Good storage practice (GSP), cold chain & temperature mapping
- 1. GOOD STORAGE PRACTICE (GSP) INCLUDING COLD CHAIN & TEMPERATURE MAPPING BY SAMUEL M.( B.PHARM, MSC)
- 3. Introduction ■ GS&DP is that part of quality assurance which ensures that the quality of medicinal products is maintained throughout all stages of the supply chain from the site of manufacturer to the pharmacy or person authorized or entitled to supply medicinal products to the public
- 5. Good Distribution Practices (GDP) ■ The procuring (purchasing), holding, storing, selling, supplying, importing, exporting or movement of medical products, with the exception of dispensing or providing medical products directly to a patient or his or her agent. ■ To maintain product quality, safety and efficacy by preventing product adulteration, counterfeiting, theft, and diversion.
- 6. Quality management system ■ The quality system shall ensure that: – GSP and GDP are adopted and implemented to ensure that the quality of – pharmaceutical products is maintained throughout their shelf life in the supply chain – operations are clearly specified in written procedures; – responsibilities are clearly specified in job descriptions; – all risks are identified and necessary, effective controls are implemented; – processes are in place to assure the management of outsourced activities;
- 7. QMS.... – There is a procedure for self-inspection and quality audits; – there is a system for quality risk management; – there are systems for managing returns, complaints and recalls; and – there are systems to manage changes, deviations and corrective an preventive actions (CAPAs).
- 8. Organization and management ■ Infrastructure includes, as applicable, • Buildings, workspace and associated utilities • Process equipment (hardware and software) • Supporting services ■ There should be an adequate organizational structure ■ Duties and responsibilities should be clearly defined through Job description. ■ A designated competent person should be appointed within the warehouse
- 9. Personnel ■ Adequate number of competent personnel at all stage ■ Appropriate education, training, skills and experience in the requirements of good distribution and storage practices ■ Personnel training should be based on written standard operating procedures (SOPs) ■ Appropriate records should be maintained, ■ Delivered trainings should cover the topic of product security, as well as aspects of product identification, the detection of counterfeits and the avoidance of counterfeits entering the supply chain.
- 10. Personnel cont.. ■ Personnel involved in the distribution of pharmaceutical products should wear garments ■ Personnel dealing with hazardous pharmaceutical products, including products containing materials that are highly active, toxic, and infectious or sensitizing, should be provided with protective garments as necessary. ■ Appropriate procedures relating to personnel hygiene, relevant to the activities to be carried out, should be established and observed. ■ Such procedures should cover health, hygiene and clothing of personnel.
- 11. Premises, warehousing and storage ■ Storage Areas – Sufficient capacity to allow the orderly storage of the various categories of pharmaceutical products – Products in quarantine, and released, rejected, returned or recalled products as well as those suspected to be counterfeits.
- 12. Storage areas ■ Designed or adapted to ensure appropriate and good storage conditions. ■ Clean and dry and maintained within acceptable temperature limits. ■ Pharmaceutical products should be stored off the floor and suitably spaced to permit cleaning and inspection. ■ Pallets should be kept in a good state of cleanliness and repair
- 13. Storage areas..... ■ Storage areas should be provided with adequate lighting to enable all operations to be carried out accurately and safely ■ Has pest control program or subcontracted ■ unauthorized persons from entering storage areas. ■ Dedicated area(s) with appropriate additional safety and security measures shall be provided
- 14. Storage conditions ■ Storage conditions for pharmaceutical products and materials should be in compliance with the labelling, which is based on the results of stability testing ■ Recorded temperature monitoring data should be available for review. ■ The equipment used for monitoring should be checked at suitable predetermined intervals and the results of such checks should be recorded and retained. ■ All monitoring records should be kept for at least the shelf-life of the stored material or product plus 1 year, or as required.
- 15. Storage and labelling conditions Normal storage conditions ■ Storage in dry, well-ventilated premises at temperatures of 15–25 °C or, depending on climatic conditions, up to 30 °C. ■ Extraneous odours, other indications of contamination, and intense light must be excluded. Defined storage Instructions ■ Drug products that must be stored under defined conditions require appropriate storage instructions. Unless otherwise specifically stated (e.g. continuous maintenance of cold storage) deviation may be tolerated only during short-term interruptions, for example, during local transportation.
