Spiroflow Systems
 Hygienic conveyors provide versatility


 The “Flexible Screw Conveyors” from Spiroflow Systems (Monroe, NC) contain a motor-driven spiral that rotates within a sealed tube to move material efficiently and gently. The machines provide constant remixing without causing segregation. The spiral is the units’ only moving part, and this simple design enables quick disassembly and easy maintenance.

The conveyors reduce the potential for contamination in several ways. For example, the devices do not incorporate bearings and seals, unlike rigid screw conveyors. In addition, the totally sealed conveying system does not use air as the conveying medium and therefore does not require a filtration system.

Users can route the flexible conveyors around obstacles such as stanchions. The device also can be mounted on a mobile frame for use in various locations within a facility. Operators can clean the conveyors using dry, wet, or clean-in-place methods. The devices are suitable for raw-material and excipient applications.

Sepha
 Scanning system performs nondestructive leak testing


 The new “BlisterScan” from Sepha (Belfast, Northern Ireland, UK) uses pressure, vacuum, and a precision laser system to check for leaks in blister packaging. The device finds leaks as small as 7 µm. Unlike the blue-dye test, the BlisterScan product uses a noncontact, nondestructive method. Operators can retrieve tested products from faulty packs and repackage them. Good packages can be placed back on the production line.

The machine is operated with touchscreen controls and does not require skilled users. After a test cycle of 1–6 min, the device displays results for each package graphically and indicates which cavities had leaks. Product changeover can be achieved in less than 30 s.

The BlisterScan tester stores test results in its blister-format library or on a separate device. The unit is available with a full 21 

Articles

PharmTech's monthly newsletter, Equipment & Processing Report, reviews the Editor's Picks for the December 2008 edition from Spiroflow Systems and Sepha.

December 2008 Editor's Picks: Products from Spiroflow Systems and Sepha

 
  The average cost of moving a new drug through the development process in the United States ranges from $300 million to $1.2 billion, and the process takes an average of 12 to 15 years. One in 10,000 candidate compounds completes the development process, and it receives just five to eight years of patent protection. A surprising amount of the discovery and development life cycle is still based on manual and disconnected process steps. Pharmaceutical companies have recognized the critical need for improvement and are quickly embracing emerging information technologies to maximize development and commercialization efficiencies, minimize errors, and realize the potential to reuse the intellectual property created during this early phase. 


  Traditionally, engineers and development scientists have used flow charts, process definitions, and paper-based recipes to document the steps of the manufacturing process. The resulting volume of complex information can be intimidating; it can total hundreds of pages of documentation and can also lead to inefficiencies in process and recipe management. In particular, the following areas call for improvement: 

 Creating and managing process-definition elements within unstructured documents provides no mechanism for reusing the elements. 

 A document-based approach does not provide a simple way of searching the content and structure of process definitions or recipes.

When a process definition included in a spreadsheet or document passes from research and development to pilot manufacturing to become a recipe, the information from the flow charts and spreadsheets is manually transferred to the manufacturing execution systems. Manual copying of process logic and parameters is time-consuming and might introduce errors in the technology transfer, putting quality at risk. 

 Authoring and document-management tools based on XML, a language that provides a format to exchange information, have changed the way that pharmaceutical companies do business. Companies are realizing the efficiency that XML-based tools bring to many elements of the development life cycle. Basing Common Technical Documents, Structured Clinical Trial Protocol documents, and Structured Product Labeling documents in XML helps identify and organize the PDF files that make up a regulatory submission. In addition, the US Food and Drug Administration is encouraging, and in some cases requiring, manufacturers to submit drug-establishment registration and drug-listing information in XML.


  XML-based tools and standards help life-science companies overcome many of the challenges they have faced with traditional documentation. BatchML, an XML implementation of the Instrumentation, Systems, and Automation Society’s (ISA) ISA-88 standard, represents the graphical process models, procedures, and terminology in ISA-88 format. In addition, companies are using BatchML to represent process definitions for regulatory submissions, recipe management, and formula management. 

 
  In early development, process definitions (represented as master recipes) are created graphically as ISA-88 procedure models, stored as BatchML, and managed centrally within a system of record. Using the ISA-88 model as a graphical user interface, scientists can draw the process flows and associate parameters with appropriate procedures in the process. Within the BatchML definition, all of the underlying critical-to-quality (CTQ) parameters are directly associated with the process model, which becomes the one authoritative version of the truth. 

  Using a drag-and-drop, visual flow chart interface familiar to development scientists and engineers, development scientists can create and edit sequential processes in a recipe. A graphical approach enables process manufacturers to do the following:

Improve information transfer between engineering and manufacturing, including third-party contractors and partners

Improve the identification and management of CTQ parameters

Increase the reuse of process definitions among products through recipe building blocks and recipe normalization

Comply with regulatory submissions of master recipes and speed up FDA’s approval process, using ISA-88 recipes as the basis for expressing and reporting CTQs.


