14th ICDRA -Singapore
2 December 2010
Workshop I
Implementation of Medicines Stability
Testing Requirements:
Globally and Locally, Worldwide and in the
Various Regional Contexts
Justina A. Molzon, M.S. Pharm., J.D.
Associate Director for International Programs
Center for Drug Evaluation and Research/USFDA
1
Introductory Comments
✦
Stability of finished pharmaceutical
products depends on:
Environmental factors -- ambient
temperature, humidity and light
✦ Product-related factors -- chemical and
physical properties of the active substance,
excipients, dosage form, manufacturing
process, container closure system and
packaging materials
✦
Shelf-life
Shelf-life should be established for climatic
conditions of marketplace
✦ Recommended storage conditions should
guarantee the quality, safety, and efficacy
of the product for the designated shelf-life
✦ It is important that the expiry date and
storage conditions are indicated on the
label
✦
Climatic Zones/Wolfgang Grimm
✦ Cool
Summer, Subarctic, Ice
Zone I
✦ Semiarid, Mediterranean, Marine W
Coast, Humid Subtropical, Tundra,
Highlands
Zone II
✦ Arid
Zone III
✦ Tropical Dry
Zone IVa
✦ Tropical Wet
Zone IVb
Goal of Harmonized Stability
Testing Conditions
Efforts regionally and interregionally to
harmonize stability testing conditions
✦ Biggest Challenge = hot and humid
✦ Generated much debate as to proper
temperature and humidity to predict drug
product quality
✦
ASEAN
Association of Southeast Asian Nations
Brunei Daruss.
Cambodia
Indonesia
Laos
Malaysia
Myanmar
The Philippines
Singapore
Thailand
Viet Nam
WHO Expert Committee
40th WHO Expert Committee on
Specifications for Pharmaceutical
Preparations—October 2005
✦ Experts recommended that WHO stability
guidelines be amended to reflect
conditions for ZONE IV:
✦
Zone IVa—30 ° C/65%Relative Humidity
✦ Zone IVb—30 ° C/75%Relative Humidity
✦
Zone Designation
✦
The Expert Committee agreed that each
individual Member State within the Former
Zone IV would need to indicate which of
these conditions (Zone IVa or IVb) would
be applicable in its territory
Workshop G: 12th WHO-ICDRA (Seoul, Korea)
Stability: Global Challenges for Harmonization
Wednesday, April 5, 2006
Recommendations
Recommendations
1. Member States should identify their stability
testing conditions in order to facilitate import to
and export from their country. Ideally these
should be based on conditions currently in use,
thus avoiding the creation of hurdles to access
to medicines
2.
Member states should make available to WHO
information regarding stability conditions to be
used within their markets.
Recommendations
3. WHO should make available Member States’
information in order to facilitate its accessibility by
manufactures and any interested party on an
international basis.
4. WHO should observe the situation and any future
developments and continue it’s efforts to find
harmonized conditions, in light of any major
changes to the current situation in the various
regions.
Recommendations
5. Any international mechanism or
organization which develops guidance
relevant for countries outside their own
regions should ensure that those countries
are made aware of these developments
and are directly approached to take part in
the consultation process. For the ICH, the
Global Cooperation Group should be
stressed as a way to work with regional
harmonization initiatives.
ICH Q1F Withdrawn
Q1F-Stability Package for Registration—
Application for Climatic Zones III and IV
✦ The ICH Steering Committee endorsed the
withdrawal of Q1F at it’s meetings in
Yokohama –June of 2006
✦ FDA withdrew Q1F and removed from its
guidance page on July 5, 2006
✦
The WHO Expert Committee on Specifications for
Pharmaceutical Preparations
October 16-20, 2006
✦
Concern was expressed by some manufacturers
on the number of storage conditions within the
various stability guidelines
In addition, there was lack of information from some
regions and countries on stability requirements
The Committee further noted the Stability Testing of
✦
✦
Active Substances and Pharmaceutical Products
guideline from the WHO Eastern Mediterranean Region
✦ It was suggested that this document could then be
used as a basis for a revision of the global WHO
guidelines on stability testing with the intention to
include a comprehensive listing of member states and
their stability testing conditions
WHO Global Consultation
✦
✦
✦
EMRO guidelines were developed during the
WHO/EMRO Consultation on Regional Guidelines
on Stability Studies of Medicines and Biologicals,
Jeddah
The final draft was adopted by the EMR Regional
Committee 25-28 February 2006
Discussion at WHO Expert Committee on
Specifications for Pharmaceutical Preparations on
adoption of EMRO guidelines to serve as global
guidelines 16-20 October 2006
WHO Global Consultation
✦
✦
✦
Correspondence with major regional
harmonization groups requesting conditions in
their regions/countries Nov. 2006 - Jan. 2007
Memorandum to WHO Regional Advisers
requesting information on conditions for long-term
stability conditions February 2007
Preparation of new draft to serve as global
guidelines, taking into consideration comments
received from mailing of document QAS/06.179
and from the Expert Committee meeting in
October 2006 February-March 2007
43rd WHO Expert Committee on Specifications for
Pharmaceutical Preparations, 13-17 October 2008
✦ Concept
of classification of
countries according to climatic
zones abandoned
✦ Member States requirements
updated as new information is
received
43rd WHO Expert Committee on Specifications for
Pharmaceutical Preparations, 13-17 October 2008
✦
Adopted Stability testing of Active
Pharmaceutical Ingredients and
Pharmaceutical Products to replace
previous guidance
✦ Included a List of WHO Member States
required long-term stability conditions as
per information received from NMRAs
✦ Concept of classification of countries
according to climatic zones abandoned
Result
Updated WHO Guideline adopted with an
attachment detailing WHO Member
States stability requirements
✦ Good collaboration and harmonization
between ICH, Regional Harmonization
Initiatives, national and regional authorities
and WHO
✦
Final Thoughts
Working together will resolve differences
✦ Regulators from countries in Zone IV should
be included in the discussion and decision
process
✦ Ultimate goal--Increased harmonization will
lead to more efficient regulatory systems and
increased availability of safe, effective and
quality pharmaceuticals on a global level
✦
Thank you for your
attention