Chris Spivey is director of Industry Relations and Strategic Partnership, MJH Life Sciences.

Chris Spivey

Data and digitalization have rapidly evolved, along with software and meta-analysis, to become the lifeblood of the pharmaceutical industry. However, decades ago, I opened a biotech conference by stating that biology was becoming one of the computer industry’s fastest growing customers, evaluating huge storehouses of data. This article attempts to demystify the difference between knowledge and information bearing in mind the aphorism of Peter Mere Latham that, “fortunate indeed is the man who takes exactly the right measure of himself, and holds a just balance between what he can acquire, and what he can use” (1). In terms of optimizing a manufacturing process or procedure, fewer data can often mean more. 

A great new challenge in pharmaceutical data governance is how to balance automation with sufficient operator oversight—ensuring that hiccups and missteps are properly captured and reported for compliance purposes. Paige Kane, a member of the Pharmaceutical Regulatory Science Team (PRST) at TU Dublin, suggested it all starts with “understanding of what our processes are, and to understand what data we are really trying to capture, to make sure that we have the right tool for that application, … to do that we need to take a risk-based approach to understand where the risks are and where the operators are intersecting with that. We don’t need to collect all the data [just] because we can, we need to understand what data are really required for the operation” (2).

Garry Wright, European Laboratory Compliance Specialist at Agilent Technologies, has stated that “every regulated company is going to be using multiple software platforms across their production quality control environments, and they are going to generate huge volumes of GxP [good manufacturing practice] data, so implementing data integrity controls across all those individual software systems is very time consuming. It requires specialist skills, and it requires dedicated support. But you can protect the integrity of that data by keeping your software platforms up to date using the latest security and technical controls that automate workflows to try to minimize human contact. Due to ageing software platforms, companies tend to implement hybrid solutions where they develop and wrap around workarounds, but it still leaves them with an element of data integrity risk. This is more susceptible to human error and deliberate falsification, and that’s really where a lot of the recent data integrity warning letters come from” (2). 

Wright went on to enumerate some of these common issues that appear to have played a role in the high-profile example of Laronde (3). Wright empathized, “Data integrity is a key part of any regulatory inspection. I remember going through my first data integrity inspection in 2013, and it really revolutionized the way I look at the laboratory and the way I prepare for inspections… [problems are] deliberate use of generic logons to protect the identity of people who are falsifying data, scientists having additional privileges that they don’t need to perform their role, [and] performance screening analysis before an official analysis. One of the biggest ones though is manipulation and falsifying by changing integration or integration events to make failing batches pass. [Or] deleting or hiding official sample data to avoid stoppages with the need to document the failure, then perform an investigation, and then retest. The last but most important is audit trails. Some companies have deliberately chosen not to activate the audit functionality. Other companies give their users privileges so that they can manipulate their information within the audit trail so they can cover up cases of falsification” (2). 

Wright concluded on a positive note. “So, these are some of the common problems that have been cited in recent warning letters, but they can all be avoided if you keep your software up to date, and if you use all those technical and security controls that are available which have been specifically designed into those software platforms to protect the data. So, if you use your software correctly, you can be data integrity compliant” (2). 

While Wright might be optimistic, the human element will have the last word. Reporting from STAT and The Boston Globe made public a story that is surprisingly common but underacknowledged. In this case, the story made headlines partly because of the therapeutic promise surrounding the approach, but mostly because of the high market valuation involved.

As reported, the company noticed difficulties reproducing results in their preclinical data in a pivotal anti-obesity therapy aimed at competing with Wegovy and Mounjaro, partly because of a lack of detailed record keeping. “It underpinned the enormous $440 million the biotech raised in a 2021 Series B funding round, according to four people with knowledge of its plans, as well as a slide from an internal slide deck, which valued the company at over $1 billion” (3). 

