Biomedical Engineering Reference
In-Depth Information
Table 3
Reporting, identification, and qualification thresholds of impurities in drug substance
Maximum
daily dose
Reporting
threshold
Identification threshold
Qualification threshold
2 g/day
0.05 %
0.10 % or 1.0 mg per day
intake (whichever is lower)
0.15 % or 1.0 mg per day
intake (whichever is lower)
>
2 g/day
0.03 %
0.05 %
0.05 %
inorganic impurities as well as acceptance criteria in a new drug
substance. Based on pharmacopoeial standard and available safety
data, acceptance criteria should also be established [
34
].
Analysis and control of residual solvents used in manufacturing
process should be discussed and need to follow guidance provided
in ICH Q3C Impurities: Residual Solvents [
35
].
3.3.3
Solvents
4 CMC of Drug Product (DP)
As previously mentioned in Section
2
QTPP should be considered
carefully as a part of drug product design criteria. Since these
products are intended for regulatory submission and obtaining
marketing approval, therefore, they must meet compendia (major
pharmacopeia) requirements and satisfy safety and regulatory
requirements. It is advisable to adhere to ICH Q8 (R2) guidance
since it encompasses most of the critical aspects of pharmaceutical
development [
30
]. In addition, other appropriate guidelines
related to stability, impurities, etc. should be adhered to as well
[
36
,
37
]. In general, the products are expected to have at least two
year of shelf life at room-temperature storage. For multidose oph-
thalmic products, a general guideline provided in Table
4
will
highlight CMC aspects that need to be considered in ophthalmic
formulation design. Overall, the design process involves that devel-
opment of drug product must be safe and efficacious, and that drug
products should be stable with desired pharmaceutical attributes.
Table
4
provides a list of the test parameters and rationale for
topical ophthalmic drug products.
As various topical ocular formulation options may be considered it
would be helpful to provide a brief description of each dosage form
to get a better understanding on CMC of drug products. A deci-
sion tree for formulation selection is presented in Fig.
3
.
4.1 Comparative
Assessment of Dosage
Form Options