- 16. The use of the following labelling instructions are recommended Label Meaning Do not store over 30 °C‖ from +2 °C to +30 °C Do not store over 25 °c from +2 °C to +25 °C Do not store over 15 °C from +2 °C to +15 °C Do not store over 8 °C from +2 °C to +8 °C ‖ Do not store over 8 °C from +2 °C to +8 °C ‖ Do not store below 8 °C from +8 °C to +25 °C Protect from moisture no more than 60% relative humidity in normal storage conditions; to be provided to the patient in a moisture- resistant container Protect from light to be provided to the patient in a light- resistant container
- 17. Stock rotation and control ■ Periodic stock reconciliation should be performed by comparing the actual and recorded stocks. ■ All significant stock discrepancies should be investigated as a check against inadvertent mix-ups and/or incorrect issue. ■ In manufacturing facilities, partly used containers of materials and pharmaceutical products should be securely reclosed and re- sealed to prevent spoilage and/or contamination during subsequent storage. ■ Materials and pharmaceutical products from containers which have been opened or partly used should be used up before those in unopened containers. ■ Damaged containers should not be issued unless the quality of the material has been shown to be unaffected. ■ Any action taken should be documented.
- 18. Vehicles and equipment ■ Sufficient capacity to allow orderly storage of the pharmaceutical products ■ Suitable for their purpose and appropriately equipped to prevent exposure of the products to conditions that could affect their stability and packaging integrity, and to prevent contamination.
- 19. Vehicles and equipment ■ Vehicles, containers and equipment should be kept clean and dry and free from accumulated waste. ■ Vehicles, containers and equipment should be kept free from rodents, vermin, birds and other pests ■ Equipment used for monitoring conditions, e.g. temperature and humidity, within vehicles and containers should be calibrated at regular intervals ■ All monitoring records should be kept for a minimum of the shelf-life of the product distributed plus one year.
- 20. Vehicles and equipment ■ Technology, such as global positioning system (GPS) electronic tracking devices and others, which would enhance the security of pharmaceutical products while in the vehicle where feasible. ■ Where third-party carriers are used, distributors should develop written agreements with carriers to ensure that appropriate measures are taken to safeguard pharmaceutical products, including maintaining appropriate documentation and records.
- 21. Dispatch and receipt ■ Pharmaceutical products should only be sold and/or distributed to persons or entities that are authorized to acquire such products. ■ Written proof of such authority must be obtained prior to the distribution of products to such persons or entities. ■ The dispatch and transportation of pharmaceutical products should be undertaken only after the receipt of a valid delivery order.
- 23. Dispatch and record ..... ■ Records for the dispatch of pharmaceutical products should be prepared and include at least the following information: Date of dispatch; Complete business name and status of the addressee (e.g. retail pharmacy, hospital or community clinic); A description of the products including, e.g. name, dosage form and strength (if applicable); Quantity Batch number and expiry date
- 24. Dispatch and record ..... ■ Records of dispatch should contain enough information to enable traceability of the pharmaceutical product. ■ Such records should facilitate the recall of a batch of a product when necessary. ■ Incoming shipments should be examined to verify the integrity of the container/closure system, ensure that tamper-evident packaging features are intact, and that labeling appears intact
- 25. Documentations ■ Written instructions and records which document all activities relating to the storage and distribution of pharmaceutical products, including all applicable receipts and issues (invoices) should be available. ■ Records should be kept ■ Procedures should be established and maintained for the preparation, review, approval, use of and control of changes to all documents relating to the distribution process.
- 26. Con’t.... ■ Distributors should keep records of all pharmaceutical products received. ■ Records should contain at least the following information: Date Name of the pharmaceutical product Quantity received or supplied Name and address of the supplier. Batch Number
- 27. Repackaging and relabeling ■ Repackaging and relabeling of pharmaceutical products should not be allowed, as these practices may represent a risk to the safety and security of the supply chain. ■ Printing and/or adding extra stickers should not be allowed unless authorized by the concerned entity. ■ The re-printing/relabelling is forbidden in the law No. 1112/2019.
