	Just as emails can be accessed anywhere from a smart phone, pharmaceutical manufacturing process data can now be made accessible remotely through new network solutions. And remote access is not limited to data on a screen. Smart glasses have moved beyond a consumer novelty to a business tool that can be particularly valuable in manufacturing. One of the primary uses today in pharmaceutical manufacturing is telepresence, by which remote personnel can literally see what an on-site person is viewing and can perform remote troubleshooting, for example. Both large pharmaceutical companies and CMOs are using or experimenting with smart glasses for various uses, including troubleshooting, maintenance, and training.


	The smart glasses concept was popularized by the Google Glass for consumers, but several other companies are also producing smart glasses. Some of these are believed to be better than Google Glass for industrial applications in the functions of information access, real-time communication, and documentation, according to a Lux Research Report published in December 2015 (1), which looked at enterprise deployments of smart glasses. Some glasses on the market for industry include Epson Moverio, Vuzix M100, Osterhout Design Group (ODG) R-7, and others.

	Developers continue to improve the glasses. “How to balance between a long battery life time and the limited available space within a pair of smart glasses will continue to be a major challenge for smart glass developers,” notes Tony Sun, the lead analyst of the Lux Research report. “Developers also need to improve the durability of the overall device construct for industrial environments, such as incorporation of smart glasses into a helmet.”


	Other companies are developing the applications needed to make smart glasses useful in manufacturing, including pharmaceutical manufacturing. Pristine focuses on the business value found in “virtualizing the expert.” “Smart glasses can multiply the availability of experts, because an operator in a plant can wear smart glasses and be connected to the expert in another plant or an office,” notes Pristine’s Lucas Schlager. Connecting two people with a video stream is relatively straightforward, but making this connection for hands-on workers in the field, such as in a manufacturing environment, comes with specific needs. “First, the user needs to easily contact the expert. Problems are usually unplanned, so a preset conference set up via email may not provide a fast enough response,” says Schlager. “Apps are designed to perform ‘pre-call magic’ to get the call from the field to the expert quickly, while the operator is in the plant with gloves on and can’t dial a phone, but can say out loud, ‘Need help.’ After connection, the expert may need to demonstrate to the operator what might need to be done, by drawing on top of the video, for example.” Data about the call or about the problem and solution can be recorded for evaluation to make the system work better or to identify trends in manufacturing problems. “We are on the ‘slope of enlightenment’ of adoption of these technologies. Early adopters have experienced the benefits of virtualized experts and others are starting to try it,” observes Schlager. He suggests that augmented reality or immersive experience (e.g., having instructions pop up on the glasses based on what the operator is viewing) will grow in the near future as smart-glass technology becomes more lightweight and higher resolution and as enterprises gain more experience with the technology.

	Apprentice Field Suite, which uses smart glasses and other mobility technology to improve processes for its pharmaceutical and biotechnology clients, designed three technology modules specifically for pharmaceutical manufacturing and R&D. The Tandem module allows an engineer to have a “telepresence” for remote troubleshooting, which minimizes travel and gives instant access to a problem. “The operator in the facility will wear the glasses and the engineer at a remote location can see the problem that the operator is looking at; this feature currently is being used at all of our global pharma clients,” explains Gary Pignata, partner at Apprentice. “If necessary, an equipment manufacturer or subject-matter expert can also be given simultaneous access. Additional tools allow the remote user to ‘draw’ on the field of vision of the glasses-wearer (e.g., to show what button to push or to indicate the specific part being discussed) so that communication can be visual as well as verbal.” The glasses are also useful for a CMO–client project relationship, notes Pignata, "A CMO protects the proprietary nature of other projects by only turning the glasses on for a specific client, while at the same time allowing that client access to their process without traveling." The Gauge module can alert operators to the condition of equipment (i.e., if a reactor is in use) and capture data from analog (and other) gauges. A Manuals component can be used during training or maintenance, for example, so that safety notices and standard operating procedures can be viewed with the glasses in a heads-up display, allowing the users' hands to remain free to perform operations.  Apprentice co-founder Angelo Stracquatanio remarks, "We are seeing significant efficiency gains and operational improvements at each of our four top-10 pharma clients, as well as the other biotechs, CMOs, and equipment manufacturers we work with".

