Revolutionize Sample Management With Automation

THE EVOLUTION OF SAMPLE MANAGEMENT AND AUTOMATION IN DRUG DISCOVERY An interview with Dr. Sue Holland-Crimmin Drug discovery has traditionally relied on high-throughput screening of small molecules, necessitating the storage, management, and testing of vast compound libraries. Early workflows were painstakingly manual and labor-intensive. At the turn of the 21st century, automation transformed pharmaceutical research by delivering massive gains in speed and efficiency. Now, the industry faces fresh obstacles with the next generation of therapeutics. Biological products and specimens require colder and more stringent storage environments, complicating how they’re managed in the lab and the clinic. Expert Insights on Sample Management and Automation We interviewed Sue Holland-Crimmin, Ph.D., to discuss the lessons learned in drug development and how pharma/biotech companies can address key challenges that impact creating more efficient workflows. Dr. Holland-Crimmin is a veteran of the pharmaceutical industry and an expert in drug discovery. Over the last two decades, she has witnessed—and helped bring about—a revolution in sample and material management. Introduction................................................................................................................................................................................ 2 Automation in Drug Development – Past, Present & Future......................................................................................................5 Biological Sample Management Needs a Revolution ................................................................................................................11 Sample Management Challenges for New Drug Modalities ....................................................................................................16 The Role of Information Technology in Sample Storage...........................................................................................................21 Market Gaps for Biological Sample and Material Storage ......................................................................................................26 Building Systems and Infrastructure for Sample Management .............................................................................................31 Contents 1 SAMPLE STORAGE BIOBANKING SAMPLE MANAGEMENT Automation in Drug Development – Past, Present & Future 5 Can you share a bit about your perspective on automation? 1 Automation in Drug Development – Past, Present & Future Automation really enables scientists to make better decisions faster. Automation is often believed to be new to pharma, but there’s been a long history of automated systems in drug discovery throughout my career. The forerunner to the Society for Laboratory Automation and Sciences (SLAS) had exhibitions that started out in the 2000s with a few tabletops and maybe a few hundred delegates. Now it’s grown to an impressive range of automation platforms and vendors that fill huge exhibition halls at the annual conferences. It’s no longer about high throughput. When we started, it was about facilitating high-throughput screening. But now it’s more about interconnecting the lab environment so we can generate better precision and increase the accuracy of results in our research. This is particularly true for the smaller biotechs and startups. They often have great ideas, but they don’t have huge resources and manpower to execute those ideas. Harnessing automation can really help lean teams to be successful and bring new medicines to market. So, for me, automation is a real enabler. 6 1 Automation in Drug Development – Past, Present & Future Automation has a stigma in a lot of research areas that it’s too expensive. How can the benefits outweigh the costs? I like to think about both the tangible and intangible benefits; they’re equally important. Some of the most important benefits include: Precision. Higher precision of equipment leads to reduced waste in the process. Quality. Increased quality is a significant driver. Automated systems tend to perform many processes with a lot less variability than a human operator can. The result is greater control and consistency of the product quality. Repetition. Repetitive tasks that are usually done manually can be carried out with ease with automated solutions. Output data from machines can be streamlined directly into the scientist’s electronic notebook, and this really reduces the risk of human errors that arise from manual recording. Productivity. Automation enables many tests to be performed by a limited number of personnel. Hence, it really can drive down the cost point. Efficiency. Automation supports the connection of lab processes, so in terms of flexibility, you can remotely control devices which allows you to conduct experiments at any time. A good example of this was a high-throughput sample storage and delivery platform that the research team built. One of the processes we put in place had the ability to start a large cherry pick of samples in the middle of the night and the samples would be plated out and ready for screening in the morning. Scalability. When we started out, we were screening or testing handfuls of samples in 96-well plates. But automation has really allowed us to move from those tens of samples to a million samples in the same time frame. That’s only been possible by being able to automate all those processes. 