Most regulatory submission delays do not come from the product itself, but from the analytical validation that should support it. Six recurring mistakes in pharmaceuticals and IVD, and how to avoid them before the first assay.
A regulatory dossier is rarely rejected because of the product itself. In most cases, the delay stems from issues in the analytical validation that should support the quality, purity, potency and stability data presented to the agency.
1. A protocol born misaligned with the dossier
It all starts when validation is treated as an isolated technical step, designed before confirming which parameters the dossier requires and to which agency it will be submitted. Specificity, working range and acceptance criteria must reflect the method's intended use and the product matrix, not a generic template reused from another project. ICH Q2(R2) and Q14, finalized in late 2023 and adopted by the FDA in March 2024, reinforce exactly this: validation consistent with the method lifecycle, not a checklist applied after development has already finished.
2. Verifying is not validating
Not every analytical method requires the same level of assessment. While methods described in official compendia, such as pharmacopeias, must have their suitability demonstrated under the laboratory's conditions, internally developed methods demand a broader validation. Knowing how to distinguish these situations helps direct the necessary studies and avoid rework during preparation for the regulatory submission.
3. A working range that is too short
It is common to demonstrate linearity and accuracy only within the product's release specification, without considering the limits results may reach over the shelf life. When, during the stability study, a result exceeds the assessed range, the need arises to demonstrate the method's suitability under that condition as well. And what was a technical detail becomes a formal agency requirement.
4. The interferent nobody tested
Proving that a method is stability-indicating requires testing it against real interferents: forced degradation products, related impurities and formulation excipients. Testing only the reference standard in pure solution leaves a gap that audits and technical requirements tend to find quickly.
5. The acceptance criterion that arrived after the result
Defining the acceptance criterion after the results are already in hand, adjusting the number to fit the obtained data, is one of the most serious mistakes on this list. It compromises data integrity from the source, violates quality principles and is practically indefensible when the protocol was signed before the first assay.
6. Robustness treated as a fill-in field
Robustness should not be just another item to fill in on the validation protocol. Assessing the effect of small deliberate variations, such as mobile phase pH, temperature, column batch or operator, helps understand which changes in method conditions may affect its performance. When these variables are not properly evaluated, difficulties may arise during method transfer, laboratory routine or the investigation of unexpected results.
In in vitro diagnostics, the same mistakes under a different vocabulary
None of this is exclusive to pharmaceuticals. In in vitro diagnostic products, governed in Brazil by RDC 830/2023, the same mistakes reappear under different names: the measurement range that does not cover the clinical decision interval, the interferent study that ignores hemolysis, lipemia, bilirubin and commonly used medications, precision assessed in a single day with a single operator, and calibrator metrological traceability that is never demonstrated. The references change, with CLSI EP05, EP06, EP07 and EP17 and ISO 17511 in place of ICH, but the logic is identical: performance must be demonstrated under real conditions of use, not under the conditions in which the method works best.
What changes with the revision of RDC 166/2017
In Brazil, ANVISA submitted to Public Consultation No. 1.391/2026, opened in April and closed in June, a proposal that revokes RDC 166/2017 and internalizes the ICH Q2(R2) and Q14 guidelines, accompanied by guides for analytical procedure development and validation. The movement mirrors what has already been consolidated abroad: more traceable protocols, a lifecycle approach and greater weight on risk management. Structuring a validation now saves time by anticipating this framework, instead of redoing the work when the new resolution takes effect.
Each of these points, in isolation, looks like a technical detail. Together, they are the most common reason a submission loses months in back-and-forth with the agency.
Base Científica supports this process end to end, from protocol design to the final report, for both pharmaceuticals and in vitro diagnostic products. If your team is validating a method before a submission, talk to us before the first assay: that is where correction costs the least.