	Software provider Vital Enterprises sees the main advantage of smart glasses in manufacturing as allowing hands-free operation with access to information and remote collaborators. The company currently has commercial applications in air and space assembly and in medical, and is beginning to work with pharmaceutical manfuacturers. “We are working with pharmaceutical innovation centers to gestate this new technology and deploy it more broadly,” says Ash Eldritch, co-founder and chief science officer of Vital Enterprises. “Companies are deploying at the pilot stage to look for cost and efficiency benefits. The gains are largest for geographically distributed teams that can benefit from telepresence and for cases where there are long process checklists, such as in technology transfer procedures.”  Another possible use is smart laboratory notebooks. “Some are using electronic notebooks already, but smart glasses have the benefit of being worn. They can also capture point-of-view video and audio notes that can be transcribed,” says Eldritch. Similarly, in a manufacturing environment, the glasses can capture expert knowledge for training or for quality checks. Smart glasses are currently being used for hands-free instructional support, with text or schematics put into the wearer’s view while they are carrying out a complex task. “Next we plan to incorporate videos, in addition to the currently available static images and text that can be read to the wearer. The challenge is creating and transferring the video content, because the traditional way of doing things is text based,” says Eldritch.


	Smart glass technology has only been in existence for a few years, and experts note there is still relatively little knowledge in the market about the potential benefits. Even so, the technology continues to get smarter. “Smart glasses are advancing in ‘contextually awareness’-rather than the operator telling the glasses what checklist is needed, for example, the glasses will leverage the sensors in the industrial internet of things (IIoT) to sense where the user is standing, who they are, and what task needs to be performed,” says Eldritch. “The convergence of IIoT and augmented reality will be the next step forward from where the technology is now, as a head-mounted display. In five to ten years, smart glasses will be able to project digital imagery directly onto physical objects, meshing digital information seamlessly and intuitively into the world around us,” he predicts.

	The use of smart glasses is expected to grow. “We expect the use of smart glasses will eventually expand from manufacturing to other roles or functions within the same company, such as customer service and online sales support,” predicts Sun. “For this to happen, smart glasses first need to scale up within manufacturing roles by improving ergonomics, learnability, and data safety.”

		T. Sun, “Better than Google Glass: Finding the Right Smart Glasses for Enterprise” Lux Research State of the Market Report, Dec. 22, 2015, 

https://portal.luxresearchinc.com/research/report_excerpt/20864

Articles

Production Trends

Smart glasses enhance remote troubleshooting and process management for pharmaceutical manufacturing.

Manufacturing Personnel Try Out Smart Glasses

	Film coatings on pharmaceutical tablets provide a broad range of functionalities, and the coating formulation and process are complex, with many variables. 

 shows the variables associated with a pan-coating process, for example. All of these factors can potentially influence critical quality attributes of the final coated product.

Film-coated products seem to exhibit more than their fair share of defects. Although many film-coating problems tend to be visual or cosmetic defects that may not negatively impact product efficacy, their existence detracts from the perception of overall product quality and may affect consumer/patient confidence. Many common problems with film-coated products and processes are understood and solutions have been discussed (1–4). Most of these problems can be avoided if a scientifically valid and proactive approach is taken when designing formulations and processes.

	Generally speaking, the key elements of any film-coated product are formulation and design of the core (to which the coating is applied), the coating formulation, and the coating process. In many cases, all three of these elements, in combination, play a key role in the presence or absence of coating defects.

	Problems associated with film-coated products may be classified as:

		Issues associated with product functionality (e.g., drug release behavior)

	Identifying visual defects (and the extent to which they occur) can be relatively simple, and there are proactive approaches to avoiding them. Product functionality and stability, however, present a more complex situation, because the existence of the problem is typically not apparent until after the coating process has been concluded, and sample selection for testing purposes often effectively precludes assessing the magnitude of the problem.

	Preventing problems is better than troubleshooting afterwards, because regulatory issues (e.g., after a product has been commercialized) may limit troubleshooting solutions. Indeed, the intent of quality-by-design practices is to investigate all aspects of the product development process and identify critical quality attributes and critical process parameters. This article provides an overview of issues that should be considered when designing film-coated products. Pan coating of tablets is used as an example, but many of the assertions are relevant to film coating in general.


	Film-coating processes are stressful, both in terms of the mechanical attrition that takes place as well as the environmental conditions (temperature and humidity) within the coating process to which the product being coated will be exposed. These stress factors become more substantial when the coating process is scaled up from the laboratory to full-scale production, because the product exposure time to such conditions increases.

