	When the COVID-19 pandemic struck, pharmaceutical manufacturing continued as a highly essential industry, but companies were suddenly faced with the challenge of many employees working remotely and the need to ensure that operators working in-person have a healthy workplace.

	“Operational teams had to become instantly virtual, which increases risks,” says Andreas Eschbach, CEO of Eschbach, which focuses on software for plant process management. He notes that operations teams need solutions to make informed decisions confidently and to reduce the stress of vastly changing work conditions and procedures. “Helping the workforce confidently collaborate and communicate electronically using digital tools is of utmost importance to maintain productivity and cohesiveness among manufacturing teams now working remotely or socially distanced,” says Eschbach. Digital monitoring of adverse events in production, quality, and safety, for example, can ensure that managers have up-to-date information for effective decision-making among remotely dispersed teams, he explains. As another example, the company’s interactive product suite provides digital shift handovers to improve communication among manufacturing team members, even with social distancing. 

	Pharma manufacturing companies have been evaluating what needs to be done to minimize the risk that workers in the facility are exposed to the novel coronavirus. Cleanrooms are already low risk with strict controls on air quality, cleaning, and control of the movement of people and materials, but non-classified areas and non-production areas might need new approaches. 

	“In addition to current thoughts on people, product, and material flows and how to adapt to the post COVID-19 era, we are also exploring new and novel approaches to protecting all areas of the facilities we design, beginning with how people initially enter the property and facility, including maintaining safe working distances, long-before they get near (or into) the production areas,” says Dave Watrous, vice-president, Advanced Technologies and Life Sciences at Fluor Corporation. Changes include adjusting designs of heating, ventilation, and air-conditioning (HVAC) systems and related air-cleaning technologies for non-production environments, as well as increasing cleaning and limiting human interactions. “There is a balance between automation, cost, and levels of effective protection in non-production areas,” notes Watrous. 

	HVAC systems serving classified spaces are considered very low risk because they use extensive filtration and are designed and validated to manage contamination, but HVAC systems serving non-classified and non-good manufacturing practice (GMP) areas are designed differently and should be evaluated, says Keith Beattie, director at life-science specialist Energy Efficiency Consultancy EECO2, which has put together a document about managing risk in pharmaceutical HVAC systems (1). The document points to building readiness guidance from the England-based Chartered Institution of Building Services Engineers (CIBSE) (2) and ASHRAE, the American Society of Heating, Refrigerating and Air-Conditioning Engineers (3). A risk assessment should “account for all direct and indirect consequences of modifying HVAC systems with respect to a hazard that is not fully understood at this time, rather than following blanket recommendations, which may not be suited to a specific system or space type,” the EECO2 document cautions (1). For example, increasing airflow may be beneficial for some areas, but doing so in an area that adjoins a GMP or pressurized space could disrupt the pressure balance. EECO2 has developed a risk assessment tool that can be used to assess HVAC system risk and recommend appropriate and practical mitigation actions.

	Computational fluid dynamics (CFD) analysis is one way to visualize and evaluate airflow. CFD can be used to model the airflow inside a room or cleanroom to evaluate air movement and find solutions to any problems with the HVAC distribution, adds Curt Firestine, senior mechanical engineer at CRB. He notes that Grade C and higher cleanrooms typically have ceiling high-efficiency particulate air (HEPA) filters, low-wall returns, and high air-change rates. “But in lower classification cleanrooms (Grade-D or ISO-9) and in unclassified support rooms, we often see ceiling supply and [ceiling] returns for HVAC systems. These areas operate at lower air-change rates, which are typically less than 15. This combination of ceiling supply and return air devices without low-wall returns does not sweep the room. … Airflow does not get down to the occupants,” explains Firestine. Additional concerns include the number of people in the room and how closely together they are working, as well as what level of gowning they are using, Firestine noted in a 

 on facility design (4). Solutions might include increasing air-change rates, using low-wall returns or exhaust registers, improving HVAC system filtration, or increasing gowning and facemasks for workers.

	While CFD can visualize airflow, other simulation tools can be used to visualize the movement of people and materials in an operation. “Process simulation techniques [can] determine how operations could be improved while distancing employees inside the room,” says Firestine. Another problem might be that, with reduced numbers of operators, getting materials in and out may become an issue, Firestine noted in the webcast (4). “CRB has utilized simulation tools successfully to demonstrate manufacturing process improvements including personnel and material flow changes,” he says. 

