Given the rapid advances being made in technologies such as cell and gene therapies, personalized vaccines, and oral biologics, odds are high that there’s some hot ticket item demanding one’s attention at any given time. While it would be foolish to detract from the monumental discoveries being made in the biopharma field, new technologies should nevertheless be approached with some degree of caution. While innovation is crucial for the benefit of patients and industry alike, many start-ups, often brimming with ideas and ultimately unrealized potential, have been felled by trying to sprint before they even stand. Leadership cannot afford to split their attention if the nuts and bolts of an organization aren’t properly fitted.

Nowhere is this more evident than in data integrity, which measures data accuracy, completeness, and cohesiveness. It certainly doesn’t have that je ne sais quoi that entices ones like a monumental technological, but it is nonetheless foundational to the day-to-day operations and overall success of a company. Perhaps Big Pharma companies can afford the occasional $8.9 billion misstep (1); but whether your Amazon (2) or Santander (3), regulatory fines can easily balloon to a painful price point.

Particularly in an industry as heavily regulated as pharma, where data silos, compliance errors, or security breaches must be taken gravely serious because of their direct impact on patient outcomes, maintaining property data integrity is absolutely paramount to a company’s success. In this vein, this article explores the common pitfalls companies run into, the consequences thereof, and how one can structure their data integrity programs.

The crux of good data integrity are software and data management tools, as they are an immense boon when working with the voluminous amounts of data typical of the pharma industry. However, one must consider the types of data they are using before building out a data integrity process. Paige Kane, member of the Pharmaceutical Regulatory Science Team at TU Dublin, and Garry Wright, European laboratory compliance Specialist at Agilent Technologies, spoke at length on this topic in an episode of 

“We need to understand what our processes are, what data we are trying to capture, and make sure that we have the right tool for that application,” said Kane. “And when we do that, we need to take a risk-based approach and understand where the risks are, and where the operators are intersecting with that and where we can be error-proof. Leveraging automation is a great way to do that.”

Per Kane, companies that are looking to tighten up their operations should consider the purpose of the data they are collecting and why they need it. Superfluous data can result in greater system and operator burden, while missing requisite data fundamentally undermines the purpose of the system.

However, this doesn’t just apply to collection methods—it also impacts who can interface with the data, and in what ways. Wright noted that some of the most common pitfalls in data integrity concern have been plaguing the data integrity industry for as long as it has existed.

“We’ve been talking about data integrity for the last 10 years, but there’s still a lot of repeated data integrity violations out there,” said Wright. “Some of them are very basic, fundamental requirements of using software in order to protect data.”

Some of the most common problems Wright listed in the interview include:

 This obfuscates which users accessed a particular system, and if given out broadly can make it difficult to trace the origin of errors or cases of intentional falsification. To enable a broadly successful data integrity system, it’s crucial to have unique logins that operators can track.

Often, scientists and various technicians are given more access to systems than needed for their role. This can lead to a conflict of interest where a bad actor approves a failed batch, or where bad test data are altered or deleted to avoid investigations or re-tests.

 Many companies have received warning letters because they have chosen to not activate certain audit privileges—making it impossible to track changes and properly oversee a system. Similarly, even when they are activated, users who shouldn’t be able to access audit technology are often able to do so, allowing bad actors to compromise data integrity.

While implementing a wholesale data integrity program can seem daunting, Kane was quick to note that there are many guidance documents and resources available that can help companies get over initial hurdles. What is pivotal is that company leadership act in good faith and invest in the types of processes and technologies that keep pharmaceutical data honest and intact—in short, enact a full-scale data governance policy.

“It’s more than just the audit trails,” said Kane. “There needs to be a holistic view and approach as to how we’re going to manage our data so that we can put forth that holistic picture to our inspectors and customers.”

