Design of stability studies

During the design of stability studies, bracketing and matrixing [10] may be used to achieve reduced testing while at the same time generating enough stability data for evaluation of shelf life. 

The design of stability studies to support submission of NDAs and MAAs are described in the ICH Guidance QIA (R2) Stability Testing of new E>mg Substances and Products (3). The sections relevant to solid dosage forms are described below. 

Drug substances used as pharmaceuticals have diverse molecular structures and are, therefore, susceptible to many and variable degradation pathways. Possible degradation pathways include hydrolysis, dehydration, isomerization and racemization, elimination, oxidation, photodegradation, and complex interactions with excipients and other drugs. It would be very useful if we could predict the chemical instability of a drug based on its molecular structure. This would help both in the design of stability studies and, at the earliest... 

During the early discovery phase, the primary function of stability studies is to determine the stability characteristics of the drug. Knowing these characteristics helps researchers select and design the most satisfactory chemical or molecular entity for the desired pharmaceutical profile and indication. The pharmaceutical profile focus on obtaining... 

Designing a stability study is based on a factorial design of experiments where a systemic procedure is used to determine the effect on the response variable of various factors and factor combinations. A linear model is used to represent the relationship between the factors and factor combinations with the response variable. Once the experimental design is established, the assays are conducted and stability data are saved to finally estimate the shelf life period. 

Microbial stability is one of the factors affecting drug product reliability. Under design and interpretation of stability studies, the Center for Drugs and Biologies... 

Veterinary Drug Availability, Basis for Selection 3 of the Dosage Form, Formulation of Veterinary Dosage Forms, Protein/Peptide Veterinary Formulations, Formulation of Vaccines, Administration Devices and Techniques, Specification Development and Stability Assessment, Bioavailability Bioequivalence Assessments, Development and Formulation of Dosage Forms, Design of Preclinical Studies... 

Design and interpretation of stability studies, 1987, in Guidelines for Submitting Documentation for the Stability of Human Drugs and Biologies, Food and Drug Administration, Rockville, MD, pp. 8-9. 

There are specific regulatory recommendations regarding the design, conduct, and use of stability studies that should be performed to support... 

A stability report must be established for internal use, registration purposes, etc., giving details of the design of the study, as well as the results and conclusions. 

---