OUTLINE
Regulation of Expiration and Beyond-Use Dating
Difficulties in Assigning Beyond-Use Dates
Assigning Beyond-Use Dates to Manufactured Products Dispensed by the Pharmacist
Assigning Beyond-Use Dates to Compounded Drug Preparations
I. DEFINITIONS
A. Expiration date: This is the date put on the label of a drug product by the manufacturer or distributor of the product. The United States Pharmacopeia (USP) defines expiration date in the following way.
The expiration date identifies the time during which the article may be expected to meet the requirements of the Pharmacopeial monograph, provided it is kept under the prescribed storage conditions. The expiration date limits the time during which the article may be dispensed or used. Where an expiration date is stated only in terms of the month and the year, it is a representation that the intended expiration date is the last day of the stated month (1).
B. Beyond-use date: This is the date put on the dispensing container by the pharmacist or pharmacy technician. According to the USP:
1. “The dispenser shall place on the label of the prescription container a suitable beyond-use date to limit the patient’s use of the article based on any information supplied by the manufacturer and the General Notices and Requirements of this Pharmacopeia. The beyond-use date placed on the label shall not be later than the expiration date on the manufacturer’s container” (1).
2. “The beyond-use date is the date after which an article must not be used” (1).
C. It should be noted that these definitions use the term “article”, which is defined in the USP as “an item for which a monograph is provided whether an official substance or an official preparation” (2). Therefore, technically these definitions apply only to official USP articles. In practice, these definitions are generalized to include nonofficial drug substances, products, and preparations and nutrients and dietary supplements.
D. As can be seen in the definition of the USP word article, the General Notices of the USP distinguish between official substances and official preparations. “Official substances” are the component ingredients of dosage forms and include the active drug entity and the pharmaceutic ingredients. The pharmaceutic ingredients are inactive formulation ingredients, such as sweeteners, preservatives, tablet binders, and so on. An “official preparation” is the finished dosage form, the drug product or preparation (2). The word “official” merely means that these entities have a USP or National Formulary (NF) monograph. The USP and NF are separate books, but are contained in the same volume, the USP–NF (2). In general, the USP has monographs of active ingredients and official preparations; whereas the NF contains the monographs for pharmaceutic ingredients.
E. Because different laws and regulations apply to manufactured versus compounded dosage forms, USP chapters that address standards for compounding use different terms to distinguish between these entities: In general, the term “product” is used to refer to manufactured dosage forms, and the term “preparation” is used for compounded dosage forms. You will notice that this book also uses this convention for these terms.
II. REGULATION OF EXPIRATION AND BEYOND-USE DATING
A. Manufactured drug products and bulk ingredients in their original containers
1. Prior to the late 1960s, except for insulin and antibiotics, most commercial packages of drug products carried no expiration date. It was common to find drug products in prescription departments of pharmacies that were 20 to 30 years old. This gradually changed during the 1970s so that by September 28, 1978, Good Manufacturing Practice regulations required expiration dates on almost all manufactured drug products.
2. Manufactured products are covered by federal regulations because they are shipped in interstate commerce. The requirement for expiration dates on these products is found in 21CFR § 211.137. This states:
(a) To assure that a drug product meets applicable standards of identity, strength, quality, and purity at the time of use, it shall bear an expiration date determined by appropriate stability testing described in Sec. 211.166.
(b) Expiration dates shall be related to any storage conditions stated on the labeling, as determined by stability studies as described in Sec. 211.166 (3).
3. The General Notices of the USP contains the following statement about the requirement for expiration dates:
The label of an official drug product, nutritional or dietary supplement product shall bear an expiration date. All articles shall display the expiration date so that it can be read by an ordinary individual under customary conditions of purchase and use (1).
4. Currently, the only exceptions for the requirement of expiration dates on manufactured drug products are for nonprescription drug products or nutritional supplements packaged in containers for sale at retail with labeling that allows no limitation of dosage, and the product must be shown to be stable (with supporting stability data) for at least 3 years under the recommended storage conditions (1,3).
