Q. We have several tablet formulations that are dwell-sensitive—they require more time under compression than other formulations. Given increasing demand, we do not have the luxury of slowing the tablet presses down in an effort to increase that dwell time. How can we maximize dwell time and maintain or increase output in our tablet presses?

A. The issue of dwell time (i.e., the brief time that the flat top surface of a punch remains in contact with a compression roll) has always been of great importance for compressing granules or powders that are not easy to form into tablets. Generally, the longer a product can remain under peak compression, the better the chances of compressing it to the required hardness. Making small changes to the size of the compression roll does not extend dwell time. An effective system recently developed by some press manufacturers allows operators to add another pair of compression rolls to the press easily. Not only does this system increase dwell time by 50%, but it also provides the user with the option of running bilayer tablets on a single-sided press, where the additional station acts as a tamping station for the first layer.

Some of the same press manufacturers have also developed technologies for dramatically increasing the number of stations on a single-sided press without increasing the overall size of the machine. The result is a single-sided press that occupies the footprint of a single-sided machine, although its output begins to approach that of a double-sided machine. The end user therefore enjoys maximized efficiency in the footprint-to-output ratio of the machine, which permits the best use of available real estate within the manufacturing area.

—Matt Bundenthal, technical writer for Fette Compacting America

If you have a problem with your equipment or process, an industry expert may have the solution. Please send your question to 

 and we may be able to provide an answer in a future issue. All questions will remain anonymous.

Articles

Troubleshooting

We have several tablet formulations that are dwell-sensitive-they require more time under compression than other formulations. Given increasing demand, we do not have the luxury of slowing the tablet presses down in an effort to increase that dwell time. How can we maximize dwell time and maintain or increase output in our tablet presses?

Increasing Dwell Time without Decreasing Output

Banner Engineering 
 Photoelectric sensor detects clear objects


 Banner Engineering has added the Q26 Series photoelectric sensor to its line of clear-object detection sensors. The unit’s polarized retro coaxial design enables it to detect clear, translucent, or opaque objects, including mirrorlike surfaces. The design also enables precise leading-edge detection, thus making the detector appropriate in high-speed applications. The sensor operates at short distances and is suitable for pharmaceutical vial-filling operations.

The Q26 has a compact cubic shape intended to allow users to install it quickly in tight locations. The unit includes an LO–DO switch that enables operators to control the output type. A single-turn potentiometer lets users adjust detection sensitivity. The Q26 unit also communicates its operation and connection status, thus allowing the user to ensure reliable sensor performance.

The photoelectric sensor operates with a response speed of 250 µs. The device is also protected against damage from potential miswiring during installation and transient voltage spikes during operation.

Eriez  
 Metal detector incorporates adjustable sensing head


The E-Z Tec DSP pharmaceutical gravity-fed metal detector from Eriez incorporates an adjustable sensing head. Operators can adjust the infeed end of the product chute to accommodate varying discharge heights on tablet press machines. In addition, users can modify the angle of the metal-detector head to control the product feed rate.

The compact device can detect and remove ferrous, nonferrous, and stainless-steel contaminants through a reject valve that users can adjust to discharge contaminated product on the left or the right. Operators do not need tools to disassemble and clean the chute. The metal-detector system is designed for installation in tight spaces within tablet and encapsulation rooms and includes circuit boards that are easily accessible and removable. Users control the device through a touch-screen interface. Its adjustable support stand incorporates casters and is manufactured from 304 stainless steel.

PharmTech's monthly newsletter, Equipment and Processing Report, reviews the Editor's Picks for the December 2011 edition from Banner Engineering and Eriez.

December 2011 Editor's Picks: Products from Banner Engineering and Eriez

Sterilization or sanitization is usually applied to kill  bacteria in a system. Equipment is cleaned to remove residues from the previous  batch of product, and subsequently flushed to remove the cleaning liquids. To ensure  that sterilization and cleaning are efficient and safe, it is not enough to  develop the appropriate procedures. Selecting the right manufacturing equipment  further improves cost efficiency, as well as patient safety.

The chosen equipment must minimize the risk of  contamination due to inappropriate product-contact surfaces. Machines should not  introduce airborne particles and dust into the environment, nor should they  entail the risk that oil or other substances required for their operation will contaminate  the product. If an operator cannot contact all equipment surfaces adequately, he  or she simply cannot clean them. To facilitate efficient cleaning, equipment  must be designed with this principle in mind.

The time, action, chemicals, and temperature (TACT)  circle originally developed by Sinner in 1960 shows the cleaning effects that these  parameters generate on the equipment surface (see Figure 1). The circle shows the  extent to which time plus at least one more parameter clean residues from a  surface. If one parameter is increased, the others may be reduced.

For example, if one dips one's greasy hands in water, they  will not become clean. If one then puts them into a soap bath, they will become  clean, but only after a long time. However, if one raises the temperature of the soap bath, one's hands will become clean more quickly. But if one then also rubs one's hands together, they will become clean even more quickly. 

The residue and the product-contact surface determine  the size, or the impact, needed for the cleaning process. The most suitable  type of chemicals and the appropriate temperature are decided according to the  residue. High surface action enables the chemicals and temperature to work better,  which makes it possible to reduce both of these parameters, as well as the  cleaning time. Because the action is often built into the equipment design, selecting  the right equipment can reduce the cost and increase the cleanability of a  system.

Cleaning action on the equipment surface is achieved by generating  high velocity or flow of cleaning fluids on all product-contact surfaces. This technique  distributes the chemicals and temperature better than low velocity does. Increased  velocity also generates high turbulence and shear force on the surface, which  ensures that the chemicals and temperatures reach deep into the residues and  dissolve or detach them safely and efficiently. 

