Digitized vs Digitalization – What is the Difference?

For decades, Quality Subject Matter Experts have been stating that it is critical for all aspects of the Medical Product industry to get off paper and digitize as soon as possible. This genesis of documentation would reduce errors as well as the potential for fraud, while accelerating development and the marketing process. Such advice comes with a steep price tag and there’s been a strong inertia in making adjustment to our “we’ve always done it that way and we’ve never had a problem” mentality. Evidence the number of programs advertised to validate your Excel spreadsheet-based systems. Some of us just like to look down at a paper document and all the better if we can walk around with it on a clipboard.

Now, more than 20 years in, organizing digitized data into highly accessible and interactive digitalized systems is becoming industry best practice and as such, is a growing expectation of regulators. What does it look like if your data is digitized but not digitalized? You may be limited to using a stability LIMS system and your program is basically paperless. All the data generated is at least accessible and you can generate data tables from them automatically, but your programs are isolated.

Digitalization is much more than computerized/digitized data; it is the process of taking data that exists in a digital format and making it more accessible and useful for both business and laboratory needs. Digitalization elevates data by putting the tools in place, so it is easier to capture, search, sort, port, and analyze it for quality decisions specifically related to the process at hand. In other words, the manufacturing information, the release results, the stability inventory, stability pull dates/times, and all test results are linked by an integrated process so handling the data for a study does not involve dipping into three or four unique data silos and pasting the data together into your report writing software or some statistical package.

The thought process shifts from,” Can we afford digitalization?” to “How can we not afford it?” and “What does that look like?” Perhaps the lab’s LIMS or even the ELN is linked to your stability LIMS, or is inherent in the same application, so some technician doesn’t have to enter the stability results in two different systems and check the specs in a third location to make sure the results passed or were not OOT. A statistical analysis of the latest results essentially involves the touch of a button to bring the lab data and stability information together into a validated report with graphs and confidence intervals included. This and many more efficiencies and compliance factors are part of the world of a digitalized stability program.

The usage of the computerized system in the regulated environment is not new. Since the early 1980s when the first computerized systems were used in laboratory and manufacturing operations, the industry has been putting in place guidelines and regulations to govern the use of these systems while promoting their use for the betterment of the industry.

All pharmaceutical corporations must adhere to regulatory controls, which have radically changed over the past five decades. Pharmaceutical regulations are designed to ensure efficacy, product quality, and ultimately patient safety. Quality Risk Management and Risk Mitigation is the name of the game these days, so regulations come, they rarely go, but the regulations do evolve, and that is especially true in this era with the flood of new digitalization technologies that are available. Take audit trails for example – it is astounding how much data is collected in the audit trail process. Not just the data, but all previous iterations of the data as well as a unique large ID number associated with the time, date, username, and ID, etc. that made the change.

Over the last two and a half decades regulators have told the industry to collect data. This was the beginning of the era of “big data” and with it came 21 CFR part 11 (1997) from the FDA, and Annex 11 (1998) from the EMA to support the collection of digitized data. More recently, regulations surrounding data integrity / ALCOA++ provide guidance to ensure the digitized data is reliable and ready to be used to make quality decisions. These regulations have set the stage to collect the data and now after having accumulated data for many years, companies are assumed to have a significant amount, and the regulators want it used appropriately.

In fact, there’s an element of historic responsibility. Your stability LIMS may have only been in place for two years now, but there could be an expectation that data from the previous LIMS system, even up to 5 or 10 years back is as easily retrieved and analyzed as last month’s data. It should all come seamlessly together.

These days, most companies use computerized systems to house their data, but for many the road to true digitalization is blocked by limited access to the data, data quality, and lack of data governance with the biggest hindrance being the use of, and continued investment into siloed legacy business applications such as ERP and LIMS. These have their own proprietary limitations and simply don’t have the ability to achieve true digitalization of the stability process. A truly digitalized system will be dedicated to the process it is designed for, not a configurable one size fits all procedures approach, that never meets all requirements and takes significant time and cost to bring online.

When the process under consideration is the Stability Function, you will want to have the dedicated software to address the ins-and-outs of stability study commitments, finding batch candidates, managing samples and sample pulls, chamber management, execution of analytical methods, data capture from HMIs (Human Machine Interfaces) and directly from instruments, and analyzing results for trends, shelf-life determination, expiration dating, and reporting and submission of the study data. A simple Excel spreadsheet is not sufficient to address all stability requirements.

A simple test for the maturity of your stability process digitalization is to review how you are analyzing your data. If your statistical tools such as p-value analysis, out of trend charts, linear and multiple regression, Arrhenius equation, and data pooling are all built into the validated digitalized solution where your data resides, then your maturity is at a good level. If your system lacks the statistical tools dedicated to the stability process and you are required to export your data to an external statistical package (SAS™, MiniTAB™, MS-Excel™, JMP™, etc..), then the digital maturity is not at a sufficiently high level. By exporting the data, you are very likely losing compliance, data integrity, and data handling efficiency needed to make quality decisions.

Rome was not built in a day, and laboratories do not become paperless overnight! Digitalization of a process like the stability function is most times gradually enhanced, and of course this begins with putting a dedicated stability software system in place which has the capability to support the four key areas that require digitalization from the beginning, and also facilitates progressive digitalization of all other key stability study-specific requirements.

These are the four critical areas where digitalization benefits are maximized for the efficient management of stability studies. These significant areas reduce the risk and workload while managing stability samples and testing thereby providing the biggest ROI and amplifying the value of the digitalization of the workflow, as explained below.

