Means, Ranges and Replicates: Improving Microbial Plate Counting

A microbial colony is a visible cluster of microorganisms growing on the surface of or within a solid medium. This may be from a single cell or an amalgam of the same organism of more than one cell or a mix of different organisms. Bioburden levels are commonly measured when conventional methods are deployed in terms of colony-forming units (CFUs). These units provide an estimation of the number of viable bacteria or fungal cells found on a sample, expressed against a unit of measurement, such as per millilitre or per milligram.

When counting CFUs on solid microbiological culture media (agar) there are some aspects of ‘counting’ that need to be considered. These are:

a) Rounding and averaging

b) Significant figures

c) Countable range

d) Statistical error from low counts

This article looks at each of these aspects of the microbial plate count.

Sandle, T. (2025) Means, Ranges and Replicates: Improving Microbial Plate Counting, European Journal of Parenteral and Pharmaceutical Sciences, 30 (1): https://www.ejpps.online/post/means-ranges-and-replicates-improving-microbial-plate-counting 
 

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

From Flat to Functional: Recreating Human Microbial Environments with 3D Bioprinting

 

Image: Bioprinting of 3D Convoluted Renal Proximal Tubules on Perfusable Chips.Source: Homan K, Kolesky D, Skylar-Scott M, Herrmann J, Obuobi H, Moisan A, Lewis J (2016). "Bioprinting of 3D Convoluted Renal Proximal Tubules on Perfusable Chips". Scientific Reports. DOI:10.1038/srep34845

Not all microorganisms are harmful. In fact, our body naturally hosts tiny organisms like bacteria, viruses, and fungi that play essential roles in maintaining our health. Together, these helpful microbes make up what is known as the human microbiome. These beneficial bacteria and fungi aid in digestion, fight off harmful germs, and strengthen our immune system.

By Hannah Vargees 

Interestingly, these microbes don’t just interact with each other—they also interact closely with host tissues, immune cells, and environmental factors like pH levels, oxygen gradients, and nutrient availability within our body. Understanding these complex interactions is vital, especially when studying diseases or developing targeted therapies.

To study these interactions, scientists have traditionally relied on 2D cell cultures and animal models. But each of these approaches has its limitations.

First, let’s understand what 2D cell culture is. It involves growing human or animal cells on flat surfaces like plastic or glass dishes. These cells absorb nutrients from the surrounding media and spread out across the flat surface. While it’s a widely used and cost-effective technique, it doesn’t truly replicate how cells grow and behave in the human body. Flat growth alters cell behavior and signaling pathways, making it hard to recreate realistic tissue environments. Additionally, 2D cultures can’t support key features like biofilm formation or mucosal layering, both of which are essential for mimicking human microbial environments.

Next, we have animal models, which are commonly used to study diseases and drug responses. However, they come with their own challenges. There are species-level differences that are difficult to account for, and the immune responses in animals often differ from those in humans. This makes it challenging to translate findings directly into clinical outcomes, limiting their usefulness in drug development and microbiome studies.

This is where 3D bioprinting offers a promising solution. It allows scientists to precisely place cells in spatial arrangements that replicate tissue-like structures, enabling a more accurate and dynamic model of the human body. To create these structures, researchers use bioinks made from hydrogels like GelMA or alginate, which help simulate the natural tissue environment more effectively.

Hydrogels are particularly useful because they closely mimic the extracellular matrix (ECM) found in real tissues. They support cell growth, differentiation, and allow for the controlled diffusion of nutrients and oxygen. Moreover, they’re biocompatible and tunable, meaning they can be adjusted to match the mechanical and biochemical properties of specific tissues or organs.

In summary, while 2D cultures and animal models have laid the groundwork, 3D bioprinting is pushing the boundaries of how we study the microbiome and human health, offering more accurate, ethical, and customizable tools for modern research.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

How Vaccines Are Shaping the Global Public Health Landscape

Vaccines have long stood as one of the most powerful tools in the arsenal of public health. From eradicating smallpox to curbing the spread of polio and mitigating the devastating effects of COVID-19, immunizations continue to transform the health trajectories of entire populations. As the 21st century unfolds, vaccines are not only protecting billions from infectious diseases but are also reshaping global healthcare systems, economies, and policy frameworks. This article explores how vaccines are redefining public health, addressing challenges, and pointing toward a more resilient and equitable future.