A star researcher, Cifuentes-Rojas, was presenting data “that was perfect. Anybody who works in in vivo [animal research] knows that’s not possible,’ said Jane van Heteren, an ex-Laronde employee who worked on the same team as Cifuentes-Rojas… Cifuentes-Rojas’ chart showed the protein levels starting at zero—an impossibility, because unless the mice were seriously ill, they would naturally produce GLP-1 of their own, van Heteren said. In an attempt to pinpoint why, she sought out Cifuentes-Rojas’ raw data, first in the company’s electronic lab notebook system and then from Cifuentes-Rojas herself. But there was no data in the company’s digital records, and Cifuentes-Rojas declined to share any with her colleague.” 

The emphasis here is that a sister company to the obviously successful company, Moderna, fell prey to the one bad apple syndrome. Reporting goes on to say that “Initially, the manufacturing staff came under scrutiny…. [as] one batch might be 60% pure eRNA, another might be 80%. That was initially cited as the reason why scientists were getting different preclinical results, but three former manufacturing team members said it was a red herring, because none of the data produced at Laronde showed a clear relationship between how much eRNA was in a batch and how well it performed inside of cells or mice” (3). 

The journey of data integrity depends fundamentally on the integrity of the people involved. A software platform can be made rigorously regulatory compliant, as long as operators’ intentions and personal integrity are in synch with that goal. 

1. Spivey, C. Gene Quantification, Introspection and RNA Meditations, Conference, February 2002, Cambridge Healthtech Institute. 

2. Playter, G. Unpacking the Science Behind Data Integrity, Drug Digest Interview with Page Kane and Garry Wright. 

3. DeAngelis, A. and Cross, R. The Inside Story of How Data Integrity Issues Roiled a Biotech Seen as ‘Moderna 2.0’. 

When referring to this article, please cite it as Spivey, C. Good Practices for Data Integrity. 

Articles

Automation can be balanced with operator oversight.

Good Practices for Data Integrity

On June 23, 2023, Eppendorf Group announced that it is awarding its Young European Investigators 2023 research prize to Maurice Michel, PhD, of the Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden. Michel was selected by an independent jury chaired by Prof. Reinhard Jahn, emeritus director, Max Planck Institute for Biophysical Chemistry, Göttingen. This marks the 28th time that Eppendorf has bestowed this award. Finalists included Alicia Michael, PhD, of the Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland, and Adel Al Jord, PhD, from Collège de France.

Michel’s research delves into artificial functions of DNA repair enzymes for the treatment of disease. Through his research he has shown that binding of a small molecule to the active site of a DNA repair enzyme not only increases the molecule’s activity, but also prompts it to carry out a reaction not found in the free protein, leading to enhanced DNA repair after oxidative damage.

Maurice Michel, PhD, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden

“These ground-breaking discoveries may have far-reaching applications in the treatment of cancer or age-related degeneration,” said the judges on the awards jury, according to an Eppendorf company press release.

Michel is also heavily involved in Target 2035, an international federation of biomedical scientists from the public and private sectors, dedicated to develop a pharmacological tool for every human protein. The federation has generated much interest from legacy companies in general, and increasingly big pharma in particular, as it pushes into previously uncharted drug discovery terrain.

Announced in a recent Target 2035 article in a medicinal chemistry journal: “The goals of Target 2035 can only be accomplished by expanding hit-finding approaches beyond traditional methods. This is especially true for un/understudied proteins that have no link to disease. Traditional hit-finding methods tend to be prohibitively resource-intensive and limited to large private sector entities” (1).

“During the past year Target 2035 launched two Public Private partnerships (PPPs), Critical Assessment of Computational Hit-finding Experiments (CACHE), and Open Chemistry Networks (OCN) … Because CACHE is a prospective hit-finding exercise, where predicted compounds are procured and tested using biophysical and biochemical methods, the metric of success is hit rate, diversity, and drug likeness rather than binding pose or docking score,” the article explains (1).

“It is an immense honor and I feel humbled to be awarded with the 2023 Eppendorf Award,” said Michel in the company press release. “This would not have been possible without the contribution and spirit of many scientists, be it colleagues or collaborators, as well as mentors and an incredible family I call mine. The award recognizes the potential of manipulating enzymatic functions in living cells at will. Using small-molecule organocatalysts, we installed new biochemical reactions within an enzyme and have thus succeeded in rewriting the base excision repair pathway … Rerouting or reducing oxidative DNA damage depending on individual needs could serve as a new strategy for the development of the precision therapeutics of the future.”

