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By Donovan Swift
Dec 29, 2025
You may have read about recent attempts to resurrect the woolly mammoth or the dire wolf using gene-editing technology. You may have even seen a certain movie about an amusement park full of genetically modified dinosaurs. What doesn’t always make it into headlines or Hollywood movies is this: The ability to edit and manipulate genes already goes far beyond the hypothetical recreation of a T-rex or Tasmanian tiger.
Scientists can now target, remove, edit, or “silence” harmful genes in the human genome. These damaged or disease-causing genes lead to conditions including sickle cell disease, hemophilia, neuromuscular disorders, and retinal diseases. Gene therapies have been developed to target these faulty genes and treat diseases that were previously thought incurable. Which means patients with genetic conditions have been given new hope by these treatments.
Gene therapies currently work best on conditions caused by a single gene, but their use is being researched more broadly. Scientists are investigating whether diseases such as cancer and HIV can also be treated with these products, so the ceiling could be even higher for these treatments.
Gene therapies are biologics, which means they’re derived from living organisms (e.g., bacteria, yeast, or animal cells), and their development is distinct from other types of pharmaceuticals. Because they use live cells, the manufacture of gene therapies and other similar products (e.g., vaccines) generally produce low-yield batches, which means there is less material to test. Stability testing is the quality-control process of determining how long and under what conditions a drug will remain safe and effective. This stage is essential to guarantee quality production, but it can use a lot of material. Therefore, it is essential to use the materials judiciously, so there is enough product left over for the market or further research.
The standard guide for minimizing the impact of stability testing on batch yield of low yield biopharmaceutical products (E3443) attempts to maximize the use of these low-yield batches. This ASTM International standard was developed by the subcommittee on process applications (E55.12), part of the committee on the manufacture of pharmaceutical and biopharmaceutical products (E55). The standard also has its roots in a BioPhorum workstream about low-yield products, according to Simon Walker, the technical lead for developing E3443 and the global change facilitator at BioPhorum. BioPhorum is an organization that brings industry leaders and experts together to discuss ways to “define future supply practices and drive best practices in areas like drug substance, fill-finish, process development, and manufacturing IT,” Walker says.
“E3443 originated from a BioPhorum Advanced Therapy Medicinal Products (ATMP) workstream, where experts from 17 companies collaborated to address the impact of testing on low-yield gene therapy products,” says Walker. “In late 2020, a survey identified stability testing as a key contributor to yield loss. Ahead of publishing their findings, BioPhorum hosted a workshop with ASTM, where it became clear that the industry recommendations could be formalized into a standard guide in the absence of appropriate regulatory guidance.”
ASTM and BioPhorum experts then worked together to craft the standard, which applies to all low-yield biopharmaceuticals, not just gene therapies.
“The goal of E3443 is to outline strategies the manufacturers of low-yield biopharmaceutical products can consider and implement to reduce the volume of product required for stability testing while still maintaining regulatory compliance,” Walker says. “These strategies, generated from industry experience and expertise, are presented alongside the ‘traditional’ approaches that are outlined in existing ICH guidelines. Through the worked example in the annex, the standard demonstrates – based on a mock product – the significant savings that can be made, ultimately conserving a larger volume of product for patients.”
If more product from each batch can be retained for further research and for patients, then manufacturers will have to produce fewer batches for the same amount of product. This allows them to operate more efficiently, avoid shortages, and develop more gene therapies and other treatments that patients need.
Given the power of these treatments, the potential impact of this standard is huge, and the development process reflects how essential it is for industry leaders and subject matter experts to collaborate as often as possible about the industry’s biggest challenges.
“BioPhorum and ASTM maintain regular touchpoints to align on industry needs and priorities across their memberships,” Walker says. “These discussions help identify BioPhorum outputs suitable for incorporation into ASTM standards, thereby leveraging existing, established collaboration. It also highlights ASTM working groups that could benefit from BioPhorum member expertise. This collaboration fosters early alignment, avoids duplication of effort, and accelerates the development of relevant, consensus-based standards – ultimately benefiting the entire biopharmaceutical industry and the patients it serves.”
Accessible and easily transferable data is also essential in the manufacture of these biopharmaceuticals. Biologics – such as gene therapies, insulin, or vaccines – are developed from living cells, which means all batches of raw materials vary slightly, and manufacturers need to know exactly what is in each batch of raw materials. Accessible data allows them to see the exact percentage of each ingredient, as well as easily plug that information into models that help measure the acceptable range for each product.
The standard guide for raw material eData transfer from material suppliers to pharmaceutical & biopharmaceutical manufacturers (E3077) seeks to create an industry-wide standard for the format and delivery of that raw material data. According to Stephen Wing, a member of E55 as well as BioPhorum, the standard was initially developed so manufacturers can better understand the raw materials they are using. “They wanted the information initially to be able to better understand what’s driving the variability in their manufacturing process,” Wing says. “Because companies are manufacturing biologic therapies using biologic materials, by definition those are natural materials. And nature is very variable.”