- 28. Compliant handling ■ There should be a written procedure in place for the handling of complaints ■ All complaints and other information concerning potentially defective and potentially counterfeit pharmaceutical products should be reviewed and investigated carefully.
- 29. Product recall ■ There should be a procedure to recall from the market, promptly and effectively, pharmaceutical products and materials known or suspected to be defective.
- 30. Product Recall ■ Recalled pharmaceutical products should be segregated during transit and clearly labeled as recalled products. ■ All recalled pharmaceutical products should be stored in a secure, segregated area pending appropriate action. ■ The effectiveness of the arrangements for recalls should be evaluated at regular intervals. ■ All records should be readily available to the designated person(s) responsible for recalls
- 31. Cold chain management ■ Cold chain management is the specialist area of the pharmaceutical and biopharmaceutical distribution system dealing with product that is required to be held and distributed in a temperature controlled environment with the objective of providing safe and effective product to the patient. ■ Cold chain equipment and temerature monitoring device
- 32. WHO available prequalified temperature monitoring devices 20-day electronic shipping indicators Cold Chain Monitor Card Irreversible freeze indicator Vaccine vial monitor Dial thermometer 30-day electronic temperature recorder
- 33. Routine use of temperature monitoring devices at each level of the supply chain ■ WHO recommends temperature monitoring devices based on the specific cold chain equipment application the intended monitoring purpose(s). • Devices with recording capabilities and alarms are essential (More Expensive) ― For cold rooms and refrigerated trucks where large quantities of vaccine are kept • less expensive devices are appropriate for transport and storage at health centres
- 34. Cold rooms and freezer rooms ■ Cold rooms and freezer rooms in primary or subnational stores contain large quantities of vaccine and should be equipped with a calibrated continuous temperature monitoring system with sensors located at points representing greatest temperature variability and alarms to indicate temperature excursions.
- 35. Cont… ■ WHO recommends that a dial thermometer (gas/vapour pressure) be available as a backup device. ■ The monitoring system should record the temperature at a minimum of six times per hour for each monitoring sensor position and the temperature data records need to be stored and be easy to access. ■ Temperatures should be manually recorded twice a day/seven days per week if automated recording is not available.
- 36. Refrigerated vehicles ■ Refrigerated vehicles should include an electronic continuous temperature monitoring system with visual dashboard mount. ■ WHO also recommends placement of one freeze indicator with the most freeze-sensitive vaccine in the shipment at the time when the vaccine is packed in the issuing store. ■ Alarms should be recorded and reported to the receiving stores.
- 37. Refrigerators ■ Refrigerators are typically used to store material and vaccines within a qualified range of 2°C to 8°C (36°F to 46°F). ■ The capability of the equipment to achieve temperature uniformity should be considered when assigning the chamber set point ■ WHO recommends that 30-day temperature recorders (30DTRs) be used to continuously monitor refrigerators and ensure equipment is functioning effectively. ■ Temperatures should be recorded twice per day/seven days per week.
- 38. Refrigerators... ■ Is there dfference between medical refrigerator and domestic refrigerator? ■ yes, they are. ■ generally not acceptable to use a domestic refrigerator for storing medicines ■ Why?
- 39. Medical Fridge vs Domestic Fridge Medical/ pharma Fridge Household Fridge
- 40. Temperature performance Medical/ pharma Fridge ■ Advanced temperature control systems and immediate recovery of temperature ■ uniform temperature distribution ■ Accurate ■ Alarm system ■ small temerature range Household Fridge ■ Less stable and temperature flactuates due to diffrent factors suchas door opening, ambient temerature variations ■ non-uniform temprature distribution ■ Poor accuracy ■ no alarm system ■ Broad temerature range
- 41. Cold box and vaccine carriers ■ WHO-prequalified cold boxes and vaccine carriers are robust insulated, reusable containers into which WHO-prequalified water-packs are placed.
