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Agnes Shanley is senior editor of Pharmaceutical Technology.
The COVID-19 pandemic has pushed more pharmaceutical companies and regulators to use new technologies for remote quality audits and inspections.
The late US President John F. Kennedy once remarked that any crisis represents both a danger and an opportunity (1). He had illustrated the point with Chinese characters, in an analogy that, like his famous Berliner quote, was found to be wrong. But the observation that good things can come out of a crisis holds true. As the COVID-19 pandemic continues to disrupt lives and business operations around the world, some drug companies are achieving unprecedented efficiency improvements. Despite travel restrictions and other limitations, a few have stepped up collaboration and slashed development times by 80%.
Many companies have started to use, or have increased their use of novel technologies—not only standard web video-conferencing tools, but platforms that incorporate video, augmented and/or virtual reality, and features such as borescopes and secondary cameras — to allow partners and regulators remote access to facilities, equipment, and documentation. For some companies, these tools had already been in use on a limited basis to audit suppliers, troubleshoot technical problems with vendors and consultants, and improve collaboration with customers. Using them for interactions with regulators represented a whole new use case.
For an industry known for its aversion to risk and new technology, the move to virtual technology was driven by necessity. Challenges had reached a high point in March 2020, when the FDA commissioner said the agency would be postponing routine on-site surveillance inspections (2). At the time, shortages were developing for commodity drugs, including some that were being used to treat COVID-19 and its associated problems.
Companies that had spent millions to develop new, non-COVID treatments could not have post-approval inspections performed, delaying progress. “Some customers were on hold and losing millions of dollars each day,” says Devon Copley, CEO and cofounder of Avatour, whose remote inspection platform focuses on immersive 360-degree video.
“The whole industry went through massive shock. Senior managers were concerned about supply chain preservation and how to even conduct normal daily operations,” says Angelo Stracquantanio, CEO and cofounder of Apprentice.io, whose remote inspection platform is centered around augmented reality and works with smartphones and other mobile devices. “There were questions of how to handle tech transfer, factory and site acceptance tests, and regulatory inspections when the world was no longer travelling,” he says. Apprentice responded in March by releasing rapid deployment kits, “do-it-yourself” packages that would allow companies to set up the technology required for remote inspections, themselves. Since July 2020, Stracquantanio says, usage of the platform has expanded by a factor of 17, and new site deployments by a factor of ten. On November 17, 2020, he says, the company received $24 million in venture-capital funding, bringing its total to $40 million in 2020. During the pandemic, the company has worked with clients to improve its Tandem platform, and recently introduced a Tandem Smart Hub specifically designed for use in cleanrooms, adds Stracquantanio.
Taking a different approach to virtual inspections is Avatour, which was established in 2017, and offers a remote inspection platform designed for location-immersed collaboration and 360-degree video. The technology, which was prototyped and beta-tested in 2019, works with smartphones, and can be used with a browser or virtual reality goggles for full immersion, says Copley.
Avatour’s cofounders are experts in this technology, having helped lead the Nokia team that invented and integrated the 360-degree video camera. Demand for the platform has been growing briskly, Copley says. Avatour has seen 25% growth per month, and roughly 12 pharma companies and consultants have deployed or are deploying the system, he says. This year, the company has released regular updates, increasing the number of people who can take part in a tour from five to nine, adding a secondary camera source, and integrating a microscope, Copley says.
Using Avatour’s platform is Lachman Consultant Services, which established a formal practice devoted to remote inspections and audits in October 2020. What began as a response to an overall top-down leadership commitment to find new ways to work, became more focused in March and April 2020, says compliance director Scott Deckebach. By the summer, Lachman had begun to engage more with the technologies and encouraged clients to do the same. Pharma companies are adopting these technologies because they find it easier to do this remotely than to let people into their facilities, Deckebach says. So far, Lachman has worked on fully, or highly, remote projects, even in China, which is one of the more difficult regions in which to do this, due to government restrictions on communications, as well as technology, time zone, and language differences.
Two parallel technology tracks are important in any remote audit, Deckebach says. The first is a more general 360-degree view. “Auditors need to be immersed in the environment in order to get an overall sense of facility flow and cleanliness. You cannot get that with a traditional camera-based technology, where the host can decide what you see,” he says. The other essential requirement is the ability to perform focused interrogations (e.g., to watch an analyst perform a method in some detail, or to zero in on a computer system or a label). Lachman establishes both tracks for its remote audits.
Pharmaceutical contract development and manufacturing organizations (CDMOs) have been enthusiastic adopters of virtual audits and inspection. Catalent Pharma Solutions, for instance, has used remote technologies since 2015, to give clients easier access to its facilities, says Joe Montano, director of customer experience, who calls remote inspections a core competency for the company. Currently, the company is working with Apprentice.io, mainly using its Tandem platform, but it is also using 360-degree video to give clients virtual tours of facilities.
Remote inspection technology was first piloted at Catalent’s Kansas City, MO facility, and has extended use of the technology since the COVID-19 pandemic began. “We were able to expand its use from a few pilot sites to more than 40 sites around the world,” Montano says. The company is now using the remote approach with all major global regulatory agencies. Since Catalent hosts or performs more than 500 audits each year, new technology has allowed the company to keep pace, while observing social distancing requirements, Montano adds. At this point, Montano says, regulators are taking a hybrid approach, sending one or two dedicated team members onsite and bringing additional inspectors in virtually. “We’ve only done a handful of audits that were fully remote, but we expect that number to increase over time,” he says.