	There has been a long-term trend toward automation in pharmaceutical production, which may accelerate due to the pandemic, notes Watrous. He says there is a rising demand for automation in non-production areas, such as warehousing and building management systems, as well. “We are already designing several post COVID-19 facilities that have less non-production space, meaning it will include more automation but spread throughout a smaller footprint,” says Watrous.

	Remote monitoring tools that allow manufacturers to evaluate machine health without entering the cleanroom have been becoming more widely used in pharmaceutical manufacturing (5), and this trend has been accelerated by the travel restrictions caused by the pandemic. 

	“Our customers are telling us that machine health and remote collaboration matter more than ever to them, and they want to expand their deployment of digital solutions in these challenging times,” said Saar Yoskovitz, CEO of Augury, in a May 2020 press release announcing its machine health monitoring tools could be installed by users in new facilities even when access is restricted, with remote guidance from Augury personnel (6).

	Although automation and remote monitoring tools can reduce some of the human interactions with the process in the cleanroom or the lab, expertise will still be needed. “While automation looks like a good solution to workplace congestion, the infrastructure and support required to maintain automation is not insignificant,” suggests Bikash Chatterjee, chief operations and science officer at Pharmatech Associates. “The lab may begin large deployments of automated solutions to run high volume assays, [for example]. However, anyone who has ever developed and implemented these systems knows they do require care to remain productive and effective.”

	“There is no doubt the workplace will look very different post-COVID-19,” concludes Chatterjee. He predicts that remote work will continue, virtual collaboration solutions will be prevalent, the use of data management solutions will expand as the need to remotely evaluate data increases, and manufacturing automation will continue to increase.  

	1.     EECO2, “COVID-19: Managing Risk in Pharmaceutical HVAC Systems,” rev. 2 

	2.     CIBSE, “Emerging from Lockdown,” 

	3.     ASHRAE, “ASHRAE Epidemic Task Force Building Readiness,” 

, “Strategies for Designing Adaptable, Resilient Bio/Pharma Facilities,” 

	5.     J. Markarian, “Optimizing Machine Health,” 

	6.     Augury, “Augury Delivers New Features and Services to Keep Machines and People Healthier and More Productive in Critical Industrial Facilities,” Press Release, May 6, 2020.

Articles

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Manufacturers are adapting with virtual work, remote monitoring, and re-evaluation of facility design to ensure worker safety.

Responding to COVID-19 in Pharma Facility Design and Operation

	Rising demand for tubes, which are a popular choice for dermatological products, is helping fuel a projected compound annual growth rate of 5.46% for the packaging format between 2020 and 2025, according to a market study by Mordor Intelligence (1). Tubes address a myriad of needs for viscous pharmaceutical products. Recent developments center on enhanced barrier structures and sustainability, more functional dispensing closures and applicators, brand-building labeling and decorating, Braille printing, and variable printing. 

	As demand grows, manufacturers are expanding capacity. ALLTUB Group recently added to its laminate tube production capacity with the startup of an ISO 15378 GMP-certified production line in an ISO 8 (Class 100,000) cleanroom space at its manufacturing operation in Langenfeld, Germany (2). The Langenfeld operation also has invested in a production line for small-diameter (13.5, 19, and 30-mm) tubes, reportedly the first 13.5-mm diameter capability in the European market (3). 

	Another Europe-headquartered tube maker, Hoffmann Neopac, established its first US manufacturing operation in 2019. The 37,000-ft

plant in Wilson, NC, has space for several high-speed tube production lines. Its first production line has an annual capacity of 80 million units and primarily produces small-diameter tubes such as the 13.5-mm Twist’n’use tube, a tamper-evident, small-volume single-dose design. Once the cap is twisted, the tube is irrevocably opened (4).

	Also tamper-evident, the SpringTube design from 3D Neopac, a Hoffmann Neopac subsidiary, features a push-on polyethylene flip-top cap and maintains its shape during use. Available in fill volumes from 40–300 mL, the tubes can be produced with an ethylene vinyl alcohol barrier layer and decorated via digital, flexo, or metallic foil processes. Variable printing can individualize each container at the unit level. Colored or metallized cap options further enhance brand identity (5). 

	The squeezable nature of tubes opens the door to custom dispensing. To provide a cleaner, more hygienic way to apply pain relief medicine, GlaxoSmithKline, Nypro, and Hoffmann Neopac collaborated on a “No Mess” thin-walled tube and applicator for Voltaren gel (diclofenac topical). An intuitive pull/push mechanism allows the massage tip to close by itself after the application and minimizes gel residue on the skin. A handle makes it easier for consumers to apply the gel to their back and shoulders. Other features include a tamper-evident TopStar closure (6).

