Fuel Monitoring Matters

Single-use solutions have been widely adopted on a global scale within the biopharmaceutical industry due to the many advantages and process improvements they offer.

Key applications for single-use assemblies include the creation of process fluid flow paths, buffer/product storage solutions and sampling systems on varying scales. 

Most of these systems will start with either a bioprocess container or a tubing option and require the ability to connect to further pieces of equipment or additional single-use systems/manifolds.

In order to achieve this connectability, some form of connection needs to be selected — but with so many different connection types available, where should biopharmaceutical manufacturers start?

There are many different options available when embarking on the selection process. Consideration must be given to whether the connection type needs to be aseptic to provide quick and easy sterile connections, (even in non-sterile environments) or non-aseptic (to provide quick and easy non-sterile connections).

The choice should be guided by the process itself — and the capability of the manufacturing plant should also be taken into account. 

Key factors which will determine the correct choice of connection type include:

• Whether the connection is to be made inside or outside of a laminar airflow hood.
• Whether the connection needs to address any specific safety requirements.
• Process conditions and compatibility.
• Bioburden control.
• Experience of operatives.
• Suitability for purpose.

Only when these factors have been addressed can the end-user begin to fully specify the connection type required. 

The Luer connector is the simplest connector. It consists of both a male and female form, and the connection is made using a twist-lock action. These connections are suited to sample lines (with syringe connectivity) and low flow narrow-bore tubing applications and can be used within a laminar airflow hood to create aseptic connections.

However, there is a downside: potential misconnections can occur when they are not mated correctly. 

Quick connectors such as the MPC, MPX or MPU from CPC (Colder Products Company) are similar to Luer connectors in that they can be used within a laminar airflow hood to create aseptic connections. They have the added security of a push-fit feature with a secure locking mechanism. 

Triclamp (sanitary style) fittings can be used as connectors. While these are effective and secure connections, care must be taken to position the required o-ring seal within the connection prior to fixing the connection using an external clamp. The sheer size of the external clamp may make this an unsuitable method for connecting narrow bore or thin-walled tubing due to the weights involved and the potential for kinking/doubling of the attached tubing. Triclamp connections can be used within a laminar airflow hood to create aseptic connections. 

Should aseptic connections be required to be made outside of a laminar airflow hood, two options are available, which both allow the connection of varying tube sizes:

The first option for connecting aseptically in a non-aseptic environment would be to use a gendered aseptic connector, such as CPC AseptiQuik® gendered, which has both a male and female version. The benefit of using a gendered connection is that it can help by safeguarding which lines can be connected to certain points in the process; this helps to mitigate against human error and the accidental connection of the incorrect lines/equipment.

When designing single-use assemblies using a gendered connector approach, care must be taken to ensure that the correct male / female side is designed into each part; this in itself can also create some areas for error to creep in. 

Should the end-user not have any concerns over an accidental connection to the incorrect lines/equipment, or simply want to remove the error of male/female connector type which can creep in during design, there is the genderless aseptic connector, such as CPC AseptiQuik® genderless. These connectors take out the requirement for designing in the correct male/female orientation and can enable universal assemblies to be manufactured and connected with many other assembly/equipment types. 

Both gendered aseptic connectors and genderless aseptic connectors operate via a mechanism that enables connection in non-sterile environments to be made possible. This is because of the use of proprietary seals which mate together before a protective seal is removed, thus keeping the process stream in its aseptic/sterile condition. 

Should sterile connections between traditional stainless steel biopharmaceutical processing equipment and single-use assemblies be required, there is another option:

Steam to connectors, such as CPC Steam-Thru®, work by allowing steam to pass through the section connected to the stainless steel equipment. Once steamed and connected, a valve within the connector is manipulated, creating a sterile or aseptic flow path. 

It is apparent that there are many connections capable of creating or maintaining an aseptic/sterile environment, but without the correct process condition assessment, operator care or design considerations, biopharmaceutical manufacturers could be looking at a costly connection failure. 

Download our white paper to find solutions to more single-use challenges: Single-Use Technology: The Next 5 Challenges to Conquer

This post was contributed by Graeme Proctor, product manager (single-use technologies), Parker Bioscience Filtration, United Kingdom.

Parker Bioscience Filtration specializes in automating and controlling single-use bioprocesses. By integrating sensory and automation technology into a process, a manufacturer can control the fluid more effectively, ensuring the quality of the final product. Visit www.parker.com/bioscience to find out more. 

