Reserve sample maintenanace


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The file contains an idea about the Reserve sample maintenance , regulatory requirements & aspect of Reserve samples.

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Reserve sample maintenanace

  2. 2. Reserve sample  Definition : Reserve samples are the representative samples of each Lot or batch of APIs, Excipients, Packaging material, Intermediates and finished products which are kept for purpose of future reference.  Also called Retention samples or control samples.
  3. 3. Purpose  Potential future evaluation of Quality of Batches.  Serves as a record of finished product or starting material that can be assessed in the event of - Quality complaint -a query relating to compliance with the market authorization. - a labeling/packaging query or a pharmacovigilance report.
  4. 4. Reference Documents  US: FDA  21 CFR.170 Reserve samples  21 CFR.180(e) Records & Reports, General Requirements.
  5. 5. Reference Documents  ICH  Guideline Q7A GMP for Active Pharmaceutical Ingredients 11.7 Reserve/Retention Samples  EU: EC  EU Guideline to GMP (Medicinal Products for Human and Veterinary Use) Annexure 19 – Reference & Retention samples.  Chapter 6 : Quality Control – Sampling 6.12 and 6.14  Chapter 1: Quality Management – Quality Control 1.4 (VIII).
  6. 6. Reference Documents  WHO :  WHO Technical report Series ,No. 863 –Thirty fourth Report. Sufficient samples of each batch of Pharmaceutical Products used in studies, together with the record of their analysis & characteristics must be kept for reference purposes under appropriate storage conditions as specified in national regulations.
  7. 7. Reference Documents  Canadian GMP Guidelines -2009 edition, version 02, GUI-0001, Samples C.02.025 & C.02.026
  8. 8. General Requirements  Reserve samples should be of at least twice the quantity necessary to perform all the required tests except for Sterility, Pyrogen test & Bacterial Endotoxin test.  Reference batch of each batch of the following must be kept at the site at which they were used :  Starting material  Intermediate Product  Primary & Printed Packaging material.
  9. 9. General Requirements  Access to these samples limited to authorized people.  Reserve samples to be stored in the same intermediate container closure system in which the item or drug product is marketed or in which having essentially the same characteristics.  Quantity to be kept as per the Specification.
  10. 10. General Requirements  Any withdrawal of retention samples to be documented & approved by QA.  Must be stored in a secure area under specified storage conditions of the material or Finish product.  Storage condition to be monitored & any deviation from the specified condition must be documented, investigated & assess impact for each retention sample.
  11. 11. General Requirements  Records of Traceability of samples to be maintained & be available for review by competent authorities.  No need to retain the reserve samples of Rejected samples or volatile solvents/gases/water used in manufacturing process or hazardous materials (acid, alkalies etc.) , flavors, liquid raw materials & excipients.
  12. 12. Drug Product(Formulation)  Reserve sample to be collected as per quantity specified in the individual specification in a manner so as to cover the entire packing of the batch.  Reserve samples to be kept in terms of number of units in the blister/ strip pack in case of tablet/capsules. E.g. if 24 tablets are required as reserve sample & each strip containing 10 tablets then 3 strips shall be retained as reserve sample.
  13. 13. Drug Product(Formulation)  If Finish product re-packed with same container closure system with same/different art work then only one unit pack to be retained as reserve sample.  If product re-packed with the same container closure system having same art work but requires different overprinting details, only one unit pack to be sampled as reserve sample.
  14. 14. Drug Product(Formulation)  If product re-packed with different container closure system, twice the quantity to be retained as required for all tests.  If product re-packed with same container closure system but with different pack size, twice the sample quantity to be retained as required for all tests.
  15. 15. Drug Product(Formulation)  If product re-packed in a same container closure system with the same artwork but analyzed again for additional tests then twice the quantity to be retained for the test required only.
