Editorial: Catch-22: FDA-CPG on Veterinary Compounding

USP Pharmacy standards for compounding that either are or may be enforced by the state boards of pharmacy require the active pharmaceutical ingredient (API) in a compounded preparation to be present in an amount equal to 90.0% to 110.0% of the label. (US Pharmacopeia General Chapter <795> Pharmaceutical Compounding-Nonsterile Preparations).

As many commercial products do not have USP monographs for public standards, the pharmacist has no way of knowing what the actual allowable range of the API may be in the manufactured product or of its actual analyzed potency. It may be 90.0% to 110.0%, or it may be 80.0% to 120.0%, or even a broader or different range. If the pharmacist does not know what the potency of the API is in the commercial product, then there is a possibility that the compounded preparation will be outside the allowable USP standards that have been adopted by most states in their laws and regulations. Consequently, obeying the CPG results in possibly being noncompliant with the state board of pharmacy rules and regulations.

For example, let's look at a situation where a pharmacist receives a prescription from a veterinarian for a tetracycline hydrochloride oral dosage form at a concentration of 500 mg per 5 g paste. The source of the drug may be tetracycline hydrochloride 500-mg capsules. Tetracycline Hydrochloride Capsules USP have a standard of not less than 90.0% and not more than 125.0% of the API. The manufactured capsule could contain anywhere between 450 mg and 625 mg of tetracycline hydrochloride, but the pharmacist has no way of knowing the exact quantity per capsule. If the manufactured capsules actually had 600 mg of tetracycline hydrochloride (which meets the USP requirement of 90.0% to 125.0%: actually 600 mg is 120% of label), and the pharmacist is required to use those capsules but has absolutely no idea that they contain 600 mg instead of the labeled 500 mg, then the final preparation that is compounded will be 120% of label which does not meet the state's requirement for compounded preparations of 90.0% to 110.0%. The pharmacist will now be noncompliant with the state board of pharmacy that enforces the 90.0% to 110.0% standard. Monographs for bulk substances or APIs generally have a tight requirement (e.g., 98% to 102%) or in the case of antibiotics must be labeled with their activity/potency as this is "lot specific." The Certificate of Analysis (lot specific) is used by pharmacists to obtain the actual strength of an API. Consequently, compounding with APIs is the most accurate way to compound in this situation.

Another difficulty is that many of the most popular veterinary drugs used as a source of the active drug in compounding do not even have a USP monograph. The manufacturers have never submitted the necessary information for a public standard to be prepared and published for professional use. This keeps healthcare professionals, especially pharmacists, in the dark and more likely to have compounded preparations that are outside of the compounding quality standards through no fault of their own.

All of this results in a "catch-22" situation that could easily be resolved by allowing veterinary compounding to use bulk substance APIs and not requiring compounding from commercial drug products.

Loyd V. Allen, Jr., PhD, RPh
Editor-in-Chief

The Doctor is in but Won't See You Now
For pharmaceutical representatives (reps), obtaining access to busy physicians grew still more difficult in 2009. The number of physicians willing to see most reps fell nearly 20 percent, the number refusing to see most reps increased by half, and the number of management-planned sales calls that were nearly impossible to complete topped 8 million.

The reporting group monitors the sales rep-related interactions of more than 500,000 physicians, nurse practitioners, and other pharmaceutical prescribers nationwide and tracks both the planned and completed sales calls of more than 41,000 pharmaceutical representatives.

The spring 2010 report of AccessMonitor reports that only slightly more than half (58 percent) of prescribers in 2009 were "rep-accessible" or they met with at least 70 percent of the sales representatives who called on them. This number declined 18 percent from the spring 2009 study.

The trend apparently reflects both the physician's busier schedule and the pharmaceutical industry's lack of new blockbuster drugs. Physicians as a whole were hesitant to see any but the most valuable pharmaceutical sales representatives.

Pharmaceutical representatives seem to be operating today in an increasingly unwelcome physician-office environment, as the number of physicians who refuse to see any reps is increasing and the number of physicians who will see most reps is declining.

The more progressive pharmaceutical companies now recognize the need to be more precise and more efficient with their sales and marketing efforts. They tend to have responded by adopting a dramatic new sales force deployment strategy called "differential resourcing," which matches sales resources to local conditions and is more flexible than conventional, "one-size-fits-all" selling models.
http://pharmalive.com/news/index.cfm?articleID=702608&categoryid=43&newsletter=1

Lilly Plans 200 Sales, Marketing Job Cuts
Eli Lilly and Co. plans to cut 200 sales and marketing support jobs, with more than half of those cuts taking place in Indianapolis. The cuts are the latest wave of the company's previously announced plans to eliminate 5,500 jobs worldwide by the end of 2011 in response to financial pressures. These recent cuts are the largest since Lilly eliminated 200 jobs from its research laboratories in March.
http://pharmalive.com/news/index.cfm?articleID=702874&categoryid=9&newsletter=1#

New Risks Emerge for Some Stomach Drugs
Proton pump inhibitors appear to be associated with fractures in postmenopausal women and with higher rates of bacterial infections, new studies show. More than 119 million prescriptions were written for proton pump inhibitors in the U.S. in 2009, and some doctors say they are overprescribed and are often used for less-severe ailments like indigestion or upset stomachs.

One federally-funded study (Women's Health Initiative) involved over 130,000 postmenopausal participants and found those taking proton pump inhibitors had a modest 25% increase in the risk of fractures over about an eight-year period as compared to those taking the type of acid-reducing drug known as an H2 blocker who had an 8% increased risk.

The other study of PPIs involved over 100,000 hospital discharges from one medical center during a five-year period. The investigators found patients with more stomach-acid reduction had a higher risk of developing C. diff infection, which can cause severe diarrhea. Patients taking PPIs daily had a 74% increased risk compared with those not taking the drugs. Patients taking H2 blockers, such as Zantac-considered less-potent stomach-acid blockers-had a 53% greater risk. Patients taking a more-than-once-a-day PPI dose more than doubled their risk of getting C. diff.
http://online.wsj.com/article/SB10001424052748703880304575236602137383786.html

� "There's right and there's wrong, and nothing in between"? (Source: Cowboy Ethics-What Wall Street Can Learn from the Code of the West).

It's What You Do, Not What You Have

Lessons can be learned from the harsh winter weather, the spring floods, and tornados that have killed and harmed people and have ravaged our "things." First, it is human life and health that is important�not the "things" that we have. Second, it is our response to these events that define us, as an individual and community, and not what we sit back and say about them to the media or to impress other people.