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March 2019
Specialty Pharma Industry News is provided by SPA Member Dr. Larry Boos
February 28
Supplement Approval Letter - FluMist   FDA has approved MedImmune, LLC's request to supplement their Biologics License Application (BLA) for Influenza Vaccine Live Internasal FluMist®.
The Center for Disease Control and Prevention (CDC) has updated its World Map of Areas Outside the US with Risk of Zika.  Countries with current reports of mosquito-born Zika transmission are shown in purple, those with the vector but no reported mosquito-born Zika transmission are shown in yellow, and those with no mosquitoes that spread Zika are shown in green.
FDA MedWatch Recall of Losartan Potassium and Valsartan Tablets Three new MedWatch Safety Alert recall medical products have been added to the FDA Recalls webpage.
* Losartan Potassium Tablets by Camber Pharmaceuticals: Recall - Due to the Detection of Trace Amounts of N-Nitroso N-Methyl 4-amino butyric acid Impurity found in the Active Pharmaceutical Ingredient (API)
* Valsatan and Amlodipine and Valsartan Tablets by Aurobindo and Acetris: Recall - Due to the Detection of N-Nitroso N-Methyl 4-amino butyric acid Impurity found in the API
* Other companies recalling these drugs: Macleods Pharmaceuticals

FDA finalizes guidance on evaluating the clinical need for outsourcing facilities to compound drugs with bulk drug substances; provides final decision on two substances.  The FDA has issued a final guidance for industry, Evaluation of Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act.   The FDA is concerned that patients face too many risks when it comes to compounded drugs.  Patients should not be put at risk of receiving a drug compounded from a bulk drug substance (aka API) when an FDA-approved drug can be used to meet patient needs.   Consequently, the FDA is issuing public notification on two bulk drug substances, nicardipine hydrochloride and vasopressin, that are not to be used in compounding by outsourcing facilities.  Others will be added as the FDA continues to develop the list.

FDA Announces Closure of OGD's Regulatory Submission Mailing Facility at 7620 Standish Place, Rockville, MD - Effective April 1, 2019.
The Rockville location will no longer receive regulatory submissions after the effective date. All physical abbreviated new drug applications (ANDAs) will be received at 5901B Ammendale Road, Beltsville, MD 20705.

FDA MedWatch Safety Communication - Caution When Using Robotically-Assisted Surgical Devices in Women's Health including Mastectomy and Other Cancer-Related Surgeries.  the  FDA is concerned that health care providers and patients may not be aware that the safety and effectiveness of these devices has not been established for use in mastectomy procedures or the prevention or treatment of cancer and the FDA encourages health care providers who use robotically-assisted surgical devices to have specialized training and practice in their use.

FDA warns CanaRx for selling unapproved, misbranded and unsafe imported drugs to unsuspecting Americans.   Operations like CanaRx use their names to imply that patients are receiving medicines approved in Canada.   If an American consumer goes to Canada and walks into a brick-and-mortar Canadian pharmacy and buys a medicine, they're getting a high-quality drug because of Canada's first-class drug regulatory process. When a consumer goes online to buy medicines purportedly from Canada, they may get a medicine sourced from elsewhere that could be counterfeit, expired, or misbranded.   A Warning Letter was sent to CanaRx on February 26. 

FDA advances enforcement policy for certain marketed tobacco products that receive a not substantially equivalent order.  The FDA has  issued a draft guidance, " Enforcement Policy for Certain Marketed Tobacco Products," which, when final, will explain the agency's current thinking regarding its enforcement policy for manufacturers, importers and distributors of certain marketed tobacco products that receive a not substantially equivalent (NSE) order and will explain the sell-off time allowed, as well as the enforcement policy for retailers with such products in their inventory.\\

FDA Drug Safety Podcast: FDA adds Boxed Warning for increased risk of death with gout medicine Uloric (febuxostat).   On February 21, 2019, the FDA concluded there is an increased risk of death with Uloric (active ingredient febuxostat) compared to another gout medicine, allopurinol. This conclusion is based on our in-depth review of results from a safety clinical trial that found an increased risk of heart-related death and death from all causes with Uloric.  The complete Data Summary can be found at www.fda.gov/DrugSafetyCommunications. 

February 27
Potential Shortages as Sterigenics Willowbrook Product Sterilization Facility Ceases Operations.   The FDA's Center for Devices and Radiological Health (CDRH) is aware that on February 15, 2019, the Illinois Environmental Protection Agency (EPA)  issued a Seal Order to stop the Sterigenics facility in Willowbrook, Illinois, from sterilizing medical products and other products with ethylene oxide.

