Hold time study in pharmaceutical manufacturing

Hold time study in pharmaceutical manufacturing.

What is hold time study?

Good manufacturing guidelines for pharmaceutical manufacturing mentions that a pharmaceutical manufacturing unit must follow time limitations for stages of manufacturing. US FDA guidelines have not provided a particular time as standard for hold time.

Definition of hold time:

It is a time period for which a particular batch of product or its intermediate or the dispensed raw material can be held at the particular stage without affecting the quality of product, without affecting the stability and purity and quality of the final product.

It is the time of storage of the raw material or bulk product until the start of processing for the next stage, here the next stage for dispensed martial will be manufacturing, and for bulk it will be filling and packing.

Why is the hold time study conducted for the pharmaceutical manufacturing process?

During the hold time process the samples of the product are drawn from the hold containers and testing for the content assay and purity is done, along with microbiological load of the product is also evaluated. And until which time these testing results are found within the acceptable limits that period is assigned as the hold time for the particular stage.

During the study it is observed that the product can be held in the given storage condition in given storage vessels without affecting the quality of product.

Some products assay and other parameters do not support holding for longer time such products will be the outcome of the hold time study, which will set alarm for lower time for holding the product.

How to do hold time study?

A protocol is prepared by quality assurance for conducting hold time study, for dispensed material hold time, bulk product hold time in manufacturing vessels, and bulk product hold time in storage vessels.

The storage vessels which will be used for holding the product are mentioned with its equipment ID and capacity, status of cleanness, etc.

How to store the bulk product, at what storage conditions of temperature and humidity are provided in protocol for hold time study. Also the intermittent sampling frequency and method of sampling of bulk for testing is also provided. After the testing is completed, evaluation for best fit hold time is arrived, based on risk assessment and availability of storage vessels.

A time period by which a product can be held at particular stages is defined as hold time for the particular product for a particular stage, this becomes added assurance for the product in event there is any situation that product is required to be held for any issues, or during vacations. This serves the purpose of addressing the good manufacturing guidelines for pharmaceutical manufacturing.

Hold time for equipment:

During cleaning validation hold time for cleaned and uncleaned equipment is done,

Here are the details provided for hold time for equipment, why it is done and how to do it.

Source: https://www.who.int/publications/m/item/trs992-annex4