In the intricate world of pharmaceutical manufacturing, where precision and purity are paramount, cleanrooms emerge as unsung heroes. These controlled environments play a crucial role in ensuring the integrity and safety of pharmaceutical products. Maintaining stringent cleanliness standards within these spaces is not just a regulatory requirement. It is a fundamental necessity for safeguarding the health of millions of patients worldwide.
The Basics of Cleanrooms
A cleanroom is a workspace designed to be free of contaminants. This is accomplished by filtering the air and cleaning surfaces to remove dust and other particles. The purpose of a cleanroom is to prevent contamination of products made in the cleanroom, which can occur through contact with these contaminants.
Cleanrooms are classified based on how much dirt they can have in them. This measurement is called “particulate matter” or PM (the amount per cubic foot). For example, a Class 100 means that there can be no more than 100 particles greater than 0.5 micrometers per cubic foot. Anything larger than this would be considered “contaminated.”
Based on the Class of the cleanroom and the applications it is used for, it has to abide by numerous regulations. The cleanliness of each cleanroom determines the applications it can be used for.
An article from News Medical Lifesciences states that an ISO 5 standard is required for high-grade cleanrooms for pharmaceutical applications. This may include the sterile filling of drugs into their vials or packaging. An ISO 7 facility is necessary for other related sub-sterile applications.
Besides cleanliness, pharmaceutical cleanrooms must also follow Good Manufacturing Practices (GMP). According to American Cleanroom Systems, GMPs are the best practices and quality control requirements crafted by the Food and Drug Administration (FDA).
GMPs were a result of poor pharmaceutical manufacturing processes that led to the deaths of many people in the 1950s and 1960s. Thus, the FDA created GMPs in the 1970s. However, since GMPs were listed decades ago, the FDA improved the best practices into Current Good Manufacturing Practices (cGMP).
Pharmaceutical manufacturers should know the difference between cGMP vs. GMP to ensure that they follow the right standards based on what they are developing. This is vital from the quality point of view so that the products do not impact the consumers.
Cleanroom Technology and Equipment
Cleanroom technology and equipment are crucial to maintaining a pharmaceutical manufacturing facility’s purity. The types of cleanrooms include Class 100, Class 1,000, and Class 10,000.
Here are key aspects of cleanroom technology and equipment used in pharmaceutical manufacturing:
- Cleanroom classifications: The classification is defined by international standards, such as ISO 14644-1. Common cleanroom classifications for pharmaceutical manufacturing include ISO Class 5 to ISO Class 9. A Class 100 or ISO 5 environment has fewer than 100 particles per cubic foot. In comparison, the air in your home may contain up to 100 million particles per cubic foot (MPCF).
- Air control systems: High-efficiency particulate air (HEPA) and ultra-low penetration air (ULPA) filters remove particles from the air. Unidirectional airflow is often employed to maintain a constant flow of clean air from the cleanest to the least clean areas.
- Cleanroom design: Non-shedding and easily cleanable materials are used in cleanroom construction to minimize particle generation. Seals and joints are designed to reduce the risk of particle intrusion and facilitate easy cleaning.
- Personnel control: These are areas where personnel change into cleanroom garments, including coveralls, gloves, masks, and hairnets. Air showers and pass-through chambers help remove contaminants from personnel before entering the cleanroom.
- Surface decontamination: Strict cleaning protocols are followed to maintain a contamination-free environment. Approved disinfectants are used to decontaminate surfaces and equipment.
- Monitoring and control systems: Continuous monitoring of temperature, humidity, particle counts, and air pressure is essential. Automated systems alert personnel to deviations from specified environmental conditions.
The Impact of Contamination
Contamination is a serious problem for pharmaceutical manufacturing. Contaminated products can lead to product failure and loss of revenue. They can also result in recalls that cost millions of dollars in replacement costs and damaged brand reputation.
For instance, a news article by The New York Times says that the FDA has recently recalled some eyedrops. The recall was because these eyedrops were linked to a drug-resistant bacteria. The bacteria has been associated with at least four deaths. The FDA recalled 26 products, which included CVS Health, Rite Aid, Rugby, and more.
In addition, contamination can have serious consequences for customers who use the drugs manufactured in your cleanrooms. If bacteria or fungi have contaminated a drug during production, it may be ineffective or even toxic at the recommended dose. This can lead to injury or death for patients taking this medication.
Cleanrooms in Action
Cleanrooms are used in various industries, including pharmaceutical manufacturing and aerospace. In the pharmaceutical industry, cleanrooms are used to produce drugs that require purity levels that cannot be achieved with normal air quality.
For pharmaceutical manufacturing, ISO 5 cleanrooms are usually used. Particles that are smaller than 0.5 µm aren’t considered in such cleanrooms. However, their concentration should be less than 3,520.
Cleanroom personnel must follow strict gowning procedures, including wearing special clothing such as coveralls, gloves, masks, and sometimes even shoe covers. This helps prevent contamination from human sources.
All equipment and materials brought into the cleanroom are thoroughly cleaned and sterilized. Pharmaceutical manufacturing equipment inside the cleanroom is designed to be easy to clean and resistant to particle generation. After meeting all these requirements listed by the FDA, you can start using cleanrooms for pharmaceutical manufacturing.
Regulatory Compliance and Quality Assurance
When it comes to pharmaceutical manufacturing, regulatory compliance, and quality assurance are key. The FDA has strict requirements for any facility that manufactures pharmaceuticals and GMP that must be followed at all times.
The FDA could reject your product or be recalled if you don’t follow these regulations. These strict requirements ensure that patients worldwide receive safe and effective medicines when needed. And this is why you should take such good care in maintaining your cleanrooms.
Cleanrooms help you maintain the purity of your products while keeping your employees safe from contamination by foreign substances like dust or bacteria. Hence, you should always follow the requirements listed by the FDA.
In its cGMP requirements, the FDA has focused on six vital things:
- Facilities and equipment
- Packaging and labeling
Through these quality controls, the FDA tries to ensure that all the pharmaceutical products manufactured meets are safe for use.
Cleanrooms are critical to the success of pharmaceutical manufacturing. They provide a controlled environment where contamination can be minimized and controlled, ensuring that each batch of medicine is as pure and safe as possible. This is especially important, considering how many people rely on these medications daily.