Also going remote for inspections and audits is Thermo Fisher Scientific’s Pharma Services. The company is currently working with a number of technologies, focusing on Microsoft HoloLens and Microsoft Teams, and the use of virtual tour software. Live facility tours are filmed with a 360-degree camera, and 3-D tours with a 3-D mapping camera, says Sandy Immerman, vice president of Information Technology (IT), Pharma Services. The company began to move in this direction during the fourth quarter of 2019 and stepped up efforts during the COVID-19 pandemic. So far this year, Immerman says, Thermo Fisher has hosted multiple regulatory inspections and more than 125 client audits, focusing efforts on current good manufacturing practice (CGMP) activities in work that has involved FDA, the European Medicines Agency, which issued formal guidance on the use of this technology last May (3), the Russian Ministry of Health (MoH), and the Swedish Medical Products Agency. Russia’s MoH has conducted the most remote/virtual inspections, she says.
Before a remote audit or inspection begins, it’s important to establish a strong partnership with clients, says Deckebach. “You can’t just pull these technologies in on day one. Use of the technology requires coordination and ensuring that the client has the right hardware and knows how to use it.” In addition, a remote audit needs to be more scripted than a standard audit if it is to succeed, he says. Tech experts will be needed on both sides to ensure that the technology is incorporated, connected, and built into their systems, says Deckebach. “They need to be confident and to break down any connection or communication barriers ahead to time to make sure things are working (e.g., firewalls, connections into networks, and general network flow). A back-end IT person is required to ensure that these networks are opened appropriately to allow information to flow,” he adds.
The extra coordination and care these remote technologies require may be a reason why regulators have been so cautious about adopting their use, says Deckebach. “These newer technologies need a bit more care and handling,” he says. “It’s not like you can simply click on a Zoom link to activate them.”
IT infrastructure is a primary challenge. “Not all facilities have installed solid wireless Internet capabilities throughout their manufacturing areas. We ask clients for layout drawings and make decisions on where we want to tour facilities. Once agreed upon, we have them complete a bandwidth survey confirming that minimal bandwidths are met,” says Deckebach.
Problems will invariably come up, but persistence and flexibility are key. “We can get into a dark spot in a warehouse and lose communication, for example, or a user may not know how to get on the system, resulting in 10–15 minute delay. These are typical things that can happen, which is why you need good plans, contingency plans, and backup systems,” says Deckebach.
A week before any audit or inspection begins, Catalent’s team holds a pre-briefing exercise with clients, to familiarize them with the technology platform and give them a high-level view of what to expect, says Hasan Daniel, Catalent Cell and Gene Therapies’ associate director of quality assurance. Through November 2020, he says, the company’s site in Gaithersburg, MD, has performed six virtual audits, the first of which took place in May. “This pre-briefing process is extremely important,” Daniel says, and must involve all staff members that will be working on the audit. In addition, it must feature a secure mechanism for sharing files, and must ensure that everyone working on the audit has full access to all required technology platforms.
One detail that might seem minor but is actually quite important is ensuring that battery-powered devices are fully charged and that enough backup batteries are available. Auditors must also be given a map of the facility, with visual indicators that outline the sequence of the tour so they can see what they are viewing at any point, relative to the whole facility, Daniel explains. Ensuring data integrity and security is of paramount importance, he says, and it usually requires two days to ensure that all documents and proprietary documentation are secure, and cannot be downloaded, printed, or corrupted in any way.
Catalent is not using virtual reality, but sees tremendous potential value in augmented reality using technology such as HoloLens, which allows text, graphics, or video to be overlaid on the user’s view. The benefits should trickle down into employee training and onboarding, says Montano, who says that Catalent is starting to explore its use in training for some standard operating procedures (SOPs) that involve high-risk processes.
While WiFi and other infrastructural issues pose some limitations to implementing remote technology, most of them can be overcome, says Immerman. Montano expects these problems to dissipate as the industry moves to 5G, Starlink, and other new communications platforms. “Training is another limitation, although it can be positioned as an opportunity if you’re willing to invest in it,” Immerman says. “Because the technology is evolving at such a rapid pace, it can also be difficult to gain visibility into the latest capabilities as well as vendor stability,” she says.
On Catalent’s wish list for the technologies would be extending battery life. Currently, says Montano, devices can run up to eight hours (in 2015 the limit was 30 minutes), yet that figure could stand to be improved. Another advantage would be allowing clients to be able to observe operations for their projects reotely, since some of the unit operatiohs are very lengthy and can take a whole day to complete, says Daniel.
However, users note considerable benefits from the technology, saving travel time and cost, and even costs for gowning supplies and consumables. “Having just one person gown in leaves much more time for Q&A and document review,” says Montano. Both Catalent and Thermo Fisher have realized significant gains from using the technology and plan to continue to expand and invest in it. Even if this technology does not replace on-site audits and inspections completely, users don’t see the industry going back to the old ways of doing these things. Deckebach sees the hybrid model, with one or two local staffers onsite and the rest of the team connected virtually, as minimizng risk yet enabling savings and other benefits.
1. J. F. Kennedy, “Speech at the Convocation of the United Negro College Fund,” Indianapolis, IN, April 12, 1959, jfklibrary.org, accessed Nov. 10, 2020.
2. FDA Press Release, “FDA Focuses on the Safety of Drug Products While Scaling Back on Domestic and Foreign Inspections,” fda.gov, March 18, 2020.
3. EMA, Guidance for Remote GCP Inspections During the Pandemic, ema.europa.eu, May 20, 2020.
Agnes Shanley is the senior editor for Pharmaceutical Technology.
Vol. 44, No. 12
When citing this article, please refer to it as A. Shanley, "Can Pharma Qiuality Go High Tech?" PharmTech 44 (12) 2020.