Testing
of Solid Oral Dosage Form
Drugs
Containing Iron
To
meet the requirements of the iron regulations, manufacturers and packagers must
determine an appropriate expiration date for the drug products in unit-dose
packages. Accelerated stability testing may be impractical because drug
products containing iron, especially multivitamin products, often do not
perform well under the artificially stressful conditions of accelerated studies.
As a result, real-time stability testing may be the only method to determine an
appropriate expiration date. However, the final iron regulations were published
only six months before they were to take effect; therefore, there may be
insufficient time for some manufacturers of solid oral drug products containing
30 mg or more of iron per dosage unit to perform real-time stability testing on
their products. To minimize the burden faced by those manufacturers who have
made good faith efforts to comply with the stability testing requirements but
were unable to do so, the FDA advises that, for a limited period of time, it
does not intend to object if a manufacturer or packager fails to comply with §§
211.137 and 211.166 under the following circumstances:
A. The firm sets an expiration
date for tablets and capsule drug products packaged in
unit-dose packaging based on the
following: (1) the expiration period does not exceed 75
percent of the expiration dating
period of the smallest version (usually the least stable) of
the previously accepted product
package and (2) the expiration period for the unit-dose
container does not exceed 18
months.
B. The firm maintains appropriate
stability data that support the expiration dating
period used on the smallest
version of the previously accepted product package.
C. The solid oral dosage form
product put into unit-dose packaging is manufactured
and formulated in the same manner
as the product put into the previously accepted
packaging.
D. The unit-dose packaging
complies with either the Class A or Class B standard
described in USP 23, under
"Single Unit Containers and Unit-Dose Containers for
Capsules and Tablets."
E. The firm monitors the
long-term stability of each marketed lot of the unit-dose
products throughout the
expiration dating period for all appropriate specifications,
including the strength of active
ingredients, by testing each lot at least once every three
months. The firm performs the
initial (time-zero) testing on a sample that has been
packaged in unit-dose packaging
for the purpose of evaluating the effect of heat sealing on
the product. Once data to support
the expiration dating period of up to 18 months have
been generated using appropriate
stability testing on at least three lots, the firm may
discontinue testing every
marketed lot in unit-dose packaging. Expiration dating periods
of longer than 18 months on
unit-dose packaging may be used once appropriate stability
data have been obtained that
fully support the expiration dating period prior to marketing
the lots.
F. If any of the testing,
examinations, or investigations performed by the firm reveal
that a product may not meet
appropriate specifications prior to the expiration date
assigned to the product, the firm
will reevaluate the expiration dating period for the
product. If, based on the
reevaluation, the firm determines that a shortened expiration
dating period is appropriate, it
will use the shortened period for subsequent marketed lots
of the same product.
G. The firm conducts a prompt
recall of any lot that falls outside of appropriate
specifications.
Comments
Post a Comment