Question: In determining a beyond-use date in USP <795>, why is the day of preparation considered as “Day 1�, but, in USP <797>, it is considered as “Day 0�?
Answer:
To date, nothing to substantiate the loss of a day in the beyond-use date determination for CNSPs has been forthcoming from USP. If it has a scientific basis, it should be revealed since USP content is described as scientifically based; if not, this should be removed from the chapter. There is no substantiation provided for using “Day 1� in the following sources:
- USP <1191> Stability Considerations in Dispensing Practice states the following:
Stability – Stability is defined as the extent to which a product retains, within specified limits, and throughout its period of storage and use (i.e., its shelf-life), the same properties and characteristics that it possessed at the time of its manufacture...
Comment: Stability is based upon the characteristics of a drug that it possessed at the time of its manufacture (or compounding), which is “Day 0� and not “Day 1.�
Comment: It should also be noted that in the current USP <795>, in the Section on “Stability Criteria and Beyond-Use Dating,� the beginning sentence reads:
“The BUD is the date after which a compounded preparation shall not be used and is determined from the date when the preparation is compounded.�
Why was there a need to change? There must be a scientifically documented reason since the USP is presented as science-based.
Comment: For a note on “throughout,� see #4 below:
- There is actually a conflict between the first two sentences in 10.3 Establishing a BUD for a CNSP, which reads:
“The BUDs indicate the days after the CNSP is prepared and beyond which the CNSP must not be used. The day that the preparation is compounded is considered Day 1.�
Comment: In counting the “days after an event,� one starts with the initial event as day “0.� However, the next sentence contradicts this as it starts at day “1�. See #3.
- USP <797> Pharmaceutical Compounding—Sterile Preparations states in the first sentence of 14.1 Terminology: “The BUD is determined from the date/time that the preparation of the CSP is initiated.�
Comment: This is not the same as it is in USP <795>. On what basis do you begin the BUD on nonsterile compounded preparations as Day 1 after compounding and on sterile compounded preparations as Day 0, the day of compounding? This is contradictory and seems inappropriate. BUD standards should be uniform, even though the length of time may differ, whether they are for nonsterile or sterile preparations.
- USP <797> Pharmaceutical Compounding—Sterile Preparations defines in its “Glossary� the term “Stability� as the extent to which a product or preparation retains physical and chemical properties and characteristics within specified limits throughout its expiration or BUD.
Comment: This definition includes the phrase “throughout its expiration or BUD,� which encompasses the time period from its preparation to its BUD or expiration date. “Throughout� is defined as “during the whole course or period or time or extent.� This obviously encompasses day “0.�
- The following documents were reviewed and do not mention or support the use of “Day 1� to begin counting an expiration date or BUD:
- FDA Guidance for Industry: Q1E Evaluation of Stability Data does not mention a loss of a time period when assigning an expiration date.
- ICH Harmonised Tripartite Guideline: Stability Testing of New Drug Substances and Products (Q1A(R2) does not mention a loss of a time period when assigning an expiration date.
- FDA Guidance for Industry: Q1A(R2) Stability Testing of New Drug Substances and Products does not mention a loss of a time period when assigning an expiration date.
In summary, it appears inappropriate for the chapter to begin counting the day of preparation as “Day 1� of the CNSP BUD resulting in the loss of one day of the BUD and use of the preparation by the patient, especially since there appears to be no scientific basis for this in the chapter.
Loyd V. Allen, Jr., PhD, RPh
Editor-in-Chief
International Journal of Pharmaceutical Compounding
Remington: The Science and Practice of Pharmacy Twenty-second edition
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