The award ceremony took place on June 22, 2023, at the Advanced Training Center of the European Molecular Biology Laboratory in Heidelberg, Germany. Further information on application modalities, selection criteria and previous winners of the Eppendorf Award for Young European Investigators can be found at 

1. Arrowsmith C.;Ackloo, S.; Antolin, A .; et al. Target 2035—An Update on Private Sector Contributions. 

The prestigious award, worth €20,000 (US$22,000), goes to Maurice Michel of the Science for Life Laboratory at Karolinska Institutet, Stockholm, Sweden. 

Maurice Michel of Sweden Wins 2023 Eppendorf Award for Young European Investigators

Chris Spivey, editorial director, speaks with Sean Hart, CEO and SCO of LumaCyte, on percent transduction for AAV measured. The full discussion can and more can be viewed 

Videos

Chris Spivey, editorial director, speaks with Sean Hart, CEO and SCO of LumaCyte, on percent transduction for AAV measured.

Transduction for AAV with Sean Hart

Following up a Washington D.C. event in early May, members of the 

 to toast to the good health of the alliance itself, and also for the myriad new therapeutic possibilities in areas as diverse as oncology, neurology, cardiology and infectious diseases more broadly. World leaders have set ambitious goals to respond more swiftly to the next pandemic, including the US goal to design, test, and review a new vaccine just 100 days after a pandemic declaration. Further, the US hopes to produce enough vaccines for the US and the world in 130 and 200 days. Past preparedness efforts have focused on innovation and reliability—culminating in the novel mRNA vaccines. Today, it’s important to consider diverse responses—and how we can make the investments we make today sustainable and “ready” for when an emergency happens. But while the last pandemic helped usher in this new era of commercial scale mRNA platforms, AMM itself rests solidly upon four principle pillars.

The next step for the Alliance is to engage with regulators and lawmakers at a congressional briefing planed for mid-September on capital hill. In terms of policy AMM advisors will engage with governments, policymakers, regulators and other stakeholders in North America, Europe and Asia Pacific (according to its website) “…to advocate for policies that encourage innovation, define regulatory standards, support manufacturing and promote access of mRNA medicines to patients.” (1)

Regarding their plans to advance knowledge, AMM “plans to bring the best minds together to overcome the most critical obstacles inhibiting the advancement of mRNA research, development and manufacturing. Furthermore, AMM will forge inclusive and collaborative partnerships with other networking forums to co-publish, augment or improve upon technical and scientific content generated by these groups.”

One of the initial council members, Baley Reeves, Interim Director at the National Center for Therapeutics Manufacturing, Texas A&M University, stresses that"In order to support the development and manufacturing of mRNA vaccines and medicines, a skilled workforce is critical component of the overall ecosystem. The lack of a pipeline of workers trained in the specific processes required for mRNA manufacturing is a major bottleneck for the field." The rapid evolution of mRNA medicines since the inception of the COVID vaccine has created a need to (1) elevate the understanding and perception of mRNA medicines to the general public and (2) develop and expand the pool of mRNA talent in the industry. From their website, AMM states it “will champion causes and projects to educate the community on the potential of mRNA technologies to improve the human condition and collaborate with institutions to uplevel and standardize the education of mRNA scientists and to retain them in the field.”

And as their last pillar, “AMM will serve as the leading convenor of mRNA stakeholders, bringing together innovators in the field to propel the future of mRNA medicine and advance scientific knowledge.”

Its an ambitious set of goals for sure, but amongst their number AMM already boasts of multiple scientific society, pharmaceutical and regenerative medicine global bodies and organizations. Combined, they have the talent and experience to navigate successfully toward not only their next goal (an early November full launch in Berlin) but also the goal of effecting positive acceleration of multiple medicines well beyond their initial vaccine starting point.

