Process Development & Validation Summary — GLPI-103

[MOCK — deep-knowledge assumption] Process development and validation for the drug substance and both drug products, including a worked PPQ deviation and the scale-up comparability assessment.

Change History

1. Lifecycle Approach (3 stages)

• Stage 1 — Process Design: development, FMEA risk assessment, and DoE characterisation of CPPs (e.g., SPPS coupling, preparative-HPLC pooling, lyophilisation; tablet compression/enhancer ratio), defining proven acceptable ranges and the design space.
• Stage 2 — Process Qualification: facility/utility/equipment qualification (IQ/OQ/PQ) and Process Performance Qualification (PPQ) of ≥3 consecutive commercial-scale batches per process.
• Stage 3 — Continued Process Verification (CPV): ongoing statistical monitoring of CPPs/CQAs (control charts) on commercial batches.

2. Drug Substance (SPPS) — PPQ

Three consecutive 2 kg PPQ batches met all CQAs (assay 99.1–99.5%, total related substances ≤1.2%, aggregates ≤0.5%, potency in range), with CPPs within their proven acceptable ranges and consistent impurity profiles. Worked deviation (QA-003 ISS-010): PPQ batch 2 raised a transient lyophiliser shelf-loading inhomogeneity flag. Investigation concluded the batch met all CQAs (deviation not product-impacting); CAPA: a revised, qualified loading pattern and an added in-process check were implemented and folded into CPV — a worked example of a managed PPQ deviation.

3. Drug Product — PPQ

• IV (aseptic): media fills (≥3, zero growth), sterilising-filter validation (bacterial retention, extractables, compatibility), depyrogenation and container-closure-integrity qualification; PPQ batches met sterility, endotoxin, particulates, and assay. (See QA-003 ISS-007 for the bulk-hold OOS investigation and its CPP CAPA.)
• Oral: blend-uniformity, compression (hardness/friability/disintegration) and dissolution qualified; PPQ batches met content uniformity and dissolution. (See QA-003 ISS-008 for the stability OOT and the packaging CAPA.)

4. Scale-Up & Comparability (Q5E/Q12)

Comparability between the development and registration scales/sites was demonstrated by side-by-side analytical characterisation (RP-HPLC/SE-HPLC/peptide map/potency) and a stability bridge; no impact on the impurity/aggregate profile or potency was observed. Post-approval changes are governed by the defined Established Conditions (ICH Q12) with appropriate reporting categories.

5. Conclusion

The drug-substance and drug-product processes are robust, reproducible, and validated to consistently produce material meeting CQAs and specifications (M3-S/M3-P); deviations encountered during qualification were investigated and resolved with verified CAPAs (QA-003), and the validated state is maintained by CPV.