7 What is the importance of software in automation and how is it enabling data integration? 1 Automation in Drug Development – Past, Present & Future When people think of automation, they immediately envisage robots and robot platforms. But no matter how fancy and sophisticated those robotic platforms get, it’s the controlling software that’s the key and provides the real brains of the operation. In the sample management arena, the software is so important if you consider the aspects of sample tracking: No matter how fancy and sophisticated those robotic platforms get, it’s the controlling software that’s the key. • where the sample is at the start • how it can be retrieved • how much is needed • where it’s going to go It’s true for small molecule drugs, but even more so for biological materials, clinical samples, and cell and gene therapies, where you’re in a more regulated workspace and need to maintain the audit trail and regulatory requirements. That’s only possible when you’ve got the right software tools which support the robotic platforms. We’ve come a long way over the years in marrying sophisticated software with those robotic platforms. 8 How is automation perceived today versus in the past? 1 Automation in Drug Development – Past, Present & Future Attitudes shape how technology is perceived and adopted. In the early days of automation in discovery life sciences, it was viewed with a bit of distrust. I remember talking to screeners about using barcode technology and people saying, “Why do we need barcodes? We need to be able to know exactly what’s on our plate with human readable labels.” But when you’re dealing with hundreds or thousands of samples, knowing what’s on a plate is irrelevant. It’s about testing and being able to take those results and analyze them into something that’s meaningful. Luckily, there’s been a shift in how automation is viewed in the scientific community. We’ve lost that distrust. The assumption that humans will be replaced by machines, according to market analysis in the early 2010s, hasn’t come to fruition. I think people now, particularly in the life sciences, see how automation is a critical tool and that it supports the work of our scientists. If you can use machines to carry out tedious and repetitive work, then our scientists can focus on more cognitive tasks. I really have seen a mind shift over the last 10 or 15 years in terms of how automation has been viewed and adopted. It’s now such an integral part of each laboratory. Why do we need barcodes? We need to be able to know exactly what’s on our plate with human readable labels. 9 How will automation grow in the next 10 years? 1 Automation in Drug Development – Past, Present & Future We’ve seen a lot of growth. One report showed that the demand for automation through 2031 will grow by 7% each year, which is a pretty huge increase in the life sciences arena. Following the outbreak of COVID, there’s been an upsurge in precision-based diagnostic and treatment solutions, which has widened the growth opportunities for lab automation. Hence, there’s real demand from the biopharmaceutical industry to accelerate the sales of lab automation in up-and-coming years. Automation can really break the linear relationship between workload growth and cost. A few years ago it took up to, say, 10 years and a billion dollars to develop a drug and bring it to market. But the pandemic has changed all of that and for the better. We’re seeing how everyone can come together using great science but also great automation to speed up development and get both therapeutics and diagnostics onto the market. We’ve seen how automation can enable that, and therefore there’s a real appetite in the community to grow and find other opportunities to expand automation in the life sciences. How will automation impact cell and gene therapy? I think there’s a real opportunity in this space. There’s such an interest in the range of applications for cell, gene, and regenerative therapies. You really need to have efficient production of that material for these novel treatment technologies. Most of their production and manufacturing processes are manual at this point, and therefore they’re ripe to be automated—not just from an efficiency point of view, but really from a compliance point of view to ensure that material is maintained, stored, and delivered in the absolute appropriate conditions. Yearly growth in demand for automation through 2031, 7% according to a recent report. SAMPLE STORAGE BIOBANKING SAMPLE MANAGEMENT Biological Sample Management Needs 2 a Revolution 11 Compared to small molecules, the approach and infrastructure for sample management for biologics in most organizations is significantly less mature. If you look at our industry over the last 20 years, there has been significant growth and implementation of automation of all types in the small molecule arena. Most