	Thus, a sensible approach uses a core material that is resistant to such stressful conditions. In the case of tablets, designing cores that have exceptional mechanical properties (in terms of both mechanical strength and friability characteristics) is essential. What is not clear, however, is what defines exceptional mechanical properties. The common practice is to define mechanical strength in terms of a tablet-breaking force, the required minimum value of which increases with increasing tablet size. For this reason, use of low friability values becomes a good surrogate to help define tablet robustness. Regardless of tablet size, tablets should possess friability values of < 0.1% if they are to be successfully film coated on the manufacturing scale.

	Examples of common defects that can be eliminated by effective core design are summarized in 


	The mechanical properties of the coating formulation are equally important to those of the core, because both are subjected to the same stresses. To some extent, the mechanical behavior of the coating will be augmented by that of the core, because the core essentially acts as a scaffold for the coating. Key attributes of the coating formulation that, if suitably optimized, can contribute to the quality attributes of the final product are discussed as follows.

Mechanical strength (tensile strength) of the coating. 

This attribute can effectively be used to prevent edge chipping and cracking of the coating, which becomes much more serious when the applied coating has a functional purpose, such as protecting the core from environmental moisture or modifying drug-release characteristics (e.g., delayed release and extended release products).

Coating flexibility (often defined in terms of elastic modulus).

 Coatings that are flexible can offset edge chipping and are less likely to suffer from logo bridging problems. Flexible coatings can more easily accommodate core dimensional changes that are associated with various factors, such as post-compaction strain recovery, core swelling due to thermal expansion on exposure to process heat, and swelling due to moisture absorption in an aqueous coating process where drying conditions are not ideal.

 The surfaces of many pharmaceutical oral solids can present adhesion problems, especially when the coating formulation is delivered from an aqueous coating system. The reasons stem from lack of adequate core porosity to the formation of high energy surfaces where a high API content, coupled with the known hydrophobic characteristics of the API (e.g., ibuprofen), present a surface that is difficult to wet (wetting is a necessary precursor to good adhesion). Although some of these deficiencies can, to some extent, be offset when employing suitable core formulation strategies, coating formulations with high adhesion characteristics, such as those based on polymer mixtures using hypromellose and copovidone or those that utilize poly(vinyl alcohol) as the primary polymer, can be useful in offsetting adhesion-related problems. Such problems include coating rub-off as the tablets tumble in the coating pan and logo bridging, where stresses that develop within the coating on drying cause the coating to become detached within the logo as a result of adhesive failure (see 

 The use of high-solids coating systems allows the amount of solvent (water) that will be sprayed to be reduced, while maintaining coating suspension well below the traditional limit of 300 cP required to produce a quality coating. These systems offers many benefits, including:

		Reducing coating process time, thus minimizing process costs, as well as exposure time of tablets to stressful process conditions

		Improving product stability, either as a result of reduced process exposure time to high processing temperatures and humidities, or by minimizing moisture penetration into the cores, especially when process conditions are less than optimal. High-solids coatings contain less water, thus presenting less of a thermodynamic challenge to the evaporative capabilities of the coating process.

		Facilitating the use of lower processing temperatures, which can be beneficial to thermolabile APIs.

	It should be recognized that today, many pharmaceutical companies prefer to buy ready-made coating systems from one of a number of suppliers. In those cases, close collaboration with the selected supplier(s) is necessary to ensure that the coating system chosen is optimal for the product being coated and the coating process that will be used.


	Although core and coating formulation need to be well understood to avoid downstream problems, the coating process also plays a major role. Three important areas of any coating process that need close attention are as follow.

 Process thermodynamics affect the ability of the process air stream to effectively remove solvent (e.g., water). The main variables are temperature, moisture content, and air mass (or volume).

 Spray dynamics influences droplet size and size distribution, velocity, and drying while in flight from the nozzle to the surface of the tablet bed. It also influences spray flux, which is a combination of spray rate and the area over which coating liquid is delivered from each spray gun onto the surface of the tablet bed. Spray flux from each spray gun in a multi-gun set up may not be identical, unless the spray rate and atomization conditions are identical for each spray nozzle. Spray dynamics also influence uniformity of the distribution of the coating. Spray dynamics can be influenced by:

		Process air flow inside the coating pan.

