Hold Time study for Pharmaceutical Drug products.
This article provides information about hold time study for pharmaceutical drug products.
Hold Time study for Pharmaceutical Drug products.
What is mean by Hold time study?
Hold time study is the time limits for Holding the material at different stages of processes with ensuring the quality of the products and ensures the results are well within the limit during hold time moreover study is performed under controlled conditions.
Hold time study for a pharmaceutical product is a process to establishing the process of determining the time duration for the products which can be hold before it undergoes significant changes in quality.
The hold time study involves testing the product at different time intervals to monitor any changes in its physical, chemical, and microbiological properties. This information is then used to establish the maximum allowable hold time for the product.
The hold time study is typically performed during the development phase of a product and is an important part of the product’s quality control program. It helps ensure that the product remains stable and meets its intended specifications throughout its shelf life, which is important for ensuring patient safety and product efficacy.
Why Hold time study required in pharmaceutical industry ?
- In pharmaceutical industry there are several intermediate steps for manufacturing of Tablet and capsules, each steps requires some specific time to complete.
- Some of the time due to unavoidable situations intermediates and bulks are hold for processing. So hold time is established for intermediate and bulk products during new product introduction at site and validation studies
- Hold time studies are important in pharmaceutical industry to ensure that products remain stable and maintain there quality over the period of time.
- They also provide information about storage conditions moreover without hold time studies, it would be difficult to ensure the quality and safety of intermediate and bulk products.
What are the Factors should be consider while performing Hold time study (HTS) ?
Several factors needs to consider while performing the Hold time studies of the intermediates and bulk products out of that some major factors enlisted as below?
- Product Type : Different product types require different hold time studies. For example, a hold time study for a liquid formulation may be different from that of a tablet or a cream.
- Storage Conditions : The storage conditions for intermediate and bulk products hold time should mimic the actual storage conditions of the product, and the temperature, humidity, and light exposure should be controlled. Storage conditions may affect the results of a hold time study.
- Analytical Instruments /Methods : The analytical instruments/methods used to assess the product’s quality should be validated and suitable for the product type. Different analytical instruments may be used for different product types, such as high-performance liquid chromatography (HPLC), gas chromatography (GC), or UV-visible spectrophotometry.
- Microbial Growth : Microbial growth may be affect the quality / stability of a product. Hence, microbial testing need to include in a hold time study to ensure that the product remains free from microbial contamination over the designed hold time.
How to Determine maximum hold Time for pharmaceuticals product ?
The maximum hold time is the longest time a product can be held without compromising its quality. This time can be determined by testing samples with appropriate method at different time intervals until degradation is observed.
Summary on Hold Time Study Protocol and Report :
Generally as per WHO Guideline TRS992 Annexure 4, Generally one or more than one batches should be taken for the Hold Time study During Hold time study evaluation of material, criteria should be more stringent than registered specifications, to provide assurance that the material is available as per specified limit.
Hold time sample should be keep in the container which is simulated container which are using in commercial production including MOC and closure system. If it is not possible then it asks for justification and risk assessment if any.
Hold time study should be performed as per the written and approved protocol and procedure which should contain Activities to be performed, Test parameters, Acceptance criteria as per the material.
The protocol and Report should be made available for hold time study which should contains data as below
- Title
- Reference Number
- Version
- Date
- Objective
- Scope
- Responsibility
- Procedure
- Description of the material or product
- Sample quantities
- Sampling method and criteria;
acceptance limits - Frequency of sampling
- Sampling locations
- Pooling of samples
- Storage conditions
- Type of container
- Methods of analysis
- Results
- Conclusion
- Recommendation
- Signatures with dates.
Below is the Tabular Representation of stages, test to be carried out and study times ; but this table may be considered based on the risk assessment and specific product requirement.
For Detailed Description on hold time study can be click on below link (WHO TRS992/Annex 04) :
Frequently Asked Questions (FAQs) :
1. Is stability study need to perform for batches from which hold time study has been performed.
Yes, Long term stability study should be performed for finished batches from which hold time study has been performed.
2. How often hold time studies should be conducted?
Hold time studies should be conducted during the development or new product introduction at site and validation of a product and periodically throughout the product’s lifecycle to ensure its reproducibility and stability.
3. What happens if a product fails a hold time study?
If a product fails a hold time study, appropriate measures can be taken to improve its stability, such as Hold time can be reduced at minimum extent level or If possible product can be Reformulated.
4. What are the analytical instruments used in Quality control to test the hold time sample for chemical analysis?
Commonly used instruments for chemical analysis are as, High-performance liquid chromatography (HPLC), gas chromatography (GC), and UV-visible spectrophotometry.
5. Can microbial testing be included in hold time studies?
Yes, microbial testing may be included in hold time studies to ensure that the product remains free from microbial contamination over the designed hold time period.
6. Can hold time studies be conducted on all pharmaceutical products?
Hold time studies can be conducted on all pharmaceutical products, which may require to hold during processing.