labs have some sort of automation, whether it’s storage, liquid handling, etc. In the biological space, it’s a little bit of the Wild West. It needs a revolution. Even in organizations that you think would be more mature, you see that the quality and the approach to how biologicals are stored is woefully inadequate. Obviously, I’m generalizing and there are some organizations that really do this very well. But often I see that material is not held in appropriate conditions. We see overcrowded freezers where temperature excursions are common. You see inappropriate containers of the wrong size or material. Things are not barcoded or even labeled appropriately. There’s no inventory tracking of the location, the freeze-thaw cycles, or how long How does management of biological materials compare to that of small molecules? 2 Biological Sample Management Needs a Revolution it’s been in the freezer. Samples are often lost or used in error. Valuable samples cannot be shared and accessed by others. Those are the drivers for me saying that we need a revolution. Compared to small molecules, biologicals require a lot of different conditions for storage. Often, temperatures are much lower, and in regulated environments, the tracking is more rigorous as well. There are things that can be done to improve the quality and the approach to storing biologicals within organizations, as well as harnessing the power of outsourcing companies to shore up the deficits. In the biological space, it’s a little bit of the Wild West. 12 My philosophy is a hybrid approach of in-house and external storage. I believe that if you have highly transacted material that’s critical for cycle times, storage is best done internally. Having said that, you need to make sure that you have the appropriate storage conditions, labeling, tracking, and training. You would also be wise to invest in IT tracking tools that allow scientists to be able to view and manage materials. There are two models for centralizing storage: internal or outsource. One benefit of centralizing, whether it’s internal or outsourced, is that you bring all the inventory together from disparate locations. You ensure that the material is held in appropriate conditions and that it’s visible to everyone. These materials are key assets and often benefit from wider use in an organization. Having that visibility is key. Centralization also reduces the facilities that are required, reducing your costs as well. If material is accessed less frequently or it’s needed, say, for a disaster recovery set, it’s best outsourced to a reliable partner. There are a lot of organizations that have great expertise in managing storage, access, and What strategy should biotech and pharma companies use for storing biological samples? 2 Biological Sample Management Needs a Revolution shipping of material. They have well-established IT infrastructure for tracking the material, and in a lot of cases, they have access to state-of-the-art automation which is required for low temperature maintenance and tracking. There are a lot of benefits to outsourcing, including cost savings and increased integrity. I think if you’re going to outsource, it’s really important to do a cost analysis up front and factor in hidden costs. Those include the cost of real estate per square foot, the facilities cost, the automation, the manpower, and the training. There is a lot that goes into cost models. Doing that analysis gives you that driver: is it better to keep it in-house or out-of-house? Also, there are certain classes of material that you probably wouldn’t want or don’t have the capability to maintain in-house. I think safe storage of biological samples is the cornerstone of successful research projects and clinical trials. Keeping samples available and useable is a key element of turning a molecule into a treatment. This is true of all sample types but particularly true of biological samples because they often need much more rigorous storage and handling conditions. Why is sample management so important for drug development? 13 It comes down to the philosophy and strategy of your organization, where you believe your skill sets and resources are best spent, and where you are going to see the biggest bang for your buck. If you consider clinical trials, most organizations don’t have the resources and infrastructure to manage all their clinical trial materials. And consider the breadth and depth of the sample types—from proteins to cells to viruses, blood products, and bacteria—they require multiple storage conditions and temperatures. Having a range of capabilities in-house and the wherewithal to do it is just not there for most organizations. A lot of clinical trials require you to hold specimens for 10 or 15 years. You’re probably not going to hold those within your own facilities. It really is best to find an appropriate partner to maintain those, and you can access them For companies trying to move fast, especially with novel therapies, does it make more sense to invest capital in building a facility or to outsource those capabilities? 