Standard Practice of sampling, storage and Holding …

1 Drug Invention Today ISSN: 0975-7619 Short Notes 37 Corresponding Author: Huma Ali, Department of Quality Assurance, Rusan Pharma Ltd, Kandla, Gandhidham, Kutch, Gujarat 370201. India. Received 25-04-2011; Revised 14-05-2011; Accepted 20-06-2011 July, 2011 Drug Invention Today, 2011, 3(7), 157-159 157 Standard Practice of sampling, storage and Holding Time for Pharmaceutical Tablet and Injection during manufacturing process Huma Ali1*, Abdul Majid Khatri1, Ashish Jain1, Ravi Modi1, Alpesh Patel1 1 Department of Quality Assurance, Rusan Pharma Ltd, Kandla Gandhidham, Kutch, Gujarat-370201, India INTRODUCTION The time during which the product is stored in the bulk container, prior to packing into the final immediate container, constitutes part of the approved shelf life, , the date of expiry remains a function of the date of manufacture, not the date of packing.

2 Bulk products, which are stored for a period of time prior to packing into the final containers for 25% or more of the approved shelf life, should be tested, with stability indicating methods, prior to packaging. Many times, industry the material is kept on hold for subsequent processing to the next stage due to any technical problem. Although regulatory agencies expect manufacturers to document and address hold times, they do not describe a process for establishing hold time Practice of sampling, storage for pharmaceutical tablet and injection during manufacturing process. The time period for which the product is on hold shall be justified with adequate data to demonstrate the product will be stable throughout the approved shelf life.

3 In such case the manufacturer shall produce sufficient data demonstrating that the product is stable for said period of time the before processing to the next stage and it will meet the acceptance criteria for the finished product as well as stability specifications. The time during which the product is stored in the bulk container, prior to packing into the final immediate container, constitutes part of the approved shelf life, , the date of expiry remains a function of the date of manufacture, not the date of packing. Bulk products, which are stored for a period of time prior to packing into the final containers for 25% or more of the approved shelf life, should be tested, with stability indicating methods, prior to packaging.

4 Hold time study establish the time limits of Holding the materials at different stages of production by assuring that the quality of the product does not deteriorate during the hold time. Hold time study protocol in tablet manufacturing process: In Hold time study initial three batches of product shall be considered. Review the manufacturing procedure of the product and break up the critical stages of manufacturing process on the basis time duration required for the particular processing stage and the impact of time period with reference to environmental condition and storage conditions. The identification of critical stages of manufacturing process is in below flow chart.

5 The time period for which the product is on hold shall be justified with adequate data to demonstrate the product will be stable throughout the approved shelf life. In such case the manufacturer shall produce sufficient data demonstrating that the product is stable for said period of time, before processing to the next stage and it will meet the acceptance criteria for the finished product as well as stability specifications. The time during which the product is stored in the bulk container, prior to packing into the final immediate container, constitutes part of the approved shelf life, , the date of expiry remains a function of the date of manufacture, not the date of packing.

6 The conclusions from this article may lead to guidelines on sampling, storage and Holding times for Pharmaceutical Tablet and Injection during manufacturing process. Most appropriate storage and preservation protocol should be based on the specific study objectives and focus. Key words: Hold time study; Pharmaceutical tablet; Pharmaceutical injection Huma Ali, et al.: Standard Practice of sampling, storage and Holding Time for Pharmaceutical Tablet and Injection during manufacturing process July, 2011 Drug Invention Today, 2011, 158 ; Sampling points and sampling technique in tablet manufacturing process: Process stage Equipment Sampling tool Sampling points Dry Mixing Rapid mixer granulator sampling rod/ scoop 5 points from right, left and middle at top, bottom and Middle portions.

7 Drying FBD sampling rod 5 points from right, left and middle at top, bottom and Middle portions. Lubrication Cage Blender sampling rod 5 points from right, left and middle at top, bottom and Middle portions. Compression Compression Machine sampling scoop From LHS and RHS, collect sample at start, pool 1 (pooled tablet samples of 20% & 40% of total blend compressed), pool 2 (pooled tablet samples of 60% & 80% of total blend compressed) and at the end of Compression activity. Mix and make composite sample. Coating Becoater Machine sampling scoop Take 3 samples from One from left top, right middle & Center bottom portion respectively. On the basses of processing time at each individual stage and subsequent stage we can find the time interval for no s of test to be performed.

8 Stage Test To Be Carried Out As Per Specifications. Study Time Binder preparation Microbial counts Initial & 24 hours Wet granulation to Drying Microbial counts Initial, 4 hours & 8 hours Dried granules to lubrication / blending Description, Assay, Loss on drying Initial, 8 hours, 24 hours & 72 hours Lubrication / Blending to compression Description, Assay, Loss on drying, Microbial limits, Bulk Density, Particle Size Initial, 3 days, & 7 days Compression to coating Description, Hardness, Disintegration time, Assay, Loss on drying, Dissolution, Related substance & Microbial limits Initial, 14 days, 30 days, 60 days & 90 days Aqueous Coating Solution Preparation Microbial counts Initial, 12, 24, 36 & 48 hours Coating to packing Description, Hardness, Disintegration time, Assay.

9 Loss on drying, Dissolution, Related substance & Microbial limits Initial, 14 days, 30 days, 60 days & 90 days * If time duration exceeds 90 days before packing then retesting is to be perform. PRECAUTIONS AND RECOMMENDATION 1. Collect samples from different location and time interval as per processing stage and perform the test on the composite sample. 2. Store the samples under similar environmental condition as that of Manufacturing / Quarantine stage. 3. Hold Time samples stored in bags/containers should have head space in proportion to bulk stored in manufacturing/ quarantine 4. Bags / construction used for storing Hold time samples should have same Material of construction (LDPE / SS/ HDPE) as that of bags / containers used in Manufacturing / quarantine.

10 Huma Ali, et al.: Standard Practice of sampling, storage and Holding Time for Pharmaceutical Tablet and Injection during manufacturing process July, 2011 Drug Invention Today, 2011, 159 Stage Test To Be Carried Out As Per Specifications. Study Time Dispensed Material Microbial counts 3 , 5, 7, 10, 15 days WFI Description , Microbial counts, Chemical parameter Initial, 8 hours, 24 hours & 72 hours Buffer Solution Description , Microbial counts, Chemical parameter Initial, 8 hours, 24 hours & 72 hours Final solution Description, Assay, related substance Microbial counts Initial, 3 days, & 7 days Filled and sealed Ampoules Description, Assay, Related substance, Microbial counts, leak test Initial, 14 days, 30 days, 60 days & 90 days CONCLUSION The conclusions from this article may lead to guidelines on sampling, storage and Holding times for Pharmaceutical Tablet and Injection during manufacturing process.