Specialty Pharma Industry News is provided by SPA Member Dr. Larry Boos
October 30
Interim Policy on Compounding Drugs Using Bulk Drug Substances
FDA issued a revised final guidance in January 2017, Guidance for Industry, Interim Policy on Compounding Using Bulk Drug Substances Under Section 503B of the Federal Food, Drug, and Cosmetic Act, which is in place while the FDA develops the 503B bulks list. The guidance describes conditions under which the agency does not intend to take action against outsourcing facilities that compound drug products from bulk drug substances that cannot otherwise be used in compounding under section 503B. The guidance documents describe three categories of bulk drug substances nominated by the public for use in compounding.

Category 1 - These substances may be eligible for inclusion on the 503B bulks list, were nominated with sufficient information for FDA to evaluate them, and do not appear on any other list.
Category 2 - These are bulk drug substances that were nominated with sufficient supporting information for FDA to evaluate them, but FDA has identified significant safety risks relating to the use of these substances in compounding pending further evaluation.
Category 3 - These substances may be eligible for inclusion on the 503B bulks list, but were nominated with insufficient supporting information for FDA to evaluate them.

Webinar Reminder: Final Guidance for Special Premarket Notification [510(k)] Pathway On September 12, 2019, the U.S. Food and Drug Administration (FDA) issued a final guidance document on the Special 510(k) Program. "The New 510(k) Paradigm: Alternate Approaches to Demonstrating Substantial Equivalence in Premarket Notifications" guidance is superseded by this final guidance document and The Abbreviated 510(k) Program, which reflects the Abbreviated 510(k) information from the New 510(k) Paradigm guidance. FDA also updated the following final guidance documents to reflect the updated Special 510(k) Program, improve alignment between the related 510(k) guidance, and reflect current policies: Format for Traditional and Abbreviated (510(k)s) Refuse to Accept Policy for 510(k)s Webinar: On October 31, 2019 at 1 pm EDT, the FDA will host a webinar to discuss these guidances.
Learn More: Device Advice - : Premarket Notification 510(k) Questions: If you have questions, please contact the Division of Industry and Consumer Education (DICE) in the Center for Devices and Radiological Health at 1-800-638-2014, 301-796-7100 or Dice@fda.hhs.gov.
October 29
Recall of Ranitidine Syrup, 15 mg/mL (Ranitidine Oral Solution USP) by Lannett   This recall is due to levels of Nitrosodimethylamine (NDMA) above the levels recently established by the FDA for Ranitidine Hydrochloride Syrup (Ranitidine Oral Solution, USP). NDMA is classified as a probable human carcinogen, a substance that can cause cancer, based on laboratory testing.  The capsule and tablet forms of this product are also being recalled by Novitium Pharma, Perrigo, and Dr. Reddys.   Also, Zantac 150, Zantac 150 Cool Mint, and Zantac 75 (all OTC ranitidine medicines) are being recalled by Sanofi.

The U.S. Food and Drug Administration (FDA) inter-agency Drug Shortages Task Force has released a report, Drug Shortages: Root Causes and Potential Solutions, that examines the root causes of drug shortages and recommends enduring solutions.  The report identifies three root causes for drug shortages: lack of incentives for manufacturers to produce less profitable drugs; limited recognition for manufacturers with "mature quality systems" that focus on continuous improvement and early detection of supply chain issues; and logistical and regulatory challenges that make it difficult for the market to recover from a shortage. 

