1、 GOOD STORAGE AND SHIPPING PRACTICES-General Chapters US . PharmacopoeiaUSP29 Search GOOD STORAGE AND SHIPPING PRACTICES-General Chapters1079 GOOD STORAGE AND SHIPPING PRACTICES This general information chapter is intended to provide general guidance concerning storing, distributing, and shipping of
2、 Pharmacopeial preparations. It describes procedures to maintain proper storage environments for individual articles and to ensure a preparations integrity, including its appearance, until it reaches the user. There is no change to any applicable requirements under Current Good Manufacturing Practic
3、es, approved labeling, state laws governing pharmacies, the USP General Notices and Requirements, or monographs. The section Preservation, Packaging, Storage, and Labeling under General Notices and Requirements provides definitions for storage conditions. All equipment used for recording, monitoring
4、, and maintaining temperatures and humidity conditions should be calibrated on a regular basis. This calibration should be based on NIST or international standards (see Monitoring DevicesTime, Temperature, and Humidity 1118). A Pharmacopeial preparation may follow several potential routes from the o
5、riginal manufacturer to the patient. Figure 1 documents present-day routes and the associated risks. These risks include exposure to temperature excursions, humidity, light, and oxygen. For a discussion of climates, stability, and mean kinetic temperature, see Pharmaceutical Stability 1150. Temperat
6、ure- or humidity-sensitive articles are to be handled in accordance with General Notices.PACKAGING AND STORAGE STATEMENT IN MONOGRAPHS Most articles have storage conditions identified by their labeling. Otherwise, it is expected that the conditions for storing the article are specified in the monogr
7、aph according to definitions provided by the General Notices and Requirements in the section Storage Temperature, and Humidity under Preservation, Packaging, Storage, and Labeling. In cases where additional information on packaging and storage is desired, a specific statement can be provided in the
8、Packaging and storage or the Labeling section of the individual monograph.STORAGE IN WAREHOUSES, PHARMACIES, TRUCKS, SHIPPING DOCKS, AND OTHER LOCATIONS Pharmacopeial articles are to be stored in locations that adhere to conditions established by the manufacturer. Where the desired conditions are no
9、t established, use storage conditions described in the General Notices and Requirements or in the applicable monograph.Warehouses Observation of the temperature variations in a warehouse should be made over a period of time to establish a meaningful temperature profile, including the temperature var
10、iations and conditions in the different parts of the warehouse. Such observations provide data and information as to where various products should and should not be stored.ESTABLISHING TEMPERATURE PROFILES Temperature profiles can be compiled by using a suitable number of thermometers or other tempe
11、rature recording instruments. They should be placed throughout the warehouse in divided sections and should record the maximum and minimum temperatures during a 24-hour period for a total of three consecutive 24-hour periods. The following factors, some of which may give rise to extreme temperatures
12、, should be considered during the process of temperature profiling: the size of the space, location of space heaters, sun-facing walls, low ceilings or roofs, and geographic location of the warehouse. Temperature profiling for warehouses already in use should be done at known times of external tempe
13、rature extremes, e.g., for a period of not less than 3 hours when air temperatures are higher than 25 or less than 15. Profiling should be conducted in both summer and winter. A mean kinetic temperature (MKT) should be obtained for any separate areas within the warehouse (see Pharmaceutical Calculat
14、ions in Prescription Compounding 1160 for samples of MKT calculations). The temperature profile report should provide recommendations for the use of each area and identification of any areas that are found unsuitable for storage of Pharmacopeial articles.CONTROLLED ROOM TEMPERATURE The General Notic
15、es provide a definition for Controlled Room Temperature. A temperature profiling study should demonstrate suitability for storing Pharmacopeial articles in areas determined to be at room or controlled room temperature. A suitable number of temperature and humidity recording instruments should be ins
16、talled to record temperatures and to provide temperature and humidity profiles. Temperature recording should be conducted to meet the recommendations for establishing mean kinetic temperature and to comply with the warehouses written procedures. These written procedures should have a reporting mecha
17、nism in place whereby a management tree is informed in the event that predefined high or low temperatures or humidity limits have been exceeded. Records can be reviewed as determined by the management system in accordance with established guidelines. Suitable training should be provided to persons w