	These process factors, even when carefully selected during process set up, rarely stay constant throughout the coating process. Although gun-to-bed distance may have been measured during gun set-up, for example, it can change as the tablet bed moves because tablets flow across the surfaces of baffles, causing the tablet surface to move back and forth as the pan rotates. In addition, as the coating is applied, the slip of the tablets can change, and the angle of the surface of the tablet bed may change with it.

This aspect of the coating process will affect attritional effects within the process (and hence mechanical damage to the tablets) and coating distribution uniformity across a batch of tablets. Tablet movement may impact drying within the tablet bed, because the faster the tablets move, the shorter the time in the spray zone, the less coating material each tablet picks up, and the faster that amount of coating material can dry. Generally, as long as the tablet cores and coating formulation are suitably robust, the faster the tablet motion within the coating pan, the better.

	When designing coating processes, any limitations that exist with respect to either the tablet cores or the coating formulation must be taken into account. Past experience with a particular piece of coating equipment should never be used as the primary reference point for selecting specific coating process conditions.

	It is also necessary to take into account that when designing a coating process for a new product, greater processing flexibility will often exist within the laboratory environment. Failure to take into account the limitations that may exist in the production setting can have dire consequences.

	Examples of common defects where close attention to the design of the coating process can be of particular value are shown in 


	While process adjustments are often applied reactively to troubleshoot and resolve problems that have already occurred, the ideal situation is to recognize the contribution that such adjustments can bring and build them into the process design proactively, so that the process design space can accommodate any formulation limitations (for both the core and coating) that might exist, thus avoiding unanticipated issues downstream.

 129 (9) 50 (1981).
	2. S. C. Porter, “A Proactive Approach to Troubleshooting the Application of Film Coatings to Oral Solid Dosage Forms,” in 

Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms

, L. A. Felton, Ed. (Taylor & Francis, 4th ed., 2016, in press).
	3. R. C. Rowe, 

 49-51 (April, 1993).
	4. R. C. Rowe, “Defects in Film-Coated Tablets; Aetiology and Solutions” in 

, D. Ganderton & T. Jones, Eds. (Academic Press, 1992), pp 65-100.


	Stuart Porter, PhD, is a senior research fellow and technical lead for Global Film Coating Technology at Ashland Specialty Ingredients, Wilmington, DE, 

February issue. When referring to this article, please cite it as S. Porter, "Preventing Film Coating Problems Through Design," 

Troubleshooting

Effective design of the tablet core and the coating process can help prevent film coating problems.

How To Prevent Tablet Coating Problems

	Near-field communication (NFC) technology can create a “smart” package with an unprecedented level of communication between consumer and product or brand. The three primary components of a smart package are an NFC tag, a smartphone equipped with NFC technology, and an application that provides access to information in the cloud or functionality such as contactless payments.


	As a radio frequency identification technology (RFID), an NFC tag can carry more data than a barcode or QR code and provide access to a virtually unlimited realm of additional information. As a result, the currently small market for NFC technology is growing rapidly with a compound annual growth rate of 37% projected between 2015 and 2020, according to a report from IDTechEx (1).

	According to Raghu Das, chief executive officer at IDTechEx and co-author of the report, “NFC is of great interest to pharmaceuticals because…[it] would allow patients to engage with the product.” Authentication, tamper detection, patient and equipment safety, and educational information are major benefits, but the potential to personalize consumer/product interaction is particularly advantageous for pharmaceuticals. “Your phone will remind you when to take your pills,” predicts Das. “Instead of confusion and micro print details on labels, your phone will more clearly display or even tell you what those drugs are. Potentially, your phone could track fitness and other parameters and therefore adjust your dosage. Data could be sent to your doctor. Elderly could be more self-sufficient and perhaps be able to stay in their homes longer.”

	The challenge to adopting NFC technology is that the supporting readers are Android-based. “Until Apple opens up its NFC platform to read NFC tags (as opposed to just Apple Pay payments), brands face the issue of paying for NFC tags on packaging when only a minority can read them,” says Das. In addition, not all Android-based phones can read all NFC tags, according to AndyTags, a website about NFC technology (2).


