SOP ON HOLD TIME STUDY

This Document describes (Standard Operating procedure) SOP on procedure for carrying out Hold time study for material, accessories and equipment.

SOP ON HOLD TIME STUDY

OBJECTIVE:

To lay down the procedure for carrying out Hold time study for material, accessories and equipments.

SCOPE:

This procedure is applicable for carrying out hold time study for dispensed raw material, intermediate products, binder/coating solutions, clean equipments, dirty equipments, sieves, screens and finger bags.

RESPONSIBILITY:

Officer/Executive-QA/Production/Microbiologist/QC shall be responsible for follow the procedure as per SOP

PROCEDURE :

Hold Time Study:

• Hold time period is defined as the period for which material / product / equipment / accessories remains idle till next use or processing of next stage.
• This study shall be performed to ensure that product / accessories / equipments maintain its predefined specification within its hold time period at predefined storage condition.
• During hold time period of material / product / equipment / accessories there may be change in the physical, chemical and / or microbiological properties which may have adverse impact on product quality. So to minimize the risk, hold time period for material / product / equipment / accessories shall be assessed and established.

Hold time study shall be carried out for following:

• Dispensed material,
• Binder solution,
• Lubricated granules (ready for tablets compression / filling)
• Coating solution
• Compressed tablets
• Coated tablets
• Cleaned equipments / accessories (sieves / screens / scoops, FBD bags)
• Dirty equipments / accessories (sieves / screens / scoops, FBD bags)
• Sterilized machine parts / rubber bungs / flip off seals / garments / accessories

Product Hold Time Study:

• For product hold time study, product is processed up to the required stage as per the respective batch manufacturing record (BMR) and after that store in simulated condition at NMT 25 °C and Relative humidity NMT 55 % or as per the condition mentioned in BMR for storage of product.
• For this study protocol shall be prepared for individual products and the quantity of sample withdrawn, the period to which study will be performed, different time interval of sample withdrawal, test to be performed and its specification and acceptance criteria shall be mentioned in the protocol.
• This study is required only for intermediate products (unpacked goods) not for its finished product (packed goods).
• This study shall be carried out during process validation of the product and it shall be performed for at least one validation batches. This study can be performed on routine manufacturing batches also based on the requirement.
• Hold time study for PL (product license) holder’s product shall be carried out as per hold time study protocol agreed by PL holder.
• This study shall be carried out based on the formulation. For common formulation one time hold time study shall be applicable to all.
• Representative samples of in-process product shall be kept in simulated condition in the same container. Where the container is bigger for the proposed sample quantity the relatively smaller container shall be used.
• In case of lubricated granules the hold time study shall be carried out in the same IPCs (in process container) or HDPE drum in which it is proposed to store during routine manufacturing operation to assess the physical characteristic of lubricated granules.
• Samples for hold time study shall store at the environmental condition as mentioned in the BMR.
• Sample shall be collected as per respective protocol sent to QC laboratory for analysis along with TRF (test request form).
• After completion of hold time study, report shall be prepared based on analytical data and hold time period of product shall be recommended and implemented.

Dispensed Raw Material Hold Time Study:

• This study of dispensed raw material shall be carried out to know the impact of temperature and humidity on the storage of raw material after dispensing.
• This study will ensure that there is no adverse impact on the quality of dispensed raw material, if it is stored under specified environmental condition before it is being used for manufacturing the product.
• During the study of hold time of dispensed raw material, it shall be stored in the dispensed material storage room in manufacturing area.
• For dispensed material hold time study, raw material shall be selected which are more susceptible to microbial growth, hygroscopic and sensitive to moisture.
• Separate hold time study protocol shall be prepared for dispensed raw material and acceptance criteria of the material shall be as per its release specification.

Clean Equipment Hold Time Study:

• Clean equipment hold time study shall be done to know the maximum holding period of any equipment after cleaning.
• For the purpose of clean equipment hold time study equipment shall be kept in the clean equipment storage area and swab for microbiological analysis shall be taken as per the procedure mentioned in respective protocol.
• Selection of equipment for the purpose of study, study period, different time interval, test to be performed, its specification and acceptance criteria shall be mentioned in their respective protocol.

Dirty Equipment Hold Time Study:

• Dirty equipment hold time study shall be carried out to know the impact of storage of dirty equipment or to decide the maximum storage period up to which dirty equipment can be stored.
• For the purpose of dirty equipment hold time study equipment shall be kept in the dirty equipment storage area and swab shall be taken as per the procedure mentioned in respective protocol for chemical as well as microbiological analysis.
• Selection of equipment for the purpose of study, study period, different time interval, test to be performed, its specification and acceptance criteria shall be mentioned in their respective protocol.

Hold Time Study of Sieves, Screens, Scoops & FBD Bag:

• Hold time study of sieves, screens, scoops, FBD bag etc shall be carried out to decide the maximum storage period of sieves, screens, scoops, FBD bag etc. after cleaning.
• For the purpose hold time study of sieves, screens, scoops, FBD bag equipment shall be kept in the respective storage area and swab shall be taken from the pre-defined location as per the procedure mentioned in respective protocol.
• Selection of sieves, screens, scoops and FBD bag for the purpose of study, study period, different time interval, test to be performed, its specification and acceptance criteria shall be mentioned in their respective protocol.

Hold Time Study of Sterilized Machine Parts, Rubber Bungs, Flip Off Seals, Garments & Accessories:

• Hold time study of sterilized machine parts, rubber bungs, flip off seals, garments, accessories etc shall be carried out to decide the maximum storage period of machine parts, rubber bungs, flip off seals, accessories etc. after sterilization.
• For the purpose of hold time study of sterilized machine parts, rubber bungs, flip off seals, garments, accessories etc shall be kept in the clean area under LAF and sample/swab for microbiological analysis shall be taken as per the procedure mentioned in respective protocol.
• Selection of sterilized machine parts, rubber bungs, flip off seals, garments, accessories etc for the purpose of study, study period, different time interval, test to be performed, its specification and acceptance criteria shall be mentioned in their respective protocol.
• After completion of hold time study of product, raw material, cleaned equipment, dirty equipment, sieves, screens, scoops and FBD bag summary shall be written in the respective protocol and maximum holding period shall be decided which shall not impact our product or process adversely.
• List of maximum holding shall be prepared as per Annexure I and Annexure II and shall be displayed in respective area for reference.
• Two different lists shall be prepared one for hold time period of different intermediates of product and another for the hold time study of equipment and different material. Both list bearing a unique prototype.
• Hold time list for the different intermediates of product bearing a prototype No. HT/PROD-00

Where,

HT stands for Hold time study

PROD stands for product name

00 shall refer revision number of the list

• Hold time list for the different equipment and material bearing a prototype No. HT/MIS-00

Where,

LST stands for list

HT stands for Hold time study

MIS stands for Miscellaneous

00 shall refer revision number of the list

• If the maximum holding period shall be altered either due to change in composition or concentration of intermediates or environmental condition than the list shall be revised bearing new revision Number.

• Annexure

• ABBREVIATIONS

Annexure I

List of Product Hold Time

Document No._________________

Annexure II

List of Miscellaneous Hold Time

Document No._________________