Inherent to the discussion of data integrity is the discussion of automation, and within that the de-emphasis of human intervention in various tasks throughout the pharma lifestyle. Human error is a major concern for pharma companies, as one mistake (or deliberate falsification) can have severe knock-on effects for the patients ultimately receiving the compromised medicines. Automated processes are a fantastic alternative, particularly for precise, time-intensive tasks that need to be repeated thousands of times a day—the ubiquity of automated
production lines is a prime example of this principle in action.

However, it is crucial that companies understand that “de-emphasis” does not mean “elimination.” It’s common corporate philosophy to have workers perform to the highest function available—a CEO isn’t typically charged with data entry, even if they’re perfectly capable of doing so, because there are higher-level functions that they are uniquely qualified for. While automated services are doing tasks that would otherwise be performed by humans, that does not mean these people are eliminated—it means that their role must shift.

Claudio Fayad, vice-president of Technology, Process Systems, and Solutions at Emerson, tackled this misperception in a video interview with 

“We’re not doing automation to eliminate humans—we’re eliminating human errors by upscaling them, by augmenting their capacity,” said Fayad. “As we can automate the more repetitive tasks, as we can give them a platform that is autonomous at the end but is giving them situational awareness all of the time, they are free now to look at the most important things and intervene when they need to intervene.”

Consequently, it is pivotal that humans maintain oversight over automated tasks. In terms of data integrity, automated digital tools are a fantastic tool for standardizing data collection and maintenance, but this is not a solution in of itself. There is consensus among experts that a proper data integrity process will conduct regular audits, consult with external regulatory experts, and implement crucial oversight systems operated by trained professionals; this, in turn, comes back to a proper data governance policy.

In practice, this could manifest itself as having an operator review random sections of internal log data generated by a regulatory program for inconsistencies. If there are mislabeled, incomplete, or missing logs, that operator can take the necessary actions to find out what caused it, determine what the potential impact may be, and work with colleagues to devise an appropriate solution as needed. In this sense, even though humans are not given edit access, minimizing the potential for human error, they provide oversight as a complementary force that is vital for proper software utilization. In other words, while software provides the means to data integrity, the humans interacting with it must engage in proper data governance to actualize its efforts.

“Every software platform can have different functionality and different controls, and different companies use different software in different ways,” said Wright. “Having that high-level governance strategy is your company’s commitment to how you’re going to control data within that individual software platform. It’s a starting point for the people who are going to configure and validate those systems, because they know what functionality they need to activate and what the best options are to control data.”

1. Playter, G. J&J Proposes $8.9 Billion Payment in Talc Powder Litigation.

2. BBC. Amazon Hit With $886m Fine for Alleged Data Law Breach. 

3. Shome, A. FCA Fines Santander UK £108 Million for Prolonged AML Breaches. 

4. Playter, G. Drug Digest: Unpacking the Science Behind Data Integrity.

5. Playter, G. Addressing Data Security with Claudio Fayad.

Articles

Features

A holistic data integrity approach can help one avoid missteps in data integrity.

Common Pitfalls in Data Integrity

Dissolution is a crucial aspect of drug product development and characterization. It is the only pharmaceutical test which is capable of determining how a formulation will perform in a patient. Over the years, the science of dissolution has needed to adapt to advances in pharmaceuticals.
At the beginning of dissolution, medicines were primarily immediate release drugs where a United States Pharmacopeia (USP) Apparatus 1 (baskets) or 2 (paddles) worked quite well at assessing how a product would perform in vivo.

As pharmaceuticals have advanced, a wide variety of new formulations have been developed, which all need dissolution testing. Dissolution evolved to accommodate dosage forms that required extended-release times, multiple
media changes, and more. More recently, drug-device combination products
further challenged dissolution testing by needing to test extremely low volumes for several days or weeks for implants. Now, making the APIs smaller into nanoparticles is the new challenge for dissolution testing.

Ken Boda is dissolution product specialist at Agilent Technologies.

Nanoparticles are increasingly being used to overcome low solubility and poor permeability.