CDC Podcast Series: Aging and Health Matters- Dementia, Healthy Lifestyles, and Your Genes  This new podcast and recent blogs (Part 1 and Part 2) describe how living a healthy lifestyle may help reduce your risk for Alzheimer's disease-the most common form of dementia. Genes may not be your destiny after all. Find out what CDC expert, Scott Bowen, has to say about your genes and the studies
October 28
Mylan Pharmaceuticals Initiates Voluntary Recall of One Lot of Alprazolam Tablets USP Class IV 0.5 mg to the Consumer Level.   This lot is being recalled due to the potential presence of foreign substance. Clinical impact from the foreign material, if present, is expected to be rare, but the remote risk of infection to a patient cannot be ruled out.   Retailers should immediately examine their inventory, quarantine and discontinue distribution of these lots.
October 25
Recently Posted Guidance Documents (Control/Click to view)
October 24
The U.S. Food and Drug Administration (FDA) recognizes that consumers may use various types of unapproved drugs, such as homeopathic drug products, to treat or relieve different diseases and conditions. These products are often marketed as natural alternatives to approved prescription and nonprescription products and are widely available in the marketplace. Homeopathic products, however, are marketed without FDA review and may not meet modern standards for safety, effectiveness, quality and labeling. FDA uses a risk-based approach to monitor these products and to evaluate reports of adverse effects.  We are taking two new steps toward clarifying this approach.  First, we have revised the 2017 draft guidance to provide further information around our approach and are asking for public input on the revised draft. Second, the agency is withdrawing the Compliance Policy Guide (CPG) 400.400, entitled "Conditions Under Which Homeopathic Drugs May be Marketed." 
October 23
GL Holdings Issues Voluntary Recall of Green Lumber Products Due to Presence of Undeclared Tadalafil (Cialis).   The presence of tadalafil in the Green Lumber products renders them unapproved drugs for which safety and efficacy have not been established, and therefor subject to recall.

Warning Letters
Linda F Ogburn, Owner, Paisley Farms LLC dba Paisley Farm & Grafts, Lawrenceburg, TN 38464
During our inspection we collected product labels for your Moringa Oleifera Leaf Powder and Moringa Oleifera Seed Powder products. The claims on your Facebook page establish that the products are drugs under section 201(g)(1)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 321(g)(1)(B)] because they are intended for use in the cure, mitigation, treatment, or prevention of disease. Additionally the product labels do not bear a statement of identity as a dietary supplement, a supplement facts panel, or other information that the products are intended to supplement the diet. Also these products are not prepared, packed, or held under conditions that meet the Current Good Manufacturing Practice (CGMP) regulations.

Mr. Sun Jai Quan, President and General Manager, Jiangsu NHWA Pharmaceutical Co., Ltd., Xuzhou Shi Jiangsu Sheng, 221000 China
This warning letter summarizes significant deviations from current good manufacturing practice (CGMP) for active pharmaceutical ingredients (API).
1. Failure to ensure that all sampling plans and test procedures are scientifically sound and appropriate to ensure that your API conform to established standards of quality and purity.
2. Failure to adequately investigate and document out-of-specification results according to a procedure and implement appropriate corrective actions.

Mr. Ryan P Collett and Mr. Cade Copeland, Rooted Apothecary LLC, Naples, FL 34116
FDA has determined that your "Teeth/TMJ - Essential Oil + CBD Infusion," "Ears - Essential Oil + CBD Infusion," "Hemp Capsules, 750 mg," "Hemp Infused Body Butter," and "Hemp Oil" products are unapproved new drugs sold in violation of sections 505(a) and 301(d) of the Federal Food, Drug, and Cosmetic Act (the FD&C Act), 21 U.S.C. 355(a) and 331(d). Furthermore, these products are misbranded drugs under section 502(f)(1) of the FD&C Act, 21 U.S.C. 352(f)(1).
The Agency is particularly concerned that you market unapproved new drugs for uses in infants and children. Such products include, but are not limited to, "Teeth/TMJ - Essential Oil + CBD Infusion" and "Ears - Essential Oil + CBD Infusion." Your products have not been evaluated by the Agency for safety, effectiveness, and quality. The use of untested drugs can have unpredictable and unintended consequences, especially in vulnerable populations.

