In the pharmaceutical industry, cleaning validation is a mandatory step: it ensures that equipment is free from any residue — product, cleaning agent, or microbial contaminant. So far, everyone agrees.

But once you have to calculate acceptance criteria, the smiles often disappear. Because while validating a cleaning process between two products may seem simple on paper, things get seriously complicated when there are 20 of them. At that point, it is no longer a validation: it is a regulatory sudoku on steroids.

Why do acceptance criteria become a nightmare to manage?

Validating a cleaning process between two products? Easy. Two products = one pair. But with 20 products?

You are not validating 20 products. You are validating 380 combinations.

And that is just the beginning. Because for each product A to product B combination, you may actually need to apply two formulas:

  • one for the toxicity-based criterion (HBEL),
  • another based on the therapeutic dose (mTD).

So 380 combinations × 2 formulas = 760 distinct calculations, each requiring its own parameters and justifications.

And these calculations must incorporate:

  • minimum therapeutic doses (mTD)
  • maximum daily dose values (MDD)
  • toxicity (HBEL: PDE or ADE)
  • safety factors associated with routes of administration
  • the actual shared surface area
  • the nature of contact (direct, indirect…)

In short, a cheerful cocktail of variables that turns your Excel file into a headache factory.

The snowball effect of multi-product environments

In a multi-product environment, production lines are shared, molecules vary, dosages change… but the requirements remain. You must:

  • identify the worst-case products, equipment, and combinations
  • document equipment equivalences (similar or identical)
  • redo all your calculations whenever a product or piece of equipment enters or leaves the scope

And of course, all of this must be ready for an inspection, at any time, with solid traceability.

Excel, the false friend

Let us be honest: we all started with Excel. But from 5 products onward, you spend more time tweaking Excel formulas and optimizing how they work than actually focusing on your cleaning process.

And when you need to justify the origin of a safety factor or track down why you rounded an ARL to 0.15 ppm… good luck.

That is when you realize that a good tool is not a luxury — it is a condition for professional survival.

The good news: tools exist

Digitalization (a.k.a. "Pharma 4.0") is not just a buzzword. It is also an opportunity to stop cobbling things together with unstable files and regain control over complexity.

At Hally-pharma, we tackled this problem head-on. Our SaaS solution was designed to handle:

  • all product combinations automatically,
  • MACO and ARL calculations, without the headache,
  • shared surfaces, exclusions, and modeling in just a few clicks,
  • and above all, clear, traceable, and actionable documentation.

In short, everything you need to turn a regulatory puzzle into a smooth process.

Conclusion

Defining acceptance criteria is like baking a multi-layer cake… except each layer can collapse if you use the wrong ingredient. The more products there are, the greater the risk of error. And the longer you wait to bring structure, the more painful the rework will be.

So yes, cleaning validation is essential. But mastering acceptance criteria in a multi-product environment is a discipline in its own right.

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