  Pharmaceutical companies are attempting to embed quality into their processes, improve productivity, and ease regulatory review by adopting XML-based graphical editors. Using a BatchML graphical editor in early development through commercialization greatly reduces the overall time to market for new drugs and indications, compared with the traditional document-based approach. The new approach enables the intellectual property contained in the process definitions to be reused within existing development environments. 

Michael Power is a senior program manager at 

Cognizant, 500 Frank W. Burr Blvd., Teaneck NJ 07666, tel. 703.431.6966, 

In the Mixer

A surprising amount of the discovery and development life cycle is still based on manual and disconnected process steps.

XML Tools for Increasing Efficiency and Product Quality

Prefilled syringes have gained popularity among patients and healthcare providers because of the convenience they offer. The dosage form has advantages for manufacturers, too. Packaging a drug in a prefilled syringe may help extend a product’s patent and distinguish it from competing products. In addition, prefilled syringes require much less overfill than vials (5–8% for prefilled syringes 

 10–20% for vials), according to Jörg Zimmermann, head of production at Vetter Pharma-Fertigung’s (Ravensburg, Germany) Langenargen facility. Reducing overfill spares the drug and decreases cost.

Two major stoppering techniques are used with prefilled syringes after filling is complete. The traditional, proven stoppering method is vented placement. In this method, a stopper is placed inside a tube that is then inserted into a syringe. A pin holds the stopper in place as the tube is removed from the syringe. The stopper then expands to fill the syringe diameter. This technique is widely accepted, repeatable, and locates the plunger precisely, according to Jeff Jackson, director of pharmaceutical-product management at Bosch Packaging Technology (Minneapolis, MN). 

Vented placement sometimes smears the Teflon coating of newer stoppers, however. During inspection, “it can appear as though the drug may have gone up into the ridges of the plungers,” which would compromise the syringe’s sterility and cause a false reject, says Jackson. The problem also occurs with stoppers that incorporate Daikyo Seiko’s (Tokyo) “Flurotec” coating, which contains Teflon. Flurotec coating is sensitive, and if an operator touches it once, it might result in a little fold. The fold does not indicate that the Flurotec cover is damaged, but it might appear that the stopper has been compromised. Slight faults in the coating can be mistaken for particles and lead to false rejects. If stoppering equipment is maintained properly and operated carefully, this problem can be avoided. But vented placement might cause problems for rigid plungers, too. When a plunger is forced through a tube, it becomes deformed. The process could damage the ribs of the plunger and possibly compromise container integrity. 

An alternative stoppering technique is vacuum placement. In this method, a vacuum is pulled in each syringe, and the vacuum draws the stopper into the syringe. Vacuum placement does not compress stoppers as much as vented placement does, says Jackson. This method creates a syringe without leaving an air bubble and eliminates the potential for oxygen to interact with a protein drug, says Patrick Begley, manager of technical services at BD Medical–Pharmaceutical (Franklin Lakes, NJ). Removing the air bubble also is preferred in the administration of highly viscous ophthalmic medicines, he adds. 

On the other hand, vacuum-placement entails potential inconveniences. The process contains more variables than vented placement, so it is less repeatable, according to Jackson. Vacuum placement also places stoppers less precisely than vented placement, he adds. 

Even though vacuum placement can require more time and decrease the syringe-filler line speed, says Begley, new, high-speed equipment can perform vacuum stopper insertion at rates of more than 300 syringes per minute. This equipment provides an alternative to slower, manually loaded vacuum-stoppering units.

Vacuum placement is gaining wider acceptance among manufacturers. “We’re seeing more requests for vacuum-stoppering machinery,” Jackson says. “I believe it’s due to the increased focus on the Teflon-coated stoppers.” Yet many drugmakers still choose vented placement. These companies want to be able to shake up their solution to check for particles, and this criterion requires the small air bubble that vented placement leaves in the syringe.

All plungers can be inserted by vented or vacuum placement, regardless of the material they’re made of, says Begley. Several equipment vendors offer lines that perform both techniques. Switching from one technique to the other requires a set of change parts and several programming steps. Some units that perform vented placement can be retrofitted with a vacuum module.

Today, prefilled syringes are manufactured with both techniques, and neither technique has serious drawbacks. Rather, vacuum stoppering offers specific benefits, and manufacturers decide between the two methods based on whether their small- or large-molecule drug needs those benefits, explains Begley. 

The choice of stoppering method depends on the needs of the drug, the syringe, and the pharmaceutical company. A company must decide how important the air bubble, stopper position, stopper coating, and line speed are, says Jackson.

Production Lines

Packaging a drug in a prefilled syringe may help extend a product's patent and distinguish it from competing products.

Equipment and Processing Report-12-17-2008

December 2008 Editor's Picks: Products from Spiroflow Systems and Sepha

XML Tools for Increasing Efficiency and Product Quality

Stoppering Techniques for Prefilled Syringes