Eliminating Leaks and Faults: Single-Use vs Stainless Steel Systems

Five Critical Challenges in Single-Use Bioprocessing

5 Benefits of Single-Use Technology vs Stainless Steel

Today, cement manufacturing plants have to contend with a double-edged sword: How do they reduce production costs and still meet environmental regulations? How do they accomplish their goals and directives while maintaining their equipment in a manner that prevents unscheduled downtime and hazardous conditions? Reducing the cost of fuel is a common strategy employed within the industry; in turn, this has led to an increase in the substitution of coal with petcoke.

One area that has been impacted by the use of petcoke is the coal mill dust collector. Coal mill dust collectors have a substantial effect on productivity, yet have received relatively little attention as companies implement cost-saving programs, like the use of petcoke as a fuel reduction measure. Petcoke is typically ground finer than coal, and it has a particularly sticky nature that makes it more difficult to clean from filter bags. Its high sulfur content increases the likelihood of corrosion. All of these things bring into question whether the dust collector in use is properly designed for the conditions and if the operation and maintenance plan is effective in preventing system upsets and safety concerns. 

Here, we'll discuss effective design, operation and maintenance tips for this critical component of the coal grinding circuit and what you can do to evaluate the readiness of your coal mill dust collector.  

For complete recommendations on maintaining and operating coal mill dust collectors and how to reduce unscheduled maintenance, downtime and emissions, download the full article.

Dust collector operators must take into consideration these items as they evaluate their current equipment design:
 

An air-to-cloth ratio that does not exceed 3.5 ACFM per 1 square foot is recommended to prevent short filter life, high differential pressure, higher emissions and operating costs.
 

An undersized system can cause an excessive buildup of combustible material on the filter bags. The use of single diaphragm pulse valves or valves that are smaller than 1.5 inches often requires an upgrade.
 

Defined as the upward velocity of dust-laden gases between filter bags, excessive can velocity can result in higher pressure drop and excessive dust accumulation. For a coal mill dust collector, velocity should not exceed 240 fpm or 1.22 m/s.

Polyester, acrylic and aramid filter bag fabric materials require a dust cake for fine particle filtration. This can lead to an increased risk of combustion. Opting for an ePTFE membrane material, like the BHA Preveil filter from Parker Hannifin does not require a dust cake, reducing the combustion risk.  

BHA Preveil filters are made from PTFE resin, a substance with inherent non-stick properties that can be used to help your dust collector operate at maximum efficiency by providing:

• 99.99% efficiency
• Higher airflow
• Better cleaning
• Optimum emissions control

Proper inlet design distributes gas flow evenly and eliminates abrasion issues, which cause holes in the bags and increased emissions.
 

A steel, air-tight housing and hopper, free of shelves or other particle accumulation areas, equipped with level and temperature measurement devices is recommended to prevent hazardous conditions. To avoid buildup of combustible materials, hopper walls should be designed with a minimum angle of 70 degrees from horizontal.
 

A lack of insulation can result in moisture and accumulation of combustible dust. When petcoke is used this can also result in the increased formation of sulfuric acid and eventual corrosion of the dust collector.
 

It is essential that material handling equipment can withstand surges. A good practice is to size the equipment to the capacity of conveying equipment, even if the actual requirement is substantially less. Equipment should be equipped with motion sensors.

With a properly designed dust collector, good operational practices can result in a reduction of downtime, emissions and hazardous conditions. The following practices are recommended:

• Startup and shutdown procedures: Establish specific, written protocols.
• Regular dust collector inspection: Checking pressure drop, visible emissions, the cleaning system, material withdrawal equipment, damper settings and fan operation once per shift is a recommended practice.
• A staggered sequence of actuation of the cleaning system pulse valves: This will reduce dust recirculation and pressure drop across the filter bags.
• Continuous operation of the cleaning system and material removal equipment: This will help to prevent the excessive dust accumulation on the filter bags and in the hopper.

For complete recommendations on maintaining and operating coal mill dust collectors and how to reduce unscheduled maintenance, downtime and emissions, download the full article.

Contributed by the Filtration Team.

Related content

Choosing the Best Dust Collector for Air Quality Control in Manufacturing

Filter Upgrade Improves Baghouse Performance in Industrial Manufacturing

Reducing Dust Collector Maintenance and Energy Costs in the Cement Industry | Case Study

Lowering Emissions to Meet NESHAP PM Limits in Cement Manufacturing

In the biopharmaceutical industry, extractables and leachables have come under the spotlight as stainless steel manufacturing systems have given way to single-use assemblies in manufacturing operations. 

Yet, there is some confusion as to what the terms 'extractables' and 'leachables' actually mean. They are often talked about interchangeably, but there are actually distinct differences between the two. 

Extractables studies are an assessment performed on a material. They are performed to identify substances that a patient may be exposed to and are typically conducted using 'worst-case' conditions. 