18、ho record temperatures, and proper quality accountability and tracking systems should be maintained.STORAGE AT “COOL,” “COLD,” “REFRIGERATOR,” AND “FREEZING” CONDITIONS The General Notices provide definitions for cool, cold, refrigerator, and freezer temperatures. A temperature profiling study can b
19、e used to establish suitable areas for storing Pharmacopeial articles designated to be stored under these conditions. Equipment used for storing Pharmacopeial articles at these low temperatures should be qualified according to written procedures provided by the management system. Recording devices c
20、an be installed within the equipment and used to enable both air and product temperatures to be recorded at regular intervals. The number and location of monitoring devices should be determined based on the result of the temperature profile. Temperature records should be examined at least once every
21、 24 hours or as provided in the equipment protocol. Cool or cold conditions are moisture-condensing conditions. Humidity-monitoring devices should be used in cases where the repackaged Pharmacopeial article is humidity-sensitive or labeled to avoid moisture. Additionally, there can be installed temp
22、erature-monitoring, and where necessary, humidity-monitoring alarm devices that have the capability of alerting personnel in the event that control is compromised. There should be protocols in place to address procedures for responding to failed temperature and humidity ranges both for normal workin
23、g hours and outside normal working hours. Temperature and humidity should be reviewed at the times designated by the established protocol. The calibration and functioning of all temperature and humidity monitoring devices, including alarms and other associated equipment, should be checked on an annu
24、al or semiannual basis. Regular maintenance protocols should be in place for refrigeration equipment. There should be written agreements in place for all maintenance and evaluation procedures, and this may include an emergency situation protocol.PERSONNEL TRAINING Suitable training should be provide
25、d for personnel who handle Pharmacopeial articles with special storage temperature requirements. Personnel should know how to monitor temperatures and how to react to situations where adverse temperatures are identified. There should be written procedures in place such that the adverse temperatures
26、are recorded and a report provided to the parties designated in the protocol.QUALIFICATION OF “COLD” EQUIPMENT OR STORES Only climate control equipment for which a contractor has provided documentation to assure its suitability for temperature and humidity requirements should be considered for use i
27、n cold storage. Qualification procedures on a regular basis should be independently conducted on equipment in cold stores to guarantee suitability and proper functioning. The procedure should demonstrate the temperature profile for both air and product temperatures when empty as well as when loaded.
28、 The procedure should also demonstrate the time taken for temperatures to exceed the maximum temperature in the event of a power failure. Qualification should consider thermal fluctuations that occur during stock replenishment and order removal. The results of the qualification should demonstrate th
29、e ability of the equipment to maintain the required temperature range in all areas, defining any zones which should not be used for storage such as those areas in close proximity to cooling coils, cold air streams from equipment ventilation, or doors. The variability of the system can be characteriz
30、ed by using the relative standard deviation. Thermal monitoring should establish that the system is rugged in that its temperature profile is consistent and reliable.DISTRIBUTION AND SHIPMENT OF Pharmacopeial ARTICLES As indicated in Figure 1, a drug can take a variety of paths from the manufacturer
31、 to the patient. In the simplest form of the distribution system, the manufacturer ships directly to the customer, such as a doctors office, clinic, or hospital. However, more often, the article leaves the manufacturers chain of control and enters a complex system of handoffs that involve the distri
32、bution chain to the patient.Figure 1. Drug product distribution.Shippers and distributors are to follow the proper storage and shipping requirements as indicated by the manufacturer. For particular cases, such as shipment of vaccines or other special care products, manufacturers may require special
33、shipping and storage conditions generally referred to as “cold-chain management”. For example, manufacturers may attach temperature-monitoring devices and/or ship under specified controlled conditions to ensure that the desired temperature is maintained during distribution (see Monitoring DevicesTim
