States Pharmacopeia (USP) to protect patient and worker safety while developing, packaging, distributing and consuming medicines and dietary supplements. Therefore, they must be adhered to in many cleanroom applications involving radio pharmaceutical development or manufacturing. 

Some of the most common USP standards in the cleanroom industry are USP 797 and USP 800 — but in this article, we’ll be discussing a more specialized one: USP 825.

What Is USP 825?

USP General Chapter 825 is the USP standard that provides the minimum requirements for preparing, compounding, dispensing, and repackaging both sterile and nonsterile radiopharmaceutical drugs. It describes facilities and engineering controls, personnel training and qualifications, and procedural requirements for processing radiopharmaceuticals in various clinical settings. All of these requirements work together to ensure that workers are protected while handling these hazardous drugs and that patients are protected while consuming them. 

Who Needs to Follow USP 825?

If you’re working with radiopharmaceutical development or manufacturing, you likely need to follow USP 825. That includes a variety of healthcare personnel and environments, including:

Personnel

• Authorized nuclear pharmacists (ANPs)
• Authorized user (AU) physicians
• Individuals in training and under supervision, like students, technicians, and trainees

Environments

• State-licensed nuclear pharmacies
• Federal-licensed nuclear pharmacies
• Nuclear medicine departments in hospitals and other specialized healthcare clinics

There are some exceptions, however. USP 825 doesn’t apply to the following processes and environments: 

• Manufacturing approved radiopharmaceuticals in FDA-registered manufacturing establishments
• Manufacturing radiopharmaceuticals as investigational agents

Why Was USP 825 Developed?

Radiopharmaceutical drugs have been around for over 70 years, but their development is really starting to take off and lead to big changes in the industry. Due to their radioactive nature, radiopharmaceuticals need to be managed and manufactured differently than traditional medicines.

USP 825 permits three environments for sterile radiopharmaceutical handling: segregated radiopharmaceutical processing areas, ambient hot air labs, and cleanroom suites. The appropriate environment depends on the particular radiopharmaceutical processing task at hand. 

In a radiopharmaceutical cleanroom environment, control is needed to ensure the safety and effectiveness of the drugs, as well as to protect the lives of workers who are handling them.

The unique characteristics of radiopharmaceutical drugs and cleanrooms make complying with the longstanding USP 797 and 800 standards a difficult, unproductive, and sometimes unsafe task. This is why nuclear medicine professionals have called for a move beyond USP 797 and 800 and the creation of a new radiopharmaceutical-specific standard, USP 825. This way, more specific policies and requirements could be established to protect the safety and repeatability of radiopharmaceutical processes.

However, it’s important to note that USP 825 has not yet been implemented due to a series of appeals during the publication process. Therefore, it’s currently used as a guideline for radiopharmaceutical cleanroom design, not a requirement. 

A Few Specific USP 825 Cleanroom Requirements

So what exactly makes USP 825 different from USP 797 and 800? It reflects the unique characteristics of radioactive drugs, emphasizes the importance of following radiation safety protocols, and provides information on how to balance the short lifespan of radiopharmaceutical drugs for clinical use and the importance of proper aseptic handling practices. It also offers guidance on how to place absorption pads in hoods, how to handle sharp utensils during compounding, and how to position radiation-measuring devices in hoods during compounding. 

To break it down more, USP 825 discusses safe practices involving:

• Radiation safety (time, distance, shielding, contamination control)
• Personnel qualification, training, and technique
• Hand hygiene & garbing
• Regular sanitation & cleanliness protocol

Build Your USP 825 Cleanroom With Angstrom Technology

Planning to install a radiopharmaceutical cleanroom in your facility? At Angstrom Technology, we can help design and install one that meets your specifications and complies with industry standards. To get started, contact our team online. 

In the cleanroom industry, there are many different quality standards that both manufacturers and facilities managers must be aware of and comply with. We’ve already discussed ISO standards and Federal 209E standards, even USP standards — but one we haven’t discussed much is GMP standards. 

Let’s explore what GMP standards are, what they entail, who needs to comply with them, and more. 

What Are GMP Standards for Cleanrooms?

GMP stands for Good Manufacturing Practices, which is a quality management system used mainly by medical and pharmaceutical manufacturers to ensure a controlled cleanroom environment. In the United States, GMP standards are established and enforced by the Food & Drug Administration (FDA), but in other countries they’re controlled by different regulatory bodies. 

Although it’s important to be aware of minor differences across the globe, the main goal of GMP standards remains the same: to minimize the risks of microbiological, particulate, and pyrogen contamination during preparation and sterilization of medicines or medical devices. This helps ensure that products are of consistent high quality, are appropriate for their intended use, and meet the requirements of product specifications. 

