Buzdar
 Portable steam-sampling cart requires no water


 Budzar (Willoughby, OH) recently introduced a portable, sanitary steam-sampling cart that operates without cooling water. The cart includes a small refrigeration unit that creates cooling capacity for the condensate, thus removing the need for a water source, according to Adrian Pop, Budzar’s engineering manager. Operators can move the cart to any sampling point near a wall outlet.

The cart incorporates a retaining tank that facilitates steam sterilization. A steam-rated hose connects to the condensate outlet, enabling the operator to handle the sterilization process safely. If the tank fills up with condensate, it can be removed and drained easily. A pressure transducer in the steam line does not allow the operator to disconnect the hose until the pressure in the steam loop is zero. In addition, a programmable logic control (PLC) guides the operator through the sampling steps, thereby reducing the amount of training needed. 

Kaeser Compressors  
 Self-protecting blower ensures longevity


 The DB 166C and DB 236C CompaK Plus blowers from Kaeser Compressors (Fredericksburg, VA) include an Omega Control Basic controller module that operates and monitors the units. Sensors transmit pressure and temperature readings to the controller, which shuts down the blower if measurements exceed specified levels, thereby increasing the blowers’ longevity.

Each unit includes a blower, motor, drive, silencers, controls, and a full enclosure. The enclosure attenuates noise, protects the package from dirt and dust, and keeps the blower properly ventilated. The integrated package is designed to facilitate maintenance and installation. Operators need only make a piping connection and an electrical connection to set up the blowers. 

The DB 166C and DB 236 units have a small footprint and are easily moved. The blowers are appropriate for pneumatic conveying of process components, chemicals, bulk powders, and pills. 

Articles

PharmTech's monthly newsletter, Equipment & Processing Report, reviews the Editor's Picks for the April 2009 edition from Buzdar and Kaeser.

April 2009 Editor's Picks: Products from Buzdar and Kaeser

The International Conference on Harmonization (ICH) guideline Q9

 and the American Society for Testing and Materials (ASTM) Standard E2500-07, 

Standard for Specification, Design and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment,

 provide a science- and risk-based approach to commissioning and qualifying pharmaceutical and biopharmaceutical manufacturing systems and equipment. A key objective of these documents is to give industry flexibility in implementing the ASTM standard through the process of verification to demonstrate that pharmaceutical manufacturing facilities are fit for useand create products with the correct product-quality attributes. These approaches, in place of traditional qualification or integrated commissioning and qualification (C&Q) using impact assessment, can make projects and processes more efficient and help facility owners and designers ensure compliance, quality, and safety when defining acceptance criteria for their critical process systems and equipment.

In addition to standardizing terms and methods, the ASTM E2500 standard describes a risk-management system and helps lay the groundwork for verification C&Q planning and execution. ICH Q9 notes the following two primary principles of risk management:

The evaluation of the risk to quality should be based on scientific knowledge and ultimately protect the patient.

    The level of effort, formality, and documentation of the quality risk management process should be commensurate with the level of risk.

Although the standard addresses the traditional scope of qualification activities that prove equipment and systems are fit for use, ASTM offers organizations greater flexibility by allowing them to develop a verification plan following ICH Q9 principles for implementation according to their own specific quality goals, time and cost constraints, and internal roles and responsibilities. 


  Under the ASTM model, principles of good engineering practice (GEP), risk management, design review, and change management influence each stage of a process, from compiling design requirements to final acceptance and release. The ASTM model has led some companies to realign their project-management teams and other resources to improve their verification processes.

Using C&Q as a foundation for system verification, the ASTM standard takes a comprehensive approach to assessing products’ and processes’ critical aspects for potential risk to product-quality attributes and patient safety. Equipment and systems that do not include critical aspects can be released for use after personnel determine that they conform to design intent, were created in accordance with GEP only, and did not require qualification activities.

To adopt the ASTM standard effectively, a company must define a systematic approach to verify that manufacturing elements-individually and collectively-are fit for their intended uses, properly installed, and operate correctly. All verification approaches must be documented to provide a level of detail commensurate with the elements’ risks to products and patients, their complexity, and their novelty. In contrast with traditional qualification methods, system verification involves a shift in emphasis from the quality-control mindset (i.e., approving every test case and respective acceptance criterion) to a broader quality-assurance perspective (i.e., approving the verification plan and the results of the completed verification execution activities). 

Under ASTM, subject matter experts (SMEs) identify and document all process attributes (i.e., functions, features, abilities, and performance or quality characteristics) that are essential to maintaining consistent product quality. To ensure that all aspects of a facility conform to design criteria, companies should also implement a mechanism for communicating specifications and other relevant data with all design and manufacturing team members. In addition, SMEs should define acceptance criteria; develop and approve system-verification plans and specifications, including verification and test strategies; and ensure that all documentation and verification has been completed. 


  The ASTM standard places new emphasis on risk management. In the past, companies relied heavily on impact assessment, which evaluates the effects of operating, controlling, alarming, and failure conditions on product quality. Impact assessment occurs after design development and focuses on systems and components rather than products and patients

Risk management evaluates the chosen process design against a set of approved product and process user requirements. It is performed throughout design development to ensure that systems and other design and operating elements can monitor and control risks to the manufacturing process (e.g., process variability and contamination). The risk-management requirements are designated as critical and include all components, functions, and features of the design that control risks. The probability and severity of risks are evaluated to determine their effect on process variation, product quality, and safety. 

In addition to risk assessment, the comprehensive ASTM approach promotes various other risk-assessment tools that are discussed in ICH Q9, including hazardous operation analysis, failure modes and effects analysis, and fault-tree analysis. 