Dissolution’s Next Challenge–Nanoparticles

A collaboration between global contract development and manufacturing organization (CDMO), Rentschler Biopharma, and pre-clinical-phase gene therapy company, Ikarovec, has been unveiled in a June 1, 2023 press release. The partnership aims to accelerate the development of novel gene therapies for the treatment of ophthalmic disease.

Under the agreement, Rentschler Biopharma will support the bioprocess development of adeno-associated virus (AAV) material in its advanced therapy medicinal product (ATMP) site in Stevenage, UK. This AAV material will then be used for pre-clinical testing of Ikarovec’s novel gene therapy, developed for the treatment of geographic atrophy—an advanced form of age-related macular degeneration.

“We are delighted to collaborate with Rentschler Biopharma on our lead program. As we look to find new and better ways to treat ophthalmic diseases, we want to get it right and ensure that our product candidates can be scaled up appropriately for each development stage and, ultimately, for commercialization,” said Katie Binley, chief scientific officer of Ikarovec, in the press release. “Thus, it is critical to work with a team that has strong AAV experience in our field and that will be a true partner every step of the way.”

“We are excited to have the opportunity to collaborate with Ikarovec, which is developing truly innovative treatments for major ophthalmic indications. With our client-focused, highly tailored approach, our seasoned team will work closely with Ikarovec scientists to enable them to move forward into pre-clinical testing as rapidly as possible,” added Robert Panting, general manager of Rentschler’s ATMP business, in the press release. “By laying the foundation with process development and scale-up work, we aim to ultimately improve development timelines and increase the chances of success for our clients, who are working tirelessly to advance potentially groundbreaking treatments.”

News

A partnership between Rentschler Biopharma and Ikarovec will support the accelerated development of novel gene therapies for the treatment of eye diseases.

Rentschler Biopharma, Ikarovec Collaboration Set to Speed Up Ophthalmic Therapy Development 

ProBioGen, a Berlin-based company specializing in the development and manufacture of APIs, announced its new lentivirus packaging cell line on May 17, 2023. Lenti.RiGHT is a lentivirus production platform based on human embryonic kidney 293 packaging cells.

According to a company press release, the new line is capable of producing lentiviral particles with titers between 107 and 108 transducing units per mL. It includes stable integration of gag-pol, rev, and vesicular stomatitis virus-G proteins.

"With our Lenti.RiGHT platform we have developed a new standard for efficient large-scale lentivirus production and CAR–T [chimeric antigen receptor T cell] manufacturing,” said Volker Sandig, chief scientific officer, ProBioGen, in the release. “It enables an inducible, scalable, and efficient production of high-titer lentiviral particles for gene transfer applications.”

New Technology

ProBioGen’s Lenti.RiGHT is a lentivirus production platform for use in gene transfer applications.

ProBioGen Launches Lentivirus Packaging Cell Line

ChargePoint Technology, a company specializing in powder transfer, and Famat Sampling, a company specializing in sampling devices, announced a collaboration technology on May 16, 2023. According to a company press release, the companies’ new integrated valve solution allows operators to take a product sample for quality analysis during the course of production while maintaining optimal containment and sterile integrity.

The new product, a combination of ChargePoint’s split butterfly valve and Famat’s 125-Threaded Cap/Occupational Exposure Limit valve, is designed to create a secure and sterile environment for high-potency and sterile powder samples to be taken. According to the release, the interconnected system forms an airtight seal that prevents a dead zone and allows for sampling of highly potent, toxic, or sterile powders to be transferred while maintaining Occupational Exposure Band 4 (OEB4) and OEB5 level compliance.

“During processing, manufacturers must prioritize sampling so that the quality of drug products can be assessed at various stages of the production process,” said Christian Dunne, head of Sterile Solutions, ChargePoint Technology, in the release. “Famat Sampling shares our high standards for quality. Joining forces as two recognized industry leaders in our respective fields was a no-brainer for our team.”

ChargePoint Technology and Famat Sampling’s combination technology is designed to allow for product sampling during the course of production.