Digitalization can allay the risks associated to stability testing, such as missing the due dates for samples to be pulled from the chamber and storing a sample for too long after the sample is pulled. These risks and others can be mitigated through technology. For example, a sample pull report could be generated daily, not only for the stability logistics team, but also for the lab, so each can check on the other, make sure samples expected were delivered, and that testing required was initiated.

Having all data available in a single system facilitates investigations and root cause analysis. An electronic notebook removes the need for paper worksheets and these workbooks detail all the steps for executing an analytical method. This also allows contract labs, regulatory, QA, R&D and internal investigators to perform deep dives as necessary to find why, for example, a series of lots are behaving unexpectedly over the last two years at Zone IVb conditions.

Most important in the digitalization effort is the automated capture of data. This process can involve equipment or other software systems and databases. For example, balances for weight loss tests and HPLC systems should feed all the data directly into the system without the ability for the user to intervene with the data during transfer. And could it be possible that we identify a specific instrument as a potential bad actor after noting a consistent pattern of lower potencies it has generated vs. other units?

Shelf-life analysis of the data in the same system as the statistical tools, with no need to export data into an external spreadsheet or statistical software. The Digitalized system and process are validated, and the data must remain under the umbrella of the validated system. Exporting data to external systems to analyze it negates the validated state of the data and goes against the whole point of having a validated digitalization software system.

With seamless validation, efficient data analysis and report generation, clear and attractive graphs become easy to include. Having all this data, tabulated, analyzed and with graphical representation at hand in the same location minimizes transcription into other packages, facilitates evaluations, enables timely decisions and allows for quicker data submission when required.

Every business both small and large should have a digital transformation master plan. Digitalization is no longer a nice to have, it’s a must have, and companies that have already embarked on their digitalization journey are a step ahead. From drug development to material testing / batch release, and stability study management, companies need to prepare for the next wave of digitalization. The quality-effectiveness of a digitalized process will be a critical factor in the years ahead as regulators continue to evolve requirements to keep up with new technologies and to encourage regulated companies to use them. Watch for our future webinars and articles focusing on digitalization and transformation of the Stability Function.

Susan B. Cleary, B.Cs, EMBA, Director of Product Development – Novatek International. Previously holding the position of Program Manager and Lead Software Engineer for multiple applications; Finished Products Analyzer, Raw Materials Management, and Environmen­tal Monitoring software programs. Susan has more than 25 years of experience in designing, developing, implementing, validating, and managing large-scale LIMS and Quality Management software projects while working with both Pharmaceutical and Biotech companies to capture their re­quirements and provide fully validated turnkey digitalized systems. Susan specializes in Laboratory Infor­mation Management, Stability Study Management, Environmental Monitoring, and Cleaning Validation processes and works with clients to digitalize their procedures and manage their data more effectively.

Parsa Famili, CEO Novatek International. Parsa Is the President and CEO of Novatek International. Prior to joining Novatek, he held senior management positions in quality departments of several North American pharmaceutical companies. He has participated and successfully completed several FDA, EMEA, TGA, and Health Canada audits. He was also an instructor of chemistry and biochemistry at Vanier College in Montreal, Quebec Canada. Parsa has helped build Novatek, bringing more than 25 years of technology industry leadership, global quality regulation expertise and executive management experience to his role with the company. In addition, Mr. Famili strongly believes in giving back to the society and communities he works in and is a strong supporter of “Hope For Dementia”, a charity he created that aims on raising awareness on Dementia and other mental disorders for our aging population. Hope for Dementia has also been recognized as “Social Organization of the Year.”

Pedro Jorge, Director of Quality Control, IVC Vita Health. Pedro has been in the pharmaceutical, biopharmaceutical and medical device industry for 30+ years. He has held positions in leadership positions in Quality Control at Biomira, Cangene Corporation, Willow Biosciences and currently at IVC Vita Health, He has also been an independent consultant assisting in the pharmaceutical and biopharmaceutical industry. He has worked for organizations producing plasma derived therapeutics, recombinant protein products, monoclonal antibodies, biosynthetic materials, natural health products and over the counter medications.

John O’Neill, BS Pharmaceutical Sciences, MS RPh. Editor at StabilityHub. John is a life-long stabilitarian with 50 years of experience in the medical product industry. His career has taken him from Registered Pharmacist to Liquids and Semi-solids Formulator at Sterling Winthrop, QC Manager at Sanofi-Aventis, Medical Device Quality Steward at Boston Scientific, Independent Consultant, Principal Stability Specialist for Biologics at Genentech, Associate Director for Stability at both Gilead and Regeneron, and is now the founder and editor of StabilityHub, an industry information website covering many aspects of the medical product stability function. John is also the founder and facilitator of the Pharmaceutical Stability Discussion Group, an organization dedicated to sharing trends, questions, solutions and experiences related to the stability function.

Walter Routh. Walter Routh is a contributing editor for StabilityHub. He is also founder and CEO of Sagana Quality Consulting dedicated to improving pharmaceutical stability programs’ efficiency, compliance, and cost savings. Walter Routh worked for 27 years in the pharmaceutical stability industry at a fortune 500 company and coordinated harmonization of stability procedures with 14 global stability sites. Through his work ranging from hands-on product stability coordination to managing the primary US stability and reference standard group he has practical experience in commercial stability issues, both on the storage and logistics side as well as on the scientific and regulatory side. Walter managed all types of stability studies for a variety of dosage forms and delivery mechanisms. During his tenure, Walter improved efficiencies, reduced costs, digitalized his programs, and worked to implement numerous cutting-edge technologies such as real time statistical analysis, validated shipping lanes, fully digital chain of custody, and automated statistical reports with graphics, for a stability program with well over 1000 active studies for over 40 product families.