When a Method Changes: Bridging Studies and What the Old Data Is Still Worth

The column is discontinued. The instrument is replaced. The supplier moves to a different analytical principle. In each case the new numbers start arriving and look much like the old ones — and the question of whether they can be compared to the old ones goes unasked, because nothing about the output announces that anything changed.

Quick answer

What is a bridging study? Work done to demonstrate that a revised or new analytical procedure remains fit for the intended purpose, and that results from it can be related to results from the procedure it replaced. ICH Q14 states that the outcome of a risk assessment informs the design and extent of the studies needed to support a change, including a bridging strategy to demonstrate that the revised or new procedure remains fit for the intended purpose.

How much work that takes is graded by how large the change was.

The three grades of change

The grading is proportionate rather than bureaucratic. Changing the physical basis of the measurement is a new measurement; changing a column within the same separation is a modification; moving buildings is neither, but is still not nothing. Transfer specifically is covered in method transfer.

The phrase that does the most work

In the top row, notice what is being asked for alongside the numbers: demonstration that the analytical procedure's ability to discriminate between acceptable and non-acceptable results remains comparable.

That is a different and better question than “do the two methods give the same number?”. Two methods can disagree consistently and still sort materials identically into pass and fail — in which case the disagreement is a known offset rather than a problem. Conversely two methods can agree closely on average while disagreeing about exactly the borderline cases that matter.

How much evidence: knowledge against risk

ICH Q14 relates the extent of study required to two variables — how much is understood about the procedure, and how risky the change is. Where knowledge is high and risk low, prior knowledge or a confirmatory study according to a study plan derived from prior knowledge may suffice. Where knowledge is low and risk high, an in-depth study according to a study plan is expected.

The guideline summarises the principle directly: when considering a bridging strategy, a greater understanding of the analytical procedure can enable a reduced study design, whereas a higher risk change may need a more in-depth study.

This is the return on the development effort described in the analytical control strategy. Understanding a method is not an aesthetic preference — it is what makes future changes cheap.

What keeps the before and after connected

ICH Q14 names the two things that hold a method's meaning constant across a change: adherence to the ATP and an analytical procedure control strategy ensures that the analytical procedure remains fit for the intended purpose after changes.

The analytical target profile matters here precisely because it was written before the method existed. It is the one statement in the file that is not about the current method, which means it survives the method being replaced. Without it, “is the new method acceptable?” has no stable referent — the subject is covered in the analytical target profile.

The guideline also notes the reverse direction: major changes in performance characteristics or additional information on quality attributes could lead to reevaluation of the ATP and/or a new procedure. Requirements can be revised too — deliberately, and on the record.

What this means for your own records

Few research buyers change analytical methods often. But the same logic governs the changes that do happen, and the practical steps are modest.

• Overlap the two methods. Measure the same samples both ways before retiring the old one. Comparative analysis of representative samples is the guideline's own instrument and the only one that works retrospectively — once the old method is gone, the bridge cannot be built.
• Record the change date in the results file, not in a separate note. A dataset with an undocumented discontinuity in it is worse than two separate datasets.
• Expect an offset and quantify it rather than hoping for agreement. A documented 6% difference is usable; an unexamined one corrupts every comparison that straddles it.
• Check discrimination, not just agreement. If your measurements exist to tell acceptable material from unacceptable, that is the capability to confirm.
• Treat a reference change as a method change. Switching the material you calibrate against alters every subsequent number, even with the procedure untouched — see reference standards.

Key takeaways

• ICH Q14 grades method changes into change of principle, change within a principle, and transfer, with different evidence expected for each.
• A change of measurement principle requires full validation of the new procedure plus comparative analysis against the old.
• A change within the same principle requires revalidation only of the characteristics the change affects.
• Beyond numerical agreement, the guideline asks whether the ability to discriminate acceptable from non-acceptable results remains comparable.
• Greater procedure understanding permits a reduced bridging study; higher risk demands a deeper one.
• Adherence to the analytical target profile and the control strategy is what keeps a procedure fit for purpose across a change.
• Comparative measurement must be done before the old method is retired — a bridge cannot be built backwards.

Frequently asked questions

Does changing a column count as a method change?

It is a change within the same analytical procedure principle — the middle row. The expectation is revalidation of the characteristics the change could plausibly affect, which for a separation usually means specificity and precision rather than everything.

My supplier changed their method. Is my old data worthless?

No, but it is now a separate dataset unless a bridge exists. Comparisons within each period remain valid; comparisons straddling the change need either an established offset or an acknowledgement that they are approximate.

What is a confirmatory study?

A limited study run to a plan derived from prior knowledge, confirming that an expected result holds — as opposed to an in-depth study that investigates an outcome not already well predicted. The guideline distinguishes the two by how much is known in advance.

Is this the same as lot-to-lot bridging?

No. Lot-to-lot bridging connects two materials measured by one method. This connects two methods measuring one material. Both are called bridging, and keeping them distinct in your records prevents a method change being recorded as a material change.

How long should I run both methods in parallel?

Long enough to cover the ordinary variation of each — which in practice means more than one day and more than one preparation, for the reasons set out in precision. A single side-by-side comparison measures one occasion, not two methods.

Sources

• International Council for Harmonisation. ICH Harmonised Guideline Q14: Analytical Procedure Development. Final version adopted 1 November 2023. ICH guideline
• International Council for Harmonisation. ICH Harmonised Guideline Q2(R2): Validation of Analytical Procedures. Final version adopted 1 November 2023. ICH guideline

Guideline text is quoted from the adopted ICH documents.

This article describes analytical methodology only. It contains no usage instructions, no dosing information and no protocols of any kind.

For laboratory and in-vitro research use only. Not for human or veterinary use.