Warning Letters
Pure Source, LLC, Doral, Florida 33172
  • Failure to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed.
  • Failure to establish and document the accuracy, sensitivity, specificity, and reproducibility of its test methods.
  • Failure 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, and to follow all of its written production and process control procedures  
  • Two of your firm's homeopathic products are misbranded drugs because they are intended for use in diagnosis, cure, mitigation, or prevention of disease. 
Proandre SL, Granollers, Barcelona, SPAIN
  • Failure to have, for each batch of drug product, appropriate laboratory determination of  satisfactory conformance to final specifications for the drug product, including the identity and  strength of each active ingredient, prior to release.
  • Failure to follow an adequate written testing program designed to assess the stability characteristics of drug products.
  • Failure to prepare batch production and control records with complete information relating to the production and control of each batch of drug product produced.  
Draft Guidance for Industry
Quality Considerations for Continuous Manufacturing Guidance for Industry (PDF - 197KB) Control/Click to view/download. FDA invites general comments to the docket on the quality considerations described in the draft guidance, including comments on control strategy, facility, and process validation considerations for continuous manufacturing of small molecule, solid oral drug products.

February 25
Safety trial finds risk of blood clots in the lungs and death with higher dose of tofacitinib (Xeljanz, Xeljanz XR) in rheumatoid arthritis patients. The FDA  is alerting the public that a safety clinical trial found an increased risk of blood clots in the lungs and death when a 10 mg twice daily dose of tofacitinib (Xeljanz, Xeljanz XR) was used in patients with rheumatoid arthritis (RA). FDA has not approved this 10 mg twice daily dose for RA; this dose is only approved in the dosing regimen for patients with ulcerative colitis. The drug manufacturer, Pfizer, is transitioning patients who were on the high 10 mg twice daily dose to the lower, currently approved dose of 5 mg twice daily. This trial will continue and is expected to be completed by the end of 2019.    Health care professionals  should follow the recommendations in the 
tofacitinib prescribing information for the specific condition they are treating. 

FDA Warns Thermography Should Not Be Used in Place of Mammography to Detect, Diagnose, or Screen for Breast Cancer.    The FDA is aware that health spas, homeopathic clinics, mobile health units, and other health care facilities are using thermography inappropriately as a standalone tool for breast cancer screening or diagnosis.  The FDA has received reports that these types of facilities provide false information that can mislead patients into believing that thermography is an alternative or better option than mammography. Some facilities make inaccurate, unsupported, and misleading claims, such as thermography can find breast cancer years before it would be detected through other methods or thermography improves detection of cancer in dense breasts.   You can read the complete  MedWatch Safety Alert that includes recommendations here.

Recall:  GoLean Detox Capsules by GoLean Detox USA Due to Presence of Undeclared     Sibutramine and Phenolphthalein - 
You can read the complete recall alert  here.

Draft Guidance for Industry, "Assessing the Effects of Food on Drugs in INDs and NDAs - Clinical Pharmacology Considerations".   Today, the FDA published this  draft guidance for industry which provides recommendations to sponsors planning to conduct food-effect (FE) studies for orally administered drug products as part of investigational new drug applications (INDs), new drug applications (NDAs), and supplements to NDAs

Draft Guidance for Industry, "Bioavailability Studies Submitted in NDAs or INDs - General Considerations"   Today, the FDA published a  draft guidance for industry that contains advice on how to meet the BA requirements set forth in 21 CFR part 320 as they apply to dosage forms intended for oral administration. The guidance is also applicable to non-orally administered drug products when it is appropriate to rely on systemic exposure measures.  When finalized, this guidance will revise and replace the FDA's March 2014 draft guidance for industry entitled, "Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs - General Considerations," which addresses BA or BE studies for INDs, NDAs, and NDA supplements.
February 22
FDA issues 74 product-specific guidances to help promote generic drug access and drug competition.   Today the FDA announced a new set of 
product-specific guidances to support industry in identifying appropriate science-based methodologies and evidence for developing generic drugs. The batch contains 74 product-specific guidances, including 22 new guidances and 52 revised guidances that, when finalized, will describe the FDA's current thinking and recommendations on how to develop generic drugs that are therapeutically equivalent to their respective reference-listed drugs.

The  FDA has issued the draft guidance, 
" Implanted Brain-Computer Interface (BCI) Devices for Patients with Paralysis or Amputation - Non-clinical Testing and Clinical Considerations."  This is a  "leapfrog" guidance, meaning the guidance is intended to provide the FDA's initial thoughts on an emerging health technology, therefore, the FDA's recommendations may change as more information becomes availa ble.