34、e, Temperature, and Humidity 1118). Validated, available temperature- and/or humidity-monitoring technologies can be used to monitor the overall environmental effect on compendial articles during shipment and distribution. In these cases, the shipping conditions of the package are recorded. In gener
35、al, extreme temperature conditions (i.e., excessive heat, freezing) should be avoided. Distribution systems chosen to deliver pharmaceutical products from the manufacturer to the consumer should take into account basic operational parameters, including timeliness and accountability. The manufacturer
36、s FDA-approved storage conditions, printed in the labeling of the product, should be observed carefully at each destination of the distribution chain (see Figure 1), unless specifically instructed otherwise in the immediate label of a shipping container. This may be the case for certain pallet-sized
37、 shipping containers where the amount of refrigerant contained (e.g., dry ice, gel packs) is based on an anticipated exterior condition approximating controlled room temperature. In such cases, placing the shipping container in a refrigerator could lead to the product inside freezing, potentially af
38、fecting its quality. Items requiring special handling conditions will have those conditions clearly indicated in the labeling for the product. The Prescription Drug Marketing Act of 1987 and the ensuing regulations in 21 CFR Part 203, Prescription Drug Marketing, and Part 205, Guidelines for State L
39、icensing of Wholesale Prescription Drug Distributors, provide the necessary regulations and guidance for several legs of the distribution chain for the prescription drug. The manufacturers and distributors should work together to establish proper distribution and product-handling requirements for th
40、e purpose of ensuring appropriate product maintenance in transit. Pharmacists and physicians should educate patients regarding proper storage of products to ensure product integrity at the patient level. Information that may be considered in determining the ability of pharmaceutical articles to main
41、tain their Pharmacopeial requirements of identity, strength, quality, and purity through the distribution channel may include, but is not limited to the following: ICH stability studies, temperature cycling studies, stability shipping studies, ongoing regulatory stability commitment studies, market
42、experience portfolio (i.e., product complaint files, historical product performance data, product development data), and product labeling commitments.Qualification Protocol Operational and performance testing should be parts of a formal qualification protocol that may use controlled environments or
43、actual field testing based on the projected transportation channel. These should reflect actual load configurations, conditions, and expected environmental extremes. Temperature and humidity monitors should be placed into the product or a representative thereof. Testing consists of consecutive repli
44、cate field transportation tests using typical loads, according to an established protocol.Physical Challenges Most products are sufficiently robust to withstand distribution with minimal protection from routine, well-understood physical and environmental hazards. Several standard test methods are av
45、ailable for evaluating package performance factors under well-documented shock, vibration, and other transit elements. The American Society for Testing and Materials document, “Standard Practice for Performance Testing of Shipping Containers and Systems” (ASTM D4169-98),and the International Safe Tr
46、ansit Associations (ISTA) specifications have similar methods for evaluation of shipping performance for various types of transit modes such as less-than-truckload (LTL), small package, rail car, air freight, etc. From the manufacturers perspective, these tests are very useful in evaluating the prod
47、uct and package durability and fragility. The tests are usually performed on shipping carton quantities of a specific stock keeping unit (SKU) as an unbroken whole. Fragility problems can be corrected with package modifications, which could include placing cotton or rayon coilers in bottles or placi
48、ng top and bottom pads in the shipping case to reduce package breakage. Not all protective packaging elements follow the SKU through the system.Basic packaging principles are observed when separating the contents of the manufacturers shipping container or pallet load into smaller quantities or when
49、shipping mixed product loads. For example, glass containers are wrapped in a bubble wrap or other shock-absorbent material, and the void spaces are filled with dunnage (e.g., foam “peanuts,” shredded or tightly crumpled paper, bubble wrap) to protect the contents from shifting and drop impact. Large-volume liquid containers may be bagged in plastic and kept isolated to prevent leakageto, or damage of, adjacent packages. “Skin packaging,” a term describing a heat-shrink film that anchors the load to fiberboard and prevents load shift, can be an excellent method of protecting some pro
