Biomedical Engineering Reference
In-Depth Information
Table 7
USP criteria of particulates in topical ocular solutions
Particulates (for solution)
NMT 50 particles/mL
10
μ
m
NMT 5 particles/mL
25
μ
m
μ
NMT 2 particles/mL
50
m
For ophthalmic solutions, emulsions and ointment particulate test
are required. Particulate test can be done by light obscuration or
microscopic method. According to USP
Particulate Test
, an ophthalmic
solution product must meet the following specification (
see
Table
7
).
It is noteworthy that the particulate specification for ophthal-
mic solutions can be considered more stringent than LVP depend-
ing on the fill size of LVP. For ophthalmic ointments, 21 CFR Part
211.167 (b) [
46
] specifically mentioned that there must be proper
control of foreign matter.
789
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>
The recommended release specification is 95-105 % of label claim
or even tighter, if possible. The shelf life specification for all regu-
latory jurisdictions should not be wider than 90-110 % of label
claim at proposed storage condition in final package. Accelerated
stability study with formulations should be carried out to justify
storage condition and estimate shelf life for IND/CTA filing. Real-
time data at proposed storage condition and three or more primary
stability batches would be required to ascertain shelf life for sub-
mission in NDA/MAA [
30
,
31
,
36
].
Active Assay
Most of the time drug product contains various impurities that
are associated with DS. It also contains impurities arising from
degradation of drug products during manufacturing and storage.
A clear understanding on the nature of these impurities is essential
and ICH guidelines, provided in Table
8
, should be followed [
47
].
Impurities
Multidose ophthalmic preparations must contain antimicrobial
agents unless one of the following conditions exists: (1) the product
consists of a radionuclide with a half-life of
Preservative Assay
24 h, (2) the active
ingredient(s) is antimicrobial, and (3) vehicle allows adequate
preservation. Therefore, preservative content is critical for multi-
dose presentation to assure patient safety.
Preservative requirement as set forth in Ph. Eur. (chapter 5.1.3)
is most difficult to meet. Although it is desirable to meet Ph. Eur.
A requirement, formulations meeting Ph. Eur. B criteria are also
acceptable by European agencies as long as appropriate scientific
justifications are provided.
Antimicrobial preservative effectiveness is usually determined
using an organism challenge test according to the methods
described in the United States Pharmacopeia 36 (USP) for category
1 products. Samples are inoculated with known levels of one or
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