“A lot of those materials that they use in manufacturing are also consumables,” Wing adds. “That means once they use it, it’s gone. So you can’t go back and say, ‘Hey, let’s try it again.’”
Using materials efficiently is key with these biologics. Even the slightest difference in the materials could disrupt a batch, meaning less product makes it to the end stage, so manufacturers began seeking data on everything down to the trace elements in the cells they were being provided. “E3077 was developed to capture not only the major components,” Wing says, “but also the capturing of data on trace elements of things like metals that would typically require a special test.”
This level of data allows manufacturers to better predict the variability of each batch and keep the product within their acceptable thresholds. Wing says, “Having this data in a structured data format allows manufacturers to input it directly into their predictive models, so they can build an analysis to see which materials are actually driving variability and then start to control it.”
The data has multiple uses, too. Manufacturers also keep this information ready for FDA or other regulatory inspections, so the goal for Wing’s recent revision to E3077 was to create a platform with which the data could be distributed to customers so they could use it however they saw fit. Previously, the raw material data sets were provided in a print format or a PDF file, but Wing’s revision included other digital formats (such as XML and cloud access) that are more universally accessible.
Standards hope to make the testing of biologics more efficient, leaving more product for the patients who need them.
“Manufacturers were saying that the suppliers were giving them information in different formats through different platforms,” Wing says. “If they had a standard, everyone would just send the same information through the same format and make the manufacturers’
lives easier.”
“The idea is: Let’s make a universal data set that can be used with any platform,” Wing says. “A lot of customers are using supply chain platforms to input the data. Some are using engineering platforms. Now they have control of the user access. So if their engineering people need the data for their analytics, they can get it. If the quality people need it to review the incoming materials, they can access it.”
All of this makes production more efficient, reduces the waste of raw materials, and ultimately lowers the cost of manufacture for the producer and, later, the consumer.
BioPhorum also played a role in the revision of this standard. “Six years ago, I didn’t know anything about the standard,” Wing says. “Then BioPhourm started a work stream called the Electronic Data Exchange to build awareness around E3077 and expand the use of it across industry.”
It was during this collaboration that Wing heard from manufacturers in the industry about what would be most helpful from the supplier’s side. “That’s where I made a lot of connections to start collaborations where we were able to run pilots with our system,” Wing says. “These discussions were very valuable, not only in terms of finding the collaborators, but also building a better understanding of what manufacturers were trying to achieve and what their pain points were.”
At the end of the day, the standard is used to increase efficiency in the production process, and universal datasets will help that goal.
“This data could help manufacturers improve operating efficiencies,” Wing says. “Even if they improve the efficiency by just one percentage point, it can mean millions of dollars saved.”
The committee also recently developed a new subcommittee on pharmaceutical and biopharmaceutical manufacturing sustainability (E55.08), which, among other things, will develop standards that aim to help manufacturers reduce waste in the pharmaceutical development process. The subcommittee has already developed three work items on waste-to-energy solutions (WK96328), green chemistry (WK96327), and reducing and recycling waste as it relates to the manufacture of pharmaceuticals (WK96326).
Linxi Chen, chair of the sustainability subcommittee (E55.08), says the goal of the subcommittee is to offer a playbook for the industry, so they can develop their products more sustainably. “The goal is to help make the manufacturing process greener and develop a kind of sustainability inventory that manufacturers can reference when they choose manufacturing steps, which equipment to use, and which materials,” Chen says. “The goal is to identify solutions or programs that help minimize impact in the processes.”
The waste produced in the manufacturing process varies from the energy used to house the ingredients and make the products, to the solid waste produced by the process itself.
“Energy is definitely a big one,” Chen says. “Also, sourcing raw materials for the pharmaceutical ingredients can produce a lot of waste, and sometimes that’s chemical waste. With the manufacturing process, you not only produce a lot of solid waste, but there’s a lot of heavy water usage. So the standards hope to address the intertwined nature of the manufacturing process. Being more efficient with energy and resource use but also reducing the solid waste that is produced at the end of the process.”
“I think the best way to think of these standards is as checklists or guidebooks that manufacturers and pharmaceutical engineers can use to choose greener processes and create less waste, while conserving water and other resources,” Chen says.
The standards aim to make the process more sustainable, which in turn could lead to higher efficiency. If energy costs go down, then manufacturers can make more product with fewer resources, saving them – and eventually the consumer – money.
“It’s a circular loop,” Chen says. “Manufacturers produce less waste and use less energy, and this will all eventually benefit the end user as well.”
Gene therapies and similar biopharmaceutical products are a unique, cutting-edge solution to illnesses that previously left patients without hope. Because these treatments are unique, the process of manufacturing them is also different than traditional pharmaceuticals, so these standards help address the challenges specific to the manufacture of biologics.
The current applications of these treatments are incredible enough, but they may help even more patients with other illnesses in the future. So their success benefits everyone, which means making the manufacturing process more efficient is not just about the bottom line: It’s about paving the way for the next medical breakthrough.●January / February 2026