The vaccines industry was valued at USD 119.1 billion in 2022 and is projected to grow at a compound annual growth rate (CAGR) of 4.2% from 2023 to 2031. By the end of 2031, the market is expected to reach USD 99.3 billion, driven by continuous innovations, increasing demand for immunization, and advancements in vaccine technology.

A Historical Turning Point

The history of vaccination dates back to the late 18th century with Edward Jenner’s smallpox vaccine. This moment marked the beginning of modern immunology and showcased the power of pre-emptive medicine. By the late 20th century, vaccines had led to the eradication of smallpox globally in 1980—a monumental achievement made possible by a coordinated international effort. The global incidence of diseases like diphtheria, measles, and tetanus dropped drastically due to widespread immunization campaigns.

The early success of vaccines laid the foundation for global public health strategies, shifting the focus from reactive treatment to proactive prevention. Over time, this has resulted in millions of lives saved, increased life expectancy, and improved quality of life across all continents.

Modern Vaccination: Expanding the Scope

In recent decades, the scope of vaccines has expanded significantly. No longer limited to childhood diseases, vaccines now target a broad spectrum of illnesses affecting people of all ages. For instance:

•    HPV vaccines help prevent cervical and other types of cancers.
•    Influenza vaccines are updated annually to combat ever-evolving viral strains.
•    COVID-19 vaccines rapidly developed using novel mRNA technology represented a leap forward in both science and logistics.

The development and deployment of new vaccines have also helped address emerging threats, such as Ebola and Zika. Importantly, the infrastructure built for COVID-19 vaccination campaigns—cold-chain logistics, data management, and public communication—now serves as a template for future public health initiatives.

Public Health Impact: Numbers That Matter

The benefits of vaccination are quantifiable and wide-ranging. According to the World Health Organization (WHO), vaccines currently prevent more than 5 million deaths annually from diseases such as measles, diphtheria, tetanus, pertussis, and influenza. A study published in The Lancet in 2021 estimated that between 2000 and 2019, vaccination efforts against ten major diseases prevented 37 million deaths globally.

Beyond mortality, vaccines reduce the burden on healthcare systems. They minimize hospital admissions, reduce the need for antibiotics (thereby combating antimicrobial resistance), and help avoid the long-term complications associated with many infectious diseases.

Economic benefits are also substantial. Every $1 spent on immunization is estimated to yield up to $44 in economic returns when considering productivity gains, healthcare savings, and avoided disease outbreaks.

Driving Equity and Access

Vaccination programs are crucial for promoting health equity. They are often the first line of healthcare in underserved communities and are integrated into national and global development agendas. Initiatives like Gavi, the Vaccine Alliance, and the COVAX facility have played pivotal roles in ensuring vaccine access in low- and middle-income countries.
Gavi, for instance, has helped immunize over 1 billion children since 2000, preventing over 17 million deaths. By subsidizing vaccine costs and supporting national health systems, such partnerships are bridging the gap between high-income and resource-poor countries.
Furthermore, immunization campaigns often reach remote and vulnerable populations, improving access to other essential health services such as nutritional support, maternal care, and disease screening.

Challenges on the Path Forward

Despite these advances, several challenges threaten to undermine global vaccination efforts:

1. Vaccine Hesitancy
One of the most pressing issues is vaccine hesitancy, fueled by misinformation, mistrust in governments, and social media conspiracies. The WHO listed vaccine hesitancy among the top 10 global health threats even before the COVID-19 pandemic. Countering this requires multifaceted approaches, including public education, transparent communication, and engaging trusted community leaders.

2. Supply Chain and Infrastructure
In many parts of the world, delivering vaccines to every individual is a logistical challenge. Poor infrastructure, lack of cold-chain storage, and conflict zones hinder access. Investments in transportation, refrigeration technology, and digital tracking systems are critical to ensure equitable distribution.

3. Emerging Diseases
New pathogens continue to emerge due to climate change, urbanization, and globalization. Rapid vaccine development, as demonstrated during COVID-19, must become the norm rather than the exception. This demands global cooperation in funding, research, and regulatory harmonization.

4. Global Disparities
There remains a stark contrast in vaccination rates between countries. While high-income countries boast over 90% coverage for most vaccines, many low-income nations struggle to surpass 60%. These gaps leave large populations vulnerable and increase the risk of disease resurgence.

