Question: In the revised USP <795> Pharmaceutical Compounding?Nonsterile Preparations:
    1.  Why is there a loss of one day in the BUDs?
    2.  Why is the day the preparation is compounded considered as
         "Day 1" in USP <795> but as "Day 0" in USP <797>?
    3.  Why the inconsistency between the two chapters?

Before answering, let's see what USP <795> says:

10. ESTABLISHING BEYOND-USE DATES
10.3 Establishing a BUD for a CNSP

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. The BUDs in Table 3 [of USP <795>] are based on the ability of the CNSP to maintain chemical and physical stability and to suppress microbial growth...

Answer:
Stability should begin with the compounding of the preparation as "Day 0," as it is reported routinely in scientific stability studies and is the industry standard. A compounded preparation should NOT lose a day of its BUD by this arbitrary assignment of the "day of compounding is considered Day 1."

Comments:
In the revised <795>, it is not clear or explained why the day a preparation is compounded is assigned as "Day 1" and not "Day 0". This is not the same in sterile compounding <797>. In <797>, a day is stated to be 24 hours. The starting point of any scientific study, etc., is "Day 0." Patients should not be penalized for this arbitrary shortening of the BUD. Also, if the day of compounding was "Day 1" in <797>, the BUD for a Category 1 CSP [Table 10 of USP <797>], which is 12 hours, would be out-of-date as soon as it was compounded.

Another Question: In USP <795>, 10.1 Terminology, the first sentence states:
Each CNSP label must state the date, or the hour and date, beyond which the preparation cannot be used and must be discarded (i.e., the BUD).

Answer:
Probably a minor point but Table 3 in <795> ONLY lists "days" and not hours. The word "hours" is only mentioned in <797> so why is it mentioned here? Is it necessary to change Beyond-Use Date to Beyond-Use Date and Time? Not sure patients would really comply and is it really "clinically significant" since most compounded preparations appear to be stable past their assigned BUDs as shown in most stability studies? (Note: Also of interest regarding Expiration Dates, see the EpiPen story below).

Next week we will begin a discussion on the use of Water Activity (Aw) the way it is applied in <795>.

Editor's Note: For those state boards of pharmacy that are NOT adopting any or all of these chapters and preparing their own or using their own modifications of the chapters, it is important that all pharmacists within the individual states clearly read, understand, and implement those state laws and regulations affecting them.

News

The FDA Moves Compounding Program to Office of Compliance
FDA-CDER plans to "institutionalize" its compounding regulatory program within the center's Office of Compliance. In recent years, the FDA has issued dozens of guidance documents related to compounding, stepped up its inspection and enforcement efforts and taken legal action against compounders found in violation of the FDCA. Within the Office of Compliance, a new compounding team has been established within the Immediate Office with responsibility for overall management of the program.
https://www.raps.org/news-and-articles/news-articles/2019/6/fda-moves-compounding-program-to-office-of-complia

Study Shows Many Epinephrine Self-injectors Retain Potency Long after Expiration Dates
EpiPens and other autoinjectors filled with epinephrine to treat severe allergic reactions may still be potent enough to work many months past their labeled expiration date, according to a new study that concludes patients might need expensive refills less often. Soaring prices and out-of-pocket costs for the autoinjectors have made it increasingly difficult for many patients to keep throwing out and replacing unused devices when they expire, researchers note in the Journal of Allergy and Clinical Immunology: In Practice.

For the study, researchers tested the contents of 46 different autoinjectors to see how much epinephrine remained after the expiration dates on the labels. Half of the devices were tested at least two years after their labeled expiration date. At this point, 80% of the devices still retained 90% or more epinephrine, indicating they were still effective under the FDA rules.

"If the expiration dating on these devices was changed, this means that patients would not need to replace their auto-injectors as frequently, limiting cost to them, their insurance, and the healthcare system, while still feeling secure that they have access to adequate treatment for anaphylactic reactions," said lead study author Lynn Kassel of Drake University College of Pharmacy & Health Sciences in Des Moines, Iowa.

Devices six months past their labeled expiration date in the study still had 100% of the original epinephrine dose. One year after the labeled expiration date, devices still had 95% of the original epinephrine dose. And all of the autoinjectors tested that were up to 30 months beyond their labeled expiration date still had 90% of the dose remaining.
https://www.reuters.com/article/us-health-allergies-epinephrine/many-epinephrine-self-injectors-still-potent-long-after-expiration-date-idUSKCN1TE2OX

Did You Know ...

...that the following obituary existed?

An Obituary!
Today we mourn the passing of a beloved old friend, Common Sense (CS), who has been with us for many years.

No one knows for sure how old CS was, since CS's birth records were long ago lost in bureaucratic red tape. CS will be remembered as having cultivated such valuable lessons as:

-Knowing when to come in out of the rain;
-Why the early bird gets the worm;
-Life isn't always fair;
-And maybe it was my fault.

Tip of the Week

It has been said that "Not many attended CS's funeral because so few realized CS was gone." Maybe we can remember and teach our kids, grandkids, and great grandkids about CS!

More next week!

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Looking Back

Drinking drivers,
Don't you know?
Great bangs from little
Binges grow!
     Burma-Shave