2 readily if you need to. The correct handling of those samples has a big impact on the course and results of a clinical trial. So, it’s crucial that the storage process is appropriate and of high quality. I think there’s a need and growth area for outsourcing cell therapy products. They’re so unique. The cold chain for cell therapy products must be capable of maintaining that living product in a viable state throughout its storage and distribution before you administer it to a patient. Compared to small molecules, cells are highly labile. They’re only viable over a narrow range of time and temperature and therefore require just-in-time delivery to patients or cryogenic storage to preserve those cells. A lot of organizations haven’t developed that skill in-house. Biological Sample Management Needs a Revolution 14 That’s a good question. For me, there are quite a few factors: the capability of the organization, their reputation, and whether or not I have an established working relationship with that organization. Trust is a big driver. I’m pleased to say that outsourcing partners have grown in terms of their experience and capability. A lot of organizations are what we call “pharma-like.” They are indistinguishable from the quality of operation that you could achieve internally, and in some cases, they have capabilities you wouldn’t or couldn’t do internally. Capability, capacity, and reputation are very important. What do you look for in an outsourcing partner? 2 What to look for in a partner: • Capabilities • Reputation • Existing relationships • Capacity • Expertise Biological Sample Management Needs a Revolution Sample Management Challenges for New Drug Modalities 3 SAMPLE STORAGE BIOBANKING SAMPLE MANAGEMENT CRYOPRESERVATION If you look at the new product launches over time, you’ll see an interesting pattern. At the turn of the century, we saw productivity declining, as measured by new product launches. But this trend seems to have reversed in the last decade. Between 2010 and 2019, the number of new medicines and drug sales increased by something like 60%. Small molecules are the mainstay of the current medicine portfolio, representing about 75% of new medicines approved in the US in 2020. However, biologics are definitely on the increase. We’ve seen this explosion in innovative biological modalities in the first two decades of the 21st century. This group is very broad. It includes proteins, antibodies, hormones, modified RNA molecules, and cell and gene therapies. Because of the substantial investment and often novel approaches that these require, the rise of biologics in recent years has been really impressive. Before COVID, the top-selling drug worldwide was Humira®, a monoclonal antibody. As of early 2020, biologics comprised seven of the top ten best-selling drugs. An AstraZeneca report shows that 30% of their current early pipeline consists of new drug modalities, including oligonucleotides, messenger RNA, etc. So many of the drugs that have been approved in recent years are what we call “specialty drugs.” They treat chronic, complex, or rare conditions. They tend to be costly to develop, hard to imitate, and frequently they are expensive. How are drug modalities changing in the pharmaceutical industry? 3 Small molecules represent about 75% 16 of new medicines approved in the US in 2020. Sample Management Challenges for New Drug Modalities 17 I’m happy to state that sample management for small molecules is now a very mature discipline. We have developed the aspects required for an efficient sample management infrastructure—including consumables, storage, liquid handling, inventory management, and IT tools. There’s a wide range of robust and reliable offerings that are available off the shelf, and that’s very different from years ago when those tended to be custom developed. Companies are now aware that they need to ensure that their platforms are easy to integrate with other vendor solutions. They can’t be an island on their own. It’s really necessary to bring all those elements together to build an end-to-end process. This is very different from where we were 10 or 20 years ago. In what ways has sample management for small molecules evolved? 3 Sample Management Challenges for New Drug Modalities Companies today need to ensure their platforms are easy to integrate with other vendor solutions. 18 I often have said that a sample is a sample. Throughout my career, I’ve tried to lead and develop the industry to broaden the disciplines and bring the technology and infrastructure developed for small molecules into the biological space. A lot of those can be leveraged. However, biologics have really pushed the boundaries of the technology in a lot of cases. The most critical difference is the need for low temperature storage, which makes aspects of sample management very difficult. That includes handling, consumables, and labeling. Over the years with small molecules, we saw the progression from storage at 4°C to -20°C. Then we saw -80°C come along, and most recently we’ve seen cryogenic temperatures. Industries have had to go outside the box in terms of leveraging expertise from other areas, say the semiconductor industry, to bring in technologies able to achieve robust automation at cryogenic temperatures. For the new drug modalities, do we need to rethink sample management? 