It is the height of arrogance for Wyeth to question the value and quality of compounded medications when they just recently received a WARNING LETTER from the US Food and Drug Administration; the letter is dated May 8, 2006. Let's look at some of the issues/deficiencies raised by the FDA. (Note: The entire letter is available at: www.fda.gov/foi/warning_letters/g5851d.htm)

1. "Failure to thoroughly investigate the unexplained discrepancies or out of specification results in batches of Triphasil 21 and Triphasil 28 tablets manufactured at your site�" During the stability interval assay for the Triphasil product, an unknown peak at high levels was detected on June 17, 2005.

   The product was still allowed to remain on the market and as of the date of this letter, "the identity and the root cause of the peak are still unknown." The FDA further states "We are concerned that while the investigation has been ongoing for months, the affected lots remain in the market." The letter also states there is no assurance that other lots are not affected by the same unknown.

   The letter expresses the concerns of the FDA that no action was considered against the affected lots in the market and an effort to identify the unknown peak and to conclude the stability investigation was not made until the issue was raised during the recent FDA inspection.

   The last paragraph in this section states "It is noteworthy that our investigators have observed seventeen other examples, occurring between December 2003 and August 2005, where adequate investigations into unknown peaks were not performed. These examples involved several different products that your firm manufactures including Ovrette, Zebeta, Alesse, Loette, Gestodene, Duofem, Velnafaxin, Rapamune, and Lo Gentrol."

2. "Failure to clean and maintain the packaging equipment at appropriate intervals to prevent contamination that would alter the safety, identity, strength, quality of the drug products�" A customer complained about the presence of a screw and two washers inside a bottle of Inderal LA Capsules. Other complaints involved the presence of a foreign metal object (ejector pins from the filling/packaging line) found inside a bottle of Protonix tablets and a bottle of Effexor tablets.

The FDA states "We are concerned that neither your cleaning procedures nor the line clearance inspections were able to detect that the affected equipment was missing some of its parts."

Comment:

It may behoove Wyeth to spend more time and money correcting its own flawed quality-assurance program instead of trying to influence the FDA that compounded bioidentical hormone preparations are the issue. What would happen if patients were to find out about the quality issues with these manufactured products and even learn about the calloused attitude of the manufacturer towards quality?

As pharmacists concerned with quality, we have always trusted the pharmaceutical industry to be "above board" and "constantly working to attain the highest quality levels." However, those days may be gone, especially if one looks at all the FDA actions of the past few years. The emphasis from the pharmaceutical industry appears to have changed from "quality and patients" to "quantity and profits"!

More next week.

Loyd V. Allen, Jr., Ph.D., R.Ph
Editor-in-Chief

This discussion group of over 1000 pharmacy personnel worldwide continues to be active, with discussions over the last week including:

• Pelvic pain and/or menstrual pain treatments
• Liability insurance carriers
• Diarrhea treatments, other than traditional or probiotics
• Serotonin source of active pharmaceutical ingredient (API)
• Treatments for degenerative rheumatoid arthritis
• Nasal rinse or irrigation bottles
• Morphine sulfate ophthalmic drops for dogs

Join the list today at www.CompoundingToday.com/CNL and read what others have to say and/or contribute, and what questions are posted. It's easy, free, and informative.

Did you know that you can search on IJPC's website 24 hours a day, 7 days a week, 365 days a year for any articles and formulas we have published over the last 10 years? Go to www.IJPC.com/editorial/SearchJournal.cfm, type in progesterone, and see all the information you can use in your pharmacy. The information obtained can also help in educating local physicians.

A review of polyunsaturated fatty acids, with 54 articles examining their roles in preventing and treating chronic diseases, cancer, inflammatory disorders, immune/autoimmune disorders, cognitive impairment, and other conditions has been added to CompoundingToday.com's literature search database.

• Accinni R, Rosina M, Bamonti F et al. Effects of combined dietary supplementation on oxidative and inflammatory status in dyslipidemic subjects. Nutr Metab Cardiovasc Dis 2006; 16(2): 121-127.
• DeFilippis AP, Sperling LS. Understanding omega-3's. Am Heart J 2006; 151(3): 564-570.
• Grimminger F, Mayser P, Papavassilis C et al. A double-blind, randomized, placebo-controlled trial of n-3 fatty acid based lipid infusion in acute, extended guttate psoriasis. Rapid improvement of clinical manifestations and changes in neutrophil leukotriene profile. Clin Investig 1993; 71(8): 634-643.
• Heller AR, Rossel T, Gottschlich B et al. Oemga-3 fatty acids improve liver and pancreas function in postoperative cancer patients. Int J Cancer 2004; 111(4): 611-616.
• Maroon JC, Bost JW. Omega-3 fatty acids (fish oil) as an anti-inflammatory: An alternative to nonsteroidal anti-inflammatory drugs for discogenic pain. Surg Neurol 2006; 65(4): 326-331.

Registered users can see all 54 articles at CompoundingToday.com/Articles/SearchResult.cfm?Batch=68

Take a look at the Veterinary Transdermals Tool on CompoundingToday.com by going to http://compoundingtoday.com/VetTransdermal/ you can see information on 29 drugs. A few drugs in this tool are atenolol, fluoxetine, methimazole, and enrofloxacin.

Mixing using small, sealable containers.
It is often wise to use mixing processes involving small containers that have a sealable cap. If the density and particle size of the powders to be mixed are similar, this is a very effective blending method. To minimize any loss of potent drug, especially if present in a very small quantity, add the excipients to the container first, affix the cap, and rotate the container. This will "coat" the interior surfaces with the excipient. Then, add the potent drug, affix the cap, and rotate the container for an extended period of time until uniformly mixed. This procedure will minimize the possibility of the active drug "sticking" to the interior surface of the container that may result in improper mixing and some loss of active drug.