Densitometry analysis of gels is a key part of quality control (QC) in the pharmaceutical drug release process. In regulated environments, electronic record-keeping can improve both traceability and efficiency – but compliance with regulations like CFR Part 11 and EU GMP Annex 11 is essential.
In this article, we discuss what implications these regulations have on workflows using gel and blot imaging systems to capture, analyze, and document images. We cover what to consider, what to look out for, and how to stay confident that workflows are — and remain — compliant.
The field of gel and blot imaging is developing quickly, and these rapid developments — especially the shift from X-ray films to digital imaging — mean that labs have many opportunities to make their analyses more efficient and reliable.
For those working in regulated environments, compliance with good laboratory practice and good manufacturing practice (GMP) guidelines help to make sure that their products are safe and meet their intended use. Scientists need to view any changes in working practices with compliance in mind. A good, effective workflow does not automatically mean a compliant workflow.
Nonetheless, labs have plenty of opportunities to improve their densitometry imaging, image analysis, and data storage in a regulated environment. The key is viewing selection and implementation with “regulatory eyes” from the start, and knowing what to look for.
Traceability. Accountability. Data integrity.
Around the world, many jurisdictions have their own guidance for regulated environments (sometimes collectively known as GxP), and these regulations extend far beyond the pharmaceutical industry. They help to make sure that only safe, high-quality products reach end users. Though differences exist, all GxP regulations focus on the principles of traceability, accountability, and data integrity.
When you apply these principles to gel and blot imaging — for example, in pharmaceutical QC — you should not only consider the acquisition of the image itself, but the workflow around it, too. Imaging is always part of a broader electrophoresis workflow, so you need to keep all steps in mind when thinking about traceability, accountability, and data integrity. These steps include sample identification, electrophoresis, image acquisition, image handling and analysis, and data storage.
In regulated environments, many of these workflows are governed by guidelines on electronic records and electronic signatures. In the U.S., it is the FDA’s Title 21 CFR Part 11, Electronic Records; Electronic Signatures - Scope and Application. In the EU, these guidelines can be found in the GMP guidelines under Annex 11: Computerised systems.
Product or process?
There is one key aspect in all these regulations — it is always the processes that need to be compliant, not individual products used in that process. You should never label a product as being certified with CFR or GMP guidelines because the product is part of a process, and it’s the process that needs to be validated.
Instead, we should focus on how well a system supports compliance, because that’s what makes a real difference in the ease of its use. Good support generally includes data traceability, audit trail documentation, and use of user groups. The next sections take a closer look at each of these aspects.
Traceability in imaging
In many gel and blot imaging applications, both the imaging itself and the analysis after have a substantial impact on the conclusions that you can draw. For example, in pharmaceutical QC labs, gel images of drug batches are a key factor in determining drug purity levels. In turn, the drug purity levels affect the main decision — can this batch be released or not?
As imaging systems and image analysis software evolve, we have increasingly more ways to maximize information from a subject. In regulated environments, the goal is to maximize data quality without compromising on consistency or traceability in any way. The main way labs can achieve this is by making sure that image files contain a full history of how the image was taken. That can include:
- Date and time of image capture
- The user taking the image
- Details of instrument taking the image
- Imaging mode and capture settings (exposure time, binning, etc.)
- Name of method used to take the image
This information is contained in metadata that the system generates together with the original image in the TIF tags. You can find the tags by viewing the image properties, enabling users to easily trace the image back to its origin and get valuable details on its capture.
Keeping track throughout the workflow
Image metadata is a key contributor to traceability, but it’s certainly not the only one. Samples and their resulting data need to be traceable throughout the entire workflow. With unique sample IDs, scientists can track a single sample across different steps of a seemingly scattered workflow.
Another important aspect is data security when moving from one step to the other. For example, imaging and image analysis often happen at different times and in different locations, leaving a gap between the secure environment of the imager and the secure environment for analysis. What happens to the image in between? How can you tell if it’s been tampered with or not?
One way to be sure is by using analysis software that checks for image authenticity. The specialized software works by recognizing a security tag embedded in the image. If the image was altered between imaging and analysis, the software takes note and treats the image differently than it would handle an authentic image.
Audit trails
The result of the comprehensive, secure tracking of activities from the time the imager is turned on is that it should be easy to generate a reliable audit trail. Audit trails are a key requirement in many GxP regulations. For example, CFR part 11 states:
“Use of secure, computer-generated, time-stamped audit trails to independently record the date and time of operator entries and actions that create, modify, or delete electronic records. Record changes shall not obscure previously recorded information.” —21 CFR 11.10e
With appropriate imaging equipment and analysis software, this type of documentation is fast and easy to generate when requested. Remember that documentation showing traceability does not begin at imaging — sample preparation and electrophoresis are both critical to the final image, and details of these parameters should be recorded. It also helps to assess how well you can integrate the imaging audit trail into the documentation for the rest of the workflow.
User access
The way in which users access images, protocols, and documentation is another area where GxP labs are fundamentally different from most other labs. For example, regulations can control how users can get access to a system, as well as which users can access different features. Controlling access helps to minimize errors, improve transparency, and reduce opportunities for malpractice.
In a compliant workflow, system access is unique for each user and uses two components of authentication (e.g., username and password) — although a single component suffices for additional logins within a continuous period of controlled system access.
To reduce ambiguity further, the system should avoid conflicts in user access. For example, the system wouldn’t let a user log into the computer’s operating system when a different user is logged into the software. To do this, scientists can align the imaging software’s login protocols with the Windows™ operating system, or take other steps to prevent these conflicts from happening.
Sometimes, users might want to leave the imager during image acquisition. A helpful feature that supports this without risking security is letting users lock the imager without interrupting the exposure.
GxP regulations also provide guidance regarding different types of access for different users. Separate access rights — different rights for users, method developers, and administrators — helps to ensure that only personnel with the right qualifications can carry out certain operations. For example, basic users often don’t need to change protocols, so it makes sense to restrict their ability to create new or amend existing methods.
Summary
The role of electronic processing and documentation is rapidly expanding, and GxP-compliant labs can benefit greatly from digitized systems. Scientists working in a regulated environment have specific requirements when choosing new equipment, and those requirements are different from most other labs. The ease with which a system maintains and demonstrates compliance is key.
Data traceability, audit trail documentation, and defined user access rights are the critical elements to get right. Combined, they can create the confidence that innovation and compliance can go hand in hand.
At Cytiva, we are passionate about supporting scientists regulated environments with their needs and goals. To this end, we offer a gel and blot imager along with image analysis software with a host of features designed to help users demonstrate full compliance with GxP regulations.
Our Amersham ImageQuant 800 GxP biomolecular imager and ImageQuant TL GxP analysis software incorporate the core principles of traceability, accountability, and data integrity — helping scientists and regulators deliver safe and effective drugs.