3 Sample Management Challenges for New Drug Modalities Let’s consider consumables. They presented a particular challenge in the development of the materials and adhesives that are robust at low temperatures below -150°C. We’ve seen innovative solutions come along which allow you to use a pre-barcoded jacket on the outside of existing vials to support the appropriate tracking and identification of the samples in them. That’s been a significant technology advancement. Biologics have really pushed the boundaries of the technology in a lot of cases. 19 It’s really challenging, and it’s important you work with a partner who has expertise in that area. Every aspect of the operation needs to be addressed—from the IT to ensure rigorous tracking of the material within a store, to the consumables and labels that we’ve talked about, down to the automation itself. Lifetime management of those samples is really important. Can you talk more about implementing automated storage at colder temperatures? 3 Sample Management Challenges for New Drug Modalities First of all, I would say it’s a really exciting area, one with a lot of opportunity. At present, there are a limited number of commercially available cell therapy products. However, there are hundreds of them in registered clinical trials, so we anticipate many on the market soon. While they share the same goals for their cold chain as standard pharmaceutical and biological products, the need to maintain appropriate temperature regimes and specifications en route to the patient is unique. I don’t think there are a wealth of solutions out there for the management of this, whether in the development, discovery, or manufacturing arenas. There’s a lot of opportunity for companies to grow their portfolios and build on what they’ve already started to put in place. Lastly, any thoughts about material management in the cell and gene therapy space? The Role of Information Technology in Sample Storage 4 SAMPLE STORAGE BIOBANKING SAMPLE MANAGEMENT DATA MANAGEMENT 21 I did. When I started in high-throughput screening assay development, we didn’t have any sophisticated IT tools. We worked primarily with Excel spreadsheets along with some in-house tools. There was nothing available to manage inventory on the market. One memory that really stands out to me is the lack of automation. We were screening primarily natural products at the time, and our weekly highthroughput screen consisted of a group of ten scientists with multi-channel pipettes. We used to collect everybody that was free on a Monday morning, and their job for an hour or so would be to pipette these natural products into plates. I’m glad to say that has changed. If you think of the millions of samples that we manage and test, certainly that operation wasn’t scalable. Have you worked in a lab with a paper inventory management system? If so, what was that like? 4 The Role of Information Technology in Sample Storage It seems that automated tools have enabled us to go from tens of plates per week to thousands. Is that fair to say? Oh yes, easily. There are some great pictures where people have shown how many microtiter plates they’ve screened in a year stacked up against the Empire State Building, and the pile goes even higher. The number of sample screens grew significantly. It’s probably reduced in recent years because we’re now able to leverage IT tools—chemoinformatic tools and artificial intelligence—that allow organizations to be more selective about what they screen. 22 I think new organizations can cope with manual process and spreadsheets for a very limited time, but then it very, very quickly becomes untenable. I would advocate to any new organization in this area to really think about software tools and automation at a very early stage. If they choose to go manually initially, there are certain fundamentals that they absolutely need to put in place—such as standardization and barcoding of the containers. The tools that are now available are much more off-the-shelf. Implementation of those along with best practices and guidelines on appropriate storage conditions can ensure that organizations can be confident that as their collections grow, their operations are truly scalable. We’ve talked about the different components of sample management for drug discovery, and it’s the IT that really is the glue that holds it all together. Data is increasingly important, and data storage is only one component. With a sample, you need to collect all the attributes such as the identity, the physical states, the quantities, the locations, the transaction histories, the restrictions, and the informed content. The only way that you track and leverage that is with a sophisticated tool. When is the right time to invest in automation and an IT infrastructure? What is the importance of IT in sample management? 4 The Role of Information Technology in Sample Storage It’s the IT that really is the glue that holds it all together. 