In order to ensure this level of control, GMP standards address cleanroom issues like: 

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

How Do GMP Standards Differ from Other Cleanroom Quality Standards?

GMP standards are different from other cleanroom quality standards, but none of them are mutually exclusive. Some cleanrooms need to meet multiple sets of standards in order to be fully controlled and compliant. 

For the sake of brevity, we won’t discuss every type of cleanroom quality standard. Instead, we’ll focus mainly on how GMP standards are different from ISO standards since they’re the most common. 

The biggest difference between GMP standards and ISO standards is that GMP standards are mainly used in medical applications. ISO standards, on the other hand, are commonly used in a diverse range of industries, from medical to automotive, plastic injection molding, and more. 

Another difference between these two standard sets is that ISO standards distinguish nine “classes,” while GMP standards distinguish four “grades.” Here’s an overview of the four GMP grades:

• Grade A – A zone for high-risk operations that need the highest level of environmental control. It’s equivalent to ISO Class 5, both at rest and in operation. 
• Grade B – A zone for aseptic preparation, filling, and compounding. It’s equivalent to ISO Class 5 at rest and ISO Class 7 in operation. 
• Grade C – A clean area for less critical stages in the manufacturing process. It’s equivalent to ISO Class 7 at rest and ISO Class 8 in operation. 
• Grade D – Another clean area for less critical stages in the manufacturing process. It’s equivalent to ISO Class 8, both at rest and in operation. 

If you’d like a more detailed description of GMP/ISO equivalents, check out these cleanroom classification comparison tables from our partners at Connect 2 Cleanrooms (C2C). 

Which Cleanrooms Need to Comply With GMP Standards?

As mentioned above, GMP standards are mostly used in medical and pharmaceutical cleanrooms. Any application that involves producing, filling, compounding, or packaging sterile medicinal products needs to comply with GMP standards. This could include cleanroom industries and applications like:

• Cell and gene therapy
• Medical device manufacturing
• Pharmaceutical manufacturing
• Radiopharmaceutical manufacturing

If you’re unsure if your cleanroom must comply with GMP standards, it’s best to consult with a cleanroom design and installation professional. They’ll be able to tell you which quality standards your space must be designed to accommodate. 

An Overview of the GMP Cleanroom Qualification & Validation Process

Qualification and validation is a critical component of GMP standards. These protocols help provide documented evidence that your cleanroom meets a high level of control, is compliant with all applicable standards, and will consistently yield high-quality products. GMP guidance calls for the following four stages of qualification and validation: 

• Design Qualification (DQ), which verifies that your cleanroom design can meet all regulatory and process requirements. 
• Installation Qualification (IQ), which verifies that your cleanroom is consistent with specified designs after installation. 
• Operational Qualification (OQ), which verifies that your cleanroom equipment achieves specified operational requirements. 
• Performance/Process Qualification (PQ), which verifies that your cleanroom equipment performs well together, in a cohesively controlled, repeatable state. 

At first glance, this may seem like a lot of qualification stages to go through — and it can be! GMP qualification and validation requires a significant amount of effort, but it must be done before you can begin operations. If you’re looking to streamline the process, a reputable and experienced cleanroom manufacturer can support you. 

GMP Cleanroom Example: RoslinCT

Want to see a GMP cleanroom project in action? Recently, our partners at C2C completed a GMP-compliant cleanroom suite for cell and gene therapy client RoslinCT. 

The cleanroom suite consisted of 33 different rooms, the breakdown being:

• 3 Grade B cleanrooms
• 2 Grade C cleanrooms
• 15 corridors, lobbies, and changing areas (Grades B, C, D)
• Sample and packing area
• Cryostorage and vaporized hydrogen peroxide (VHP) staging area
• Training laboratory
• Waste room, warehouse, and plant room
• Stairwells, foyers, and bathrooms
• Offices and conference rooms

The large facility obtained full GMP qualification and now operates according to both US and EU GMP standards — ensuring consistent, high-quality results in the rapidly growing, life-saving field of cell and gene therapy.

If you’d like to learn more about this GMP cleanroom project, you can find the full project description here. 

Build Your GMP Cleanroom With Angstrom Technology

Have questions about GMP standards and how they relate to your cleanroom design? Get in touch with our team at Angstrom Technology. As cleanroom design and installation experts, we’re happy to guide you through the GMP qualification and validation process and to ensure your cleanroom is built for safe, controlled operations.