Leachables studies are an assessment performed on the drug product to identify substances that patients are potentially exposed to and are typically conducted using 'true process' conditions. 

Learn about different approaches to extractables and leachables testing in our white paper: Demystifying Extractables Testing

Due to the nature of plastics and the potential release agents and plasticizers used in their manufacturing processes, there is potential for some of these to be released into the biopharmaceutical process stream. 

In a single-use assembly, numerous components have the potential to contribute to extractables and leachables. These include tubing, connectors, bags, bottles and filters. Therefore, the whole assembly should be assessed collectively. 

Every plastic will have some degree of compound leaching or release, but each compound may not be given equal importance with regard to what is allowed or is applicable to the process stream. 

As there is no 'one size fits all' with regard to what is and isn't allowed for many compounds, end-users need to assess the risk based on a number of factors. 

Risks and assessment can be categorised into:

• Those which impact on patient safety, for example toxicological effects
• Those which relate to technical factors, such as process control and regulatory approval
• Those which relate to social factors and perceived negativities, such as social media trending of compound 'buzz words'.
   

Vendors usually take on the responsibility of performing extractables studies, while end-users taken the leachables part - as these studies should be conducted using 'true process' conditions. However, there remains some confusion over what a vendor should provide. 

In our Demystifying Extractables Testing webinar, we asked participants what their expectation was of a single-use vendor's role in extractables and leachables studies. 

While more than 70 percent of respondents believed that the vendor could only offer extractables data, more than 20 percent responded that both extractables and leachables data should be supplied by the vendor. However, leachables data needs to come from a true process stream that only the end-user would have access to. 
 

The vendor would take the following steps:

• Selection of component parts - selection and materials of construction would be scrutinized, ensuring that as much as possible, industry-standard components or materials are used
• The material of construction - product contact materials and additives would be considered
• Assessment of stability to irradiation
• Assessment of stability to common biopharmaceutical process solutions and chemicals
• Assessment of further manufacturing process steps which would have the ability to change or add compounds which could be released

The vendor would then either perform their own extractables study, or obtain the extractable data set from their supply chain in order to identify 'worst-case' released compounds under extreme conditions. 

The outcome from the vendor's point of view would be to:

• Ensure that products have patient safety at the forefront
• Instill confidence with their customers that they are supplying good quality characterized consumables
• Ensure that, throughout the supply chain, there is control over the individual component parts
• Understand any interactions which may occur that could have the ability to negatively affect customer processes
   

The customer would take the following steps:

• Selection of component parts - customers may have experienced negative effects on their own processes with specific components used within singe-use assemblies. This may inform their choices

• The material of construction - product contact areas and any additional additives would be key considerations
• Stability to irradiation, process streams, solvents and chemicals would be assessed

The process would then be mapped out to ensure that all components are compatible for their intended use. The next step would be to take the 'worst-case' extractables data from the vendor and risk assess this based upon knowledge of their process.

This helps the customer understand how componentry will behave, but to satisfy regulatory bodies, further 'leachable' studies may need to be performed using the actual process stream intended for use with the assembly. There is generally more process risk from extractables and leachables as the process progresses. Released compounds early in the process may be removed through processing steps, but as the process reaches its final formulation, the risk attached to any released compounds present exponentially increases. 

The outcome of this data generation from the customer's point of view would again be to:

• Ensure that the products they supply always have patient safety at the forefront
• Ensure that their manufacturing process and drug product is consistent and 'in-control', in order to receive regulatory approval
• Ensure that there is control over the individual component parts throughout the supply chain, and to understand any interactions which may occur and could negatively affect processes
   

It is vital that there is clarity across the biopharmaceutical manufacturing industry on the importance of extractables and leachables studies and who should carry out the studies. And, while both vendors and customers may have different reasons for carrying out testing, the end goal for both parties is the same. 

Learn more about extractables and leachables testing in our white paper: Demystifying Extractables Testing

This post was contributed by Graeme Proctor, product manager (single-use technologies), Parker Bioscience Filtration, United Kingdom.

Parker Bioscience Filtration specializes in automating and controlling single-use bioprocesses. By integrating sensory and automation technology into a process, a manufacturer can control the fluid more effectively, ensuring the quality of the final product. Visit www.parker.com/bioscience to find out more. 

5 Benefits of Single-Use Technology vs Stainless Steel

Five Critical Challenges in Single-Use Bioprocessing

Filtration and Biopharmaceutical Process Protection

Eliminating Leaks and Faults: Single-Use vs Stainless Steel Systems

Design Space and its Use in Single-use Bioprocessing

Has Single-use Customization Gone too Far?