Product development firm Cambridge Consultants introduced its Vortik technology that allows different liquids to be mixed at the point of spray without altering the spray characteristics. Pharmaceutical applications could include tablet coating and drug delivery outside of the respirable range (e.g., dermatological cream or nasal or buccal application).


  
  Conventional atomizers use either high pressure or high airflow to create a spray. This new fluid handling technology combines low-pressure air and liquid in a specially shaped cyclone chamber. Shear between swirling air and the liquids creates the desired droplet size for spraying.
  
  Allowing active ingredients to be mixed at the point of delivery overcomes shelf-life and stability issues. The technology provides consistent spray quality and tighter control of concentration and particle size. 

Articles

Cyclonic-spray technology improves spray consistency and allows mixing at the point of delivery.

Cambridge Consultants Introduces Vortik Design For Liquid Spray Systems

Asset management and redeployment are gaining recognition as important parts of managing pharmaceutical equipment. “We are seeing more formal programs and procedures in place to redeploy unused assets,” says Matthew Hicks, COO of Federal Equipment, which specializes in asset management of process equipment.  “Some companies now have an in-house asset disposition department or, more commonly, a person charged with asset management who will work with a service provider to handle the details.” 

Many types of used laboratory and process equipment are available. Used laboratory equipment (e.g., mass spectrometers, high-performance liquid chromatography equipment) has always been widely available, and the industry is also seeing more growth in available processing equipment than 5 or 10 years ago, comments Roger Gallo, CEO and president of EquipNet, a Boston-based broker and auctioneer of laboratory and manufacturing equipment. Most of what would be needed for a complete solid-dosage or liquids manufacturing and packaging operation is available in the used equipment market, adds Hicks. 
   
  Factors such as budget restrictions and the recognition that assets must be handled efficiently have led to global, mainstream adoption of buying and selling used equipment by both Big Pharma and mid-size and smaller organizations, said Tom Burton, executive vice-president and president of the Capital Assets Group at Liquidity Services in a 

Value-proposition for purchasers of used equipment


Used equipment offers two main benefits for purchasers—cost-savings and quick availability—and buyers are increasingly interested. Original equipment manufacturers (OEMs) have increasingly tight schedules for supplying new equipment, which can make it difficult to get equipment quickly, notes Gallo. Second-hand equipment can be obtained without long lead times.   

“Used equipment can be a good option for anyone who has an urgent need for equipment—anything from having equipment down and needing to replace it to wanting to meet a market need,” adds Hicks.   

Cost savings of used equipment compared to new can be significant, although the savings depend somewhat on the purchase method. Buyers can find used equipment through private transactions made directly with the seller, from the inventory of used-equipment providers, and through online liquidations or auctions. 

For transactions made directly with a seller, much information is available. It could be known, for example, what the equipment was used for, when it was last used, and where it had been stored. Large companies typically keep good records on their equipment, adds Gallo, and a potential buyer might even be able to speak with an engineer who knows the equipment. Purchasing equipment that comes straight from the working environment of a reputable company is one way to know that the equipment has been maintained, noted Burton (1). 

In an auction of a specific facility closure, information would be relatively available about the equipment and how it was used. In an auction that is run by a dealer or an exchange, equipment often comes from various sources, there is less information about the equipment available, and there is greater risk. Pricing, however, generally reflects this uncertainty and risk, and the cost at auctions can be attractive, notes Gallo.

Buyers should consider removal and shipping costs, as well as installation costs at their facility, in their purchase decision, said Burton (1).  


  Most importantly, buyers should know what they are purchasing, because equipment is generally sold “as is.” “A buyer should very carefully read the description and examine the picture of the equipment to make sure that there is no question in their mind as to what is or is not included,” warns Gallo. A picture, for example, may show something in the background that is not part of the sale as listed in the description. 

Buyers should also ensure that the equipment meets their needs, because it may be older technology. Buyers should know if the equipment they are purchasing is supported by the OEM. “We recommend buying equipment that is supported by the OEM for installing, revalidating, and upgrading,” says Hicks. “We have relationships with the OEMs so that if a piece of equipment or its controls, for example, are no longer supported, we can make the buyer aware.”  

