Hold Time Study

INTRODUCTION

• Hold Time studies establish the time limits for holding the materials at different stages of production to ensure that the quality of the product does not degrade significantly during the hold time at a required temperature and Relative Humidity. When appropriate, time limits for the completion of each phase of production shall be established to assure the quality of the drug product.
• Hold time study is stability establishment tool for each and every stage in the drug product manufacturing. In the drug product development, hold time stability is an important tool for establishing the in-process hold time. Hold time stability results should meet the product specifications. Hold time study shall be carried out with the storage container packing’s only. If the dosage form is stored in bulk containers for over 30 days, real-time stability data under specified conditions should be generated to demonstrate comparable stability to the dosage form in the marketed package.
• Generally, one lot can be used for validating hold times if any inconsistency results were observed then another two lots can be used for this study.

Hold time study provides the re-assurance of the quality at each in-process stages.

Hold Time Stability Study Flow in the Pharmaceutical Industry:

Hold time studies are performing during the product development, i.e scale up stage and commercial validation stages. Before starting the hold study, formulation scientist needs to select the critical stages (where the study is required), time points and tests. The flow of hold study has represented in the (Figure 1). In the pharmaceutical industry the hold study can be carried with the following steps.

i. Selection of critical steps

ii. Hold study time points and tests

iii. Hold study protocol

iv. Hold study analysis

v. Hold study report and

vi. Hold study results evaluation.

Hold Study Required Stages:

The selection of hold time stability study conditions is very important for starting the hold study. These conditions are same with the manufacturing area/hold area conditions, so these conditions are may vary with the product to product. Based on the manufacturing process of the dosage forms hold study stages can be decided. Hold study required stages are summarised in the table 1 . All pharmaceutical dosage forms hold study stages and study time requirements are discussed in detail like tablets, capsules, liquids, semi solids and injections.

STAGES, STUDY TIMES AND TESTS TO BE CONSIDERED:

Recommendations and Conclusion:

Hold study evaluation plays a main role for manufacturing the new products in GMP conditions. Based on the hold time study establishment and shelf life product manufacturing plan can be decided. If not performed the hold study in the product development stage then in commercial level need to perform the hold study for first three commercial batches . The conclusion should state whether the outcome of the activity was successful or not.

REVALIDATION:

The hold time study shall be performed again in case of any major change in product specification.