Documentation is something all scientists learn to do when they first start taking science classes in elementary school. But keeping track of everything is especially critical in the cell culture field, as illustrated by a recent case in Japan, where on April 1 Haruko Obokata, a prominent stem cell researcher from the RIKEN Center for Developmental Biology in Kobe, was found guilty of misconduct after other scientists questioned her research findings. Those findings, published in two papers in January, were subjected to a committee investigation made up of a group of independent researchers from RIKEN.^1,2

Obokata’s research involved a technique known as stimulus-triggered activation of pluripotency (STAP), which claimed to allow for easier creation of stem cells using regular cells. However, other researchers were unable to replicate the experiment, and problems were found with the presentation and handling of the stem cell images, data, and text in the papers, leading some to claim they were altered or faked.^1,2

From this incident, it’s clear that proper documentation is essential, to ensure that the data from cell culture research is accurate and to prevent incorrect information from being published.

“If you don’t accurately document what you’ve done in your experiment, then you can’t accurately publish that material—or if you do, then it could have some flaws in it,” says Philip H. Schwartz, PhD, director of the National Human Neural Stem Cell Resource at the Children's Hospital of Orange County Research Institute (Orange, CA). “Documentation and writing in your lab notebook, etc., is something that we train our scientists to do even when they’re in middle school.”

Documentation is also necessary to allow cell culture labs to solve any problems they may encounter in experiments, as it lets them trace such problems back to their source. That means that everything these labs use in their experiments, such as reagents and even plasticware, must be tracked, as there are differences in how those supplies and equipment are manufactured that could impact cell culture capabilities, Schwartz explains.

“If we did not keep accurate documentation of the equipment and reagents and supplies that we use, we couldn’t [backtrack to find problems],” he says. “We’d be stumbling around in the dark when things went wrong.”

Documenting everything is also critical for Sandro Matosevic, senior scientist at Akron Biotech (Boca Raton, FL), for those same reasons.

“Proper documentation is crucial in maintaining a record of experimental procedures during research and development, and particularly when working with a new product or technique,” Matosevic explains. Such tracking is important at Akron—a global supplier that manufactures and distributes components and raw materials for the cell therapy industry—for two other reasons.

“Documentation is also important for reproducibility and to allow different scientists to share experimental details and procedures, which helps in maintaining consistency and for training purposes,” Matosevic says. “Finally, thorough documentation is of critical importance for regulated labs such as ours, as it is a crucial part of meeting regulations.”

For Simin Zaidi, vice president of operations and bioprocessing at Stamford Bioprocess Technologies (Santa Ana, CA), documentation is critical to the company’s cell culture lab, which develops cell lines or processes that are used in clinical product manufacturing.

“Cell line traceability and traceability of design data, why we have selected a certain process parameter for manufacturing, need to be properly documented,” she says. “In the case of our preclinical and diagnostic protein production customers, proper documentation ensures the ability for Stamford Bioprocess to repeat the process consistently. This ensures that product quality doesn’t change from batch to batch.”

How it’s done

The way documentation is carried out varies from lab to lab, but most use a combination of hard-copy notebooks and files and computer systems. It also depends on what exactly is being documented.

“For most of the reagents, we keep a logbook, where we simply put a hard copy of the certificate of analysis and data sheets associated with a given reagent,” Schwartz says, adding that reagents are organized by type. Along with those reagents and supplies used, Schwartz and his team must keep track of the many cell lines they generate, which involves another approach.

“There are many different kinds [of cell lines], and they have been treated many different ways, so we have a fairly elaborate tracking system for those,” he explains. “Otherwise, in order to identify what a particular cell line is, you’d have to go back through the logbooks, essentially page by page, and identify everything that’s happened to that cell line to make it what it is.”

Schwartz’s lab’s documentation process for its cell lines involves a nomenclature system that describes the history of each line from beginning to end, along with a computer-based inventory system with bar code labeling.

At Stamford, for similar processes such as media formulation or analytical methods, the lab uses forms that are filled out by the scientist, while logbooks are used for equipment, such as pH meters, to record the relevant data. Researchers use lab notebooks when they are developing or optimizing a process, and for developed processes, a Stamford scientist or engineer fills out batch records, Zaidi says.

Stamford uses Excel spreadsheets and printouts from some of its analytical equipment, and they record some data on computers, but Zaidi says electronic technologies haven’t taken over her lab.

“I haven’t found any electronic systems that can fully replace notebooks just yet, particularly in a lab where development is being performed and activities can vary greatly,” she explains.

The Akron lab also uses both paper and digital recordkeeping methods, depending on what is being kept track of.

