When organisations discuss paperless validation, Computer System Validation (CSV) is almost always the first topic on the table. This comes as no surprise — electronic hardware and software have become deeply embedded in every facet of modern manufacturing. Yet, while digital systems serve an important supporting function, they are not what ultimately produces a product. The most critical component in any manufacturing operation is the equipment itself. Without equipment, nothing gets made. That is why paperless validation should focus strongly on the equipment level.
Whether introducing new equipment or modifying an existing asset, the end goal seems to be always the same: to qualify the equipment or update its qualification records. In the case of an existing piece of equipment, this might involve changes to the PLC logic or the replacement and upgrade of key components. But is that enough?
What matters most when teams make these changes is not simply whether they have updated the qualification records correctly. Far more important is the effect these changes have had on process parameters. Regulators and auditors are primarily concerned with whether manufacturing and cleaning processes continue to perform consistently — whether there is variation within a batch and from one batch to the next. That is the question of interest.
This article addresses an often-missed link in this chain: the data that the process validation team needs after the equipment qualification team completes its work. This handover of critical information is, in reality, the most important activity in the entire process. Because it determines whether the process remains compliant. One cannot operate equipment in a range that was not qualified.
Process Paramters
Process parameters are not merely operational settings — they are the critical link between equipment performance and product quality. They have a direct and measurable effect on the Critical Quality Attributes (CQAs) that define whether a drug product meets its specification. A shift in even 1 process parameter, however small, can alter the quality profile of the final product. This is precisely why teams must carefully assess every equipment modification and consider its downstream impact on process parameters and, ultimately, patient safety.
The same principle applies when purchasing new equipment. Does the new equipment truly match the existing one? Teams must analyse and document this comparison before moving forward with procurement.
Consider a real example. A site plans to replace an old granulation mixer with a new model featuring an updated, more efficient bowl design and a PLC-controlled mixing cycle.
The new mixer requires equipment qualification before the site can put it into production. But qualification should not be the starting point. Before defining the additional equipment and software qualification steps, the team should ask at least two questions to determine what it needs to demonstrate through PPQ and CV runs to ensure the product meets its specifications, both in-process and in the finished product.
- Is the new equipment identical to the equipment it will replace? If differences exist, what are they? How could those differences affect product quality? For example, has the bowl geometry changed in a way that alters the product-contact surface area or mixing dynamics?
- Will the site purchase the equipment “off the shelf,” or will the supplier customise it?
The new bowl design may alter the fundamental fluid dynamics and mass movement within the mixer. As a result, the existing ranges for critical process parameters such as mixing speed, shear profile, mixing time to endpoint, and torque curves may no longer remain valid. The team would therefore need to repeat PPQ runs on the new equipment to demonstrate that the process still meets the required product specifications.
A change in PLC logic could also fundamentally alter how the equipment controls and sequences the process. The original PPQ runs used a specific set of automated controls, including defined ramp rates, hold times, interlocks, alarm thresholds, and parameter sequencing. These controls consistently delivered product that met its CQAs.
If the new PLC logic manages these same parameters differently — perhaps through different control algorithms, tighter or wider deadbands, altered timing sequences, or different response characteristics to process deviations — the previously validated process no longer represents the new operating conditions. The team must therefore conduct new PPQ runs to demonstrate that the new control logic, while governing the same critical process parameters, still produces a product that consistently meets its drug product specifications, batch after batch. Parameters, still produces a product that consistently meets its drug product specifications, batch after batch.
3 Runs Completed Successfully – Tell us more about the process
Three successful PPQ runs may satisfy the immediate qualification requirement, but they do not provide the full picture. They represent a limited snapshot — a demonstration that the process can produce compliant product under controlled conditions on three occasions. What they cannot tell us is how tightly the product specification remains within tolerance over time. This is precisely why Continued Process Verification (CPV) exists — to confirm that the results demonstrated during the three PPQ runs remain consistent at batch fifty, batch one hundred, and beyond. Without sustained monitoring during the CPV stage, those three successful runs can create false assurance while leaving the risk of slow, undetected drift from the drug product specification unaddressed.
The team must not only monitor the process after PPQ runs; it must also monitor the equipment and the PLC logic that controls it. PLC logic does not remain static. Software updates, firmware patches, sensor recalibration, and even subtle electrical degradation can change how the control system behaves over time. A timing sequence can drift by milliseconds, maintenance can inadvertently overwrite an alarm threshold, or a control loop can respond differently to input signals — and any of these changes can shift process parameters without triggering a single deviation.
Equally, the physical equipment is subject to wear and tear that no PLC can detect — bowl surfaces that degrade over time, impeller blades that erode and alter shear profiles, seals that harden and introduce dead spots, or contact surfaces that pit and roughen, changing both product interaction and cleanability. If the organisation monitors only the product and the process but neglects the equipment’s control logic and its physical condition, it creates a blind spot where the root cause of a future quality failure — whether digital or mechanical — will remain invisible until it manifests as out-of-specification product in the hands of the patient.
Paperless Validation Must Evolve Too
If validation is a lifecycle, then paperless validation must evolve with it. The objective is not simply to replace paper with electronic records. It is to make validation easier to manage throughout its entire lifecycle — from initial qualification through process validation, change control, monitoring and ongoing verification.
This means paperless validation must look beyond electronic components, software, and PLC logic alone. The equipment in its entirety must be qualified — its mechanical systems, its control logic, its physical condition and its interaction with other equipment. This is not a novel concept. ISPE Baseline Guide Volume 5 on Commissioning and Qualification makes this point clearly: qualification should encompass the complete equipment system, not just its individual automated elements. A paperless approach that captures only the digital layer while ignoring the physical asset beneath it is not simplifying the lifecycle — it is leaving critical gaps in it.
Positioning PQMS Suite
This is where an integrated platform such as Quascenta’s PQMS Suite can support the broader validation lifecycle.
ValDoc Pro supports all qualification & computer system validation activities; eProcess Pro manages PPQ runs and CPV runs; eResidue Pro supports cleaning process management; eLog Pro enables electronic logging and recording of routine operational activities to support ongoing monitoring and control; and QMS Pro manages the change control, CAPAs, and non-conformances that changes like this can trigger.
Together, these capabilities allow organisations to move beyond simply converting paper-based validation tasks into electronic format. Instead, they create a connected digital environment that brings qualification, process validation, cleaning validation, change control, and ongoing monitoring together within one coherent, living system.