23 4 The Role of Information Technology in Sample Storage First of all, I think organizations need to be considering what their operation will look like in the next one to five years to ensure that they’re not just planning for now but planning for the future. They should identify the key attributes and elements that are critical and put them in a well-constructed matrix that weights those requirements in order of importance. How do you identify and implement the right IT system? From there, I suggest attending exhibitions and conferences. I’ll do a plug for the Society of Laboratory Automation and Screening (SLAS), which showcases the vendors and exhibitors that have these tools. Go around and talk to them. See demonstrations. Invite those vendors into your organization to show and demonstrate. Talk to other people that have used them and leverage those experiences. In the sample management arena, there are not a huge number of software tools, so it can be relatively quick to identify which are the key players and then determine which offer the best organizational fit. 24 I think by 2025 the FDA predicts that they will be approving, say, 10 or 20 cell and gene therapies per year, which is a huge increase. The potential impact of those therapies is massive. But delivery of those therapies relies on the infrastructure and supply chain, which is more complex than for small molecules. The rigor required is nothing like we’ve seen before. If you consider that these therapies are mammalian cells, they are only viable within a very limited time and temperature range. Tracking the material to ensure it has maintained the proper temperature range is absolutely critical. The financial cost of these therapies is high, and the impact for a therapy being administered inappropriately or the material not being viable is huge. Are there any software requirements for advanced therapies and biologics, which perhaps are different than those for small molecules? 4 The Role of Information Technology in Sample Storage For clinical samples, having sample visibility is so valuable. Think of the example where you may have samples that were collected for indication A but then can be used for indications B and C by leveraging the data and using AI tools to analyze those samples. It can be a game changer and ensures that you can leverage the power of those materials. It significantly improves their usability. What role does IT play in clinical sample management? By 2025, the FDA predicts they will approve 10-20 cell and gene therapies per year. Market Gaps for Biological Sample and Material Storage 5 SAMPLE STORAGE BIOBANKING SAMPLE MANAGEMENT QUALITY MANAGEMENT 26 Are there lessons to be learned from managing small molecules that can be applied to biological samples? 5 Market Gaps for Biological Sample and Material Storage I think there are a lot of approaches that have been developed for small molecules that can be applied to biologics: • the standardization of consumables • the labeling • the barcoding • the importance of inventory systems • the requirement to move from manual to automated processes to scale • the importance of quality from start to finish For high-throughput screening of small molecules, there was such a push for automation but the attention to the quality was sort of left behind. That seems counterintuitive now, but it really was the case. A lot of companies put a lot of effort in bringing together automation and building screening decks, and then they realized, “Hold on a minute. What’s the quality of those screening decks?” So they went back and put in QC procedures to measure the purity and surety of compounds. That meant they had to analyze collections, throw away bad samples, and do a clean-up operation. I think the lesson learned there is that it’s critical to pay attention to quality right from the beginning. 27 In the small molecule world, quality is really around the purity and surety of the compounds. How pure are they? Are they the right structure? Are they the right compound? Is the concentration accurate? When you’re in a screening environment and you’re testing a compound for potency, you want to have an accurate concentration in order to drive the development of the various chemotypes and drill down on finding the most potent compound. There was a great paper showing that a higher initial purity of a compound leads to a long shelf life for a DMSO stock solution. For biologics, the integrity of the sample is important. You wouldn’t call it purity per se, but rather surety. Is it the right structure? Is it the right DNA sequence or RNA sequence or cell type? For cell cultures, maintaining sterility throughout the process is a big factor. Also, temperature monitoring is extremely important for biological and human samples. How should quality be monitored for biological samples? Is it different than small molecules? 5 Market Gaps for Biological Sample and Material Storage There are a number of areas where I think we need to see development and maturity in this space. Automation at low temperatures is a key one. As the temperature drops, the availability of automation reduces significantly. It is encouraging that we’re starting to see a number of good options for -80°C storage, but we’re still seeing very little for cryogenic temperatures. That’s an area that needs further development. Consumables and labeling are other areas that tend to lack standards in this space. Having fit-for-purpose consumables is key for effective storage and delivery of materials. For managing biological samples and new therapies, what are some areas in the market that need to get better? 