If we do not release, that is only a business risk.

I have heard versions of this sentence many times: “If we do not release the batch, that is only a business risk.”

I understand where it comes from. If there is uncertainty about whether a batch meets its requirements, we do not release it. That is exactly what the quality system is supposed to do: protect the patient from receiving a product that should not be administered.

But I have always struggled with one word in that sentence: only.

Because in radiopharma, if we do not deliver today, there is no simple “Fine. Then send it tomorrow.” The product is time-sensitive, but so is everything around it. A patient has been scheduled, hospital resources have been coordinated, clinical teams are ready and transport has been organised. For therapeutic radiopharmaceuticals in particular, the patient may already have gone through significant preparation before the product is due to arrive. There is a patient at the other end of that delivery.

What does “no delivery today” actually mean?

Some years ago, at a radiopharmaceutical manufacturing site I was responsible for, we had problems late in the day and eventually reached the point where recovery was no longer realistic. We had to tell one of our larger customers that there would be no delivery that day.

They were not happy, to put it mildly.

I visited them afterwards. Part of the purpose was to explain what had happened, what we were changing and why we believed those improvements would reduce the likelihood of it happening again. But I also wanted to understand the impact from their side in even greater detail. What does “no delivery today” actually mean when the patient is already planned?

The answer reinforced something I already understood, but knowing the principle and understanding the operational consequence are not quite the same thing. In radiopharma, the logistics around treatment are complex. The site I was responsible for supplied both diagnostic and therapeutic products, and especially for therapy, a missed delivery is not simply a shipment that can be moved one day to the right on a planning board.

There is knowing, and there is knowing

That experience connected with something I had noticed when I became operationally responsible for the full site. My colleagues absolutely knew that they were making medicines for patients. They were committed to doing things properly, they understood GMP, and they understood the importance of the products we manufactured. I did too. This was never about teaching people that there was a patient at the end of the process.

But there is knowing, and there is knowing.

At one point, we invited a patient to visit the site. We showed her what we did and explained what happened behind the scenes before a product eventually reached the hospital. She was impressed by what she saw, but what stayed with me more was how much her story affected us.

She explained what happened before her therapy, what preparation was required, what the treatment day looked like and what the days afterwards involved. Suddenly, details that we all understood professionally acquired another dimension. Not because the patient had somehow been absent from our thinking before, but because the complete process became more tangible.

A few people called that type of interaction “emotional blackmail”. I disagreed then, and I still do. It would be emotional blackmail if the message were: Look at this patient, therefore release the batch anyway. That would be completely inappropriate. The point was the opposite: to create awareness of the whole responsibility, including the things that happen long before batch release.

Patient focus starts long before the release decision

Doing it right also means preventing a critical raw material from going out of stock when that alone would stop a batch from being produced. It means maintaining equipment well enough that its reliability does not deteriorate until somebody has to make a hurried decision at the end of the day. It means understanding capacity, interfaces, supplier reliability, lead times and process vulnerability before one of them becomes tomorrow’s reason for non-delivery.

That is why I do not think availability belongs only in the commercial-risk column.

The regulatory frameworks reflect that as well. In the United States, section 506C(j) of the FD&C Act requires certain manufacturers to develop, maintain and implement, as appropriate, redundancy risk-management plans that identify and evaluate risks to the supply of the drug for each establishment where the drug or its active ingredient is manufactured. FDA also requires notification of certain manufacturing interruptions that are likely to lead to a meaningful disruption in supply, with the objective of enabling prevention or mitigation of shortages.

In Europe, the framework is expressed somewhat differently. Article 81 of Directive 2001/83/EC requires, within the relevant responsibilities, appropriate and continued supplies so that patient needs are covered, while the EU shortage framework increasingly emphasises early notification, prevention and resilience. EMA guidance for industry recommends robust shortage-prevention and management plans, resilient supply chains and early action to minimise the impact of shortages.

Those expectations matter because they make the underlying point visible: supply reliability is not merely a commercial matter. It can affect patient care.

The release decision may be right while the wider system still failed

So when a batch is not released, the immediate quality decision may be entirely correct while the wider system may still have failed. If a deviation repeatedly leaves Quality with only one defensible option — do not release — then congratulating ourselves because the final barrier worked is not enough. We should also ask why the process keeps bringing us to that barrier.

Could the failure have been prevented? Could it have been detected earlier? Was the equipment sufficiently reliable? Was maintenance effective? Did we have the right materials available? Were supplier and logistics risks understood? Was the process robust enough? Were the interfaces clear? Had we designed enough resilience into the operation?

The release decision belongs at the end of that chain. Reliability is built much earlier.

There is a third track

In the previous What Am I Missing?, I wrote about the trolley problem between quality and safety. But there is a third track running alongside them: delivery.

That changes the problem. Our role in radiopharma should not be to decide whether delivery trumps quality, whether quality trumps delivery, or whether safety can somehow be traded against either of them. Quality and safety limits remain limits. If the product should not be released, it should not be released.

But that cannot be where our professional responsibility ends. Our responsibility is also to design and operate the system so that we are not repeatedly forced into those choices.

Quali(ty) + (Ef)ficiency

That is where Quali(ty) + (Ef)ficiency matters to me.

Efficiency is not producing faster at the expense of GMP. Quality is not accepting an unreliable operation because every failed batch is eventually caught and rejected correctly. A good system does both: it protects the patient from receiving a product that should not be used, while also being sufficiently reliable, resilient and well controlled to deliver the product that patient needs when it is supposed to be there.

That is where compliance meets performance.

So when I hear “If we do not release, that is only a business risk”, my question is no longer simply whether the release decision was correct. I also want to know what made non-delivery possible in the first place, whether we understood that risk before it happened, and what we are doing to prevent the patient from becoming the person who experiences the consequence of a system we could have made more reliable.

What am I missing?

#WhatAmIMissing #Radiopharma #GMP #PatientFocus #OperationalExcellence

Regulatory context

FDA — CARES Act Drug Shortage Mitigation Efforts
FDA — Risk Management Plans to Mitigate the Potential for Drug Shortages
Directive 2001/83/EC — Article 81
EMA — Medicine shortages and availability issues: guidance for companies

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