While we usually discuss ISO standards, there are plenty of other cleanroom standards that help us design and build highly effective and controlled environments that are specific to an industry — one of them being USP standards. Let’s discuss what USP standards are and how to know if your cleanroom must comply with them. 

What Are USP Standards?

The United States Pharmacopeia (USP) is an independent, scientific nonprofit organization that establishes and enforces quality standards for pharmaceutical products. USP standards help protect patient and worker safety while developing, packaging, distributing, and consuming medicines and dietary supplements. They’re often used to inform decisions made by the United States Food and Drug Administration (FDA), and they’re an important set of standards to keep in mind when it comes to designing, installing, and operating cleanrooms. 

USP Standards vs. ISO Standards

USP and ISO are both types of cleanroom quality standards, but they’re not the same. 

USP standards are most commonly used for pharmaceutical applications and must be followed along with ISO classification standards. Alternatively, ISO standards are much less specific and are followed by a broad range of industries and applications, including pharmaceuticals. 

You may think of this in the same way that you think about squares and rectangles. All squares are rectangles, but only some rectangles are squares. Similarly, all cleanrooms follow an ISO standard, but only some need to adhere to both ISO and USP standards. 

Who Needs to Follow USP Standards for Cleanrooms? 

So, how do you know if you need to follow USP standards while designing, installing, or operating your cleanroom? Simply put, if you’re working with pharmaceutical development or manufacturing, you need to follow USP standards. 

Common USP Standards for Cleanrooms

A USP-compliant cleanroom needs to follow all the requirements set by its applicable standard. In pharmaceutical compounding cleanroom applications, USP 797 and USP 800 are the two most common.

While both of these USP standards call for stringent cleanliness requirements, they do have different goals and design specifications. Let’s take a closer look at them below. 

USP General Chapter 797 — Sterile, Non-Hazardous Pharmaceutical Compounding Preparation

USP 797 outlines the procedures and requirements for pharmaceutical cleanroom applications that involve compounding sterile products (CSPs). These products are non-hazardous to humans and the surrounding environment, some examples being: 

• Syringes
• Injections
• IV medications
• Eye-drops

Compliance with this standard’s requirements is critical — otherwise, pharmaceuticals could be mishandled and cause harm, even death, in patients due to contamination, strength variation, poor-quality ingredients, and more. 

As you can likely determine, the most important safety precaution here is ensuring that the pharmaceutical products aren’t altered by external factors like contaminants and operators. For this reason, USP 797 cleanrooms require ISO 7 Classification, required temperature and humidity specifications, and continuous differential positive pressure to minimize airflow from an area with lower air quality classification to an area of higher air quality classification. They also have other requirements relating to:

• Unidirectional airflow using a primary engineering control (PEC) certified to meet ISO Class 5 or better
• Workstation and door placement to facilitate better control
• Operator technique
• Garbing & donning
• Proper hand hygiene
• Regular sanitation & cleanliness protocol

USP General Chapter 800 — Sterile, Hazardous Drug Handling in Healthcare Settings

USP 800 outlines the procedures and requirements for pharmaceutical cleanroom applications that involve hazardous drugs. These products can threaten patients, personnel working in this environment, and the environment. A drug is considered hazardous if it exhibits one or more of the following characteristics in humans or animals: 

• Carcinogenicity 
• Teratogenicity or developmental toxicity
• Organ toxicity
• Reproductive toxicity
• Genotoxicity
• Structure and toxicity profiles of new drugs that mimic existing hazardous drugs

There are two types of hazardous drugs found in healthcare settings: antineoplastic drugs, which are used to treat cancer, and non-antineoplastic drugs, which are used to treat various other conditions but can pose serious reproductive risks for men and women if they are not managed safely. 

Compliance with USP 800 requirements is critical in order to mitigate risk to cleanroom operators as they work with hazardous substances and promote patient safety. Therefore, USP 800 cleanrooms require an ISO 7 Gowning Room with positive pressure, an ISO 7 Cleanroom with negative pressure between 0.01-0.03 inches of water column relative to all adjacent spaces. They also have other requirements relating to: 

• Receipt of material
• Safe storage with secure access & detailed product labeling
• Primary Engineering Control (PEC) certified to meet ISO 5 Class or better with external ventilation 
• Proper hand hygiene with emergency safety precautions
• Workstation and door placement to eliminate cross contamination
• Garbing & donning
• Regular sanitation & cleanliness protocol

Building a pharmaceutical cleanroom that needs to meet USP 797 or 800 standards? Contact Angstrom Technology. Our cleanroom design experts have experience working on many pharmaceutical and radiopharmaceutical cleanroom projects, and we’re happy to help you build yours in a way that supports your specific needs.