Articles should discuss process equipment, the design of facilities, and utility systems that support the critical physical and chemical requirements of drug products, in addition to other aspects of the product specification. Topics include design and construction/installation, commissioning and qualification, operation and maintenance, and controls and automation.
Pharmaceutical manufacturing facilities produce a variety of products, including highly potent products that require safety measures to prevent adverse health effects on patients and operators. To ensure safety, these facilities use containment equipment to minimize the risk of contamination. This article presents criteria for selecting containment equipment, considering both...
Pharmaceutical critical utilities are typically built of 316L stainless steel; nevertheless, surface degradation has been reported due to the occurrence of different phenomena. This article aims to explain how field electrochemical techniques using a portable tool can be an effective method for surface inspection, qualification, and monitoring. The surface finish assessment considered...
The biotechnology and pharmaceutical sectors have pledged to reduce greenhouse gas (GHG) emissions as the climate concerns of consumers, investors, and regulators continue to grow. In seeking to benefit from this demand for sustainability and the potential for cost-saving opportunities, life science product manufacturers have started to evaluate the climate impact of their own labs and...
Cell therapies have been used to treat thousands of patients worldwide ever since the CAR T cell medication Kymriah was the first cell therapy approved by the FDA in 2017. Yet significant manufacturing challenges continue to hamper patient access to life-saving cell therapies, particularly the high cost of these treatments. Kymriah can cost as much as $475,000 per dose and an allogeneic...
Pharmaceutical manufacturing facilities produce a variety of products, including highly potent products that require safety measures to prevent adverse health effects on patients and operators. To ensure safety, these facilities use containment equipment to minimize the risk of contamination. This article presents criteria for selecting containment equipment, considering both...
Pharmaceutical critical utilities are typically built of 316L stainless steel; nevertheless, surface degradation has been reported due to the occurrence of different phenomena. This article aims to explain how field electrochemical techniques using a portable tool can be an effective method for surface inspection, qualification, and monitoring. The surface finish assessment considered...
The biotechnology and pharmaceutical sectors have pledged to reduce greenhouse gas (GHG) emissions as the climate concerns of consumers, investors, and regulators continue to grow. In seeking to benefit from this demand for sustainability and the potential for cost-saving opportunities, life science product manufacturers have started to evaluate the climate impact of their own labs and...
Cell therapies have been used to treat thousands of patients worldwide ever since the CAR T cell medication Kymriah was the first cell therapy approved by the FDA in 2017. Yet significant manufacturing challenges continue to hamper patient access to life-saving cell therapies, particularly the high cost of these treatments. Kymriah can cost as much as $475,000 per dose and an allogeneic...
Facility design decisions made early in conceptual design can have a significant impact on the cost of goods sold (COGS) in the manufacture of autologous and allogeneic cell therapy products. Understanding the impact of a COGS analysis is an important aspect of the early-phase design process.
Since 2005, ISPE’s Facility of the Year Awards (FOYA) have recognized state-of-the-art projects utilizing new, innovative technologies to improve the quality of products, reduce the cost of producing high-quality...
The adoption of continuous manufacturing (CM) in the pharmaceutical industry is increasing because of the advantages and opportunities it offers, including the ability to handle hazardous reactions, a higher degree of process integration, and improved sustainability. This article discusses the considerations and approaches adopted by Pfizer, Eli Lilly, GSK, and Amgen in designing and...
To improve the energy efficiency of cleanrooms, the Roche Global Engineering and Oceanside facilities and Engineering team collaborated to implement a risk-based approach to achieve lower air changes during operation without adversely impacting the facility, equipment, or reliability, while meeting environmental requirements.
North Carolina’s Research Triangle is the largest of its kind in the US. Thanks to years of effort from industry, pharmaceutical professionals, and education institutions, it is synonymous with pharmaceutical and biotechnology excellence.
Many emerging tools and technologies support the environmental sustainability of the pharmaceutical industry. In facility design, solutions are derived through science-based analyses of environmental impacts from the materials, processes, services, and architecture. From greener energy sources to a reduction in the type and amount of emissions, we are seeing improvement in this sector’s...
The expected FDA approval for a Treprostinil dry powder inhaler revealed a need for the manufacturer to expand its warehousing and logistics capabilities to support its growing operations. The company’s senior leadership wanted to ensure this expansion came with as minimal an impact on the environment as possible, so a key priority was to provide a net zero energy facility. With a vision for...
Computational fluid dynamics (CFD) can reduce or eliminate the uncertainty associated with a cleanroom facility as the planned design can be simulated to predict performance to a high degree of accuracy. This article discusses the use of CFD for the purpose of predicting and optimizing the performance of a cleanroom facility in terms of steady-state airborne particulate levels and for...
Many organizations are evaluating how advanced therapy medicinal products (ATMPs) and other traditional modalities may be combined within the same facility or within a newly constructed agnostic building. This article outlines a broad framework to evaluate different types of modalities that may be accommodated concurrently in a new or existing facility and then uses a case study to explain how...
