The Core Gap: Technology Without Change

According to Dr. Afnan, the biggest gap in today’s pharmaceutical manufacturing is not technological. The tools exist, the analyzers work and the regulatory framework supports their use. The real challenge is that companies continue running their processes exactly as before, even after installing PAT tools. As he puts it, “We invest in the equipment, but we do not change the behavior.”
Fluid bed drying illustrates this clearly. Many companies install near infrared sensors on their dryers, yet still determine the endpoint using traditional loss on drying measurements and fixed drying times. The process is monitored, but it is not controlled. Companies spend money without gaining benefit. Dr. Afnan’s view is unambiguous. PAT is process control. Measurement is only the means. As he simply puts it: “It is not enough to look at the rain. You need to pick up an umbrella not to get wet.”

Regulators Are Not the Barrier

A common claim in the industry is that regulators resist PAT driven control strategies. Dr. Afnan disputes this. Regulators care about product quality and consistency, not about repeating old validation rituals. The misconception arises when manufacturers confuse operational consistency with actual product quality. A process can be consistently wrong.

Traditional validation assumes raw material attributes remain stable across multiple batches, but in practice they do not. Each batch arrives with different moisture levels and characteristics, even when they meet specification. When inputs are variable but the process is fixed, the output will be variable (even if within specification). PAT, when used for measurement and control, allows manufacturers to respond to variability and adjust the process accordingly, leading to greater product consistency.

Dr. Afnan points out that regulators have already accepted such approaches. In early NIR controlled dryer projects, “variable drying times were not a problem for the FDA at all,” he recalls. The only requirement was that the process remained controlled and the outcome justified.

Lessons From Early PAT Implementations

Dr. Afnan recounts his involvement in one of the first near-infrared-controlled fluid-bed dryers in the late 1990s. At the time, both Glatt engineers and pharmaceutical teams questioned whether a variable drying time would ever be approved. Yet regulators raised no objection. The aim was to narrow the moisture range and run every batch to the same target. Variability dropped dramatically. End point loss on drying tests were no longer necessary.

He also describes similar gains in tablet compression. Traditionally, tablets are often allowed to vary by plus or minus ten percent in active ingredient content. Dr. Afnan challenges this tolerance. “You would never accept a loaf of bread that varies by ten or twenty percent in weight,” he says. With real time assay measurements and immediate adjustments during compression, content uniformity can be greatly improved.

These projects demonstrated a simple truth. When measurement informs process control, quality improves. When measurement is only observed, nothing changes.

Why Adoption Stalls, Especially in SMEs

Large companies have incorporated aspects of PAT, while many smaller firms remain hesitant. The reason, in Dr. Afnan’s view, is straightforward. If PAT is not used for control, its financial value remains limited. Without clear financial return, adoption slows.

He also notes deeper structural issues. Pharmaceutical processes are often designed by pharmacists or chemists, not by process engineers. The result is a process defined early, validated quickly and then frozen. It operates on the assumption that repeating the same steps ensures quality. “We validate a process by doing it three times and then we test it,” he says. “That is not control.”

For SMEs under pressure to move fast, this mindset is reinforced. They often follow established paths even when they lead to unnecessarily long cycle times and heavy dependence on QC.

Cost, Cycle Time and the Case for Real Time Release

Economic drivers are likely to push the industry toward genuine process control. Manufacturing costs are increasing, reshoring is underway and cycle times remain long. Pharmaceutical production often involves weeks of work waiting for release testing. As a result, large quantities of product sit in warehouses as work in progress.

Dr. Afnan references earlier analyses showing that QC often operates at very high sigma levels while manufacturing operates at much lower capability. This raises operational costs. Real time release, as originally intended in the PAT guidance, addresses this imbalance. When measurement and control are integrated into the process, end product testing is either reduced or becomes unnecessary. Products can be released immediately.

Dr. Afnan draws a pointed comparison. Industries with much lower societal impact achieve tighter control than pharma. Cigarettes, for example, are manufactured with more consistent draw resistance, a quality attribute, than many pharmaceutical tablets achieve for assay. “The product that causes disease is more consistent and higher quality than the one that treats it,” he says.

PAT for Biologics and Advanced Therapies

When discussing biologics and advanced therapies, Dr. Afnan emphasizes that the logic of PAT does not change. What changes is the system being controlled. Instead of granules, companies work with cells and biological systems. First principles understanding becomes essential.

The challenge in both small molecules and biologics is the same. Attributes cannot be called critical if they are not linked to controllable parameters. “Show me the knob you can turn,” he says, “otherwise it is not a critical attribute.” Whether feeding microbes in fermentation or drying granules in a fluid bed, the principle remains identical. Identify the variables that matter and design the process to act on them.

The Role of Conferences and the Next Generation

Dr. Afnan supports conferences focused on PAT, provided they go beyond measurement case studies. The industry does not need more presentations that end with archived data. It needs examples where PAT has been used for real control and measurable business value.

He also stresses the importance of exposing students and early career professionals to this mindset. Changing the industry requires reaching people before traditional habits take hold. For them, process control must become the natural way to design and operate pharmaceutical processes.

A Matter of Will, Not Capability

In conclusion, Dr. Afnan’s message is direct. The pharmaceutical industry already has the tools, knowledge and regulatory support for effective PAT. The remaining barrier is willingness. “The tools are here,” he says. “The will to connect them is not.”
Measurement does not improve quality. Control does. Companies that embrace this will see better quality, lower cost and shorter cycle times. Those that continue relying on fixed recipes and end product testing will face increasing pressure in an industry that cannot afford inefficiency.