	An applicator-equipped tube for Canesten cream (clotrimazole topical), an athlete’s foot treatment from Bayer Consumer Health, earned a German Packaging Award in 2019 from the Deutsches Verpackungsinstitut in Berlin. The soft thermoplastic elastomer applicator on the Polyfoil barrier tube from Hoffmann Neopac eases application even to the skin between the toes. A ribbed, rotating ring prevents leakage, protects the product, and simplifies use for all age groups. An On/Off marking indicates whether the applicator is open or closed (6). 

	To simplify dosing of preservative-free ophthalmic drops and prevent contamination of the product during days, weeks, or even months of use, Aptar Pharma and Hoffmann Neopac have developed the SteriDrop tube. When the Polyfoil tube from Neopac is squeezed, the mechanical dispensing system from Aptar Pharma releases a precisely measured drop and prevents any liquid from flowing back into the tube. Caps and flow rates can be customized to meet the required drop formation (6).

	Tube manufacturers also are addressing the need for more sustainable structures. Berry Global Group can incorporate post-consumer recycled (PCR) resin in its recently introduced oval tube. The two-inch tube is extruded, formed, and decorated at its vertically integrated manufacturing facility in Easthampton, MA, and is available with premium decoration including silk screen with up to eight colors, and up to five colors with cold foil (7). 

	CCL Tube, part of CCL Industries, also offers a structure with PCR content. Its Earthtube can contain up to 70% PCR resin in the tube sleeve and head. A three-layer extrusion sandwiches the PCR layer between virgin layers to separate it from the tube’s contents and is compatible with premium decorating and labeling (8). 

	Essel Propack introduced the Platina 250 and Green Maple Leaf 300 Lamitubes in November 2019. The sustainable designs feature a high-density polyethylene (HDPE) barrier structure that meets or exceeds recyclability guidance from the Association of Plastic Recyclers and are recyclable in the #2 HDPE recycling stream. The stiffness of the HDPE also permits resource-conserving downgauging. The two recyclable designs join another sustainable offering from Essel Propack, the Etain tube, which features up to 25% PCR content (9). 

	Hoffmann Neopac offers an EcoDesign portfolio (10) and also plans to launch a recyclable barrier tube before the end of 2020. The Polyfoil MMB (mono-material barrier) tube consists of more than 95% PE with inks, adhesives, and barrier layers that do not negatively affect recycling. A thin-wall structure means a weight reduction of up to 40% compared to standard Polyfoil tubes with aluminum barrier layers. “Technology must play a role in meeting higher recycling standards, and mono-material barrier tubes will represent a sizable step forward in packaging science,” said Martina Christiansen, director Sales Tubes Neopac, in a press release (11). 

	1. Mordor Intelligence, “Tube Packaging Market–Growth, Trends, and Forecast (2020-2025),” www.mordorintelligence.com/industry-reports/tube-packaging-market, accessed June 1, 2020.  

	2. ALLTUB Group, “New Cleanroom Production for Laminate Tubes,” Press Release, April 1, 2019. 

	3. ALLTUB Group, “New Small Diameter Capability for Laminate Tubes,” Press Release, April 1, 2019. 

	4. Hoffmann Neopac, “Neopac Opens First US Facility with Site Tours and Demos of High-Speed Tube Production Line,” Press Release, May 20, 2019. 

	5. Hoffmann Neopac, “At Pharmapack, Neopac to Showcase SpringTube for Skin Health Products,” Press Release, June 1, 2020. 

	6. Hoffmann Neopac, “Neopac Wins Three Prestigious Healthcare Sector Packaging Awards,” Press Release, Sept. 16, 2019. 

	7. Berry Global Group, “Berry Global Introduces Oval Tube Assembled in the United States,” Press Release, Feb. 26, 2020. 

	8. CCL Industries, “Tubes-Earthtube (PCR),” https://ccllabel.com/portfolios/tubes-earthtube-pcr/, accessed June 1, 2020. 

	9. Essel Propack, “Essel Propack Unveils Recyclable Tube Packaging-Platina and Green Maple Leaf Lamitubes,” Press Release, Nov. 4, 2019. 

	11. Hoffmann Neopac, “Continuing Sustainability Efforts, Neopac Moves Toward Mono-Material Barrier Tubes Designed for Recyclability,” Press Release, May 13, 2020.  

New options for pharmaceutical tubes enhance functionality, sustainability, and brand identity. 

Equipment and Processing Report-06-17-2020

Responding to COVID-19 in Pharma Facility Design and Operation

Pharma Packaging Focus on Tubes