Innovation and the Future of Vaccines

Science is continuously advancing the potential of vaccines. A few promising developments include:

•    mRNA Technology: Beyond COVID-19, mRNA platforms are being explored for HIV, tuberculosis, and cancer vaccines. Their adaptability and faster production cycles could revolutionize global response to new diseases.

•    Needle-free Vaccines: Innovations such as microneedle patches or oral vaccines aim to make immunization more accessible and acceptable, especially for children and those with needle anxiety.

•    Personalized Vaccines: For diseases like cancer, researchers are working on individualized vaccines based on a patient’s genetic profile to target specific tumor antigens.

•    Universal Vaccines: Projects like a universal flu vaccine aim to protect against all strains, reducing the need for annual updates and increasing reliability.

Vaccine Diplomacy and Global Cooperation

Vaccines have also become instruments of soft power and diplomacy. Countries that produce and distribute vaccines often gain geopolitical influence, building alliances and promoting international goodwill. However, the pandemic also exposed the darker side of “vaccine nationalism,” where wealthier nations hoarded doses, delaying access for poorer countries.

To build a more just system, the global community must embrace collaborative frameworks that prioritize collective security over individual gain. Mechanisms such as the Pandemic Treaty being discussed by WHO aim to ensure more equitable access and preparedness for future health emergencies.

Gather more insights about the market drivers, restrains and growth of the Vaccines Industry

CGMP Requirements For Automated Facility Monitoring Systems

 

Monitoring systems (image by Tim Sandle)

In pharmaceuticals and healthcare, “facility” refers to the operational space, such as a cleanroom. The critical controls that maintain the facility are delivered through key utilities like air handling systems. To assess facility control, most organizations use facility monitoring systems (FMSs) to monitor the manufacturing workspaces continuously. Such systems are designed to be always on when the facility is in the operational state, ensuring compliance with important parameters across identified ranges. An important element for microbiological control is particle counting, which verifies the class of the cleanroom and indicates how well control is being maintained. Interconnected devices provide continuous monitoring of facilities, including aseptic and controlled environments. Other environmental data is also of importance for the contamination control strategy, including temperature, humidity, air velocity, and pressure. The design of these automated environmental monitoring systems should be based on quality risk management principles.

Sandle, T. (2023) CGMP Requirements For Automated Facility Monitoring Systems, Outsourced Pharma, August 2023: https://www.outsourcedpharma.com/doc/cgmp-requirements-for-automated-facility-monitoring-systems-0001

Also in:

BioProcess Online: https://www.bioprocessonline.com/doc/cgmp-requirements-for-automated-facility-monitoring-systems-0001
Pharmaceutical Online: https://www.pharmaceuticalonline.com/doc/cgmp-requirements-for-automated-facility-monitoring-systems-0001
Cell and Gene: https://www.cellandgene.com/doc/cgmp-requirements-for-automated-facility-monitoring-systems-0001
Biosimilar Development: https://www.biosimilardevelopment.com/doc/cgmp-requirements-for-automated-facility-monitoring-systems-0001
 

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Addressing human factors in decontamination

Ensuring that surgical processing departments are well-run is of great importance, as these departments are responsible for decontaminating reusable surgical equipment and for delivering it, as required, to operating theatres. Decontamination involves several  processes, occurring within dedicated facilities, including cleaning, disinfection and sterilisation, which ensures reusable surgical instruments are safe for further use on patients.

The operation requires maintaining a well-ordered facility, ensuring it is clean and decontamination practices can be consistently reproduced. While most units have well-written procedures, human errors will happen and these can sometimes lead, in the most serious cases, to the transference of contamination and patient infection (healthcare-associated infections). While human failure is normal and predictable, it can be identified and managed. Hence, errors can be reduced by reviewing how surgical processing departments are managed and how personnel operate, in particular, by reducing the level of variability. An approach that can deliver success in this area is the ‘human factors method’.

This article looks at three areas where human factors approaches can assist with improving performance through lowering variability and, hence, reducing contamination rates. These are: Development of procedures; Training; Space and ergonomics. Prior to this, the article introduces the subject of human factors and looks at sources of variability within surgical processing departments.