Cell and gene therapies (C>) have unique needs in manufacturing suites that differ from those for classic product biopharmaceuticals. Facilities must be created with flexibility in mind, able to run multiple products and production types to remain viable.
Chlorine dioxide has been shown effective in decontaminating various types of chambers and volumes such as rooms, isolators, processing tanks, and entire facilities, but its use to decontaminate compressed gas piping systems has not been documented. This article discusses using dry gaseous chlorine dioxide (ClO2) to decontaminate an oxygen (O2) feed piping system in a...
In a recent advanced therapy medicinal products (ATMPs) innovator survey, two-thirds of respondents reported that they are developing multiple drug platforms.1 Without a guarantee of commercial success for any single product, many...
Two sessions at the 2022 ISPE Facilities of the Future Conference in early February captured varied views of emerging technologies in the pharmaceutical industry, and the industry’s work to embrace...
What do recipients of ISPE’s prestigious Facilities of the Year Award (FOYA) know that has helped their projects succeed? What are the lessons learned from achievements in facilities development, including forward-looking projects that encompass and inspire changes in the industry? Pharmaceutical Engineering® spoke with nine FOYA winners from recent years about the lessons they learned and...
Advanced therapy medicinal products (ATMPs) pose specific manufacturing challenges beyond those typically addressed by pharmaceutical chemistry. Often in current ATMP applications, a change in approach is introduced at some point in the development process out of convenience or necessity, which then results in a change in technology. This article analyzes the possibility of transferring a cell...
Realizing the promise of any novel viral vector therapeutic depends on the innovator’s ability to constantly meet evolving program requirements set in the product’s preclinical; clinical; chemistry, manufacturing, and controls (CMC); and market strategies. A key enabler to success is establishing a robust yet nimble viral vector manufacturing platform that delivers high-quality product on time...
Aseptic process simulation (APS) is essential for validation of an aseptic manufacturing process and is required by regulators to demonstrate the aseptic capability of such processes. A successful program of APS and aseptic manufacturing requires significant operator training, skills, and supervision; thorough maintenance; effective cleaning and disinfection; significant oversight of every...
This article presents the results of applying artificial intelligence (AI), such as machine learning algorithms, to identifying and predicting anomalies for corrective maintenance in a water for injection (WFI) processing plant. The aim is to avoid the yearly stoppage of the water for injection plant for preventive maintenance activities, common in the industry, and use a more scientific...
This article revisits the concept of phased engineering, procurement, and construction (EPC) and updates it with risk-based considerations specifically regarding the commissioning, qualification, and validation (CQV) of general life-cycle principles for pharma and biotech projects. Enhancing the relationship between phases of a project, advanced planning, and more formal management of...
![Figure 1: Seasonal comfort (temperature and RH). ©ASHRAE, www.ashrae.org. Used with permission from 2017 ANSI/ASHRAE Standard 55 [4].](/sites/default/files/styles/teaser_image/public/2021-08/0921_PE_SO_TechHaycock_01.jpg?itok=mJiPGN_X)
Defining room temperature and humidity limits is a frequent topic of debate when designing and operating pharmaceutical and biotechnology facilities. What are appropriate alarm limits and acceptable durations for an alarm condition? Understanding the source of temperature and humidity requirements, and strategies for setting limits, can ensure both compliance and optimum use of energy. This...
Cleanrooms and controlled contamination environments are increasingly being used across many industrial sectors, including the pharmaceutical industry. An important issue is the operating cost associated with cleanroom energy consumption and, consequently, the identification of applicable energy containment measures. This article reviews pharmaceutical cleanroom calculations for...
The ISPE OSD Community of Practice Continuous Manufacturing Subcommittee is planning a Good Practice Guide to capture information developed over several years by the team to establish equipment requirements, identify opportunities for harmonization and flexible integration, and suggest where current equipment may be enhanced to work with continuous manufacturing platforms of the future.
One of the goals of the cleaning validation design phase is to define critical process parameters (inputs) and acceptance criteria (outputs) of the cleaning process. This article explores the selection of a master soil as part of the cleaning validation design phase for automated parts washers. The selection and qualification of a master soil through laboratory testing and during factory...
In many critical ways, the design of facilities for multiple cell therapy processes is unlike the design of conventional pharmaceutical facilities. This article surveys several of the key issues to consider when designing facilities capable of manufacturing multiple cell therapies, including regulatory definitions, product life cycles, processing systems, relevant cell therapy technologies and...
Designing new facilities for cell and gene therapy manufacturing is a challenging task given the many uncertainties in this industry sector, including varying potential demand for any given new therapy, evolving platforms and technology, questions about equipment reliability, learning curves for analysts and operators, possible sourcing issues, and variable lead times for key raw materials....
Each year, ISPE celebrates innovations and advances in pharmaceutical manufacturing technology with its Facility of the Year Awards (FOYA) program. This year, we added a new category, Social Impact, to recognize companies that developed new standards and practices to prevent drug shortages and increase patients’ access to medicine, designed new tools or techniques that reduced the cost of drug...