5. Notice that both the USP and CFR requirements are for drug products, not for bulk drugs or chemicals. Though most bulk drugs and many pharmaceutic ingredients are labeled with expiration dates, some are not. When these are used in the manufacturing process, the manufacturer assays the ingredients prior to use. Because most pharmacies do not have this analytical capability, sound scientific and professional judgment and good procedures are needed when dealing with these ingredients.
a. When possible, purchase bulk ingredients labeled with expiration dates.
b. For bulk ingredients not labeled with an expiration date, label the container with the date when you received the ingredient from the supplier, and develop a reasonable written standard for the length of time the ingredient can be retained and used in compounding.
c. For all bulk ingredients, request a certificate of analysis from the supplier. These certificates give helpful information, such as expiration dates, re-test dates, or quality control release dates. If a re-test date is given, you can contact the supplier on that date to determine whether the expiration date can be extended on the basis of recent analysis conducted on that lot by the supplier. For quality control release dates, the supplier will have standard dating policies (e.g., 1 year from the quality control release date) for assurance of specifications stated on the certificate of analysis.
B. Drug products labeled, packaged, and dispensed on prescription orders
1. Because the dispensing of prescribed drug products to patients is regulated by state law, the requirements for beyond-use dates on most prescription containers are regulated by state statutes. The NABP Model Rules for the Practice of Pharmacy recommends that a beyond-use date be included on the prescription label (4). As a result, many states have adopted this standard. Check the regulations for the state in which you are practicing for information about requirements for labeling prescription containers with beyond-use dates.
2. As quoted earlier in the definitions section, the General Notices of the USP state that the dispenser (this includes both pharmacists and dispensing physicians) shall label a prescription container with a beyond-use date (1).
3. One area in which federal law has jurisdiction in regulating the labeling of prescriptions is for drug products dispensed for nursing home patients; the Code of Federal Regulations specifies that FDA and USP requirements be followed for prescriptions dispensed to nursing home patients in intermediate-care and skilled nursing facilities. Therefore, prescriptions for these patients must be labeled with beyond-use dates.
4. Even when it is not required by law, most pharmacists feel that the labels of all prescription containers should include beyond-use dates; they feel it is their professional responsibility to provide their patients with a date after which a medication may no longer have its labeled potency. It is well known that many patients keep any unused portion of their prescription drugs in case they need it in the future, so many households have partially used prescription drug products that could unknowingly be used well past their expiration date if the container were not labeled with a beyond-use date.
5. Many dispensing software programs automatically place a 1-year beyond-use date on all labels for prescriptions. The pharmacist or pharmacy technician must verify that this date is within the expiration date given on the container of the product dispensed. As stated in the section on definitions, when an expiration date is given with just a month and year, this means that the intended expiration date is the last day of the given month (1).
III. DIFFICULTIES IN ASSIGNING BEYOND-USE DATES
A. Assigning beyond-use dates is a complex issue because we are dealing with drug molecules with multiple reactive functional groups, various added pharmaceutic ingredients, dispensing containers and closures, and varying conditions of storage and use. Though patient safety and intended therapy are of primary importance, this must be balanced against both economic and ecological concerns; we do not want to unnecessarily discard drug products that still have their labeled potency.
B. A major stumbling block to assigning and labeling dispensed drug products with beyond-use dates has been the lack of adequate stability information available to the pharmacist. The question is, how should the pharmacist determine a valid beyond-use date without the benefit of stability studies conducted with the drug product in the dispensing container stored in the uncontrolled home environment?
C. This problem was recognized in Resolution No. 11 at the 1990 United States Pharmacopeial Convention:
The United States Pharmacopeial Convention is encouraged to explore with the Food and Drug Administration the development of mechanisms by which reliable data and information can be generated to establish scientifically sound beyond-use dates for repackaged products (5).
D. The USP has taken the initiative to address this concern. Studies have been conducted by the USP and pharmaceutical manufacturers, stakeholder conferences have been held, and the Pharmacopeial Forum
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