Follow
1.0 OBJECTIVE : To establish a procedure to determine holding time limits of intermediate materials/products, equipments, chemicals/reagents.
2.0 SCOPE : This procedure is applicable for all products to be manufactured at (Company Name).
3.0 RESPONSIBILITY
3.1 Production/Engineering department shall be responsible to perform the activity as per procedure.
3.2 Quality Control department shall be responsible to provide analytical support.
3.3 Quality Assurance shall be responsible for preparation of Hold time study protocol.
3.4 Quality Assurance shall be responsible for effective implementation of procedure and approval of protocol & report.
4.0 ACCOUNTABILITY
4.1 Head of QA
5.0 PRECAUTIONS
NA
6.0 PROCEDURE
6.1 The holding period for all binder solution, coating suspension, intermediate products and in-use, dirty & cleaned manufacturing equipment must be fixed based on the holding time study. So, hold time study must be done for these materials and equipment.
Hold time study of a material or equipment can be used as in determining holding time of similar materials (even different products) or similar equipment. In such cases, no hold time study will be required for these materials and equipment. But if there is any specific regulatory/customer/ in-house requirement, it will be fulfilled based on scientific judgment.
The sampling & testing frequency of intermediate products – granules, core tablet, and coated tablets will be 15 days; 30 days, 45 days, 60 days & 90 days or the frequency may be fixed based on the customer/in-house/specific requirement.
For binder solution and coating suspension, if the composition remains same but only concentration varies for different products then hold time study for one product shall be considered sufficient.
The sampling and testing frequency for coating suspension will be selected considering process lead time mentioned in the BMR. Time point shall be immediately just after
preparation (T0), maximum lead time as per BMR (T1) and additional one or two times points or the frequency based on the customer/in-house/specific requirement.
Time point for wet mass and binder solution shall be initially after preparation (T0) thereafter (T8), (T24) & (T32) hours’ time points. If there is any specific regulatory / customer/in-house requirement regarding the hold time study then that requirement shall be full filled.
However, if it is experienced that prolong holding period of binder lead to irreversible transformation like lump formation, thickening/hardening or crust formation then such observations shall be addressed in the report and holding time period shall be declared considering those factors.
6.2 During previous occasion holding time study of both moisture sensitive (e.g. Ranitidine Hydrochloride) and non sensitive (e.g. Pantoprazole, Esomeprazole, Paracetamol etc) API containing products were considered. The previous data analysis reveals that granules/blend for 30 days, core tablets for 45 days and coated tablets for 60 days can withstand the environmental condition (The environmental condition of Track-II OSD facility is; %RH: NMT 60.0% and Temperature NMT 25°C).
Again the existing data assessment reveals that the coating suspension can be used up to 24 hours since its preparation. For all products this time line will be followed accordingly.
However, if there is any specific regulatory/customer/ in-house requirement, it will be fulfilled based on scientific judgment.
6.2.1 If the holding period of intermediates/bulk tablets/coating suspension is required more than the time period specified in this SOP then further assessment/retesting to be conducted before further proceeding.
6.3 The numbering of hold time study protocol & report for products shall be assigned as per the SOP for document numbering system (QA003).
6.4 The product specific protocol shall be prepared by R&D or QA and approved by Head of Quality.
6.5 Sampling, analytical testing shall be conducted according to the product specific protocol.
6.6 Data shall be compiled and used for establishing in-process holding time limits for different stages of product manufacturer.
6.7 These limits shall be incorporated into the Batch Production Record (Manufacturing & Packing) and SOP.
6.8 QA shall ensure the compliance to these limits during routine manufacturing of products.
6.9 The hold time study for in-use, dirty and clean equipment should be considered. Based on the documented data the equipment holding time period will be established. The sampling and testing will be followed as per protocol.
6.10 Dispensed materials stored in containers similar to those in which material was supplied from the original manufacturer and under the same controlled conditions can be stored for 30 days in post dispensing area.
If the material is stored in different container other than the supplier then the storage period of materials after dispensing will not be more than 15 days in post dispensing area.
However if the API storage requirement is controlled/cold temperature then the material will be processed immediately after dispensing.
6.11 If it is necessary to conduct hold time study of different types of materials/chemical solution or reagent /s then case specific protocol to be followed for execution.
