Data traceability: ask the experts

Written by RegMedNet
Manufacturing & scale-up
data traceability

In this ‘Ask the experts’ feature, a panel of key thought leaders share their perspectives on current obstacles and future developments in data traceability. For example, what are the challenges in applying good laboratory practice (GLP) to early-stage research and development? How might traceability and accountability be improved in pharma and biotech organizations? How do you see data traceability evolving in the future? Discover more about this from our expert panelists, Ellen Harrington (Bioprocess Engineering Services, BPES; Kent, UK), Ben Werdelmann (SYNENTEC; Schleswig-Holstein, Germany), Jesús Chaparro García (Regional University Hospital of Málaga; Spain) and Ioannis Papantoniou (Katholieke Universiteit Leuven; Belgium).

Raw material questions:

Please introduce yourself and your institution.

Ellen Harrington (EH): My name is Ellen Harrington, I am a Technical Sales Specialist at BPES. BPES is a specialist vendor of instruments, equipment and services to customers in the biopharma, biotech and cell and gene therapy sectors, along with universities and research organizations. I work with scientists to provide solutions for maximizing the efficiency of their cell line development workflows; our customers are typically developing monoclonal antibodies, vaccines and advanced therapy medicinal products (ATMPs).

Ben Werdelmann (BW): My name is Ben Werdelmann, I’m responsible for Business Development and Applications at SYNENTEC. SYNENTEC is a leading manufacturer of automated high-throughput cell imaging systems and robotics. The company provides cutting-edge customized imaging solutions for cell line development, drug discovery, virology, cancer research, stem cell research and scientific research as well as ATMPs.

Jesús Chaparro García (JCG): My name is Jesús Chaparro García and I am the Quality Assurance Manager of the Cell Manufacturing Unit of the Regional University Hospital of Málaga. We are an authorized academic manufacturer that develops cell-based medicinal products following cGMP guidelines to be tested in clinical trials or used as treatment in approved compassionate use by the regulatory agencies.

Ioannis Papantoniou (IP): I am an Associate Professor and Head of the Tissue Engineering and Lab, Prometheus, in the division of skeletal tissue engineering, Skeletal Biology & Engineering Research Centre, Department of Development & Regeneration, KU Leuven. We have been active in developing novel biomanufacturing pipelines tailored for bottom-up tissue engineering. These technologies are designed for the exploitation of the regenerative capacity of spheroid and organoid modules. This biomanufacturing paradigm consists in the integration of technologies such as bioreactors, bioprinters and robotics making these ATMPs accessible to patient populations. 

What are the challenges in applying good laboratory practice (GLP) to early-stage research and development? 

EH: One of the biggest challenges in applying GLP to early-stage research and development is where to begin the implementation. Most laboratories have years of research and data that have been conducted and collected according to evolving protocols which then must be molded to fit stringent GLP requirements.

BW: The regulatory framework and the extensive documentation accompanying GLP can often result in an unflexible workflow, the kind often required for early-stage research and development. On the other hand, the transition from early-stage research and development into regulated environments, where GLP or good manufacturing practice (GMP) are required, greatly benefits from well-established and documented procedures; ultimately, this reduces timelines in the commercialization of biologics or other active substances, such as chemically synthesized drugs.

JCG: In our case, since we belong to a public academic institution, resources are obtained from R&D calls for public funds. The equipment, personnel and infrastructures maintenance we have access to is limited, so, in order to comply with cGMP requirements, proper assessment and management of resources is of utmost importance to consistently fulfill demand. 

IP: There is a lack of facilities and dedicated staff as well as the generic lack – or high cost – of technologies that would enable and facilitate the implementation of GLP at that stage.

What are the benefits of considering quality assurance protocols earlier in the development process?

EH: Reproducibility of results is a critical aspect of R&D, so adhering precisely to protocols and eliminating variables as early as possible will result in consistent products. Also, thorough documentation at the earliest steps allows for a more seamless and faster transition between the development processes.

BW: Assay development is a highly complex task that is greatly aided by exact and timely documentation of assay parameters and results. In particular, assays with biological systems can show a high inherent variability that can only be controlled by using reproducible assay conditions to reduce the influence of inherent variation and precisely measure the effect of interest.

JCG: The goal of each manufacturer is establishing an efficient, robust and standardized manufacturing process that guarantees the quality and consistency among batches. This can be feasibly achieved by designing quality assurance protocols, by which the process could be reproduced equally regardless of intrinsic factors of variation, such as operator’s background or technical issues.

