Chemistry Reference
In-Depth Information
TABLE 11 . 3 . Summary of Critical Quality Attributes for Telaprevir
Quality
Attributes
Spray-Dried
Dispersion
Drug
Product
Potential Impact on Quality, Safety, and/or Efficacy
Identification
X
X
Ensures correct active ingredient
Appearance
X
X
Visual indicator of product quality
Assay
X
X
Ensures potency of subsequent tablet
Degradation
products
X
X
Ensure that levels of impurities do not affect assay
or safety (by exceeding the levels deemed safe in
toxicology or clinical studies)
Residual
solvents
X
Affect safety, potency, and physical stability of the
product
Water
content
X
X
Ensures that water content is not so high as to lower
chemical stability or impact physical stability
during the product's shelf life
X
a
X
a
Physical
form
Ensures that telaprevir remains amorphous and,
therefore, bioavailable
Particle size
X
Affects flowability and compactability of the
powder during tableting, which could lead to low
potency or broken tablets (efficacy). Incorrect
particle size affects downstream manufacturability
through inability to meet content uniformity, tablet
weight, and/or hardness. Particle size may impact
dissolution
Powder bulk
density
X
Affects flowability and compactability of the
powder during tableting, which could lead to low
potency or broken tablets (efficacy). Incorrect bulk
density affects downstream manufacturability
through inability to meet content uniformity, tablet
weight, hardness, and/or appearance. These
variations could have an impact on tablet
dissolution
Tablet
hardness
X
Ensures that the integrity of tablets is not
compromised
Dose
uniformity
X
Ensures dose is uniform across the batch
Dissolution
X
Impacts the rate of drug release
Microbial
limits
X
Ensures safety of the drug product
a
Physical form should be amorphous for dispersion and tablet.
and responses considered for each of the potentially critical process steps identi
ed to
affect tablet CQA of dissolution. Table 11.6 provides an overview of experiments that
either need to be performed on individual unit operations or need to be linked across
multiple operations to de
ne process design space for tablet CQA of dissolution.
SDD material attributes that could affect tablet dissolution are SDD particle size and
bulk density, as well as physical form. The SDD physical form must be amorphous in