Sandle, T. (2023) Addressing human factors in decontamination, Clinical Services Journal, 22 (7): 39-43
 

To read, see: Human Factors

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Glove disinfection and aseptic technique: Creating a schema for the cleanroom and laboratory

 

There are different elements that contribute to good aseptic technique within the cleanroom and the laboratory. One such element is the donning of gloves, handling items appropriately, and keeping gloves regularly disinfected. Glove disinfection is an essential step for bacteriological control, although how successful control is maintained is dependent upon the type of disinfectant (these are generally alcohols for gloved hands), frequency of application, volume of disinfectant, application technique and the contact time. Other variables include purchasing gloves of a suitable material and design, and appropriate training. Aa an added control with more critical areas, the gloves are pre sterilised before donning (often purchased sterile by radiation or ethylene oxide).

As with other types of disinfection, the aim is not ‘sterilisation’ but to bring any bacterial density present on the gloves down to a level that is as low as possible (what is sometimes referred to as the "irreducible minimum"). Assessment, when required, is commonly through the use of agar contact plates onto the fingertips of each gloved hand (four fingers and the thumb) to create the ‘finger plate’ or ‘finger dab’. To avoid false negatives, the agar needs to be formulated with an appropriate disinfectant neutraliser.  

For cleanroom and laboratory managers seeking to maximise the maintenance of asepsis, glove control is an important element. This should take the form of a good practice schema and for this to be transitioned into a training module, supported by regular prompts in practice.  

In terms of what such a schema should look like, this article appraises the research that underpins an appropriate glove ‘sanitisation’ schema. This includes the central concerns of when and how effective glove disinfection is to be achieved. The key findings are that a 30 second disinfection time is suitable for both cleanroom and laboratory operations, provided a suitable technique is deployed and an alcohol-based disinfectant used. However, controls need to be in place to avoid the over disinfection of gloves since repeated applications increase the likelihood of microperforations occurring and thereby effective glove disinfection needs to be supported by a regular glove change procedure.  

Sandle, T. Glove disinfection and aseptic technique: Creating a schema for the cleanroom and laboratory, European Journal of Parenteral and Pharmaceutical Sciences, 28 (2): https://doi.org/10.37521/ejpps.28201
 

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Key considerations for the selection of pharmaceutical equipment cleaning chemicals

Cleaning validation verifies the effectiveness of cleaning processes within pharmaceutical and healthcare facilities. It should be directed to situations or process steps where contamination or the carryover of materials pose the greatest risk to product quality (1), as evaluated to appropriate limits (2). To ensure cleaning process robustness, care must be taken in the selection of cleaning chemicals. This article looks at the choices available and some of the important selection factors for cleaning chemicals.

To determine the most appropriate chemicals, an understanding of the products is needed, especially with the selection of the most appropriate in-process material for the cleaning validation (3). This choice should be based on factors like solubility, difficulty of cleaning, the different types of equipment to be cleaned and the calculation of residue limits based on potency, toxicity, and stability.

Sandle, T.: Key considerations for the selection of pharmaceutical equipment cleaning chemicals, RSSL Insights, April 2023: https://www.rssl.com/insights/life-science-pharmaceuticals/key-considerations-for-the-selection-of-pharmaceutical-equipment-cleaning-chemicals/
 
Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Small Steps to Giant Leaps: Advancing Data Integrity in Sterility Testing

Webinar

With Sterility Testing serving as the final critical data point for product release to the public, the Pharmaceutical Industry is continually looking to methods which will increase efficiencies and reduce errors.

What if there was a software that could work with your existing Steritest^® Symbio pump and also allow you to digitally capture every step of the Sterility test? 

You may have already about the M-Trace^® 21 CFR Part 11 compliant solution, giving step-by-step handling instructions, while collecting all relevant data in realtime. The system has launched its second version, which is now Microsoft Windows compatible, providing easier integration in your company IT infrastructure.

Agenda:

• M-Trace^® solution existing and new features that enable seamless integration with your Steritest^® Symbio pump and with your current IT environment
• Importance of capturing every action during Sterility Testing to improve operational efficiency and reduce errors
• Practical examples of how digitalization can transform your facility's testing procedures and support compliance with Standard Operating Procedures (SOPs)
• Live Q&A

Speakers:

• Michel van Musschenbroek: Regional Application & Commercial Tactics Manager, North America, Merck KGaA
• Nicolas Lelièvre: Regional Application & Commercial Tactics Manager, Western Europe, Merck KGaA

Language:

• English, but live translation in Japanese and Spanish (subtitles)

Time and date

May 13 at 10:00am CEST (Paris) / 4:00pm SGT (Singapore) / 5:00pm JST (Tokyo)     

Link to register: https://event.on24.com/wcc/r/4903610/5BDE8D3C78E8CDB11007DF9A05049616?partnerref=PMRWeb

 

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

New store for microbiology themed gifts: BabblingBacteria

 

BabblingBacteria is a new shop selling a range of microbiology themed gifts, uniquely designed by Tim Sandle.