IP: This advice has been around for a long time; the advantage of an early consideration of quality assurance protocols is that the developed process and product can meet regulatory requirements from its inception. This approach can result in effectively building quality attributes in your ATMP. By organically embedding quality assurance protocols early-on, the risk of redesigning the process at a late-stage is mitigated. This could be detrimental for small organizations.

Why do you think a lot of early-stage and R&D groups have not started implementing quality assurance protocols?

EH: I think many R&D groups are unsure where to begin with implementation. It is without a doubt a daunting process and a significant change to the way things may have been done previously – particularly for organizations which still rely heavily on paper-based systems – and may require a substantial amount of work to meet the requirements.

BW: Mainly because it is not required and is also complex to implement QA protocols in a highly flexible development process.

JCG: Writing a quality assurance protocol is a difficult, time-consuming task and usually involves a multidisciplinary team. For this reason, I think many groups tend to start implementing them at a later stage once they have gained sufficient experience and covered the weak points they have noticed. This is because there are many features that go unnoticed when you first design a certain process and it is not until you test it in real conditions that process improvement is truly achieved.

IP: I think the same reasoning applies as for the implementation of GMP at this stage.

What common mistakes do you see manufacturers making when it comes to data traceability, particularly regarding 21 CFR part 11 regulations?

EH: One mistake I commonly come across when it comes to 21 CFR part 11 and data traceability is that the requirements are complex and often not fully understood, leading to some companies believing they are compliant when in reality they are not. Another mistake is waiting too long to investigate and learn about the requirements and not taking early action to improve data traceability.

BW: With the uptake of electronic lab notebooks in a lot of companies, traceability has greatly increased due to data availability and centralized searchable databases. The regulations are put in place due to a lot of the primary and derived data being electronically generated, analyzed and stored, so data integrity monitoring is paramount to being able to prove that the data is valid and un-altered. Data integrity monitoring is often not conducted thoroughly; instead, the data is often just removed from un-authorized access to comply to the regulations in place. SYNENTEC has taken up 160 bit digital fingerprinting technology to allow our customers a highly accurate validation process that is part of the audit trailing, so the data integrity can be proven at all times regardless of where the data is stored.

JCG: In our case, we are not obliged to comply with FDA 21 CFR part 11, but our regulation has analogous requirements regarding data traceability and computerized systems (EU GMP annex 11). Most manufacturers trust suppliers to acquire equipment and software for their routine use in analysis of the manufactured products. These are usually employed in basic research and do not comply with current data integrity regulations. Moreover, there are currently available programs that are commercialized with a premium version that actually includes the requested functions. In this case, each manufacturer should carefully assess if the product fulfills their needs and is compliant with the regulations. 

IP: There is a lack of tools to enable digital batch records and the formation and build-up of a paper trail, which can be difficult to manage, compile and ultimately review. This makes life difficult for both manufacturers and regulators.

How might traceability and accountability be improved in pharma and biotech organizations?

EH: First and foremost, planning ahead. Data traceability and validation are topics that are swiftly gaining importance across biopharma and biotech organizations, so it is important to make a plan early for how this might be handled and identify resources to help. It would be a distinct advantage when preparing to start a research project to have these discussions and plans laid out to encourage more formal lab processes early on. At BPES I help scientists to find solutions for their workflows daily, such as SYNENTEC’s (Germany) cGMP validation software, YT Audit. Additionally, dedicated and regular training for staff should be introduced to keep everyone up to date with requirements and to help employees understand why it is important.

BW: To my understanding, automation is key to improve traceability and accountability in pharma and biotech organizations. Automation must be detached from only being considered in manufacturing and high-throughput screening, but also on the data side of things. Having automated solutions that are user-friendly and quick while maintaining flexibility are of high importance moving forward.

SYNENTEC has developed YT-Audit from a user’s perspective, arranging the software in a non-intrusive and highly automated way. Our intention was to change the user’s experience with YT-Audit as little as we could compared to the non-regulated software, so the user can easily generate validated data while maintaining flexibility and having the highest level of confidence in their data.

JCG: A key point is to consider data traceability and accountability as a current topic in the risk assessment of the organization. The identification and description of the actual mechanisms to ensure data integrity and traceability is the starting point to identify vulnerable steps and proceed with their improvement. Even though many biotech companies offer specialized software and solutions to support manufacturers in this issue, there are other traditional approaches that could benefit data traceability, for instance the establishment of handwritten registries or logbooks and the periodic review and follow-up of these by the quality assurance department. Another important aspect to consider is the formation and training of the active personnel in the organization. It is a matter of concern that only personnel with the adequate level of qualification have access to certain information or equipment. Training sessions should not only cover the procedure to keep record traceability updated (highlighting the Good Documentation Practices), but also raise awareness of why it is important for the global workflow of the process.