- 42. Conditioned icepacks ■ When an icepack is removed from the icepack freezer, its temperature may be as low as -20°C. If you use these icepacks immediately there is a risk that you will damage freeze-sensitive vaccines. ■ A ‘conditioned’ icepack is an icepack that has been left outside the freezer for long enough to stabilize at 0°C. This point is reached when the ice inside the icepack begins to melt.
- 43. Routine temperature monitoring, Record keeping and reporting ■ Effective monitoring and record-keeping achieves the following objectives: a. Verification of storage temperatures are within the acceptable ranges of +2°C to +8°C in cold rooms and refrigerators and -25°C to ‑15°C in freezer rooms and vaccine freezers; b. Detection of out-of-range storage temperatures; c. Detection of out-of-range transport temperatures. ■ Well-maintained records can be used to assess the quality of the cold chain supply chain, ■ Regardless of the temperature monitoring device used, temperatures in fixed storage locations should continue to be recorded manually twice per day and seven days per week.
- 44. Temeratur e mapping ■ Temperature mapping is the process of recording and mapping temperatures within three-dimensional (3D) spaces, such as cold and freezer rooms, dry storage areas, and refrigerator and freezer units. ■ Temperatures will not be the same everywhere within the storage area. ■ For example Temperatures in the corners will most likely be different from those measured in the centre or close to cooling units. ■ In dry stores, the temperatures close to the ceiling tend to be higher than those close to the floor. ■ For example, temperature will be coldest next to the cooling fans and likely to be warmest close to the doors.
- 45. Temperature mapping studies o Temperature mapping and temperature monitoring are integral to the appropriate storage conditions for pharmaceuticals. o All new temperature- controlled storage areas must be temperature-mapped
- 46. Temperature mapping ■ All new temperature-controlled storage areas must be temperature-mapped ■ Temperature mapping is important for identifying the safe areas of storage for vaccines within new refrigerators, cold rooms and freezers. ■ It is important to know where the “hot spots” and “cold spots” are in each in order to ensure that vaccines are kept in the right places, based on their sensitivity to heat and freezing.
- 47. Mapping cold rooms and freezer rooms ■ Temperature mapping must be done for all cold rooms and freezer rooms, regardless of where they were purchased from. ■ Vaccines should not be stored in a cold room or freezer room until the temperature mapping exercise has been completed, and the results are analyzed. ■ Mapping should be repeated if there are changes to the cooling equipment and/or the organization of products in the store.
- 48. Mapping refrigerators ■ The WHO recommends that only prequalified refrigerators be purchased and used as they are designed and validated for /pharma/medical/vaccine storage. ■ WHO prequalified refrigerators will already have their temperature mapping completed by the manufacturer. ■ If domestic/household refrigerators are used, temperature mapping can help to identify the safest areas for vaccine storage.
- 49. Calibration and maintenance of temperature monitoring devices ■ Temperature monitoring devices must periodically be calibrated in order to prove their accuracy over the full operating temperature range ■ Proven accuracy is mandatory in order to avoid inaccurate readings which might lead to a false sense of security and place vaccines at risk. ■ Some devices are covered by calibration certificates from the device manufacturer. ■ These certificates are valid for a defined period of time and the associated devices may be used throughout this period without additional calibration.
- 50. Calibration…. Circumstances under which proper device calibration or re-calibration is needed. o A calibration certificate is not available because it has been lost. o Device is used longer than the period covered by the calibration certificate, either at the user’s risk or with the approval of the manufacturer. o Device was used or treated beyond the manufacturer's data sheet limitations (e.g. excessive temperature, shock, etc.). o Device battery was replaced. o Device's measurements are suspect. o Manufacturer specifies that a calibration procedure should be carried out at regular intervals. o Regulatory bodies require regular proof of calibration and this evidence of calibration proof cannot be provided by the manufacturer’s certificate. o Calibrate devices against a certified, traceable reference standard at least once a year, unless otherwise justified.
- 51. Temperature recording ■ In fixed storage locations, manual temperature record charts should be displayed on the door of each piece of cold chain equipment, labelled with the equipment’s name or unique ID. ■ Temperature graphs are preferable to tables because they clearly show trends away from the normal pattern of daily fluctuation. ■ This helps staff to identify performance issues before alarms are generated.
- 52. Thank you for listening