BinMaster
 Process connection provides long service life


 BinMaster’s (Lincoln, NE) stainless-steel process connection for the BMRX and MAXIMA+ rotary level indicators is designed especially to withstand corrosive materials. The device fits into existing 1.25- and 1.5-in. standard process connections and can be installed easily without special fittings or adapters. The solid stainless-steel construction of the process connection is designed to be stronger and to last longer than the normal connection on a standard rotary, according to the company. Rotaries are appropriate for detecting the level of material in bins, hoppers, and silos to ensure continuous operation or manage inventory.

Operators can use a rotary with the process connection with three-vane, two-vane, insertable, and bayonet-style stainless-steel paddles. BinMaster’s insertable paddle collapses to fit through a standard 1.5- or 1.25-in. opening, and the rotary can be installed without entering the bin. Employees choose the proper paddle according to the type and weight of the material.

Silverson Machines
 Machine produces agglomerate-free mixes


The Flashmix from Silverson Machines (East Longmeadow, MA) is a high-shear mixer designed for powder–liquid mixing. The machine brings liquids and powders together in the high-shear region of its precision-engineered rotor–stator workhead assembly, thus subjecting materials to focused high shear to create an agglomerate-free dispersion. The mixer’s modified rotor–stator workhead also boosts its pumping performance, thus eliminating the need for an additional pump.

The Flashmix machine wets out powders at rates as high as 250 lb/min. Operators do not have to adjust the mixer’s valves to balance powder incorporation and liquid-flow rates as viscosity rises. The mixer incorporates a clean-in-place loop intended to simplify operation. Users can install the machine in an existing process easily, and the unit has a lower power requirement than competing mixers because it does not need an additional feed pump.

Articles

PharmTech's monthly newsletter, Equipment and Processing Report, reviews the Editor's Picks for the November 2010 edition from BinMaster and Silverson Machines.

November 2010 Editor's Picks: Products from BinMaster and Silverson Machines

The abbreviated approval pathway for follow-on biologics gives innovators and follow-on companies alike an incentive to distinguish their products from those of their competitors. One way for an injectable biologic to stand out is to be sold with a novel device that is comfortable for patients and improves compliance. Antares Pharma (Ewing, NJ) developed a needle-free delivery device to deliver Teva Pharmaceutical Industries’s (Petach Tikva, Israel) Tev-Tropin, a human growth hormone originally administered with a needle and syringe. To find out about the regulatory, formulation, and manufacturing considerations involved in the transition, 

 talked to Paul Wotton, CEO of Antares Pharma. 

EPR: What technical considerations must be examined before moving from a drug-delivery method such as a syringe to an autoinjector or needle-free injection device? 

Wotton: You have to show that the injection you’re giving with the new delivery device gives you the same clinical performance as the needle-and-syringe version of the drug. You also have to show that the patient can use your device. A company that wants to launch a generic version of a drug marketed in a device must also prove to the US Food and Drug Administration that the patient will use the new device the same way he or she uses the original device. 

EPR: Does the product’s formulation need to be reevaluated when a company moves to a new device?

Wotton: The formulation that’s used in needle-free Tev-Tropin is exactly the same as that delivered by the needle and syringe. You might need to change the formulation of a very viscous product, for example. But I would not recommend changing the formulation to fit into a device. You're better off trying to reengineer the device to accommodate the formulation.

EPR: Is that because of the clinical studies required for reformulated biologics?

Wotton: You’d have to do studies to show that the new formulation is the same as the old one, as well as show that the change in delivery method hasn’t affected the performance of the drug. On top of that, if you change the formulation, you’d have to go back through some of the pharmaceutical development work and stability studies to show that the new formulation behaves the same on storage as the old formulation in every sense.

EPR: Do a biological’s properties affect the kind of device that a company can choose? 

Wotton: Highly viscous products such as antibodies cannot be delivered with certain devices. The main consideration is engineering the device to deliver the drug through the needle’s small orifice. Sometimes you need a device that delivers the drug with the right amount of force at the right time. Our Vibex autoinjector is capable of giving biological products subcutaneously, even if they’re highly viscous. A strong force has to be maintained over the correct interval of time to deliver the drug from the device. 

EPR: Is it more challenging to develop a drug for delivery through a needle-free device than it is for delivery through a syringe?

Wotton: The challenges can be different for a needle-free injector. You can deliver viscous products through a needle-free injector, but you have to treat it on a case-by-case basis. You probably would find it more difficult to deliver a viscous drug with a pen injector such as those used with [Eli Lilly’s (Indianapolis, IN)] Byetta. It would be hard for a patient because a pen injector is not necessarily mechanically assisted like an autoinjector is.

EPR: What other drug properties might influence a company’s choice of device?

Wotton: Another consideration is the volume you need to deliver, in the case of a subcutaneous injection. You could use either a needle-free injector or an autoinjector to deliver a drug that’s given in a volume of less than 1 mL. But if you were looking at a volume of more than 2 mL, then that would rule out most needle-free approaches and force you to use an autoinjector.

The force you need to deliver 2 mL from a needle-free injector is quite high. This approach puts a lot of volume into the skin using needle-free delivery technology, which is difficult to do. An autoinjector, which has a needle and goes through the skin, is a more precise way of delivering [the drug] subcutaneously.

EPR: Do you foresee more manufacturers pursuing new devices to deliver their biologics?

Wotton: The injectable market is growing. Everyone’s focused on the biosimilar market because it’s a large market opportunity, but many small molecules could be delivered better using autoinjectors, for example. Devices provide an intelligent way to differentiate a product in the biosimilars segment, as our experience with Tev-Tropin has shown clearly. We also believe that some small molecules are not being delivered adequately today. We think that there’s a huge opportunity for developing drug–device combinations that make it easier for patients. 