Ms. Eleanor Palmer, President, Coral Pharmaceuticals, LTD, Freeport City, Grand Bahama, Bahamas
This warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See 21 CFR, parts 210 and 211.
1. Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a).
2. Your firm failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to validate and establish the reliability of your component supplier's test analyses at appropriate intervals (21 CFR 211.84(d)(1) and (2)).
3. Your firm failed to establish an adequate quality control unit and procedures applicable to the quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in- process materials, packaging materials, labeling, and drug products, including drug products manufactured, processed, packed or held under contract by another company (211.22(a) and (d)).
October 22
The  FDA will host a workshop, Repurposing Off-Patent Drugs: Research and Regulatory Challenges, on December 5-6, 2019 in Rockville, MD.
Representatives from government, industry, academia and patient advocacy communities will participate in the workshop. For more information and to register, please visit FDA's  Repurposing Off-Patent Drugs: Research and Regulatory Challenges webpage. 

CDC's Emergency Kit Checklist for Pets   Emergencies come in many forms: fires, hurricanes, earthquakes, tornadoes, floods, violent storms, and even terrorism. They can affect everyone, including pets. Are you prepared to protect your entire family? Read below for important preparedness checklists and visit our website for even more information on keeping pets safe during an emergency.
October 21
FDA Approved New Breakthrough Therapy for Cystic Fibrosis.  The U.S. Food and Drug Administration today approved Trikafta (elexacaftor/ivacaftor/tezacaftor), the first triple combination therapy available to treat patients with the most common cystic fibrosis mutation. Trikafta is approved for patients 12 years and older with cystic fibrosis who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which is estimated to represent 90% of the cystic fibrosis population.
October 18
FDA Announces Availability of Draft Guidance entitled "Drug Master Files."  This guidance provides information about preparing and submitting DMFs. It describes DMF types, the information needed in DMF submissions, and FDA's DMF review processes. For additional information, see FDA’s DMF web pages.
October 15
2019 CDER Prescription Drug Labeling Conference  December 4-5, 2019, College Park MD. Free  Our 2019 CDER Prescription Drug Labeling Conference is intended for industry, academia, payors, healthcare information providers, and healthcare providers who review, develop, submit, or use the Prescribing Information  Instructions for Use, and/or carton/container labeling or create or submit Structured Product Labeling files to the FDA.  Register here.
October 11
FDA Approves New Treatment for Patients With Migraine.  The U.S. Food and Drug Administration today approved Reyvow (lasmiditan) tablets for the acute (active but short-term) treatment of migraine with or without aura (a sensory phenomenon or visual disturbance) in adults. Reyvow is not indicated for the preventive treatment of migraine.  Migraines can often be triggered by various factors including stress, hormonal changes, bright or flashing lights, lack of food or sleep, and diet. Migraine is three times more common in women than in men and affects more than 10% of people worldwide.  In two studies, the percentages of patients whose pain resolved and whose most bothersome migraine symptom (nausea, light sensitivity, or sound sensitivity) resolved two hours after treatment were significantly greater among patients receiving Reyvow at all doses compared to those receiving placebo. 
October 3
Tainted Products Marketed as Dietary Supplements. All contain hidden drug ingredients. 
Tainted Sexual Enhancement Products: Anaconda Strong Formula (sildenafil), Le Pepa Negra (sildenafil), Lung Leader (sildenafil), LOBO (sildenafil), and Mero Macho (tadalafil). 
Tainted Weight Loss Products: Lanugar (sibutramine and N-desmethylsibutramine), JaDera Plus sibutramine, N-desmethylsibutramine, and benproperine), Sheaya Lender (sibutramine and fluoxetine), and Love in S (sibutramine and N-desmethylsibutramine .
October 1
ANDA Action Letters Transitioning to Email Only.  Starting this month, abbreviated new drug application (ANDA) applicants with secure email accounts will begin receiving action letters (approvals, tentative approvals, complete responses) by secure electronic communication only as the U.S. Food and Drug Administration (FDA), including its Office of Generic Drugs (OGD), continues to move away from paper communications.