Bullard
 Respirator maintains constant airflow


 The Evolutionary Air (EVA) powered air-purifying respirator (PAPR) from Bullard (Cynthiana, KY) incorporates the company’s Active Flow Technology that automatically maintains constant airflow. The unit’s quiet, brushless motor has a lifespan of about 10,000 h, according to Jeanette Gaunce, product specialist for Bullard’s respiratory line. A two-speed blower allows the user to choose more or less cooling and airflow.

An operator can check the status of the battery charge by pushing a button that displays a fuel gauge. The EVA sounds an alarm when the battery power is low and rings a second alarm when airflow is low. The alarm sounds travel through the breathing tube to the wearer’s ear. In addition, the EVA unit’s filter-locking tab notifies the user that the filter is in place with a visual indication and an audible click. The PAPR is appropriate for applications that pose particulate hazards.

Teledyne Tekmar  
 Total organic carbon and total nitrogen analyzer features high sensitivity 


 The Torch Combustion instrument from Teledyne Tekmar (Mason, OH) uses static pressure concentration to analyze total organic carbon and total nitrogen. Unlike a flow-through cell, the device’s detector outlet remains closed until all combusted carbon dioxide is in the detector. This technique provides a sensitive analysis because all carbon dioxide is read at once, says Tom Hartlein, the company’s product-line manager.

If a sample falls outside the instrument’s calibration range, an Intellidilution feature automatically dilutes the sample according to an algorithm to bring it within the calibration range. In addition, the machine automatically takes aliquots or dilutes from stock standards to generate calibration ranges. This feature reduces labor and removes the opportunity for human error.

The instrument’s software maintains sample logs and includes a leak-checking process. Operators can use the software to change flow and set the required pressures, thus improving test results’ reproducibility.

Articles

PharmTech's monthly newsletter, Equipment & Processing Report, reviews the Editor's Picks for the May 2009 edition from Bullard and Teledyne Tekmar.

June 2009 Editor's Picks: Products from Bullard and Teledyne Tekmar

The emergence of influenza A (H1N1) and the efforts to provide 

 to the vulnerable are timely examples of biopharmaceuticals’ continuing importance. These medicines pose unique challenges to drug manufacturers, however, mainly because the molecules of their active ingredients can be quite big. The size of a biopharmaceutical is partly attributed to its complex molecular structure: essentially a polymer of many amino acids onto which additional large molecules such as carbohydrates might be attached.

Large-molecule drugs also exhibit great variation. Living cells do not create homogeneous sets of molecules, but rather generate products that contain sequence diversity. And biological cells’ sensitivity to manufacturing-process parameters also contributes to variations in the end product. The growth and purification conditions in biopharmaceutical production processes yield preparations that are roughly 95% pure, according to Jim Green, senior vice-president of preclinical and clinical development sciences at Biogen Idec (Cambridge, MA). 

Not only can the basic amino-acid sequence differ between proteins, but the number, type, and placement of attached carbohydrates can also differ between otherwise similar proteins. The combination of sequence variation and variations in carbohydrate-attachment sites can produce similar molecules that the immune system perceives in dramatically different ways.

In recent years, the US Food and Drug Administration has been emphasizing that greater process understanding and control helps manufacturers create products of consistent quality. But biopharmaceuticals’ size, heterogeneity, and sensitivity to process parameters make it difficult for even innovator companies to produce them exactly the same way every time, says Jeffrey R. Mazzeo, biopharmaceutical business director at Waters (Milford, MA).

 Time and technological advances, however, have increased manufacturers’ ability to control their processes and products. During the past 10 years, new equipment has greatly improved the manufacture, and characterization of monoclonal antibodies, says Bill Haddad, CEO of Biogenerics (Brewster, NY). Technological advances have made it easier to perform analytical testing and create master and working cell banks. New technologies also have allowed manufacturers to control their processes within tighter specifications and produce recombinant proteins with highly specific, predefined quality characteristics.

In addition, scientists have developed platform technologies that enable antibodies and fusion proteins to be manufactured consistently. Platform technologies are standardized manufacturing methods that allow streamlined protein production, says Green. They ensure that the major operating principles used to manufacture different antibodies within one facility or company are maintained. 

A process that incorporates platform technology could include the following steps: 

One or two additional chromatography steps 

“To the extent that platform technologies become part of standard manufacturing practice and can be used by any company,” Green adds, “some degree of consistency may be obtained in product quality.”

 Regulatory initiatives can also aid biopharmaceutical production. FDA’s quality-by-design initiative is meant to be a way for manufacturers to control variability, says Mazzeo. The maker of a follow-on glycoprotein biologic, for example, must study key parameters such as glycosylation (i.e., the attachment of carbohydrates) to determine the specifications that will yield a high-quality product. Performing design of experiments and refining the manufacturing process helps manufacturers ensure that their products’ characteristics stay within the appropriate range.

An in-process surveillance program that incorporates process analytical technology (PAT) would also help ensure process understanding and control. PAT would allow operators to observe trends and predict when products will be outside specifications. But establishing in-process quality control can be much more difficult for biologics than for small molecules because of biological systems’ greater inherent complexity, says Marc Goshko, executive director of legal affairs at Teva Pharmaceuticals (North Wales, PA).

Although the complexity of large-molecule drugs presents difficulties for manufacturers, recent scientific and technological advances have given the industry greater control over product variability than before. As the industry’s understanding improves, it will be able to provide high-quality biopharmaceuticals such as vaccines more efficiently and reliably.

Production Lines

The emergence of influenza A (H1N1) and the efforts to provide vaccines to the vulnerable are timely examples of biopharmaceuticals' continuing importance.

Could We Make Large Molecules with Less Labor?

To address the increasing popularity of drug-injector systems, the US Food and Drug Administration last week released a draft guidance for industry titled 

Technical Considerations for Pen, Jet, and Related Injectors Intended for Use with Drugs and Biological Products

The draft guidance applies to, but is not limited to, jet, pen, needle-free, and mechanically operated injectors as well as piston syringes and injectors with computerized or electronic elements. Injectors are categorized into three groups: those intended for use with a wide range of currently marketed drugs or biological products, those intended for use with a specific class or product line, and those intended for use with a specific product. 

Depending on the system and its applications, these elements may fall under various regulatory provisions such as 21 

 3.2(e) or 510(k). The document discusses the scientific and technical considerations that may be relevant when developing these systems, regardless of the regulatory provisions that apply.

The draft guidance discusses design features as well as general use, conditions of use (e.g., personal use, use by healthcare professional, and disposable or reusable products), and injector materials used to construct or manufacture each device. The document provides a list of the various performance testing standards (ISO and ASTM) that are recommended and discusses separate tests such as biocompatibility, dose accuracy, shelf-life stability, and expiration dating. Sterilization and sterility testing is also discussed in detail. 

 for the purposes of providing a comment.

See related PharmTech articles:
 
S. Sutton, EPT, 

Designing and Delivering Therapeutic Proteins

Big Shot: Developments in Prefilled Syringes

Developing First Disposable Injector for a Biopharmaceutical

In the Mixer

To address the increasing popularity of drug-injector systems, the US Food and Drug Administration last week released a Draft Guidance for Industry titled, Technical Considerations for Pen, Jet, and Related Injectors Intended for Use with Drugs and Biological Products.

Equipment and Processing Report-06-17-2009

June 2009 Editor's Picks: Products from Bullard and Teledyne Tekmar

Could We Make Large Molecules with Less Labor?

Draft Guidance Issued for Injectors Development