In 2000, the U.S. Green Building Council (USGBC) introduced Leadership in Energy and Environmental Design (LEED) to create a methodology to promote sustainability-focused practices in the building industry. This article reviews the earliest protype that we know of for a LEED manufacturing facility, presents a real-world case study of a pharmaceutical manufacturing facility achieving LEED Gold,...
We have some clarity over the desired end point of zero carbon within the next 30 years (or sooner for some pharma companies), but our industry is uncertain how we will achieve this objective. As pharma engineers, we will all play a role in delivering this end point through the continuous improvement of existing facilities and by designing, equipping, and building new facilities that will be...
The article appraises the real-world experiences of two pharmaceutical companies approaching the rollout of energy- and water-reduction programs to selected facilities around the world. It is the result of more than two years of collaboration between the company corporate teams, individual site teams, and an external specialist consultant.
Sustainability is a key principle for pharmaceutical companies in 2020. However, translating corporate goals into meaningful improvements can be a challenge, particularly when competing factors such as complex technical requirements or ambitious project schedules are involved.
Manual decontamination procedures are laborious processes and can be costly, requiring significant time and resources to complete. Manual procedures also may need to be repeated if initial efforts do not fully kill pathogens. To reduce failures and potentially reduce cost, chlorine dioxide gas decontamination was investigated as an alternative solution.
Since the early 1990s, when the “upstart” biotech industry realized that its future success would be heavily influenced by the ability to manufacture multiple products within the same facility,1 the quest for flexible...
Cleanrooms and laboratories can save a significant amount of energy by reducing airflow of air handling units (AHUs) after closing hours. Although challenging, airflow reduction is a successful energy reduction measure and has been implemented within the energy reduction program of Janssen Vaccines & Prevention B.V. in Leiden, the Netherlands.
How CMOs keep conditions controlled and reduce costs with temporary power, climate control, 100% oil-free air
The unavailability of a backup pharmaceutical water system has been a severe limitation for pharmaceutical manufacturers. Until recently, qualification concepts that adhered to current Good Manufacturing Practice (GMP) guidelines hindered the rapid setup of a water system. A new, tailor-made qualification concept for mobile water treatment has been developed to align with guidance from various...
It is a common practice in the pharmaceutical and biopharmaceutical industries to execute a factory acceptance test (FAT) for equipment involved with various drug manufacturing processes. The FAT is a project milestone in purchasing good manufacturing practice–compliant equipment.
Although other industry publications have explored the effect of surface finish on biofilm formation, background data indicating that imperfections exceeding the American Society of Mechanical Engineers (ASME) Bioprocessing Equipment (BPE) standard are detrimental to chemical cleaning performance are lacking.1
Although it includes some background material, this article is based predominantly on a series of interviews with SMEs at Eli Lilly, Janssen, Hovione, C-SOPS, and Patheon from October to December 2017. The comments and observations that follow are theirs.
An overview of pass-through boxes as they relate to the life sciences industry, defining their purpose, applications, and available options.
Recent cyberattacks like WannaCry and Petya have affected GxP computerized systems, prompting questions on how to address risk from cyberspace using traditional computerized systems validation according to GAMP® 5. This article explores life cycle management of GxP computerized systems and associated cybersecurity risks that can affect patient safety.
Double-wall containment: an answer to unsafe piping systems
While most in the pharmaceutical industry understand the need for double-wall containment piping systems, our field observations indicate that many companies do not. We frequently see pipes that should be (but are not) double-wall containment systems. This article presents an overview of the topic, so that readers who...
Spurred by pressure from governments and consumers to curb rising drug prices, pharmaceutical manufacturers are increasingly willing to look beyond traditional batch processing to cut costs and increase efficiency. One of the industry's most dramatic innovations on this front is continuous manufacturing (CM). The technology, which produces drugs in an uninterrupted process, benefits...
ISPE's 2018 Facilities of the Future Conference highlighted emerging technologies that are driving change in pharmaceutical manufacturing. Topics included virtual reality, robotics, artificial learning, machine learning, and 3D printing. Education sessions were divided into Industry 4.0 and continuous manufacturing (CM) tracks.
This article shares a process used to evaluate terminal HEPA filter maintenance programs serving a parenteral manufacturing plant. The evaluation determines whether maintenance history data supports extending preventive maintenance frequency.
Integrated VPHP systems offer a versatile, automated, sporicidal process for cleanroom suites, isolators, RABS, chambers, and pass-throughs.
Despite the advantages of ozone technology as a powerful commercially available oxidant and disinfectant, this technology has not been adopted broadly by the pharmaceutical industry. This article contains the rationale for applying ozone technology in a packaged system, which offers greater reliability and efficacy, using best practices that eliminate variables common in on-site integrated...
The following is an example of an evaluation of room air change rates for potential reduction using QRM, providing more detail on engineering considerations.
This article presents current research on the problem of rouge in clean steam generators and their distribution systems, as well as possible deleterious effects on capital equipment and final drug products.
What is cleaning validation and where does it fall in the life cycle validation scheme? How can an automated washing system be validated? This article provides insights that may help answer these questions.
