A lightning talk at PDA Week 2025 argued for a lean approach to analytical panels in cleaning validation. The independent framework to justify it already exists in ASTM E3106 and ICH Q9(R1) — but only if the arithmetic is documented.
Standfirst: A seven-minute lightning talk at PDA Week 2025 asked whether the analytical panels most sites inherit from legacy protocols still reflect actual risk — and whether "lean" is now defensible rather than merely convenient.
What happened
PDA Week 2025 ran from 6 to 11 April 2025 at the Palm Springs Convention Center, California, under the theme "Embracing Change: Catalysts for Disruption." On 9 April, during Lightning Session 2, Brian Bosso (Manager, Technical Services, STERIS) presented Lean Approach to Analytical Panels to Support Cleaning Validation. It was a vendor talk and should be labelled as one, but its premise is not vendor-specific: that many cleaning validation programmes run more analytical tests than their risk profile supports.
Why it matters
Cleaning validation panels accumulate by accretion. A programme inherits TOC, conductivity, pH, detergent-specific assays and an API-specific HPLC method because each was added to answer a question at a specific moment — not because a risk assessment concluded that all were necessary. Every method carries a lifecycle cost: validation, transfer, LOQ demonstration, swab and rinse recovery studies, analyst training and sample stability data, on top of the per-run analytical burden.
The independent framework for revisiting that panel is already published. ASTM E3106 (2017, revised 2022) states that analytical method selection "should be science and risk based" and that "the goal should be to use a method that is fit for use and can be justified." ASTM E3470 maps HBEL-derived toxicity against cleaning process capability (Cpu) on a Shirokizawa matrix, and ASTM E3219 standardises HBEL derivation. ICH Q9(R1) supplies the principle: effort, formality and documentation commensurate with the level of risk.
What is particularly interesting
The uncomfortable part is the direction of travel. Replacing the 1/1000th-dose and 10 ppm criteria with HBEL-based limits frequently raises the numerically permissible residue level, which makes non-specific methods — TOC, conductivity, UV-Vis, visual inspection — adequate for compounds where a specific HPLC method was historically mandated. Lean panels are therefore more often a consequence of correct HBEL work than of cost pressure.
The argument is two-sided, however. EMA's Q&A to its HBEL guideline sets conditions for visual inspection as a release method, and ASTM E3263 addresses how to qualify inspectors to meet them. Visual inspection alone is acceptable only where the risk assessment says so, where the surface is inspectable under defined viewing conditions, and where detection limits are demonstrated against the actual limit rather than assumed. A lean panel that cannot show its arithmetic is not lean — it is undocumented.
Questions for our programme
- When was your analytical panel last justified as a set, rather than method by method in isolation?
- For each residue of concern, what is the ratio between your method's LOQ and the current HBEL-derived surface limit?
- Where a specific and a non-specific method are both run for the same residue, what unique information does the specific method add?
- Does your visual inspection programme meet the EMA criteria for use as a release method, or does it only support other data?
Wider context
The ASTM cleaning standards series — E3106, E3219, E3263, E3470, G122, alongside work items on programme-level risk assessment — has progressively supplied the tools that make panel reduction defensible. The direction is consistent across regulators and standards bodies, and the burden now sits with the programme: documenting why each remaining test earns its place.
Sources
- STERIS Life Sciences, PDA Week 2025 (event page; session listing) — https://www.sterislifesciences.com/Events/2025/April/PDA-Week-2025
- PDA, PDA Week 2025 (event detail: 06–11 April 2025, Palm Springs Convention Center) — https://www.pda.org/global-event-calendar/event-detail/pda-week-2025
- Pharmaceutical Online / Institute of Validation Technology, Risk-Based Analytical Method Selection in Cleaning Validation Using ASTM International Standards — https://www.pharmaceuticalonline.com/doc/risk-based-analytical-method-selection-in-cleaning-validation-using-astm-international-standards-0001
- ASTM International, E3106 Standard Guide for Science-Based and Risk-Based Cleaning Process Development and Validation — https://store.astm.org/e3106-22.html
- EMA, Guideline on setting health-based exposure limits (HBEL) for use in risk identification — Q&A
- ICH, Q9(R1) Quality Risk Management
Validation takeaway
A lean analytical panel is defensible only when the risk assessment — HBEL toxicity versus cleaning process capability — is documented and the chosen methods' limits of quantitation are demonstrated against the resulting surface limits. Reducing tests without that arithmetic weakens the validation rather than simplifying it.
Questions worth asking in our own programme
- When was your analytical panel last justified as a set, rather than method by method in isolation?
- For each residue of concern, what is the ratio between your method's LOQ and the current HBEL-derived surface limit?
- Where a specific and a non-specific method are both run for the same residue, what unique information does the specific method add?
- Does your visual inspection programme meet the EMA criteria for use as a release method, or does it only support other data?