28 In the biological sample or clinical sample world, a lot of the processes are very manual, and that’s very difficult to scale going from discovery to development to manufacturing. Automation brings process efficiency, cost reduction, and improvement in regulatory compliance. It can pave the way towards commercialization and mass production. If you consider the number of new launches for cell and gene therapy over the next five years or so, they need to be able to scale those. Automation provides control and standardization of the process. By removing the manual handling completely, the safety and efficacy of these cell-based products can be enhanced. When is the right time for an organization to invest? That’s a difficult question. I would like to see people invest in automation from a very early point. Having said that, I think the offerings in this space are limited. We need a marriage or partnership between the vendor and user communities to drive the uptake of automation and the availability of platforms that have been validated and are reliable and robust. At what point should you consider automation for managing sample collections? 5 Market Gaps for Biological Sample and Material Storage A lot of the processes are very manual, and that’s very difficult to scale. Automation brings process efficiency, cost reduction, and improvement in regulatory compliance. 29 The best solutions in my experience have always resulted from a close partnership between the users and the companies developing the equipment. I have multiple examples from my own experience of working with companies to improve things like consumables, liquid handling devices, and automation platforms. Newly developed instruments go out to a beta test site where a user puts it through its paces and then helps the company refine the product. That’s really important in these new areas and new modalities. How can you work with vendors to develop the right tools? 5 Market Gaps for Biological Sample and Material Storage For example, I worked on cryogenic platforms with Azenta. Following its installation, we started to put it through its paces and then suggested quite a few changes to its functionality that were ultimately incorporated, particularly in the software. So that type of partnership is important to develop technologies and corresponding applications. Building Systems and Infrastructure for Sample Management 6 BIOBANKING SAMPLE MANAGEMENT CRYOPRESERVATION SAMPLE STANDARDIZATION SAMPLE STORAGE 31 Originally, sample management operations were shoehorned into existing lab space—the traditional small research laboratory—with little regard to ergonomics and process flow. As the need for automation grew and developed, organizations recognized the need for purpose-built facilities with enough space for the bigger automation platforms, specialized infrastructure like heating and ventilation systems to minimize DMSO odor, cold storage, and specialized fire suppression systems to protect assets. But these tended to occupy valuable real estate in organizations. Then there was a shift. We saw the migration to the open-space, hangar-type environment that could be fitted with flexible services. I think that was a good step forward. How have storage facilities for samples and biomaterials evolved in pharmaceutical companies? 6 Absolutely. Big pharma tends to have a lot more space and areas to install facilities. Biotechs tend to have a much smaller property footprint, but luckily the footprint for automation has become smaller and modular. It’s easier to put this equipment in smaller spaces. I think organizations have become savvy about what to keep in-house and what to outsource, as a trend. That has become a lot easier as the capabilities of outsourced companies have grown. Better design of facilities, smaller footprint, modular automation, and the ability to outsource certain pieces have all come together to create the modern sample management infrastructure. Do biotechs face different challenges than big pharma with regards to sample storage? Building Systems and Infrastructure for Sample Management 32 Requirements. First and foremost, if you’re considering an automated platform for storage, you’ve got to make sure that the platform meets your fundamental requirements for things like throughput, storage capacity, and flexibility. Space. Space considerations come into play: how you get your automation into buildings needs to be worked through. For example, does it need to go through an elevator? Or across a lab floor which has fixed equipment in place? I can recall an installation of cryo automation at our facility that required bringing in a crane to lift large Dewar tanks up an incline into a building because they wouldn’t fit through an elevator. Flexibility. Having storage facilities that are one type or format—say, a store that just holds one type of container—is probably a luxury we can’t afford these days. If you look at clinical samples, despite best efforts at standardization, they’re coming in all different containers and sizes. So, flexibility of handing containers is really important. What are some key considerations when making the jump from manual storage to an automated platform? 