IP: The adoption of electronic batch records that are compliant with CFR part 11 regulations, as well as the use of technologies that already encompass digital elements, including sensors or biosensors, will significantly contribute towards this direction. There are developments in all process units in this regard involved in cell therapy manufacture.

In addition, several companies are starting to offer products that also enable operators to digitalize existing paper trails improving data quality and data integrity.

How do you see data traceability evolving in the future?

EH: I expect there will be more reliance on software-based solutions, so no more paper lab books or paper-based logs and protocols. Correspondingly, data security will become more advanced, with biometrics or something similar introduced to further improve data integrity and accountability.

BW: Moving forward in an age of decentralized, cloud-based infrastructure, a next step in the evolution of data traceability and data integrity monitoring could be the uptake of next-generation security measures, such as crypto algorithms as well as blockchain, to protect valuable information from alteration.

JCG: In my opinion, the less human involvement in data traceability, the better. There’s always a certain chance of making a mistake or forgetting to fill the forms that is inherent to all of us. Humans have always been subject to committing mistakes, it is part of our nature. For this, I think the future of data traceability lies in technological advances and computer systems. The development of specialized scientific software shall carry the burden of data traceability, integrity and long-term secure storage of information. More affordable IT services will be available for manufacturers to implement in each process of their organization. Paper-based support will be gradually replaced by digital format (electronic records) with a wide range of online services available. Activity and operators would be automatically monitored by active, not alterable audit trails, and information could be safely backed up and uploaded to high-end computer servers and databases.

IP: By full digitalization and adoption of data security technologies, an end-to-end digital trail will be developed for all batches. In addition, data restructuring and harmonization will render them suitable for advanced data analytics. This will enable full traceability and also enable the transition to a 4.0 biomanufacturing era. Finally, the development of digital-based tools for process design and control will enable the true implementation of quality by design.

Meet the experts

Ellen Harrington | Technical Sales Specialist at BPES

Ellen Harrington is a Technical Sales Specialist at BPES. Ellen works with scientists in Cell and Gene Therapy to match their laboratory needs with our market-leading products, helping to maximize workflow efficiency and shorten the time to market.

BPES is a highly specialized team ready to help you find solutions to maximize the efficiency of your workflows. They connect market-leading technologies to their customers in the Cell and Gene Therapy, Biopharma, and Biotech sectors. Their customers range from small start-ups to universities, research organizations, equipment vendors and global pharmaceutical companies. Their portfolio of products have applications ranging from CLD through upstream to downstream processing. As a highly customer-focused business, they believe their strength is in combining our equipment expertise with trusted ongoing support services.

Ben Werdelmann | Director of Business Development & Applications at SYNENTEC

At SYNENTEC, Ben Werdelmann manages relations, collaborations and requested developments, with new and existing customers and partners. Ben also oversees the applications department for new developments or testing and interfaces all that with software and hardware development when required. As a trained biologist, he has a lot of time for their customer’s projects and processes, and enjoys watching their journey and supporting them with innovative solutions.

Jesús Chaparro García | Quality Assurance Manager at the Cell Manufacturing Unit, University of Málaga

My name is Jesús Chaparro García, I am a BSc Graduate in Biochemistry with Mention in Biotechnology from the University of Málaga. I hold an MSc in control and manufacturing of ATMPs, the field where I have developed my professional career since 2017.

I initially started working in the Cell Manufacturing Unit under cGMP guidelines in the production of expanded MSCs derived from adipose tissue and I later moved on to the Quality department. Currently, as head of the Quality Assurance department, I am committed to guaranteeing process efficiency and standardization to bring high-quality medicinal products to patients.

Ioannis Papantoniou | Associate Professor at the Department of Development & Regeneration & Prometheus, KU Leuven

Ioannis is an Associate Professor at the Department of Development & Regeneration & Prometheus, the division of skeletal tissue engineering, KU Leuven. At KU Leuven, he has established an independent stem cell bioprocessing and tissue engineering team through national and international funding. His research aim is to produce compliant 3D cell-based products with predictive functionality linked to orthogonal quality attributes using high precision technologies. He has published more than 45 journal articles, 60 conference proceedings and holds 1 patent. He has been involved in several collaborative research projects and R&D activities with companies active in Regenerative Medicine Manufacturing, he is coordinator of the H2020 project Jointpromise (Grant number: 874837) and member of the consortium of the H2020 project AIDPATH both targeting automation for biomanufacturing of organoid-based implants and CAR-T cells respectively.

Disclaimers

The opinions expressed in this interview are those of the interviewees and do not necessarily reflect the views of RegMedNet or Future Science Group.

This feature was produced in association with BPES – BioProcessing Equipment Specialists.