Production Lines

To find out about the regulatory, formulation, and manufacturing considerations involved in developing a new device to deliver a drug, Equipment and Processing Report talked to Paul Wotton, CEO of Antares Pharma.

Product Differentiation: The Prize for the Winning Drug–Device Combination

Controlling particulate contamination is essential in pharmaceutical cleanrooms. Operators are particularly concerned with particles of 10 µm or smaller, which are mainly invisible to the naked eye, occur in differing shapes, and derive from various sources. These particles include human hairs (i.e., 50–150 µm), dust (i.e., 1–100 µm), and bacteria (0.5–10 µm). Particles larger than 40 µm generally can be seen by the human eye. Pharmaceutical companies are particularly worried about particle sizes between 0.5 and 5 µm.

Human operators are a major source of contamination. The body’s regenerative processes (e.g., shedding skin, oils, and hair), behavior (e.g., movement, sneezing, and coughing), and attitude (e.g., work habits and communication) all contribute to contamination. Employees’ activity rapidly accelerates the rate at which particles are generated. The control of particulate contamination from personnel movement thus is a crucial factor in manufacturing operations undertaken under cleanroom conditions. If unchecked, human contamination could affect product yield, productivity, a company’s costs, and product quality.

Large numbers of viable and nonviable particulates are carried on operators’ feet or on cart wheels. The systematic removal of foot-borne small particulates is essential. Normal industrial practice is to control foot-borne contamination with adhesive peel-off disposable mats, but polymeric contamination-control flooring, such as CleanZone Technology from Dycem (Bristol, UK) is now a more popular choice.

Peel-off mats are made up of multiple sheets of polyethylene film coated with acrylic adhesive that traps particles. Operators rip up and dispose of peel-off sheets when they are dirty, which typically occurs several times during a shift. This process frequently sheds entrapped particles, however, thus greatly reducing the mats’ effectiveness.

Polymeric products are made from a blend of pure polymeric compounds and have a three- to five-year life cycle. When a polymeric surface becomes dirty, operators can clean it with a sponge and a mop with detergent. Finally, operators can dry the surface with a squeegee. This quick cleaning process can be incorporated into the facility’s regular wet-clean cycle. 

Control of foot- and wheel-borne contamination

 
 Polymeric flooring and peel-off mats reduce contamination by particles larger than 25 µm at roughly similar rates (i.e., 80–95%). On the other hand, polymeric flooring can be two to five times more effective than peel-off mats at reducing contamination from particulates of 10 µm and smaller.

A typical peel-off mat has a coating of acrylic adhesive that is less than 10 µm thick. Particles larger than 10 µm tend to stick to the adhesive and prevent smaller particles from contacting and sticking to the coating. In contrast, the polymeric surface of contamination-control flooring allows contact with all particle sizes. It thus collects and contains more than 99% of particles between the sizes of 0.2 and 100 µm. Therefore, polymeric flooring can control viable, biologically active particulates under circumstances where adhesive peel-off mats can be ineffective.

Polymeric flooring also removes particulates over a much larger control area than adhesive peel-off mats do. The polymeric flooring’s electrostatic forces enable it to attract and contain airborne particles above its surface, as well as trapping particles through foot and wheel contact.

Several groups have compared the efficiency of polymeric products and disposable mats. For example, GlaxoSmithKline (London) reported that polymeric flooring effectively prevented 99.9% of viable and nonviable foot- and wheel-borne particulates from entering a critical area. In contrast, peel-off mats prevented 27% of this contamination from entering the area (1). These results indicate that polymeric flooring can be an effective means of controlling foot and wheel-borne contamination, thereby reducing the number of microorganisms entering critical environments.


Cost:
 • Material cost
 • Maintenance cost
 • Total cost


$251,550
$125,656 (replace/dispose)
$402,110

Materials:
 • Product
 • Packaging
 • Total materials
 

Energy used in manufacture (per kg):
 • Materials
 • Conversion
 • Total energy per kg
 • Total energy/2 yrs
 

Greenhouse gas (CO2) emissions:
 • Manufacture
 • Disposal (incineration)
 • Total
 

 
In addition to their efficiency at reducing contamination, cleanroom operators must also consider the operating costs that their solutions entail. Table I shows that cost savings can be achieved over the service life of polymeric flooring, compared with peel-off mats (2).

In addition, cleanroom operators increasingly seek to reduce the environmental effect of their operations. At the end of its service life, a peel-off mat generates an eight-inch ball of consumable waste that usually is disposed of in a landfill. On completion of their service life, the polymeric flooring products may be readily recycled for less crucial uses. Table I shows a comparison of the environmental effects of peel-off mats and polymeric flooring.

 
 Peel-off mats had been the preferred method of controlling foot- and wheel-borne contamination in pharmaceutical cleanrooms for some time. Now, polymeric flooring’s comparatively greater efficiency at controlling small particles, coupled with environmental and cost considerations, has made it the solution of choice. Cleanroom operators must weigh various factors when choosing contamination-control products. Selecting the appropriate solution can help improve a facility’s productivity and reduce its costs. 

Gerry Prout is managing director at Kennet Bioservices and Kennet Coacs, 6 Kingsdown Orchard, Hyde Road, Swindon, SN2 7RR, UK, tel. +44 0 7774 965265, 

In the Mixer

Normal industrial practice is to control foot-borne contamination with adhesive peel-off disposable mats, but polymeric contamination-control flooring is becoming increasingly popular.

Equipment and Processing Report-11-17-2010

November 2010 Editor's Picks: Products from BinMaster and Silverson Machines

Product Differentiation: The Prize for the Winning Drug–Device Combination

A Comparison of Polymeric Flooring and Disposable Mats in Pharmaceutical Cleanrooms