ChargePoint Technology and Famat Sampling Collaborate on Novel Sampling Technology

Gilead Sciences and Arcus Biosciences, a US-based clinical-stage biopharmaceutical company, announced on May 15, 2023 that they are expanding a previously announced research collaboration to now include development of therapies for treating inflammatory diseases. Their initial collaboration agreement, worth potentially more than $1.6 billion, focused on oncology (1).

Under the expanded collaboration, Arcus will receive an upfront payment of $35 million. Arcus will initiate research programs against up to four targets that are jointly selected by both parties and that are applicable to inflammatory diseases. Gilead would have the option to license each program at two separate, prespecified time points. If Gilead exercises its option for the first two target programs at the earlier time point, then Arcus would be eligible to receive up to $420 million in option and milestone payments as well as tiered royalties for each optioned program. For any other option exercised by Gilead for the four target programs, the two parties would have rights to co-develop the candidates. In addition, both parties would share global development costs and co-commercialize and share profits in the United States for optioned programs.

“We are pleased to build upon Gilead’s efforts in inflammation with the expansion of our strategic collaboration with Arcus,” said Flavius Martin, executive vice-president, Research, Gilead Sciences, in a company press release. “Arcus is an excellent partner with clear strengths in discovery and development, and we believe this partnership will significantly accelerate our progress in developing transformative new therapies for inflammatory diseases.”

“Since its founding, Arcus has been creating and developing therapeutic interventions that can modulate the immune system to treat cancer. Through this expansion of our partnership with Gilead, we can combine our research expertise in immunology and small-molecule drug discovery with Gilead’s strong clinical experience in inflammation,” said Terry Rosen, CEO, Arcus, in the release. “The research collaboration facilitates much earlier alignment between Gilead and Arcus on our discovery and development activities, while enabling Arcus to expand into inflammation in a capital-efficient manner.”

1. Gilead Sciences, Gilead Sciences and Arcus Biosciences Establish 10-year Partnership to Co-develop and Co-commercialize Next-generation Cancer Immunotherapies. Press Release, May 27, 2020.

Gilead Sciences and Arcus Biosciences have expanded their research collaboration to include inflammatory diseases in addition to oncology. 

Gilead Sciences and Arcus Biosciences Expand Research Partnership

Sony, a wholly owned subsidiary of Sony Group, which handles entertainment, technology, and services, and Astellas Pharma announced a collaborative research agreement on May 16, 2023. Under the agreement, the companies will work to discover a novel antibody-drug conjugate (ADC) platform in oncology based on Sony’s “KIRAVIA Backbone” organic polymer.

According to a company press release, both companies will jointly develop and optimize a new ADC platform using Sony’s organic polymer as a linker. Additionally, Astellas will conduct non-clinical trials of development candidates. The companies also indicated that they are continuing discussions to expand research partnerships on non-ADC drug discovery platforms.

"Sony's life science business has accumulated substantial knowledge in the field of cell analysis," said Katsunori Ogawa, head of Life Science & Technology Business Unit, Sony, in the release. "Through this collaboration, Sony is striving to contribute to the medical and drug discovery fields and provide further social value by leveraging Sony's technological capabilities in the development of anti-cancer drugs therapy, which are expected to grow."

"We are pleased to enter into a joint research agreement with Sony," said Yoshitsugu Shitaka, chief scientific officer, Astellas Pharma, in the release. "Astellas is working to create innovative drugs from a multifaceted perspective called the Focus Area approach, which identifies combinations of biology, therapeutic modality or technology, and diseases with high unmet medical needs. The partnership will further strengthen our ability to utilize suitable modalities. It is our expectation that the collaboration will lead to the continuous creation of innovative drugs for patients around the world."

Astellas and Sony will collaborate to discover a novel ADC platform for use in oncology.

Astellas and Sony Enter ADC Platform Collaboration

On May 15, 2023, BiOneCure Therapeutics, a US-based clinical-stage biopharmaceutical company focused on developing antibody-drug conjugates (ADCs), announced that it has entered into a strategic collaboration with China- based Nanjing Leads Biolabs, a clinical-stage biopharmaceutical company focused on second-generation immuno-oncology therapeutics, to develop a range of innovative ADCs for treating solid tumors.

