Registration stability testing

ICH Expert Working Group, Q1A Stability Testing of New Drug Substances and Products, International Conference on Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use, 1994. 

Final methods are developed for transfer to operational quality control (QC) laboratories for the release testing of production batches. Additionally, the methods are intended to be applied during Registration Stability studies and for the release of the DP or DS validation batches during the pre-approval development stage. The analytical methods should last for the entire product lifetime therefore, the aim of final method development is to generate fast, robust, reliable, and transferable HPLC methods (preferably isocratic and at low cost). 

For APIs, the registration stability study acceptance criteria should be derived from the quality profile of the material used in preclinical and clinical studies. The acceptance criteria should be numerical limits, ranges, and other criteria for specific tests, and should include limits for individual and total impurities and degradation products. 

Table 3 Testing Frequency for Registration Stability Studies...

Rationale for bracketing and matrixing Storage conditions Container orientations Test methods Acceptance criteria Retest/expiration dating period Storage conditions for different types of protocols Clinical trial material Registration stability Annual batches Postapproval changes Special studies Test Parameters... 

The International Conference on Harmonization (ICH) has developed guidelines for stability testing of new drug substances and products [12-14], The guideline outlines the core stability data package required for Registration Applications. 

There are three types of stability testing (technical, clinical, and registration) performed during formulation development. Requirements of a stability program increases going from technical to clinical to registration. The major requirements for each of these are summarized in Table 15-7. In addition, the... 

Wooton AB. Design, installation and commissioning of photostabUity test cabinets, IBC Technical Services Ltd. Conference on Stability Testing Design and Interpretation of Data for International Registration of Pharmaceuticals, London, April 27-28,1994. 

Confirmatory studies should be conducted on both the drug substance and the final formulation as part of the formal stability studies for registration, and may be regarded as an accelerated stability test (2). It is very important that the physical state of the sample be in its manufactured and / or marketed form (i.e., final crystal form, particle size, and hydration state) during exposure. Techniques used to alter the physical state of the sample (e.g., such as grinding to reduce particle size) as recommended in some publications (7) should be avoided. 

Notification No. 698, Pharmaceutical Affairs Bureau, Japanese Ministry of Health and Welfare, Tokyo, 1980. Draft Policy to Handle Stability Data Required in Applying for Approval to Manufacture (Import) Drugs and Draft Guidelines on Methods to Perform Stability Test. Ministry of Health and Welfare The First Evaluation and Registration Division, Pharmaceutical Affairs Bureau, 1990. 

The guidelines (Notification No. 30 of the PAB in 1994) conform to the ICH guidelines on stability testing of new drug substances and new products for a registration application within the 3 arecis of the European Community (EC), Japan and the United States. The results of stability testing conducted in accordance with the tripartite stability guidelines can be used as attached data in Japan. 

Screening of New Applications for registration of orthodox medicines 4/98 Exemption from identification and cissay of imported products 10/97 Guidelines for stability testing... 

For selecting the definitive registration batches for stability testing there are minimum requirements provided by the guidelines from the agencies. The ICH and WHO requirements are the following ... 

Quality of Biotechnological Products Stability Testing of Biotechnological/Biological Products, Q5C. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use Geneva Switzerland, 1995. 

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