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Editorial: Sterility Testing

This week we will discuss what United States Pharmacopeia (USP) Chapters <795> and <797> say about sterility testing requirements for compounded sterile preparations (CSPs).

Topic: Must ALL CSPs Be Sterility-tested?

There are two situations related to sterility testing in USP <797>. First, let's look at batches of more than 25 identical individual single-dose packages or multiple-dose vials. USP <797> states:

"All high-risk level CSPs that are prepared in groups of more than 25 identical individual single-dose packages (e.g., ampuls, bags, syringes, vials) or in multiple-dose vials (MDVs) for administration to multiple patients or that are exposed longer than 12 hours at 2 to 8� and longer than 6 hours at warmer than 8� before they are sterilized shall meet the sterility test (see Sterility Tests <71>) before they are dispensed or administered."

[Note regarding dispensing: The next paragraph states that "When high-risk level CSPs are dispensed before receiving the results of their sterility tests, there shall be a written procedure requiring daily observation of the incubating test specimens and immediate recall of the dispensed CSPs when there is any evidence of microbial growth in the test specimens."]

It is quite clear in the above statement under one set of conditions sterility testing is required. Now, let's look at a second situation which provides default beyond-use dates (BUDs) if no sterility-testing is done. Chapter <797> provides BUDs for different risk-level CSPs when they are not sterility tested; the default dates. Notice that for all risk levels, the storage periods are given for "in the absence of passing a sterility test."

"For a sterilized high-risk level preparation, in the absence of passing a sterility test, the storage periods cannot exceed the following time periods:�"

"For a medium-risk preparation, in the absence of passing a sterility test, the storage periods cannot exceed the following time periods:�"

"For a low-risk level preparation, in the absence of passing a sterility test, the storage periods cannot exceed the following time periods:�"

In other words, the CSPs can be dispensed and used with no sterility testing if using the default BUDs provided in <797>.

We also see in the statement below that sterility testing "may" be applied�.This is not a requirement.

<797> VERIFICATION OF COMPOUNDING ACCURACY AND STERILITY

"For example, sterility testing may be applied to specimens of low- and medium-risk level CSPs and standard self-contained biological indicators (BI) shall be added to nondispensable specimens of high-risk level CSPs before terminal sterilization for subsequent evaluation to determine whether the sterilization cycle was adequate."

In summary, to require every CSP to be sterility tested would bring pharmacy practice and patient care almost to a standstill in many settings. Does one expect every single IV admixture in hospitals, every single in-syringe mixture in hospitals and clinics, every single chemo combo, every TPN, etc. to be sterility tested prior to use? Obviously this is ridiculous. This is why the allowance is made for shorter BUDs when sterility testing is NOT done. So, the response to the question posed above is, "No, <797> does not require that all CSPs be sterility-tested."


Loyd V. Allen, Jr., PhD, RPh
Editor-in-Chief
International Journal of Pharmaceutical Compounding
Remington: The Science and Practice of Pharmacy Twenty-second edition

Laboratory Results Prompt More Pharmacy Recalls
The FDA has announced that three more compounding pharmacies have issued recalls related to sterility concerns. Two of the recalls involve Front Range Laboratories, of Loveland, Colorado. After an inspection, the FDA issued an alert to pharmacies stating that "the methods used by Front Range to assess sterility and other qualities (e.g., strength and stability) may have resulted in pharmacies receiving inaccurate/unreliable laboratory test results. The FDA recommends that, at this time, pharmacies not use this laboratory.
http://www.medscape.com/viewarticle/810085

Drug Shortage Situation-302 at end of July 2013
Fewer new drugs have been added to the shortage list in the last year, but those already on the list show few signs of moving off. There have only been 86 new shortages through July 31 this year, down from 204 in all of last year, 267 in 2011, and 211 in 2010. But, the actual number of active shortages as of the end of July 2013 was 302. The existing shortages continue to be a problem due to the protracted time it takes companies to resolve their manufacturing problems that cause the shortages.

An interesting twist is that a July 23 decision in the Court of Appeals for the District of Columbia Circuit permanently enjoined the FDA from allowing imported versions of thiopental (for executions). It is unknown how this importation restriction will affect drug shortages; it may be interpreted broadly and prevent the FDA from allowing imports of other drugs.
http://www.medpagetoday.com/Washington-Watch/FDAGeneral/41157

Novartis Recalls 4.4 Million Bottles of Maalox; Other Problems Persist
The closing of a Novartis plant in Nebraska may not be the cause of heartburn in Canada but it certainly is contributing to it. The popular over-the-counter acid relief product Maalox, which was made at the Lincoln, Nebraska plant, is running out in Canada. Shortages of a number of OTC products are likely. The plant closing has affected everything from opioids to pet medications and was Novartis' largest OTC manufacturing facility, producing its entire Excedrin line, as well as NoDoz, Bufferin, and Gas-X Prevention products. The company also makes products like Percocet for Endo Health Solutions and hypertension products for GlaxoSmithKline.

Serious concerns were raised by the FDA over manufacturing at the plant, which was closed in December. Included in the problems; there was a chance that chipped particles of one drug made it into the bottles of other drugs. Unclean lines and more than 1,300 consumer complaints that had not been addressed were also found.
http://www.fiercepharma.com/story/novartis-plant-closure-contributes-maalox-shortage-canada/2012-05-30?utm_medium=nl&utm_source=internal

Ranbaxy Drug Quality Being Investigated by India Government
The government of India has ordered the Drug Controller General of India (DCGI) to check the quality of drugs produced by Ranbaxy Laboratories for compliance with standard manufacturing norms. Earlier this year in the U.S., Ranbaxy had pleaded guilty to "felony charges" for the manufacture and distribution of certain drugs not in conformity with the GMP regulation and agreed to pay a fine of $500 million (US). The generic drugs at issue were manufactured at Ranbaxy's facilities in Paonta Sahib and Dewas in India.
http://articles.economictimes.indiatimes.com/2013-08-23/news/41440804_1_gmp-srikant-kumar-jena-ranbaxy-laboratories

Anti-overdose Drug for "First Responders"?
The White House wants more first responders to carry naloxone injection to reverse the effects of drug overdoses; from heroin or other opioids. "By equipping first responders with this lifesaving drug we can begin to turn the tide on overdose death," stated Michael Botticelli, deputy director of the White House's Office of National Drug Control Policy. Also, the Substance Abuse and Mental Health Services Administration is releasing a toolkit that is designed to help patients, first responders, and overdose survivors combat overdoses.
http://thehill.com/blogs/regwatch/administration/319155-white-house-pushes-anti-overdose-drug

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PCAB is proud to announce the accreditation of the following pharmacies:

Cherokee Custom Script, Canton, Georgia; Dale Coker, RPh, dmcoker@bellsouth.net. Re-accreditation for Sterile & Nonsterile Compounding

Lamar Plaza Drug Store, Austin, Texas; Kathryn Van Besien, PharmD, kathryn@cpdwellness.com. Initial Accreditation for Nonsterile Compounding