In pharmaceutical manufacturing, quality control testing is often the point at which a product gets its final analytical assessment. But from my experience in pharmaceutical quality control, one principle is worth emphasizing: QC testing is essential, but QC testing alone cannot assure product quality.
A laboratory can tell us whether a tested sample meets its specifications. What it cannot do by itself is prove that every part of the manufacturing process was consistently controlled.
That is why pharmaceutical quality has to be built into the product and process from the beginning.
ICH Q8(R2) makes this principle explicit: pharmaceutical development should be aimed at designing a quality product and manufacturing process that can consistently deliver the intended performance, and quality cannot simply be tested into a product. WHO GMP likewise emphasizes controlled and documented manufacturing processes, suitable personnel, premises and equipment, rather than relying on final-product testing alone.
Quality starts before manufacturing
One of the first places where quality is built is the selection and qualification of suppliers and materials.
For a raw-material supplier, I would not look at a Certificate of Analysis (CoA) alone. A supplier’s broader quality system matters. Depending on the material and supplier, this can include its quality-management certification, SOPs, employee training records, complaint-handling system, quality policy, QA and QC functions, preventive-maintenance programme, breakdown records, HVAC controls, quarantine arrangements, area-monitoring records and relevant certifications.
The CoA tells us something about a particular material or batch. Supplier qualification helps us understand whether the supplier has a system capable of consistently producing and controlling material of the required quality.
The same principle continues into product development.
For an API, characteristics such as identity, purity, physical properties, impurities and microbiological quality may need to be understood. For excipients, functional characteristics and pharmacopoeial compliance can be important. Depending on the dosage form, development may also consider bioavailability, bioequivalence where applicable, dissolution, stability, palatability and other product attributes.
Importantly, development should not be treated as a one-trial exercise. Multiple formulation and process trials may be needed to optimize variables and identify a robust manufacturing approach.
Equipment must be fit for purpose
The equipment used to manufacture and test a medicine also has to be controlled.
Equipment qualification establishes that equipment is suitable for its intended purpose. Calibration then provides ongoing verification that instruments used for measurement continue to provide reliable results within defined requirements.
This distinction is particularly important for sensitive measuring instruments. In a pharmaceutical laboratory, instruments such as pH meters, conductivity meters and analytical balances may require frequent calibration or verification according to their procedures and intended use.
If the equipment generating the data is not suitably qualified or its measurements cannot be trusted, the analytical result itself becomes questionable.
A validated process is more than a successful final test
Process validation is another major part of building quality into manufacturing.
Consider a tablet manufacturing process. Quality does not suddenly appear when the finished tablets reach the QC laboratory. It is monitored at different stages of manufacturing.
During granulation, for example, QA can verify that the approved procedure described in the Batch Manufacturing Record is being followed. After granulation, relevant properties such as moisture can be checked against the applicable specification. Representative samples may then be taken from multiple locations so that the material submitted for testing provides meaningful information about the batch.
Once the required checks are satisfactory, compression can proceed. At the compression stage, in-process checks may include average tablet weight, disintegration time, hardness, friability, thickness and diameter, depending on the product and established controls.
QC testing can then provide additional assurance, including tests such as content uniformity where applicable.
After coating, further in-process checks can confirm that the coating process has achieved the intended result. Subsequent QC testing, such as dissolution, provides another important assessment before the product moves toward packaging and release.
The exact division of responsibilities between QA and QC varies by site and procedure. The broader principle, however, remains the same: quality is monitored throughout the process rather than being left entirely to the final laboratory test.
OOS and OOT results should trigger learning
Another practical example is the difference between an Out of Specification (OOS) result and an Out of Trend (OOT) result.
If a specification is 90–110 and a result is below 90 or above 110, that is an OOS result.
An OOT result can be different. The result may still fall within specification, but it can depart significantly from the established historical pattern. For example, if the previous ten batches consistently produced results around 97–100 and the current batch produces 90 or 105, the result may warrant an OOT investigation even though it has not necessarily failed the specification.
The purpose is not simply to label the result. The purpose is to understand what happened.
The investigation may begin by examining the laboratory side: the analyst, instrument, method and other potential analytical factors. If no laboratory-related cause is identified, the investigation can move into the manufacturing process and relevant records.
Once the root cause is identified, appropriate corrective and preventive actions can be established. If an analyst-related problem is identified, for example, retraining may be appropriate. If the cause is associated with manufacturing, equipment, materials or process conditions, the CAPA should address the actual root cause.
Most importantly, CAPA should not end when the paperwork is completed. Its effectiveness should be assessed to determine whether the problem has actually been controlled.
Quality risk management should be proactive
This is where quality risk management becomes particularly important.
ICH Q9(R1) promotes a systematic approach to assessing, controlling, communicating and reviewing quality risks, with the level of effort and formality being appropriate to the level of risk.
In practical terms, this means we should not wait for a product failure before thinking about what can go wrong.
Risk should be considered during development, material selection, process design, equipment selection, manufacturing and ongoing monitoring. A strong quality system attempts to identify and control potential sources of variation before they become failures.
PQR turns historical data into improvement
One of the most useful tools for this ongoing learning is the Product Quality Review (PQR).
A PQR provides an opportunity to look beyond an individual batch and examine the product and process over time. Trends in deviations, complaints, analytical results, process performance and other quality indicators can reveal problems that may not be obvious from looking at a single batch.
For example, process capability indicators such as Ppk and Cpk, where appropriately applied to relevant key attributes, can help identify opportunities to improve process capability. Recurring deviations can also be evaluated, with CAPA implemented and its effectiveness subsequently reviewed.
If the CAPA is effective, we should see evidence that the recurring problem has been controlled and that process performance has improved rather than simply seeing another completed CAPA report.
That is what continual improvement should mean in practice: using previous experience to make the next batch and the next process more robust.
Quality is a system, not a laboratory result
From a QC perspective, I do not see quality control testing as less important because quality cannot be tested into a product. Quite the opposite: QC testing remains an essential part of the pharmaceutical quality system.
The point is that the laboratory is one component of a much larger system.
Quality depends on suitable materials and suppliers, scientifically sound product development, trained personnel, controlled premises, qualified and calibrated equipment, validated processes, appropriate in-process controls, reliable laboratory testing, investigation of OOS and OOT results, effective CAPA, risk management and continual review of process performance.
ICH Q10 describes this broader Pharmaceutical Quality System as a lifecycle approach that supports product realisation, maintaining a state of control and continual improvement.
Ultimately, a passing QC result is important. But it is the result of a controlled system, not a replacement for one.
That is why, in pharmaceutical manufacturing, the strongest approach is not to ask only, “Did the finished product pass the test?”
We should also ask:
“Did we design, control and continuously improve the system that produced it?”
That is where pharmaceutical quality is truly built.
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