September 10, 2021: Pharmaceutical Interview Questions and Answers

#HoldTimeStudyGuideFDA #HoldTimeStudyGuideEMA #HoldTimeStudyGuideWHO

1. Which FDA guidance or Code of Federal Regulation suggests having hold time studies of the products?

Establishing production time limits is an example of a control to prevent growth of objectionable microorganisms. Per 21 CFR 211.111, time limits for the completion of each phase of production, when appropriate, must be established and followed. For example, if a firm finds it necessary to hold a bulk topical or liquid product for several months until it is filled, the firm might establish a holding time limit to help prevent objectionable microbial buildup. Validation and control over microbial content of purified water systems used in certain topical products are also examples of such procedures (see FDA guidance, referenced below).


21 CFR 211.113: Control of microbiological contamination

21 CFR 211.165: Testing and release for distribution

21 CFR 211.111: Time limitations on production

FDA Guidance for Industry, 2011, Process Validation: General Principles and Practices

2. Which EMA guidance suggests having hold time studies of the products?

4 July 2017, EMA/CHMP/QWP/245074/2015, Committee for Human Medicinal Products (CHMP), Guideline on manufacture of the finished dosage form

As per guideline

“Depending on the nature of the process and the product (e.g. sterile products), manufacturing durations of critical steps and hold times should be stated and justified”.

“Where relevant, the maximum holding times of the bulk product or, alternatively, the maximum batch manufacturing time from start of product manufacture to completion of packaging into the final primary container for marketing should be stated, appropriately justified and supported by data in relevant parts of the dossier (e.g. challenging the maximum hold time in process validation studies or providing dedicated stability studies for the bulk storage)”.

3. Which WHO guidance suggests having hold time studies of the products?

WHO Technical Report Series No. 992, 2015, Annex 4, General guidance on hold-time studies.

As per guidance

“Normally, intermediate and bulk products should not be stored beyond the established hold time. The choice of maximum holding period should be supported by relevant data. Studies may extend beyond the chosen maximum but it is not necessary to extend testing to determine the extreme limits at which failure occurs”.

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