Stability report, documentation

Research reports—Research reports such as stability reports, method validation and transfer reports, and pharmaceutical development reports are key documents used for NDA/MAA filings. These documents are strictly version controlled. 

I. Chemistry Documentation. Application/compendial product release requirements. Notification of change and submission of updated executed batch records. Stability testing First production batch on long-term stability reported in annual report. 

The validation protocol and report may also include copies of the product stability report or its summary as well as validation documentation on cleaning and analytical methods. 

The testing and qualification of reference standards should continue such that the necessary documentation (internal and external reports, certificates of analysis, stability reports, supporting raw data) is complete from both a regulatory and scientific standpoint at the time of the NDA filing. 

Test attributes procedures and acceptance criteria selection of batches testing frequency storage containers, conditions, and period, as well as data evaluation are discussed in great detail. Data evaluation considers out-of-specification results. Documentation covers protocols and protocol amendments, deviation reports, out-of-specification reports, test results and raw data, and stability reports. 

INTRODUCTION OPERATIONAL ISSUES A. Introduction Protocols Documentation Schedules Stability Reports Audits and Inspections... 

The protocol is the written document that describes the studies to be conducted. The information contained in the protocol will be used to complete the stability report at the end of the study. The information to be included in the protocol is... 

The culmination of the conduction of the stability plan design in the protocol and the data generated from the stability studies is the stability report. This may be a formal document or a similar presentation of the study plan and results in a regulatory submission. The report presents the data evaluation and the conclusions of expiration date and storage requirements. 

A stability report is written to document expiration dates and a storage statement for the registration batches for the formal stability studies. It is also used to document the expiration date for formulations that are being used in the clinic. In this case, the expiration date is generally a date when the product should be discontinued or that additional data are required to extend the expiration date. A more detailed discussion of the information included in the stability report is given in Section lI.E. 

Many companies have developed the practice of composing what is termed the transfer file as a means of ensuring that all key documents and relevant information are imparted to operations or the receiving laboratory. This file is merely a collection of important reports. For analytical methods, such documents include the method development and validation reports, impurity profiling report, stability reports and tables, and specification archive. The power of such an approach is that it ensures that all information is conveyed to the receiving laboratory. This strategy is useful if operations will be relied on to continue the development process. Examples include development for... 

The U.S. Application Summary, EU Expert Report, stability reports, and drug product specifications will frequently define the time-critical path for NDA filing. These documents may be prototyped based on data from clinical batches and available data from registration batches. They cannot be finalized until the last stability data points are reported. 

The stability data generated from the stability study, the data analysis, interpretations, and conclusions are reported at the end of the study. The stability report contents are an important component in any regulatory submission and the report is one of the documents reviewed in most audits and/or inspections. Figure 13.9 shows sections that contribute to a stability report. 

The stability portion of the Chemistry and Manufacturing Controls (CMC) dossier contains the sections from the stability report described above. The requirements for the CMC sections can be found in 21 CFR Part 312 for IND application and Part 314 for NDA and Abbreviated New Drug Application (ANDA). Tables 13.1 and 13.2 provide the requirements for the CMC, and the location of the stability related documents within the CMC are highlighted in Table 13.2. 

In contrast to arylboronic acids, early reports document the great stability of alkyl-boronic acids under aqueous acidic solutions. For example, various simple alkyl-boronic adds were unaffected by prolonged heating in 40% aqueous HBr or HI [40]. Like arylboronic acids, however, deboronation is observed in hot basic aqueous solutions [76]. Alkenylboronic esters undergo protonolysis in refluxing AcOH [85], and alkynylboronic acids were reported to be quite unstable in basic aqueous solutions (Section 1.3.5). 

In instances where the stability constants documented in the source publications are dependent on the spectroscopic properties of the evaluated species in solution they are presented here as observed stability constants (itobs) to denote apparent values. Where the stability of the complexes formed was reported in the form of dissociation constants or logarithmically, the values have been converted to (observed) stability constants (K or Alobs) within this book to provide consistent and comparable results. To avoid the introduction of mathematical errors through rounding, the values are reported to two significant figures (where appropriate) to match the general level of accuracy found for these values within the scientific literature. 

In 1963, a detailed report on the various technical aspects of sodium sulfosuccinate monoesters was given [11] physical properties, stability, surface tension, and detergency. Mildness to skin and eyes are documented for the first time in this paper. 

By comparison with the measured data presented above, it can be seen that the local PECs are generally below, or in the order of, the maximum values measured in the aquatic environment. By way of exception, the values reported for methyltins, and in particular dimeth-yltin dichloride, from stabilizer production using the Technical Guidance Document (CEC, 2003) equations are significantly higher than the maximum measured values reported in the environment. 

Part ICl contains an expert report on the chemical, pharmaceutical, and biological documentation. Topics presented include composition, method of preparation, control of starting materials, control tests on intermediate products, control tests on hnished product, stability, and information on the pharmaceutical expert. An example is given in Exhibit 8.5. 

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