The companies intend to leverage their complementary technologies in the collaboration, which they expect will strengthen their R&D and product development capabilities. BiOneCure’s technology includes several proprietary ADC payload-linker platforms. Its first product, BIO-106, is an anti-Trop-2 ADC that is currently in a Phase I clinical study. Leads Biolabs’ portfolio holds more than 20 novel mono- or bispecific antibody drug projects to fulfill unmet medical needs, according to a company press release.

"We are excited to collaborate with Leads Biolabs to develop ADC drugs," said Haifeng Bao, CEO of BiOneCure, in the press release. "Through this collaboration, we aim to accelerate innovation and development in the ADC field and provide better treatment options for patients."

"We believe that BiOneCure has leading ADC technology platforms, and [its] ADC molecule is in the clinical stage," said Xiaoqiang Kang, founder and chairman of Leads Biolabs, in the release. "Leads Biolabs is a clinical-stage antibody new drug company, with multiple antibody technology platforms. We are convinced that this collaboration will greatly expand the innovative R&D capabilities of both parties."

Under the collaboration, BiOneCure Therapeutics and Nanjing Leads Biolabs intend to develop a range of innovative antibody-drug conjugates for treating solid tumors.

BiOneCure Therapeutics and Nanjing Leads Biolabs Partner to Develop ADCs for Solid Tumors

Agilent released an announcement of its Agilent 8697 Headspace Sampler -XL Tray, which features 120-vial capacity, in addition to their existing 48-vial capacity tray. In addition to the capacity increase, the new tray includes new instrument intelligence features that are designed for increased uptime and operator ease-of-use relative to its predecessor.

According to a press release from May 1, 2023, the device’s intelligence features are enabled through self-monitoring operations and guiding operators that use various troubleshooting and maintenance procedures. The system performs automated system checks, including leak checks, early maintenance feedback, and self-diagnostics. Additionally, the new tray can be run with alternate carrier gasses due to the separation of vial pressurization and the sample loop for added method flexibility.

“Labs that run headspace GC [gas chromatography] systems know that if they encounter problems during a sequence, and the vials are punctured, they may have to rerun or recollect samples,” said Mike Zhang, vice-president and general manager of Agilent’s Gas Phase Separations Division. “The 8697 and now the 8697 Headspace Sampler-XL Tray virtually eliminate that problem. The complete GC headspace system checks to ensure that the system and data quality are up to SOP [standard operating procedure] standards, avoiding recollection of samples and reruns.”

The Agilent 8697 Headspace Sampler-XL Tray has a 120-vial capacity.

Agilent Releases New Vial Sampler Tray Capacity

Mekonos, Inc. announced a new research collaboration with bit.bio on May 4, 2023 to test and optimize non-viral delivery of bit.bio’s patented safe harbor gene-targeting approach. This approach is defined as being used to express transcription factor combinations to reprogram human induced pluripotent stem cells (iPSCs).

A gene-targeting route is meant to be an alternative for viral vector delivery, which will allow bit.bio to engineer stem cells into any mature, functional human cell type with higher efficiency, speed, and control, according to the press release.

“The combination of Mekonos’ unique, silicon chip-based delivery platform with bit.bio’s leading cellular reprogramming technologies will enable powerful new levels of precision and efficiency in the engineering of iPSCs,” said Jake Lesnik, VP of Business Development at Mekonos, in a press release. “We are excited to partner with the world-class team at bit.bio— leaders in synthetic biology and the engineering of human cells—and to leverage Mekonos’ unique non-viral platform for 

 delivery of reprogramming factors to engineer human cells at unprecedented scale and efficiency.”

 This approach is defined as being used to express transcription factor combinations to reprogram human induced pluripotent stem cells (iPSCs).

Pharmaceutical Technology's In the Lab eNewsletter, June 2023