To test the influence of the TACT parameters, the author  designed a tank-cleaning test incorporating two tank-cleaning devices that  generated different amounts of action. A static spray ball typically generates  a wall shear stress of 2–5 Pa (i.e., falling film stress, depending on liquid  temperature). A rotating jet head typically generates a wall shear stress of 40–1000  Pa (i.e., jet impingement, depending on jet pattern mesh).

To clean the tank sufficiently, two static spray balls  operated for 48 min at a flow rate of 20 m

/h and a pressure of 2.5  bar. But one rotating jet head achieved better results when it operated for 14  min at a flow rate of 6 m

/h and a pressure of 5.0 bar (see Figures  2 and 3 and Table I).

The test shows that the theory of the TACT circle works  in practice. To clean a certain residue from a certain surface, the parameters  in the TACT circle can be adjusted for cost optimization (see Figure 3). With  increased action, it was possible to reduce the time, the amount of chemicals,  and the heating energy and still achieve an equal or better result. High shear  forces can remove residues from most surfaces by themselves, without chemicals  or high temperatures. This technique can reduce the risk of contamination and  dramatically reduce cleaning costs.

Per-Åke Ohlsson is global  manager for Alfa Laval’s Pharma and Personal Care Market Unit, Box  74, Rudeboksvägen 1, SE-221 00 Lund, Sweden, tel.  +46 46 36 74 18, 

In the Mixer

Sterilization or sanitization is usually applied to kill bacteria in a system. Equipment is cleaned to remove residues from the previous batch of product, and subsequently flushed to remove the cleaning liquids. To ensure that sterilization and cleaning are efficient and safe, it is not enough to develop the appropriate procedures. Selecting the right manufacturing equipment further improves cost efficiency, as well as patient safety.

Equipment Design and Appropriate Procedures Improve Cleaning

Risk assessment is not a new concept to the pharmaceutical industry, but lately the phrase has become a mantra. FDA’s recent guidance on process validation relies heavily on the concept, which regulators partly view as a way to make process changes possible. The industry has performed risk assessment in manufacturing and validation to reduce disruptions and ensure patients’ safety. But ICH Q9 has prompted regulators to ask for more formal documentation of the assessments than before. A systemic, science-based way to manage risk is becoming essential to meeting the spirit and letter of FDA requirements.


  A company’s method of collecting product and process knowledge and of managing risk should be the same throughout the product life cycle. The goal should be to create a single framework for product and process knowledge that the whole company shares. A key element of that framework is the technical risk profile, a document that identifies areas of great process variability that strongly influence the quality of the finished product, says Philippe Cini, vice-president and leader of process and operational improvement practice at Tunnell Consulting. 

In addition to quantitative process data, it’s crucial for the technical risk profile to include scientists’ and engineers’ assessments about what the main sources of variability in the manufacturing process are, says Cini. The experts’ knowledge lends weight to certain process data over others, which makes it easier to understand correlations between the input (i.e., raw-material properties and process conditions) and the output (i.e., finished-product properties). After experts identify areas of risk, the company designs experiments to confirm them before developing means to control them. 

To determine the probability of various failures, personnel may calculate process capability as one of several strategies. This effort requires a significant amount of data—as much as 100 or 200 lots’ worth. To come up with an estimate before these data are collected, companies “can look to similar processes for evidence of process capability and probability of defects,” says Jason Orloff, engineering statistician at PharmStat. Companies that run many processes with long histories can take this approach, but startup companies will need to rely more heavily on subject-matter experts, advanced statistical techniques, and the design of experiments.

Regulators expect firms to use a formal process to determine what risk is excessive, what risk needs to be reduced, and what can be accepted, says Mike Long, director of consulting services at Concordia ValSource. The failures that have the most severe effects on patients or processes, have relatively high occurrence rates, and are poorly controlled should be addressed first. When companies identify a way to modify the process to reduce a given risk, they must follow the change-control procedure, which includes documenting that process change and checking its effectiveness. 


  After a company has completed a formal risk assessment of a product or process, it must review that assessment periodically. Regulatory guidance documents do not state how often the review must occur, but it should be done at least once a year as part of an annual review, says Long. Some agencies expect companies to review risk during quality-management reviews. “Also, any time a change is made to a product or process, risk assessments must be reviewed,” says Long. Whenever risk-management reviews occur, senior management levels of a firm should be made aware of the hazards that pose the greatest risk.

Any time a deviation happens or a process is changed, personnel should update the risk assessments to include the new information. “The risk assessments are living documents. They’re not just there to sit on the shelf,” says Long.


  The industry’s approach to risk is more sophisticated now, but still has room for improvement. “We need to formalize and reinforce those business processes that will help us understand exactly how a process and materials behave,” says Cini. Drug companies sometimes lack certain capabilities that could help enhance product and process knowledge. For example, they may not have statisticians on their staff or individuals who can manage large amounts of data, and they “need to strenghten those capabilities,” says Cini.

In next few years, the pharmaceutical industry is likely to become more data-driven, and to embrace and exploit quality by design to a greater extent. These changes will enhance product and process knowledge, thus improving companies’ ability to design robust processes and mitigate risk effectively. As a result, firms will enjoy fewer disruptions, and patients will benefit from medicines with high and reliable quality.

Production Lines

Risk assessment is not a new concept to the pharmaceutical industry, but lately the phrase has become a mantra. A systemic, science-based way to manage risk is becoming essential to meeting the spirit and letter of FDA requirements.

Equipment and Processing Report-12-21-2011

Increasing Dwell Time without Decreasing Output

December 2011 Editor's Picks: Products from Banner Engineering and Eriez

Equipment Design and Appropriate Procedures Improve Cleaning

Moving from a Reactive to a Systemic Approach to Manage Risk