To begin the process of identifying which products or categories of drug products are demonstrably difficult to compound, the FDA convened an internal Agency work group. The workgroup identified six criteria to use in evaluating whether a drug product or category of drug products is demonstrably difficult to compound under sections 503A and 503B. The criteria are as follows:

1. Complex Formation
   A formulation in which the ingredients are required to have certain unique characteristics or properties that are necessary to achieve and maintain the proper performance of the drug product. Examples may include crystalline (including polymorphs) or amorphous forms, chirality, particle size.
2. Complex Drug Delivery Mechanism
   The way in which the drug product is targeted for delivery and/or released from the dosage form in the body to achieve the desired therapeutic effect. Examples may include coated beads, polymeric matrices, liposomes.
3. Complex Dosage Form
   Physical dosage units with characteristics that are difficult to consistently achieve and maintain. Examples may include propellant based aerosolized products and dry powder inhalers.
4. Bioavailability
   The rate and extent to which the active ingredient, or its active moiety, is absorbed into the body and becomes available at the site of action. Examples may include characteristics of the API or compounded drug product resulting in inconsistent bioavailability.
5. Compounding Process Complexity
   Compounding the drug product requires multiple, complicated, or interrelated steps and/or specialized facilities and/or equipment to achieve the appropriate drug product. Examples may include creating multi-particulate dosage forms of solid oral beads (requires wet granulation, extrusion, spheronization, fluid bed drying, coating or curing before they are processed into the final dosage form).
6. Physicochemical or Analytical Testing Complexity
   The challenges presented with confirming the end-product testing for batch-to-batch uniformity, potency, purity, and quality of a drug product. Examples may include specialized analytical instruments and/or training for identifying constituents of complex mixtures by nuclear magnetic resonance, mass spectrometry, and/or X-ray powder diffraction. Cell-based assays for performance characterization.

Application
The above criteria are not mutually exclusive; a drug product, or category of drug products, may meet one or more of these criteria. These criteria will be considered individually and collectively when evaluating whether a drug product or category of drug products is demonstrably difficult to compound. No single criterion will be considered dispositive.

The FDA received 71 nominations for difficult to compound drug products and categories of drug products, and the FDA has identified some potential categories separately. The focus will be on products that are known to be difficult to manufacture with: (1) evidence in the literature, (2) FDA experience reviewing NDAs and ANDAs, and (3) the potential to affect the public health.

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

News

CVS Controlling Cholesterol-lowering Drugs
CVS, the No 2 manager of drug benefit plans for U.S. employers and insurers, will wait until a second new cholesterol-lowering drug is approved by regulators before negotiating for price discounts or adding either of new drugs to its list of covered medications. The FDA has approved Praluent, which works by blocking a protein called PCSK9 that helps "bad" LDL cholesterol stay in the bloodstream. An FDA decision on a second PCSK9 inhibitor, Repatha, is expected later this month.
http://uk.reuters.com/article/2015/08/10/us-health-cholesterol-costs-idUKKCN0QF05120150810?rpc=401

PBMs Wield "Potent Weapon" Controlling Drugs
Geoffrey Porges, a Sanford C. Bernstein analyst, calls the coverage exclusions a "potent weapon" for PBMs and estimates the number of drugs excluded by at least one of the two major PBMs will rise to 165 in 2016 from 130 this year. Express Scripts CMO stated, "We're often able to extract over-sized discounts from the pharma manufacturers" by holding out the option of coverage exclusion. Historically, PBMs wouldn't typically exclude drugs from coverage but would try to direct patients to cheaper options by requiring them to pay more out-of-pocket for less favored drugs. However, CVS began excluding drugs from its preferred list in 2012, and Express Scripts later followed suit.
http://www.wsj.com/articles/drug-plan-managers-wield-potent-weapon-1438905295

CVS Health Paying Government $450,000 to Settle Dispute
CVS Health has agreed to pay $450,000 to the federal government to settle allegations that some of its retail pharmacies in Rhode Island filled forged and invalid CDS prescriptions. The agreement is the culmination of a two-year investigation by the U.S. Attorney's office and the DEA Office of Diversion Control into several of the Woonsocket, Rhode Island-based CVS's retail pharmacy locations.
http://abcnews.go.com/US/wireStory/cvs-health-pay-government-450000-settle-dispute-32989940

358,000 Inhalers Recalled by Boehringer Ingelheim
Inhalers can be difficult to manufacture and for the second time in two weeks there is another recall because the devices may not deliver any drug. Last week's recall was by AstraZeneca in Denmark. Boehringer Ingelheim is recalling one lot consisting of 358,647 Combivent Respimat inhalers because the delivery system is defective and may provide insufficient spray, or none at all. These propellant-free inhalers were manufactured in Germany. In Denmark last week, AstraZeneca issued a recall of a lot of its Bricanyl Turbuhalers after discovering they may contain no powder.
http://www.fiercepharmamanufacturing.com/story/boehringer-ingelheim-recalls-more-358000-inhalers/2015-08-11

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Did You Know ...

�that today is the celebration of Victory over Japan Day (also known as Victory in the Pacific Day, V-J Day, or V-P Day)? This is the day on which Japan surrendered in World War II, effectively ending the war. Actually, V-J Day has been applied to both of the days on which the initial announcement of Japan's surrender was made—to the afternoon of August 15, 1945, in Japan, and, because of time zone differences—to August 14, 1945 (when it was announced in the U.S. and the rest of the Americas and Eastern Pacific Islands). Also, it is applied to September 2, 1945, when the signing of the surrender document occurred, officially ending World War II.

Tip of the Week

With all the "tools" we have today to look things up and learn, spend a few minutes each day or week looking back at our history. The Internet can be used for good and bad, depending upon the user. Use it for good and for learning to enhance your knowledge base.

Looking Back

Don't leave safety,
To mere chance.
That's why belts,
Are sold with pants!
     Burma Shave