6 Reliability. Reliability of the automation, particularly with more regulated materials, and the ease of use of the software are key. The software needs to provide a full audit trail of the transactions regardless of sample type, but for more regulated biologics, it’s extremely important. Backup. Also, duty standby and disaster recovery are necessary. Having valuable inventory stored in systems means that failure is not an option. You’ve got to have proper duty standby refrigeration for cold temperatures and the appropriate backup. Vendor. Lastly, for me, it’s about working with a vendor that you can trust and that you’ve established a good working relationship with or one with a strong recommendation from a colleague or a reliable source. Building Systems and Infrastructure for Sample Management 33 Back in the early 2000s, the microtiter plate was moving from a 96-well plate to 384, and eventually 1536. Manufacturers were having a field day making all these different types of plates for specific assay types—for cell culture, for storage of small molecules, and many others. The microtiter plate is really the currency within a research lab that needs to go from system to system, such as going from a dispenser to a reader. At the time, there was no standardization of the parameters of plates, which made it impossible for people to move easily between these platforms and different types of automation. For example, the plates couldn’t be gripped properly by certain automated grippers, they didn’t fit on the pipetting platforms, etc. With small molecules, the Society for Biomolecular Screening (SBS) microplate standard made sample management very efficient. Can you provide a brief history? 6 The 5 Standards Established by the SLAS Microplate Standards Advisory Committee: • footprint dimensions • height dimensions • bottom outside flange dimensions • well positions • well bottom elevation Building Systems and Infrastructure for Sample Management 34 There was such an explosion of automation platforms that were developed. With standardization, there was confidence that automation could deal with a whole range of different microtiter plates. The flexibility to have a 96- or 384- or 1536-well plate on an automated platform enabled an efficient drug discovery process, allowing you to go faster. Being able to dispense very low volumes—nanoliters—into a 1536-well plate wouldn’t have been possible without the development of the microtiter plate standard. Acoustic dispensing was a breakthrough for drug discovery and sample management, but it was only possible for many years from a microtiter plate format. How did standardization change the automation industry? 6 The development of the acoustic tube made an incremental step forward in this technology. It allows you to dispense directly from a tube using the acoustic technology and fits into the standard 96-well format of tube racks—the standard unit of currency between instrumentation. There are significant benefits of being able to dispense directly from a tube rather than a plate in terms of efficiency and preserving your compound collection. Building Systems and Infrastructure for Sample Management 35 There’s a general lack of standards for cryo storage. For cell and gene therapy, that will impact the speed of how quickly automation can advance the field forward. There is a real need for standardization. There are several parties that have done a lot in this space. My call to action is this: it takes groups of interested parties that are willing to give their time, energy, and expertise to develop these standards for the good of the whole community so that we can advance the scientific discipline. So, if you have an interest in these areas, please step up. I personally will be working with the SLAS team to see if we can do more and take standards forward in this space. What is the current state of standards in the cell and gene therapy space? 6 Organizations creating standards: • SLAS has done a lot of work to create a microtiter plate standard, and that group would be in a good place to look at cryo box standardization. • ISBER has done a great job on standardization in the biobank field. For example, they developed SPREC, the standard preanalytical code, which manages and tracks preanalytical variations impacting biospecimen integrity. • The Allotrope Foundation has been working to develop a single, universal data format to store linked data that connects people with the raw data, the results, and the evidence needed to do great science. • The SCB, a regenerative medicine standards group, has made some good strides forward in standardization, but there’s much more to do in the cell therapy, gene therapy, and tissue engineering fields. Building Systems and Infrastructure for Sample Management ABOUT AZENTA LIFE SCIENCES Azenta, Inc. 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