WHO Drug Information Vol. 18, No. 2, 2004 - World Health ...

WHO Drug Information Vol 18, No. 2, 2004
Table 2.
Temperature/Relative Humidity Absolute Humidity Kg water /Kg dry air
(*) ASEAN average
30 o C /60% RH 0.0161
25 o C /80% RH 0.0160
30 o C /65% RH 0.0174
30 o C /70% RH 0.0188
30 o C /75% RH 0.0202
40 o C /75% RH 0.0361
27.76 o C /78.79% RH 0.0186 (*)
It was also noted that the pair 40 o C/75% RH
used in accelerated studies represents a better
stress than the 25 o C/80% RH proposed for stress
testing in the ICH Q1F Guideline. On this basis,
the meeting agreed to eliminate the requirement
for stress testing if data on accelerated studies
conducted at 40 o C /75% RH are made available.
Stability and packaging materials
Stability is obviously affected to a large extent by
the permeability of primary packaging materials.
Products packed in primary containers demonstrated
to be impermeable to water vapour do not
require testing at any specific RH, storage at
constant temperature of 30 o C throughout real
time testing being sufficient. However, guidelines
will be needed to specify parameters, such as a
thickness and permeability coefficient, which
indicates demonstrated impermeability of packaging
materials.
Cost implications for
setup of new test conditions
It was noted that no significant costs are imposed
on manufacturers to set up testing conditions at
different RHs. The most practical approach would
be to fill a container up to a certain level with an
appropriate saturated salt solution that can keep
the air in container at the required RH when the
container is hermetically closed. The test samples
would then be enclosed in the container kept in a
room of constant temperature of 30 ˚C for the
entire duration of the study.
Implementation strategies
Implementation of the above decision will be
preceded by a transition period during which
existing national guidelines will still be applicable.
In addition, a science-based approach will be
taken to ensure correct evaluation when submitted
data is based on conditions that are less
stressful than those required (e.g. 30 o C/65%
RH). Factors to be taken into consideration
include:
• complementary data provided to enable proper
scientific evaluation;
• detected instability
• data obtained under accelerated conditions
• when more protective packaging is provided
• commitment to generate data under the new
guideline conditions (30 o C/75% RH, or 40 o C/
75% RH, or both) within a specified period.
A suitable label recommendation such as “Store
below 30 o C and protect from moisture” may also
be applied.
Additional inputs from member countries will be
considered during finalization and throughout the
implementation of this new ASEAN guideline. In
the light of the above there may be a need to
review the WHO and ICH guidelines.
References
Aspects of Quality Assurance
1. World Health Organization. Expert Committee on
Specifications for Pharmaceutical Preparations.
Technical Report Series, No. 863 Annex 5. (1996) on:
http://www.who.int/medicines/strategy/quality_safety/
annex5_trs863.doc
2. World Health Organization. WHO guidelines for
stability testing of pharmaceutical products containing
well-established drug substances in conventional
dosage forms. http://www.who.int/medicines/qsm and in:
WHO Drug Information, 16(1): 35, (2002), on http://
www.who.int/druginformation/vol16num1_2002/16-
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