T-shirts, color chnaging mugs, cool posters, light catching decorations and even a special irradiation fragrenced candle!

Please visit here: Babbling Bacteria.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Best practices for pharmaceutical microbial data investigations

Assessing microbiological data and undertaking investigations into the origins of contamination, establishing root causes, and setting appropriate preventative actions constitutes a core part of the contamination control strategy. Despite the importance of this process, regulatory findings frequently cite poor quality microbial investigations.

This article looks at the main steps involved for conducting investigations and provides some best practice advice for the company microbiologist. The goals here are to help to structure investigations that are:

Simple:    Easy to execute and to understand,
Effective:    Producing the correct result.

The advice is presented as a series of phases. While the phases represent activity blocks, they should not necessarily be thought of as discrete entities for they can run concurrently or may overlap. This is especially useful in order to complete a detailed and thorough investigation within a reasonable timeframe (as with other investigations undertaken within pharmaceuticals, a target of 30 days is often applied).
 

See:  https://www.americanpharmaceuticalreview.com/Featured-Articles/596293-Assessing-Microbial-Contamination-Best-Practices-for-Pharmaceutical-Microbial-Data-Investigations/?cid=26759

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Cleaning Up in BioPharma

As the therapeutic landscape grows more complex, so too must the analytical techniques for cleaning validation to ensure the utmost cleanliness is achieved.

Within the bio/pharma industry, there is a certain expectation for companies to maintain required levels of cleanliness within their facilities to ensure products that are manufactured are at minimal risk of contamination. All cleaning processes must also be validated for effectiveness and reproducibility.

As drug products become more complex and sensitive to potential contaminants, there is an increasing demand for cleaning validation throughout industry. According to market research, the cleaning validation market is forecasted to grow by a compound annual growth rate of 5.7% between 2021 and 2027.

See: https://www.biopharminternational.com/view/cleaning-up-in-bio-pharma
 

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Four Ways to Minimize Operational Risk in Cleanrooms

What would it cost your business if your cleanroom was down for a day? A week? A month? The financial impact could be staggering, with potential revenue losses reaching into the millions. On average, there are over 500,000 detectable earthquakes each year. Of those, at least one major earthquake—those with a magnitude of 7.0 or higher— takes place each month, bringing the risk of severe damage and even casualties.

For the pharmaceutical industry, cleanroom downtime can cost between $10,000 and $50,000 per day. For semiconductor manufacturing, that cost rises significantly, ranging from $100,000 to $1 million per day. With their potential to disrupt structural integrity, airflow, and equipment, earthquakes can quickly compromise the very essence of what makes a cleanroom effective: cleanliness and contamination control.

Seismic-rated cleanrooms are becoming increasingly important, particularly in earthquake-prone regions such as California, Oregon, and Washington. In this article, we highlight the six considerations cleanroom professionals need to keep in mind when building a seismic-rated cleanroom and why these precautions are vital for operational safety, regulatory compliance, and avoiding cleanroom downtime.

How Earthquakes Impact Cleanrooms

In its simplest form, a cleanroom is designed to prevent particle contamination and create a controlled environment, factoring in temperature regulation, air filtration, and air flow. Seismic events can cause structural damage to cleanrooms, including cracks in the walls, damaging internal partitions, and even result in collapsed ceilings. When this occurs, the delicate, controlled environment can quickly become contaminated, jeopardizing both operations and the safety of those working within it.


“During an earthquake, the shifting foundation of the building that the cleanroom sits on and the goal of maintaining the precise environment is the biggest challenge,” said Mark Zabala, senior sales manager at SERVICOR™ by Nortek Air Solutions. “Cleanrooms in areas with earthquake risk need to be designed to not only survive the event, but also to maintain their cleanroom classification level in order to remain operable.”


Seismic standards are put in place to ensure that buildings and structures can withstand the forces of an earthquake. During an earthquake, not only is the structural integrity of the building at risk, but so is the safety of occupants and the delicate process taking place in the cleanroom.


