eChapter 70 (Part 2): The Goodman & Gilman Year in Review: 2012 New and Noteworthy FDA Approvals

The FDA approved 42 new drugs and biologics of note in 2012. About half are pharmacologically similar to others already marketed (see Table 70-2). Among the remainder are 16 first-in-class agents indicated for the management of a variety of conditions, including several for targeted specific genetic anomalies (see Part 1 of this series). While FDA published draft guidance on biosimilar product development in the federal register in 2012, there were no "firsts" approved under these rules in the U.S. last year.¹ By comparison, at least 14 biosimilars are approved for use in the European Union.² Despite the name similarities, FDA is deliberate in pointing out that two 2012 approvals, tbo-filgastim and ziv-aflibercept (see Table 70-2) were not approved under the biosimilar rules. On a different note, three previously marketed, unapproved pancreatic enzyme products were licensed in 2012, doubling the number of products marketed to improve digestion in patients with pancreatic insufficiency. FDA affirmation of these previously "marketed, unapproved" drugs established the good manufacturing practices necessary to assure the batch-to-batch reliability of their pharmacological activity.³ On the medical devices forefront, FDA extended a biological license for BIO-SEAL as a lung biopsy tract plug system to reduce the risk of a collapsed lung following percutaneous transthoracic needle biopsies. This approval represents an innovative use of an existing device that contains a dyed gel in a delivery system designed to attach to the biopsy needle following tissue extraction. The gel is injected into the empty space in the biopsy tract and expands as it rehydrates to form a seal that prevents air from leaking out of the lung. The seal is visible on imaging to expedite follow-on surgical procedures that may be indicated by the results of the biopsy. The gel is absorbed by the body as the puncture site heals. Other 2012 noteworthy FDA regulatory activities are assembled and characterized below. Table 70-3 lists established drugs that were extended for a new indication or significantly reformulated in 2012.

Market Withdrawals/Suspensions:

• In 2012, no drugs were suspended from marketing in the U.S. due to an emerging safety risk.

• Marketed Unapproved Single-Ingredient, Immediate-Release Oxycodone Products : Unapproved and/or misbranded single-ingredient, immediate-release oxycodone products were the subject of FDA's 18^th notice of enforcement actions against drugs that are not proven to be safe, effective, or of high quality. To avert potential harm to patients from confusion between products, the Federal Register notice of this regulatory action includes language to discourage manufacturers from reformulating their products into unapproved new products (without oxycodone) and marketing them under the same or substantially the same name. The regulatory action by FDA to eliminate unapproved oxycodone from the U.S. market is not expected to adversely affect the supply available to treat patients.⁴

• Marketed Dietary Supplements Containing Dimethylamylamine: FDA took steps to halt the sale of dietary supplements containing dimethylamylamine (DMAA, 1,3-dimethylamylamine, methylhexanamine, geranium extract) because the products have not been proven safe for use as "natural" stimulants. Prior to the action, DMAA products were widely used for weight loss, body building, and to enhance physical conditioning in conjunction to workout sessions.⁵ DMAA is known to constrict blood vessels and arteries, which may lead to cardiovascular consequences. Nervous system disorders, psychiatric disorders, and death have been reported in association with products containing DMAA. Some of the products contain synthetically produced DMAA which is not eligible to be marketed as a "dietary ingredient."

Immunobiologic Licenses

• Available as an orphan drug product for many years, FDA approved varicella zoster immune globulin (varizig) for post-exposure prophylaxis of patients at risk for potentially fatal consequences of chickenpox infection. These groups include immuno-compromised children and adults, newborns of mothers with varicella shortly before or after delivery, premature infants, infants less than one year of age, adults without evidence of immunity, and pregnant women.

• Meningococcal Groups C and Y and Haemophilus b Tetanus Toxoid Conjugate Vaccine (menhibrix) was licensed for active immunization to prevent invasive disease caused by Neisseria meningitidis serogroups C and Y and Haemophilus influenzae type b for children 6 weeks of age through 18 months of age.⁶

• Quadravalent Influenza Vaccines (fluarix , flumist): Intramuscular (fluarix) vaccine was licensed for active immunization of individuals >3 years of age and intranasal (flumist) vaccine was licensed for active immunization of individuals 2-49 years of age for the prevention of disease caused by influenza A subtype viruses and type B viruses contained in the vaccine. The quadravalent vaccines will contain two strains each of inactivated influenza A and B viruses and are expected to be made available for the 2013-2014 flu season along with traditional trivalent vaccines.^{7, 8}

• Trivalent Influenza Vaccine manufactured using cell culture technology (flucelvax): Intramuscular flucelvax is an inactivated influenza virus vaccine prepared from virus grown in Madin Darby Canine Kidney cells. Traditional influenza virus vaccines are grown in chicken eggs and carry a warning for patients allergic to eggs.⁹