Introduction
New drug storage and distribution guidelines, soon to be proposed by the United States Pharmacopeia (USP), could have a significant impact on the way drugs are delivered to the pharmacy and handled by the pharmacist.
In draft guidelines due to be published in the January/February or March/April edition of the Pharmacopeial Forum, USP will propose that drugs be stored and transported at controlled room temperature unless otherwise stated in the monograph or on the product label. In a separate set of guidelines, the organization will recommend special handling of products designated "labile." The provisions could affect every link in the chain of distribution from manufacturer to patient.
The goal is to protect the quality of medications, said Loyd V. Allen Jr., PhD, president of APhA's Academy of Pharmaceutical Research & Science and professor emeritus of the University of Oklahoma College of Pharmacy. Allen, who sits on both the USP committee of revision and its subcommittee on packaging, stability, and distribution, said the organization had received reports from consumers and practitioners that products were being damaged by exposure to the elements during mailing, shipping, and storage. At the Open Meeting on Packaging, Storage, and Distribution last fall, USP Executive Vice President Jerome A. Halperin said the organization hopes that the revisions "do not impose unreasonable or unrealistic requirements upon manufacturers and pharmacists."
The proposals, however, are being met with opposition. "This is a solution in search of a problem," Robert Borger, director of standards and guidelines at the National Wholesale Druggists' Association (NWDA), told Pharmacy Today. "No one has proven through a formal, careful study that there is a problem. Before we apply new standards that have the possibility of adding a huge amount of cost and removing a huge amount of product from the system, let's first make sure there is a problem."
Interested parties will be able to comment on the proposals following their publication this winter. The proposals will then be revised as necessary, finalized, and incorporated into the United States Pharmacopeia/National Formulary (USP-NF), perhaps as early as this summer. State boards adhere to USP standards and, upon publication in the USP-NF, will ensure that pharmacies adhear to the guidelines.
Pharmacies will be required to track and record in-store temperatures to comply with the storage temperature guideline, Allen said. The process could be as simple as recording the temperature in a log once a day. After an as-yet-unspecified length of time, the pharmacist would then calculate the mean kinetic temperature (MKT). MKT corresponds roughly to average room-air temperature and should not exceed 25°C (77°F), according to the proposed standards. Acknowledging the possibility that a pharmacy could lose power during a storm or some other natural disaster, USP would allow temperature spikes up to 40°C (104°F) as long as they do not exceed 24 hours.
"The amount of time and money this will take is minimal," Allen said. "An instrument is available for $100 that will record temperature daily. Simple software is also available to calculate the mean kinetic temperature. If a state board inspector comes in and wants to see the record, all the pharmacist will have to do is show it to him or her." If the pharmacy is out of compliance, the inspector might assess a fine, but this would depend on particular state practices.
"This isn't really anything for most pharmacies to worry about," Allen explained. Most pharmacies already maintain their facility at an appropriate temperature. However, pharmacists who are accustomed to turning off the air conditioner or heating system when the pharmacy is closed may have to abandon the practice. "During summer, temperatures during the off hours may climb to 90°F or more in some parts of the country. Some drugs and drug products could start to degrade at this temperature," Allen said.
Shipment At Room Temperature
The new guidelines will also require that medications be shipped at controlled room temperature. The measure is aimed mostly at protecting products delivered through the U.S. mail, which usually takes from 3 to 5 days but can take longer. "If a drug is shipped out in the South on July 20, and sits in a mailbox that reaches 140°F, obviously that's a problem," Allen said. Delivery during winter is also problematic. Freezing in unheated trucks has destroyed entire shipments of medications, especially liquids. To assess compliance with the shipping guidelines, state boards might spot-check products ordered through the mail.
Internet pharmacies will likely have little problem meeting the guidelines because most deliver through Federal Express and other next-day delivery services. Manufacturers, wholesalers, and mail order pharmacies might have a harder time, however. NWDA members, Borger said, will have to substantially increase the number of products they ship under refrigeration. For small package delivery through United Parcel Service, medications will have to be packed in insulated containers with dry ice or some other type of coolant.
Borger said that there is just no proof that the extra efforts are needed for the majority of products. "We have a group of products here for which the manufacturer has given no specific temperature requirements," he said. "If the product needed to be handled a specific way, the manufacturer should have said so, and our members would have shipped it appropriately." USP's goals would be better met, Borger suggested, by identifying specific products that need special treatment.
Patrick Donoho, vice president of government affairs and public policy at the Pharmaceutical Care Management Association, a trade group that represents mail order pharmacies, told Pharmacy Today that his group will submit comments when the draft guidelines are published in the Pharmacopeial Forum. NWDA will do the same. Donoho noted that many mail order companies already ship medications with refrigerator packs or in insulated containers.
USP is sensitive to the concerns of industry. "It's often a question of packaging, transport, ecology, weather, and logistics," Halperin told Pharmacy Today. "We'll let industry and organizations take charge of trying to meet our requirement."
Protecting Labile Products
In a separate set of guidelines, USP will recommend -- not require -- that labile products carry special time-temperature indicators (TTIs) throughout the distribution process. USP will consider a product labile if it fails one of four tests. An oral dosage formulation, for example, would be classified as labile if it no longer conformed to monograph specifications following a 30-day exposure to room air at 25°C and relative humidity of 60%.
USP will also recommend storing labile drugs at controlled room temperature and limiting containers to a 35-day supply. The goal is to limit the exposure of the product to humidity and temperature fluctuations. "If you dispense a 90-day supply of something that's taken three times a day, that container will be open and shut 270 times before it is gone," Allen said. "That's a lot of exposure for a delicate product."
Unreliable TTIs
NWDA will oppose the use of indicators in its comments to USP. Current TTIs, Borger said, are unreliable. "Any chemist or engineer can start making these products in their garage," he explained, noting that TTIs are not subject to manufacturing or testing standards. They may work fine for vaccines, which typically are stored at low temperatures and delivered from manufacturer to patient in short order. "But we are talking about much higher temperatures here, room temperature," Borger said. "Also, we may have products with a shelf life of 3 years. If the indicator goes bad in 1 [year], that's a problem."
"If we have to take products out of the marketplace," Borger said, "there will be a big increase in returns and a big waste of money." Until TTI technology is improved, "We won't really know if the product is bad," he explained. "All that we'll know is that the time-temperature indicator is bad."
Older Formulations Labile
USP estimates that fewer than 1% of existing drugs would be considered labile. Older tablets and capsules, some of which were formulated more than 50 years ago, are among the most likely. "We realized that a few of these products are particularly sensitive to temperature and humidity. We wanted to protect their integrity and quality," Halperin said.
"Producers might stop manufacturing some of these products instead of spending the money to reformulate them," he added. "The provisions might also impose a new testing burden on producers. It is not an intention of the new standards, but it is a possible outcome."
Even though USP will only recommend special treatment of labile products, Allen thinks most pharmacists will attempt to adhere to the suggestions, if only for legal reasons. "If it is brought out in court that a pharmacy is not following USP recommendations, that could be a problem," he said.
"Pharmacists have already been dealing with labile products for years," Allen noted. "Nitroglycerin, for example. This is nothing out of the ordinary. If nothing else, pharmacists will at least have more confidence in the quality of the products they give to patients."
Pharmacy Today. 2000;6(1) © 2000 American Pharmacists Association
All material from Pharmacy Today is copyrighted by the American Pharmaceutical Association, and all rights are reserved by the Association.
Cite this: USP To Issue New Storage/Distribution Guidelines - Medscape - Jan 01, 2000.
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