California sits in a seismic zone 4 and experiences two to three major earthquakes each year. “In California alone, our modular cleanrooms, SERVICOR™, have experienced at least 90 earthquakes since 1983,” explained Zabala. “When we design a cleanroom for seismic rating, we engineer the cleanroom to exceed seismic zone 4 requirements, not only ensuring that operations continue after a seismic event, but eliminating the concern that if relocated to a different location, the cleanroom would need to be re-engineered to meet stricter seismic zone requirements.”


From the destruction of expensive equipment to contamination risks, or even the injury of personnel, a poorly designed cleanroom could expose an organization to catastrophic losses. The seismic rating of a cleanroom ensures that both the building and its contents are secure in case of an earthquake.


Each day of downtime means halted production, missed deadlines, and dissatisfied customers. In an industry where precision and reliability are paramount, even a minor disruption can have major financial repercussions.


Designing to Minimize Risk and Revenue Loss

Taking into account the frequency of earthquakes and where the cleanroom will operate, there are four factors to keep in mind:


1. Meeting versus Exceeding Seismic Ratings

Before designing a cleanroom, it’s crucial to understand the seismic requirements specific to its future location. In the U.S., there are four seismic zones based on the level of seismic activity, with zone 4 attributed to the highest risk zone.


Pacific coast states California, Oregon, and Washington are in high seismic zones, requiring their cleanroom structures to be built to withstand earthquakes of considerable size. Specifically, California requires all cleanrooms to meet seismic zone 4 standards. With the likelihood of a magnitude 8 or larger earthquake hitting California in the next 30 years rising from 4.7% to 7.0%, designing for seismic activity continues to be more important than ever.


With the flexibility in modular cleanrooms to be adaptable and moveable for future use, cleanroom owners should consider the lifespan of their cleanroom needs, not just where the cleanroom will sit today. “We designed SERVICOR™ to exceed seismic zone 4 requirements, eliminating the need for retrofitting the cleanroom if it is moved to a higher seismic zone and giving operators the peace of mind, no matter where the cleanroom sits,” said Zabala.


2. Designing for Load Distribution

Weight load distribution is critical in seismic-rated cleanrooms. Each piece of equipment should be appropriately anchored to ensure that it does not shift, tip, or fall during seismic activity. “When we design a cleanroom with steel ceilings, like SERVICOR™ Modular Cleanrooms, we eliminate the need for hangers, which allows us to design a self-supporting cleanroom and ultimately achieve a seismic rating,” said Zabala. The welded ceiling grid modules cradle the often heavy ceiling components including lights, ceiling tiles, and fan filter units. These features create the sturdy structure, while minimizing additional load and strain to the existing structure.


A self-supported cleanroom system does not rely on support from the building’s structure and is designed with floor anchors to ensure stability, minimizing the risk of a cleanroom being damaged or collapsing during an earthquake. This approach prevents unnecessary load on the building’s existing infrastructure and reduces the potential for cascading failures.


3. Working with a Structural Engineer

One of the key steps when building a seismic-rated cleanroom is collaborating with licensed structural engineers to perform thorough calculations and provide certification. Structural engineers are critical in evaluating the seismic impact on cleanroom systems and ensuring that the design meets local codes and regulations.


Engineers will conduct detailed analyses to ensure that the cleanroom’s materials and systems are designed to absorb and distribute seismic forces evenly, reducing the risk of structural failure. “Once the drawing process is complete, plans are sent to a structural engineer to confirm compliance,” explained Zabala. “If any modifications are required, they’ll be submitted for customer approval and proceed with manufacturing.”


4. Maintaining the Cleanroom

Maintenance and inspections are standard requirements to ensure that a cleanroom is operating at the required class level/ISO level. Cleanrooms are dynamic environments with equipment that needs continual monitoring, in fact the lack of appropriate monitoring and documentation is one of the most common pitfalls cleanroom operators have. With modular cleanrooms providing ultimate flexibility, any future upgrades or reconfigurations need to adhere to seismic rating standards.

The Risk of Not Being Prepared

Not only is there significant revenue loss when a cleanroom is down, but there are the significant costs of replacing damaged equipment. In fact, the cost of non-structural elements in a cleanroom accounts for nearly 80-90% of the total cleanroom cost, including the costs of repairs, replacing damaged equipment, and the lost productivity.