“In the lab, we use standard laboratory notebooks to record experimental details,” Matosevic says. “We also use digital tools, such as file-sharing systems, as well as networked drives to keep a record of laboratory information, such as raw data, images, and files. When it comes to regulatory documentation, we do it exclusively using computers.”

While such software and digital tools make documentation easier, they do pose some challenges to researchers and managers. Matosevic says one of the biggest issues the lab at Akron faces is standardizing laboratory record keeping across the spectrum of its laboratory operations and finding a digital platform that will let workers maintain the lab more efficiently than they’ve been able to do with lab notebooks.

“This relates to keeping track of laboratory operations as our lab grows and maintaining the same level of control as multiple scientists work on multiple projects,” he says. “I think the key is to have consistency in the way multiple users record their data. We work through this by training and evaluating our laboratory personnel in efficient and thorough record keeping.”

Currently, Akron is evaluating LabArchives and similar electronic platforms to determine how well researchers’ needs will be handled in terms of digital file storage, note taking, data analysis, etc.

Schwartz also faces some technology-related challenges in his lab, mostly dealing with software updates or having to switch to a new operating system.

“For us, Windows XP is going away, so we have to go to Windows 7—and now the software doesn’t work on Windows 7,” he says. “There’s always a struggle with keeping the software up to date and keeping it communicating with the operating system without having to buy this stuff over and over again.”

However, he says the main challenge for his lab is simply making sure documentation is being done, and done properly.

“The biggest challenge, really, is to make sure that your staff is adequately trained to keep track of the documentation in the appropriate manner and understand the importance of doing so,” Schwartz says. “Ultimately, all of this depends on somebody doing something. If somebody doesn’t do that something, it doesn’t get done and the system fails.”

Making sure it’s done

“Ensuring everyone consistently captures all pertinent information” is also the main challenge in Zaidi’s lab, one that Stamford Bioprocess tackles through proper training and having staff review each other’s work, she says. “Our scientists know the importance of documenting the work, as we will often be asked about a particular detail of the project. If they don’t have the requested information, then it can cause their work to come into question. No good scientist wants to be in that situation, and management emphasizes this aspect.”

For Schwartz’s lab, maintaining an air of transparency is the key to ensuring that staff members are documenting everything.

“By having complete transparency, accountability follows, because if you’re not doing your job and everything’s transparent, everyone knows it,” he explains, adding that his lab has staff meetings once a week to discuss in detail what everyone’s doing and how they are doing it.

Along with training in proper lab record keeping, Akron also has regular meetings and checks from lab management to ensure that documentation is always proper and up to date.

“Preparation of batch records for regulated processes is always done from ‘raw data’—i.e., the contents of the lab notebook—which makes laboratory personnel aware of the importance of keeping the lab record up to date,” Matosevic adds.

For those new to documentation in the cell culture world, proper planning is essential to avoid a potential mess.

“Assess your needs and never forget about regulations,” Matosevic advises. “If you are starting out, consider a digital (e-notebook) platform, as it allows you to keep a close eye on every user in the lab and address issues promptly. Train personnel in record keeping and ensure they follow standards.”

Zaidi adds that scientists should always write everything down and keep lab notebooks simple, limiting the information recorded to the purpose, equipment, materials, parameters, raw data, and observations, rather than including complicated calculations for resulting data analysis.

“These extra calculations add more for the reviewer to check, and it wastes time,” she explains. “The raw data can later be entered into a pre-established spreadsheet, such as Excel, which performs the calculations and graphing for you. This way, you can be relatively sure of the accuracy of the data and spend time focusing on the interpretation, not crunching and reviewing data.”

Schwartz says having a plan in place for documentation right from the start is essential.

“That is a much easier way to do things than to decide a year or two down the line that you really should be documenting things better—because then you have to go and dig through all these old records to bring them up to speed,” he says. “The single best piece of advice I would give is to make it a priority of the lab, such that it’s done right from the beginning.”

Not doing documentation properly can lead to much bigger problems than having to retrieve and update old files.

“It would be detrimental to our R&D and potentially harmful to the development of a new product,” Matosevic says about what would happen if Akron didn’t document everything correctly. “Regulations require detailed experimental procedures to be recorded, so not having that would be a big issue.”

References:

1. Haruko Obokata, Who Claimed Stem Cell Breakthrough, Found Guilty of Scientific Misconduct, Newsweek,. April 2014. http://www.newsweek.com/haruko-obokata-who-claimed-stem-cell-breakthroughfound-guilty-scientific-239000 

2. Information update on STAP cell research and publications, RIKEN Center for Developmental Biology. April 2014. http://www.cdb.riken.jp/en/index_stap.html