  16. 16. APIs & Excipients  Reserve sample to be collected from the composite sample prepared from each batch.  For Sterile Sodium chloride solution received as raw materials, reserve sample to be retained as per procedure.  Samples to be stored in self-sealing polythene bags in a fiberboard container.
  17. 17. APIs & Excipients  Sample container must assure APIs and Excipients are protected throughout the retention period.  Light sensitive samples to be stored in black colored polythene bags.  No need to keep the reserve sample for a code to code transfer if testing is not required for the same. If testing required as per new code , keep single quantity for API & twice the quantity for Excipients sufficient to perform the required test analysis.
  18. 18. APIs & Excipients  If only identification test or test required only small qty then no need to keep the reserve sample for the same.  No need to keep the pre-shipment samples (Purchase samples) received from Vendor for Vendor approval.
  19. 19. Packaging Material  In case of Printed/Primary packaging material, one sample to be kept as reserve sample attached to report. If not possible then to be maintained in a dedicated place in reserve sample room with the proper labeling under appropriate storage conditions.  No need to keep the sample of Corrugated box.
  20. 20. Packaging Material  One multi-up sheet to be collected as reserve sample for consignments received with Multi-up sheets.  For those without multi-up sheets, at least one sample from each up to be collected as reserve sample.  In case of STM/Reanalysis & code transfer GRN, one checked sample to be stored as reserve sample.
  21. 21. Storage Requirements  Appropriate storage conditions in suitable area.  Sufficient capacity to allow orderly storage of various categories of materials & products.  Proper labeling with at least following details : o Product Name o Batch Number o Manufacturing/Expiry Details o Storage conditions o Direction for Use & Warning & Precautions if any o Manufacturer’s Details & Address.
  22. 22. Storage Requirements  Temperature & Humidity of the Reserve sample Storage Area to be monitored either with automated system or manually at least once a day with max. & min. value.  Calculate Mean Kinetic Temperature of Storage area once a year using 12 month data of Temperature records (USP <1150>). MKT should be within the storage condition of reserve sample.
  23. 23. Mean Kinetic Temperature  Mean Kinetic Temperature – a useful tool to determine the degradation of the drug substance/product.  A single calculated temperature which degrades the same amount of the drug as degraded by different temperatures during the particular time period is called Mean Kinetic Temperature (MKT).
  24. 24. Mean Kinetic Temperature  Degradation of any drug depends upon storage conditions.  Temperature of the storage room fluctuates from the set value. Suppose a temperature 30°C but it shall be 29.4°C , 29.8°C & 30.2°C many times & degradation of product found 0.6 %. MKT is calculated to determine the single temperature at which the drug would degrade by 0.6% in that period.
  25. 25. Mean Kinetic Temperature
  26. 26. Storage Period  Recipients  API#  Drug Product  Packaging Material  5 years from the date of Release  10 Years from the date of Release  1 year from the Expiry date  6 Years from the date of Release Category Storage Period
  27. 27. Storage Period  Re-Analysis /Retest and STM.  Formulation in Bulk Pack ##  Formulation in Bulk Pack having Expiry  6 Years from the date of Expiry.  1.5 years from date of Release  1 Year from the date of Release. Category Storage period
  28. 28. Storage Period  # Shelf life can be reduced for Sensitive API . Expiry of API & Drug Product to be considered while deciding the Shelf Life.  ## Formulation in bulk pack means drug product packed & dispatched for further packing.  As per EU GMP, Annexure 19, Reference & Retention samples, 3.2 Duration of Storage, Packaging material should be retained for duration of Shelf life of Finished product concerned.  As per EU GMP, Annexure 19, Reference & Retention samples, 3.2 Duration of Storage, Staring materials other than Solvents, Gases or water used in manufacturing shall be retained for at least two years after the release of Product unless no longer storage requirement is required under the Law of Member State of Manufacture.
  29. 29. Disposition  Disposition as per Product Specification Procedure.  Monitoring of Reserve samples Record after every six months or when required.  Approval required of QC Head before destruction of Reserve samples.  Destruction to be recorded in concerned register.  Samples attached with PM report to be destroyed along with he report destruction.
  30. 30. Thank You