Equipment Replacement: Cleanrooms often house sensitive equipment, including microscopes, manufacturing tools, and other specialized equipment. All would need to be tested to ensure it is properly functioning and potentially replaced.


Contamination Control: If a contamination occurred during an earthquake, not only would the products within it be compromised and lead to quality issues, but the cleanroom itself would need extensive cleaning and decontamination to restore to proper usability.


Managing Insurance Premiums: Buildings with seismic ratings often have lower insurance premiums due to the reduction in risk, which can range from 10-20%. On the flip side, premiums may increase after an earthquake if the cleanroom is not rated for the correct seismic zone.

“A seismic-rated cleanroom isn’t just about surviving an earthquake,” concludes Zabala. “It’s ensuring that operations can continue as smoothly as possible. With the right partner, materials, systems, and planning, you can create a space that is as resilient as it is clean.”


With an increase in cleanroom demand, designing for structural resilience and maintaining the integrity of cleanroom systems, even during a power outage, are important to minimizing contamination within a cleanroom. With experienced cleanroom partners and proper planning, cleanrooms can withstand seismic events and maintain required cleanliness levels.


About Mark Zabala

With 19 years of experience in the cleanroom industry, Mark Zabala’s comprehensive skill-set spans field installations, site coordination, cleanroom design, and engineering. Mark has been involved with IEST as a voting/contributing member in several working groups, as well as an active member of ISPE, ASHRAE, and SEMI. His extensive background enables him to gather critical insights in his role as senior sales manager at Nortek Air Solutions CleanSpace that lead to the successful implementation of cleanroom systems for customers and partners alike.


About Nortek Air Solutions

With world-class brands like CleanPak®, Huntair®, SERVICOR®, Temtrol®, Governair® and Mammoth® Nortek Air Solutions produces innovative, safe cleanroom solutions that meet and exceed strict contaminant and particulate-free environment standards so that customers can continue creating products that make the world safer, healthier, and more productive. Nortek Air Solutions has engineered over 20 million square feet of cleanroom systems that exceed strict contaminant and particulate-free regulations to keep the world’s most innovative spaces running. Learn more about NortekAir.com. 

Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Pharmaceutical Water and Its Critical Role in Biopharmaceutical Manufacturing

 

Pharmaceutical water is a vital component in biopharmaceutical manufacturing, playing a critical role in various processes, from drug formulation to cleaning and sterilization. Water quality directly impacts the safety, efficacy, and consistency of pharmaceutical products. The stringent regulatory standards set by agencies such as the United States Pharmacopeia (USP), European Pharmacopoeia (EP), and the World Health Organization (WHO) underscore the importance of maintaining high purity levels. This article explores the types, production, regulatory requirements, and significance of pharmaceutical water in biopharmaceutical manufacturing.

Global pharmaceutical water industry, valued at US$ 37.1 billion in 2023, is expected to grow at a CAGR of 8.3% from 2024 to 2034, reaching US$ 89.9 billion by 2034.
Increase in demand for pharmaceutical production and continuous implication of regulatory compliance and quality standards is fueling the global pharmaceutical water market trajectory. Pharmaceutical water is essential in drug formulation, manufacturing, and research, as specific grades, such as Water for Injection (WFI) and Purified Water, are vital to ensuring the efficacy and safety of medicines.

Types of Pharmaceutical Water

There are multiple grades of pharmaceutical water, each designed for specific applications in biopharmaceutical manufacturing. The most commonly used types include:

1.    Purified Water (PW) – Used in the preparation of non-sterile pharmaceutical products, cleaning, and as a raw material in drug formulation.

2.    Water for Injection (WFI) – Highly purified water free from pyrogens, used in the production of parenteral drugs and cleaning processes.

3.    Highly Purified Water (HPW) – Used in processes requiring extremely high purity, such as ophthalmic and inhalation solutions.

4.    Sterile Water for Injection (SWFI) – Used as a diluent for injectable drugs and must be free from microbial contamination.

5.    Bacteriostatic Water for Injection (BWFI) – Contains antimicrobial agents and is used in multiple-dose injections.

6.    Water for Hemodialysis – Specially treated water used in dialysis treatments to prevent contamination in the bloodstream.

Each type of water has stringent quality specifications, requiring advanced purification processes to meet regulatory standards.

