This is a ready-to-use log for capturing anticipated regulatory questions while a CMC filing’s process validation content, S.2.5, P.3.5, and their Quality Overall Summary counterparts, is still being drafted. It is the proactive counterpart to a review-cycle response log: the questions here are the ones raised internally, before submission, in the hope that answering them in the original text makes the after-the-fact version of this exercise shorter. Replace every <<FILL: ...>> placeholder with your own specifics. A worked filled sample row follows.
Purpose
This log tracks every question a careful internal reviewer raises about the validation narrative while <<FILL: submission, e.g. BLA 761XXX>> is still in draft, so each one is either answered in the text before submission or consciously accepted as an open point, rather than surfacing for the first time as an agency question under a review-cycle clock.
Scope
Applies to internal review of the process validation content of <<FILL: submission>>, including S.2.5, P.3.5, and the corresponding Quality Overall Summary sections, from first draft through final QA and regulatory sign-off.
Field table
| Field | Format | Required | Who records it | When |
|---|---|---|---|---|
| Log entry ID | <<FILL: format, e.g. AQ-2026-014>> | Yes | Reviewer raising the question | On raising |
| Raised by | Name/role | Yes | Reviewer raising the question | On raising |
| Date raised | Date | Yes | Reviewer raising the question | On raising |
| Section referenced | <<FILL: e.g. 3.2.S.2.5, 2.3.P.3.5>> | Yes | Reviewer raising the question | On raising |
| Anticipated question, in the reviewer’s own words | Text | Yes | Reviewer raising the question | On raising |
| Why a real reviewer might ask this | Text | Yes | Reviewer raising the question | On raising |
| Resolution | <<FILL: text edited to answer it in place / accepted as an open point with rationale / determined not applicable>> | Yes | Section author | Before QA review |
| Text location of the answer, if resolved by edit | <<FILL: section and paragraph>> | If resolved by edit | Section author | Before QA review |
| Checked against final text before submission (Yes/No) | Yes/No | Yes | Section author | Before submission |
Instructions
Run this exercise deliberately, not passively: ask each reviewer of a validation section to read it as a skeptical stranger and write down every question that reading raises, not only the ones that feel serious. The value of this log is inversely related to how comfortable it is to fill out; a log with no entries after a real adversarial read is more likely to mean the exercise was skipped than that the section was already airtight. Before submission, check every entry’s resolution against the final text, since a section can drift after the question was first answered.
Retention
Retain alongside the submission’s internal regulatory file per <<FILL: site document retention procedure>>, and cross-reference against the actual review-cycle response log after the agency’s questions arrive, since a mismatch between what was anticipated and what was actually asked is itself useful information for the next filing.
Filled sample row
| Field | Entry |
|---|---|
| Log entry ID | AQ-2026-014 |
| Raised by | <<FILL: name, Statistics Lead>> |
| Date raised | 2026-05-02 |
| Section referenced | 3.2.S.2.5, 3.2.S.4.1 |
| Anticipated question | Is the potency acceptance range in 3.2.S.4.1 derived the same way as the range referenced in 3.2.S.2.5’s PPQ conclusion, or could a reviewer read them as two independent claims? |
| Why a real reviewer might ask this | The two sections were drafted by different authors at different times and use slightly different phrasing to describe the same range |
| Resolution | Resolved by edit: added an explicit cross-reference sentence in 3.2.S.2.5 stating the range is the same one defined in 3.2.S.4.1, with no independent derivation |
| Text location of the answer | 3.2.S.2.5, final paragraph |
| Checked against final text before submission | Yes, 2026-06-20 |
Common findings this log prevents
- The exact question an internal reviewer thought of during drafting arriving later as a formal agency question, at a real cost in review-cycle time, because it was never written down or resolved.
- A question resolved during drafting that quietly stops being true after a later text revision, discovered only when the agency asks it for real.
- An adversarial internal review skipped entirely because no one was asked to do it in a structured, documented way.
How to adapt this log
- Set the submission identifier and run this exercise section by section as each is drafted, not once at the end.
- Assign at least one reviewer per section who did not author it, since an author’s own blind spots are exactly what this log exists to catch.
- Before submission, reconcile this log against the final text in one pass, confirming every “resolved by edit” entry still matches what the section actually says.