World leaders have set ambitious goals to respond more swiftly to the next pandemic, including the US goal to design, test, and review a new vaccine just 100 days after a pandemic declaration. 

mRNA Global Alliance Tests the Waters at BIO

The BIO International Convention 2023 was held from June 4 to June 8 in Boston, Mass.

Its been a while since I attended the BIO conference, this year held in Boston. I’d forgotten how key a feature the speed dating booths are to the success of many attendees time at the event. Post pandemic these booths were figuratively bursting at the seams with energetic conversation.

To follow-up an alliance dialogue with Scott Ripley, general manager of Nucleic Acids at Cytiva, I stopped by their booth. Having missed Scott, who took a flight home already, I wound up talking with their commercial lead Fiona Fitzgerald. As a consequence Fiona attended the 

 (AMM) soft launch reception, which consisted of very high level industry leaders participating in support of this Alliance, 

Cytiva then expressed interest in not only learning more about AMM, but learning more about the wider therapeutic application mRNA is now being turned toward. In return I wound up learning a good deal more about Cytiva’s nucleic acid group and what their future plans pivot around. The newly formed nucleic acids team at Cytiva supports customers throughout the manufacturing workflow for oligonucleotides and purification of mRNA drug substances. In collaboration with their colleagues at Precision Nanosystems, they help bring mRNA lipid nanoparticle therapeutics to market.

BIO is a powerful business development conference and can help make a lot of deals become reality. It’s power hinges on its ability to draw in the best and the brightest from all of Biotech increasingly extensive web of activities.

BIO is a powerful business development conference that can help make a lot of deals become reality.

Business of Being at BIO

On June 8th, at the Bio conference in Boston, Samsung Biologics announced a long-term agreement with Pfizer that enlarges and extends a March $183M manufacturing deal between the two. This strategic collaboration will focus on long-term biosimilars manufacturing, and more specifically for the Pfizer biosimilars portfolio group; the agreement is estimated at an initial $411 million, according to 

 by the CDMO. To get to this point Samsung appears to have leveraged positive word of mouth from its partnership to produce COVID-19 vaccine material for Moderna.

According to a company press release, Samsung Biologics will provide Pfizer with additional capacity for large-scale manufacturing for a multi-product biosimilars portfolio covering oncology, inflammation, and immunology. Samsung will use its newest facility, Plant 4, for the manufacturing.

“We are pleased to extend the strategic collaboration with Pfizer as we share and support their strong vision to bring innovative solutions for patients around the globe,” said John Rim, president and CEO, Samsung Biologics, in the release. “This new meaningful partnership comes just as our Plant 4 is fully completed early this month as we had previously committed and are on the move for future expansion into our second campus in order to provide our clients with even more flexible and advanced manufacturing technology.”

“Our collaboration with Samsung Biologics will have the potential to significantly improve the lives of patients globally,” added Dong-Wook Oh, country manager, Pfizer Korea.

With the blockbuster Humira now open to biosimilar competition, that production application seems likely to be an early target. However, while biosimilar introductions have not drastically reduced prices as originally hoped, at least 

 Humira biosimilars are expected over the next few months and some could debut with heavily discounted prices. This includes Amgen’s Amjevita, Samsung’s [partnering with Bioepis/organon] Hadima, and Pfizer’s Abrilada. AbbVie has made 

Samsung biologics also announced that the company will start operating its fifth plant in April 2025, five months earlier than its original schedule, in order to meet a rush of orders from global big pharma companies. Upon the plant's full completion, the company will have a biomanufacturing capacity totaling 

 of finalized terms from July 3, 2023, disclosed that the two deals to manufacture Pfizer's multiproduct biosimilar portfolio are now worth a combined $897 million. The finalized terms on the June deal indicate that it alone is now worth approximately $704 million, making it the single-largest contract granted to Samsung Biologics. As of this latest update, the company has inked deals worth approximately $1.5 billion in 2023.

The collaboration between Samsung Biologics and Pfizer will focus on long-term biosimilars manufacturing.