  To determine the best approach for implementing ASTM verification, designers and manufacturers must define what they are trying to achieve. Potential goals include improving compliance, enhancing product quality, minimizing capital costs, and minimizing contamination risk. When these goals have been defined, a company can develop a request for proposal and initiate negotiations with qualified engineering experts who specialize in the complex commissioning and qualification process. In addition to saving owners time and capital, the ASTM approach can also help to optimize manufacturing processes and supporting quality systems, thus resulting in improved efficiency and compliance. 

Steve Wisniewski is a senior associate and director of compliance at Integrated Project Services, 2001 Joshua Rd., Lafayette Hill, PA 19444, tel. 610.828.4090 x1254, 

In the Mixer

ATSM and ICH approaches, in place of traditional qualification or integrated commissioning and qualification (C&Q) using impact assessment, can make projects and processes more efficient and help facility owners and designers ensure compliance, quality, and safety when defining acceptance criteria for their critical process systems and equipment.

How the ASTM Standard Offers a New Approach to Verification

Business factors such as meager pipelines, slowing prescription drug sales, and increasing competition from generic drug companies have heightened pressure on pharmaceutical manufacturers to identify and reduce waste in their processes. Inefficiency can be harmful from an environmental perspective as well because it can result in unnecessary energy consumption and excessive greenhouse-gas emissions. Many drugmakers have begun to evaluate and improve their manufacturing operations to become more economically and environmentally sustainable. Schering-Plough (Kenilworth, NJ) 

 the Environmental Protection Agency’s Energy Star for reducing its energy use.

 
 Heating, ventilation, and air-conditioning (HVAC) systems typically consume a large portion of the energy used in pharmaceutical manufacturing facilities. These systems are essential for controlling temperature, humidity, and particulates, but can be a major source of energy waste if not managed carefully. Pfizer (New York) uses a quality risk-management approach to examine its operating parameters to ensure that the temperature, humidity, and airflow of each system is appropriate for the products’ needs, according to Martin Brown, the company’s senior manager of global engineering.

  Some of Pfizer’s compounds require large exchanges of air to maintain proper space conditions, but several suites were operated at excessively high air-exchange rates. The company now evaluates its HVAC operating parameters and adjusts them accordingly. In some instances, Pfizer has reduced HVAC energy usage by 40%, says Brown. 

  Schering-Plough also modified its air exchanges to reduce energy consumption. The company decreased the number of air changes in the reactor building at its active pharmaceutical ingredient site in Rathdrum, Ireland, after performing a hazards analysis of the area. The reaction building had been using only outside air, and reducing airflow significantly decreased energy use, according to Thomas Pagliuco, director of energy at Schering-Plough.

 
 Schering-Plough also reduced energy use by converting one of its chiller plants from a traditional primary–secondary system to a variable-primary chiller plant. This design provides variable flow through the chiller at all times and compensates for decreases in the differential temperature. The modification increased the plant’s chilled-water capacity and eliminated the need to invest in an additional chiller. To improve the chilled-water pumps’ performance, Schering-Plough used adaptive control. This advanced process-control technique monitors operating conditions and adjusts components to enable them to operate in the most efficient part of their range, says Pagliuco. 

 
 Wyeth (Madison, NJ) has improved the overall efficiency of its manufacturing facilities by investing in cogeneration, the creation of electricity and heat from a single fuel source. The company generates electricity, captures the excess heat the process emits, and uses that heat to make steam, according to Gregg Belardo, Wyeth’s senior director of environment, health, and safety.

  Using the same principle, Schering-Plough recovers waste heat to make steam, hot water, and chilled water. The technique provides electricity twice as efficiently as the electrical grid and reduces carbon-dioxide emissions more than renewable energy sources, according to Pagliuco.

  Pfizer captures and reuses waste energy in other ways. The company has installed economizers and blowdown heat exchangers on boilers and used heat exchangers to harness the energy in exhaust air. 


 By expanding its use of barrier-isolation technology, Wyeth further improved the efficiency of its manufacturing suites. The technology greatly reduces the amount of air that must be heated and cooled, thus decreasing energy consumption and carbon-dioxide emissions, Belardo says.

  Equipment modifications can also reduce waste. Schering-Plough uses a technique called retrocommissioning to find operational and maintenance inefficiencies. The technique also tunes up the company’s equipment and facilities, according to Pagliuco.

  Pfizer and other companies have replaced old equipment with a new generation of chillers, boilers, and air compressors that is much more energy efficient. The improved technology cuts energy consumption by 15–20%, says Brown.

 
 These and other initiatives have improved drugmakers’ environmental footprints. As a result of its energy-reduction projects, Wyeth reduced its carbon-dioxide emissions by 41%, normalized to revenue, between 2000 and 2008, according to Belardo. In the same period, Pfizer decreased greenhouse-gas emissions by 43% per dollar of sales, says Brown. Pfizer’s new goal is to reduce emissions 20% by 2012.

  The companies’ bottom lines have improved as well. Since the inception of Wyeth’s corporate energy program in 1998, the company has saved $120 million in energy costs, says Belardo. Pfizer’s cumulative cost reductions resulting from conservation efforts during the past five years amounted to more than $115 million, according to Brown. The experience of these pharmaceutical manufacturers shows that business and environmental interests can be met through critical evaluations of and intelligent modifications to manufacturing operations.

Production Lines

Many drugmakers have begun to evaluate and improve their manufacturing operations to become more economically and environmentally sustainable.

Equipment and Processing Report-04-15-2009

April 2009 Editor's Picks: Products from Buzdar and Kaeser

How the ASTM Standard Offers a New Approach to Verification

Efficiency Improvements Save Money and the Environment