Issue: film-coated tablets packed in blisters: out of specification for hydrolysis products after 9 and 12 months stability storage for the early registration batches.

Cause: residual moisture in the early batches

Cost: several Quality Control laboratory investigations; unnecessary further development in R&D lab; delayed regulatory approval and launch of product.

Issue: tablet water content outside pharmacopoeia specification by Karl-Fischer.

Cause: tablets rapidly absorbing moisture during production and whilst awaiting testing.

Cost: repeated analysis and investigation of out of specification results; further investigation into production; batches withheld from the market

Issue: active ingredient failing content assay.

Cause: absorption of moisture by a sample awaiting assay.

Cost: repeated analysis and investigation of out of specification results;
batches withheld from the market

Issue: tablets on stability for 18 and 24 months showing physical/chemical problems. Stability samples found to have increased ERH compared to newly manufactured batches.

Cause: significant ingress of moisture leading to a higher ERH and in this case actual moisture release from the tablets.

Cost: internal investigations into stability results; possible implications for the approved shelf-life of the product; external specialist resource for testing and reporting; delay in manufacture until cause of problem resolved.

Issue: tablets made from salt of an active ingredient giving very high
assay results.

Cause: salt moiety caused moisture uptake in the tablets adding significantly to the tablet weight. Relequa® ERH measurement showed that the tablets had taken up moisture, but this free-moisture was lost in the powdered tablet granule.

Cost: laboratory investigations; further development to explain the differences between new batches and validation samples held for testing; external specialist to investigate and arrive at a solution; delayed regulatory approval and
launch of product.

Issue: product in hard-gelatin capsules: showing rapid release of moisture after short time on stability demonstrated by Relequa® ERH profiling.

Cause: packaging not providing a sufficient barrier to moisture. Sensitivity of the Relequa ERH measurement picked this up very early in the stability trial.

Cost: laboratory investigations; further stability testing required; time added to development programme.