In pharmaceutical development, overages often feel uncomfortable-adding extra quantity of API (very common) or excipients beyond the label claim challenges our instinct for pure science and many of us quietly question whether this is truly fair.
We often say overages are acceptable if justified but that statement is incomplete without understanding what agencies actually expect. Regulatory agencies do not view overage as a right instead they view it as a last resort risk control.
Their expectations are clear, even if not always stated explicitly:
- Overage must be minimal and scientifically necessary
- It must be supported by real stability and degradation data, not assumptions
- It must not compensate for known formulation or process weaknesses
- It must be clinically safe across the full shelf life and importantly, it must be continuously challenged and reduced over the product lifecycle
This becomes especially critical for sensitive products, where small deviations can directly impact patient safety:
- Narrow therapeutic index drugs (high risk)
- Pediatric & geriatric medicines
- Biologics, peptides, & labile molecules
- MR
- FDC
In such cases, overage is no longer just a technical decision, it becomes a clinical and ethical one. A fair question then arises. If overage is used to manage a known weakness, how would agencies even know?
The reality is regulators may not always see a weakness directly but they detect it indirectly: through stability trends, batch variability, disproportionate overage levels, lifecycle commitments, and post-approval behavior.
Regulation may not catch intent-but it almost always catches patterns and consequences.
This is where science is expected to bridge the gap not by writing better justifications but by:
- Improving formulation robustness
- Strengthening process understanding and control
- Reducing variability rather than buffering it
- Revisiting shelf life instead of stretching it
- Treating overage as temporary technical debt, not a permanent solution
Science is respected when overage is minimal, data-driven, and progressively reduced. Science is compromised when overage becomes routine, convenient, or permanent. For me, overage sits at the intersection of science, regulation, and patient responsibility.
It should never be comfortable, It should never be a default and it should always trigger the question what must improve so this becomes unnecessary??because real scientific integrity isn’t about claiming perfection, it’s about managing uncertainty responsibly while never losing sight of the patient.
Read also: Pharmaceutical Development Report (PDR)
Resource Person: Chetan Rajak