If the OEM is no longer supporting the equipment, buyers should be sure that they have someone that is capable of servicing the equipment (e.g., fixing a control panel, calibrating an instrument) and that replacement parts are available, adds Gallo. 

Relatively new equipment can be available, however, from companies that upgrade their equipment on a regular basis, companies that purchase an item and then find they do not need it, or facility closures, explained Burton (1). 

“In process equipment, we are seeing high-quality inventory of late-model equipment that is well taken care of,” adds Hicks. An increase in availability of recent models may be due partly to consolidation and facility closures and partly to the increasing use of asset-management services.  

Production Trends

Buying and selling used laboratory and process equipment has become mainstream; experts offer tips to potential buyers.

Buying Used Equipment

A challenge for process analytical technology is finding suitable entry points in reactors to analyze reactions in real time. SensoTech and valve manufacturer SchuF developed MultiProbe, a bottom outlet valve combined with SensoTech’s LiquiSonic sensor, to enable process analysis even in low-volume batches without additional process adapters.  LiquiSonic systems consist of one or more sensors and a controller that records measurements and transfers them to the process control system. The system provides precise data about concentration and density in liquids, detects phase transitions, and monitors reactions.

A bottom-outlet valve with combined sensor is a new process analytical technology tool.

SensoTech and SchuF Introduce a Combination Valve and Sensor for Real-Time Process Analysis

Today, it is common for pharmaceutical products to be sourced in a complex maze of processing and handling throughout the course of manufacturing, storage, and distribution--all against a global supply-chain backdrop. Before a product even reaches the patient, it is likely that multiple ingredient manufacturers, suppliers, and distributors from different parts of the world have had a hand in making, storing, and handling the finished drug product. Multiply this complex chain of events by the number of available drugs and countries involved in both producing and consuming medicines and the vulnerable areas within the global pharmaceutical supply chain become quite evident. In response to the rapid transformations taking place in the global pharmaceutical supply chain, the United States Pharmacopeial Convention (USP) is developing and revising standards to aid manufacturers, transportation providers, and other stakeholders to deal with many of these complex issues.

  To help protect product quality, USP is developing a series of informational general chapters on good distribution practices that will appear in the 

United States Pharmacopeia--National Formulary (USP-NF),

 USP’s compendia of public quality standards. Detailed in a stimuli article published in the July-August 2013 issue of 

--USP’s free, online journal for posting and receiving public comments to developing standards--the chapters are being developed in a collaborative effort involving four USP Expert Committees: Compounding; Monographs--Excipients; Packaging, Storage, and Distribution; and Physical Analysis.

The general chapters will address four key areas, highlighting key principles as well as practices related to good distribution: 
  • Quality management system. Topics will include documentation control and resources management; nonconformances, complaints, and corrective actions; and the role of continuous improvements.
  • Good importation and exportation practices. Topics will include audits and supply agreements; container seals, cargo inspection, customers, and brokers; and verifying product and firm compliance with regulations.
  • Supply-chain integrity and security. Topics will include adulteration and counterfeiting; diversion and theft; and product recall procedures.
  • Environmental control management. Topics will include building/facility (storage), transportation vehicles (shipping), and controlled-temperature environments.


  For its proposed general chapter on environmental control management, USP’s Expert Committees are placing a strong emphasis on understanding the environmental impacts to which a product may be exposed during distribution. By framing the chapter in terms of management of environmental controls, USP encourages manufacturers to look at external factors that could affect product quality whether in cold-temperature, ambient, or extreme heat conditions.

This chapter also addresses cold-chain products, for which many well-established robust temperature monitoring systems are available. Measures such as packaging systems with dry ice and containers with active cooling systems are often employed to help ensure product quality throughout the course of distribution and many regulations currently exist that specifically address shipment of cold-chain products. 

Aligned with its current thinking about the role that environmental control management plays in product quality, USP is also proposing a change in its definition of “controlled-room temperature.” USP’s current temperature range for a usual and customary working environment is 20 to 25 °C. In a 

 article in the November-December 2013 issue of PF, USP proposes the expansion of this range to 8 to 30 °C. In part, the motivation for this change is to encourage companies to put broader temperature ranges on product labels, allowing for greater flexibility in how products are distributed. The appropriateness of expanding the temperature range for a product is based on stability data that have been generated on the product. 