	Several firms provide NFC-equipped labels or packaging including MPI Label Systems, NXP, Jones Packaging, Avery Dennison, and PPi Technologies. MPI, which has been producing RFID labels since the early 2000s, introduced NFC labels in 2011. Its RFID/NFC division in Alliance, OH, not far from its headquarters in Sebring, OH, can encode NFC labels to direct the user to a website or set the smartphone to perform a specific task. In addition to facilitating two-way communication with consumers, the tags allow consumers to share experiences with each other and can launch special promotions and reinforce brand values and messages (3).  

	“MPI is involved in numerous proprietary NFC applications in the pharmaceutical/healthcare industry,” reports Shauna Woolf, RFID general manager at MPI Label. “We work with all of the major NFC inlay suppliers: Smartrac, Identive, Avery, MiKron, etc.,” she explains. To minimize lead times, MPI maintains an inventory of common tag sizes and memory types. In addition, Woolf, says, “We can provide any face stock and adhesive combination that is needed. This is of utmost importance to make sure the label meets the application requirements.”

	NXP has introduced an NFC-enabled sensor designed to be integrated into blister packs or pill bottles. It tracks when medication is removed from the package. Tapping the package with a smartphone records the data, which can be used to prompt delivery of personalized services to improve compliance and support patient, caregiver, or healthcare professional.

	Jones Packaging, a converter of packaging materials and contract packaging service provider for the pharmaceutical industry, plans to launch an NFC-equipped carton for a commercial product before the end of 2016. Jones Packaging is collaborating with Thin Film Electronics ASA (Thinfilm) to integrate the latter’s OpenSense NFC labels on prescription and over-the-counter product packaging.

	Already in use in the spirits and wine industries and on auto-injector pens from Ypsomed to support product tracking and patient compliance, OpenSense labels are based on printed electronics, rather than traditional chip/antenna inlays. With a tap of an NFC-enabled smartphone, the thin, flexible labels can report whether the product is factory sealed or opened, so appropriate information can be delivered in return. “The ability to recognize open and closed is a big differentiator,” says Matthew Bright, senior director, product and technical marketing at Thinfilm. “Other NFC technologies generally are not usable after the package is opened,” he explains.

	Thinfilm’s “Tag Talks First” technology enables a read speed that is up to 20 times faster than conventional NFC solutions (4). This means integration of the smart label does not cause bottlenecks on converting or packaging lines. In addition, labels destined for application to aerosol cans or foil blisters may be equipped with a ferrite shield, overcoming interference problems experienced with conventional RFID tags when mounted on metallic surfaces. Bright says, “The ferrite shield lamination provides a barrier that allows RF energy to power the tag and enable it to transmit data to an inline reader or smartphone.”

	Each OpenSense tag has a unique identifier that cannot be erased or modified, thus enabling tracking to the item level, product authentication, and delivery of information tailored to the consumer. The unique identifier also can support serialization. “We haven’t developed a plan to execute serialization yet, but we could capture track-and-trace data from any point where we install a reader,” says James Lee, director, technology and innovation at Jones Packaging.

	More immediate benefits will come from the ability to provide personalized information about how the product will meet a consumer’s needs. “The potential to store an unlimited amount of information in the cloud overcomes space limitations on the package,” says Lee. For example, he says, tapping a smartphone on a nutraceutical label could open a window requesting input about prescribed medications and return any contraindications. Another possibility would be to provide instructions in a language other than what’s on the package/label.

	“When the package is shown to be open, the program could provide smartphone alerts for expiration date or suggest reordering. The combination of unique identification, smartphone readability, and dynamic, personalized information delivery could benefit many products,” concludes Lee.

		R. Das and P. Harrop, “RFID Forecasts, Players and Opportunities 2016-2026,” IDTechEx Market Study, October 2015.	

		AndyTags, “Mifare Classic NFC Tags Compatibility Issues,” 

www.andytags.com/nfc-tags-compatibility-issues.html

		MPI Label Systems, “NFC Labels–Customized or Encoded,” 

www.mpilabels.com/products/rfid/nfc-labels-customized-or-encoded

		Jones Packaging Inc., “Jones and Thinfilm Create ‘Smart Packaging’ Solution for Top Pharmaceutical Brands,” Press Release, Jan. 5, 2016. 

Packaging

Near-field communication labels communicate with consumers and support personalized medicine.

Equipment and Processing Report-02-17-2016

Manufacturing Personnel Try Out Smart Glasses

How To Prevent Tablet Coating Problems

Smart Labels Enhance Drug Packaging