Production and Purification Processes

The production of pharmaceutical water involves multiple purification technologies to remove contaminants, microorganisms, and endotoxins. Some of the most common purification methods include:

•    Reverse Osmosis (RO): Uses semi-permeable membranes to remove dissolved salts, bacteria, and other impurities.

•    Distillation: A process that involves boiling water to produce steam, then condensing it back into liquid form to ensure high purity.

•    Ultrafiltration: Removes particles and high molecular weight substances such as pyrogens and endotoxins.

•    Deionization (DI): Utilizes ion-exchange resins to remove charged particles, including heavy metals and minerals.

•    UV Radiation: Used for microbial control by disrupting the DNA of bacteria and viruses.

A combination of these methods ensures that pharmaceutical water meets the necessary purity standards for its intended use.

Regulatory Standards and Compliance

Regulatory agencies have established strict guidelines to ensure the safety and efficacy of pharmaceutical water. Some key standards include:

•    USP <1231> Water for Pharmaceutical Purposes: Provides guidelines on the production, quality, and validation of pharmaceutical water.
•    EP Monographs: Defines specifications for different grades of pharmaceutical water in Europe.
•    WHO Guidelines: Outlines best practices for pharmaceutical water systems, particularly for WFI and PW.
•    Good Manufacturing Practices (GMP): Ensures that water systems are validated and consistently produce high-quality water.
Manufacturers must implement routine monitoring, validation, and documentation practices to comply with these regulatory requirements.

Role of Pharmaceutical Water in Biopharmaceutical Manufacturing

Pharmaceutical water is integral to every stage of biopharmaceutical manufacturing. Its applications include:

1. Drug Formulation

Water serves as a solvent in the preparation of liquid, injectable, and ophthalmic drugs. The purity of water ensures that there are no contaminants that could affect drug stability or patient safety.

2. Cleaning and Sterilization

High-purity water is used for cleaning production equipment, vessels, and surfaces in pharmaceutical facilities. Proper sterilization prevents cross-contamination and maintains aseptic conditions.

3. Cell Culture and Bioprocessing

In biopharmaceutical manufacturing, water is used in cell culture media preparation, buffer solutions, and upstream processing. High-purity water prevents microbial growth and ensures optimal conditions for cell development.

4. Parenteral Drug Production

Water for Injection (WFI) is essential for the manufacture of intravenous drugs, vaccines, and biologics. Its pyrogen-free nature is crucial for patient safety.

5. Quality Control and Analysis

Pharmaceutical water is used in analytical laboratories for sample preparation, reagent formulation, and instrument calibration, ensuring accuracy in quality control tests.

Challenges and Considerations in Pharmaceutical Water Systems

1. Microbial Contamination

Maintaining microbial control in pharmaceutical water systems is critical. Bacteria and biofilm formation can compromise water quality, necessitating regular sanitization and monitoring.

2. System Design and Maintenance

Pharmaceutical water systems must be designed with minimal dead legs, proper flow rates, and appropriate material selection to prevent contamination and corrosion.

3. Regulatory Compliance

Manufacturers must continuously validate water systems, conduct risk assessments, and adhere to evolving regulatory requirements to maintain compliance.

4. Energy and Resource Efficiency

Water purification is energy-intensive, requiring strategies to optimize energy use and reduce waste. Implementing closed-loop systems and recycling water can improve sustainability.

Future Trends in Pharmaceutical Water Systems

1. Advanced Purification Technologies

Innovations in Nano filtration, membrane bioreactors, and electro-deionization are enhancing the efficiency and sustainability of pharmaceutical water systems.

2. Automation and Real-Time Monitoring

The integration of automated monitoring systems and real-time analytics is improving quality control, reducing contamination risks, and ensuring regulatory compliance.

3. Sustainable Water Management

As environmental concerns grow, pharmaceutical manufacturers are investing in water reuse, desalination, and green technologies to minimize water consumption and reduce waste.

4. Regulatory Evolution

Regulatory bodies are continuously updating guidelines to incorporate new scientific insights and technological advancements in pharmaceutical water systems.

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Author

Kaustubh Ravan is a passionate market research analyst and writer specializing in emerging industry trends and market dynamics. With expertise in diverse sectors, he delivers in-depth insights and data-driven reports. His work helps businesses navigate evolving markets and make informed decisions. Kaustubh analytical approach and keen industry foresight make him a trusted voice in market research.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)