Public comments on USP proposed standards

 article on USP’s definition of “controlled-room temperature” will be received until Jan. 31, 2014. USP’s proposed suite of general chapters on good distribution practices is scheduled to publish in 

in early 2014. For more information or comments on these standards, please direct all communications to Desmond Hunt at dgh@usp.org.

Desmond Hunt, PhD, is senior scientific liaison, General Chapters, US Pharmacopeial Convention, dgh@usp.org.

Packaging

USP is developing and revising distribution standards in response to changes in the global supply chain.

USP Plans Standards on Good Distribution Practices

Weight is a crucial parameter of any finished drug tablet, whether prescription, over-the-counter, or nutritional supplement. Overweight tablets can result in too much of an ingredient, which may lead to a harmful effect. But tablets that are too light are also problematic because they may not offer enough of a particular ingredient to bring about an intended therapeutic benefit.  A manufacturer’s goal should be two-fold: do not produce off-weight tablets in the first place, and catch and reject them, accurately and reliably, if they are produced. The best ways to prevent the manufacturing of off-weight tablets begin before product is loaded into the hopper—through comprehensive operator training, diligent and rigorous preventive maintenance, and regularly scheduled calibration of the press and its subassemblies. 


  The best and first line of defense is training on both press and process. Operators should be tested regularly to ascertain and reconfirm their proficiency with making a tablet in the absence of automation (i.e., “Tableting 101”) and with making tablets using the specific equipment their company employs as part of the manufacturing process. Training should cover the prevention of virtually all the potential causes of off-weight tablets, including how to avoid the following common causes: 

Incorrect or suboptimal weight-related machine settings, such as filling depth

Improperly set (or missing) recirculation components

Tablet back-up at the take-off, where rogue tablets may jump the bar and potentially re-enter a feeder

No rejection of start-up material or improper settings related to start-up 

Improper manipulation of a feeder by the operator or a poor understanding of how a feeder configuration can be modified to better suit a particular product’s flow characteristics. 

The importance of training cannot be overstated.  Companies should have standard operating procedures (SOPs) and ensure that operators follow the SOPs. A tablet-press vendor should be able to demonstrate and confer comprehensive knowledge of their technology and of how it can be used to manufacture tablets of optimal quality. 

A press vendor can provide training specific to understanding the feeder and optimizing its use, because the feeder has a direct correlation to maintaining acceptable tablet weights. Users should also understand and use the relationship between feeder speeds and consistent die filling. 


  Thorough preventive maintenance and regular inspection and calibration should be conducted on the entire tablet press.  In particular, users should maintain calibration of devices controlling filling depth regulation on a press.  Tooling and cams should be consistently and carefully inspected. Cam-wear indicators should be used whenever possible. A guideline for what constitutes a worn tool should be established, and it should serve as a prompt for timely replacement.

A force-based relative standard deviation should be used as an indicator of consistent tablet weights. Given the correlation between force and final tablet weight, this statistic allows an operator, with a quick glance, to determine how consistently they are compressing tablets. Many modern presses calculate this figure for the user, further streamlining the ability to quickly analyze results in real time. 


  Companies should solicit the help of third-party experts such as tablet-press vendors, reputable consultants, or specialists in overall equipment effectiveness. Such assessments can immediately uncover multiple inadequacies in the process, machine, and/or user. The engagement of these individuals or organizations is especially valuable because they generally view the situation through a different lens, rather than being focused on getting product out the door. Off-weight tablets warrant serious attention, but through collaborative efforts this problem should be reversible and avoidable. 

Matt Bundenthal is direct sales and communications manager at 

For further information on this topic, read the January 2014 issue of 

 for the full article, “Battling Off-Weight Tablets.” 

Troubleshooting

Operator training, preventive maintenance, and regularly scheduled calibration help prevent the manufacture of off-weight tablets.

Equipment and Processing Report-12-18-2013

Cambridge Consultants Introduces Vortik Design For Liquid Spray Systems

Buying Used Equipment

SensoTech and SchuF Introduce a Combination Valve and Sensor for Real-Time Process Analysis

USP Plans Standards on Good Distribution Practices

Preventing Off-weight Tablets