February 21
FDA/CDER Small Business and Industry Assistance presents the Regulatory Education for Industry (REdI) Generic Drug Forum,  April 3-4, 2019,  College Park MD.     Registration, Agenda, and Conference Information Attend in-person or virtually.   Registration is free.  Advanced registration is required.  You should attend if you are a member of thegeneric drug industry, consultants, regulatory affairs professionals, or contractors with an emphasis on those who:
  • Plan to submit an ANDA or are in the process of submitting an ANDA
  • Involved in generic drug development
  • Work on bioequivalence, stability, dissolution and impurity testing
  • Submit Drug Master Files (DMFs)
  • Prepare regulatory submissions
Today the FDA i ssued a  proposed rule  that would update regulatory requirements for most sunscreen products in the United States.  
The agency is issuing this proposed rule to put into effect final monograph regulations for OTC sunscreen drug products as required by the 
Sunscreen Innovation Act .  Of the 16 currently marketed active ingredients, two ingredients - zinc oxide and titanium dioxide - are GRASE for use in sunscreens; two ingredients - PABA and trolamine salicylate - are not GRASE for use in sunscreens due to safety issues. There are 12 ingredients for which there are insufficient safety data to make a positive GRASE determination at this time.  This rule proposes that dosage forms that are GRASE for use as sunscreens include sprays, oils, lotions, creams, gels, butters, pastes, ointments and sticks.  To learn more about this proposal control/click on the colored words in the title.
February 19
Important Information about Young Donor Plasma Infusions for Profit   The Food and Drug Administration (FDA) is advising consumers to be cautious about establishments offering infusions of plasma obtained from young human donors with the claim that the infused plasma will treat a variety of conditions ranging from normal aging to memory loss.  There is no proven clinical benefit of the infusion of plasma from young donors in the prevention of conditions such as aging or memory loss, or for the treatment of such conditions as dementia, Parkinson's disease, multiple sclerosis, Alzheimer's disease, heart disease, or post-traumatic stress disorder.  The dosing of these infusions, which can involve large administered volumes, is also not guided by evidence from adequate and well controlled trials. In addition, the infusion of plasma can be associated with infectious, allergic, respiratory, and cardiovascular risks. Read more at:  

Kingston Pharma, LLC is voluntarily recalling all lots of "DG™ Baby Gripe Water herbal supplement with organic ginger and fennel extracts" to the consumer level due to the presence of an undissolved ingredient, citrus flavonoid.   Read more here.

The FDA Reauthorization Act of 2017, or FDARA, 2 15 created a new pathway by which FDA may, at the request of the applicant, designate a drug with "inadequate generic competition" as a competitive generic therapy (CGT). This guidance also includes information on the actions FDA may take to expedite the development and review of ANDAs for drugs designated as CGTs. This guidance also provides information on how FDA implements the statutory provision for a 180-day exclusivity period for certain first approved applicants that submit ANDAs for CGTs. Download here.

February 15
Researchers genetically modified an indoor houseplant to purify certain airborne chemicals commonly found in the home that have been linked to cancer.    To test whether this gene could be used in indoor houseplants to more effectively purify indoor air for volatile organic compounds (VOCs), a team led by Dr. Stuart E. Strand at the University of Washington genetically modified the common houseplant pothos ivy (Epipremnum aureum) to produce 2E1. The research was supported in part by NIH's National Institute of Environmental Health Sciences (NIEHS).  The team tested whether these genetically modified plants could remove two VOCs, benzene and chloroform. They placed modified plants and unmodified (wild-type) plants in glass containers that were filled with one of these chemicals for eleven days.  The genetically modified plants also decreased the concentration of chloroform by 82% during the first 3 days and almost completely after 6 days. In contrast, the wild-type plants did not clear any chloroform from the air. Strand says that 2E1 can be beneficial for the plant, too, as it turns chloroform into carbon dioxide and chloride ions, and benzene into a chemical called phenol. "Plants use carbon dioxide to make their food, and they use phenol to help make components of their cell walls."
February 11
FDA takes action against 17 companies for illegally selling products claiming to treat Alzheimer's disease.   The  U.S. Food and Drug Administration today posted 12  warning letters and 5 online advisory lettersissued to foreign and domestic companies that are illegally selling more than 58 products, many that are sold as dietary supplements, which are unapproved new drugs and/or misbranded drugs that claim to prevent, treat or cure Alzheimer's disease and a number of other serious diseases and health conditions.  These products may be ineffective, unsafe and could prevent a person from seeking an appropriate diagnosis and treatment.
February 8
Anaplastic Large Cell Lymphoma (BIA-ALCL) Associated with Breast Implants - Letter to Health Care Providers.  The Food and Drug Administration (FDA) wants to increase awareness about an association between all breast implants, regardless of filling or texture, and Breast Implant Associated- Anaplastic Large Cell Lymphoma (BIA-ALCL). The FDA received reports indicating that patients with breast implants have an increased risk of developing this disease within the scar capsule adjacent to the implant.  The FDA wants all healthcare providers to be aware of BIA-ALCL, particularly in patients with new swelling, lumps, or pain around breast implants, to expedite diagnosis of this malignancy.   The number of identified cases of BIA-ALCL is small compared to the estimated 1.5 million patients who receive breast implants worldwide every year; specifically, as of the latest medical device reports (MDRs) update, the FDA has received a total of 660 MDRs of BIA-ALCL. 
February 6
Federal court enters consent decree against Ranier's Rx Laboratory of Jeanette, Pennsylvania, and owner for manufacturing purportedly sterile drug products in insanitary conditions.  
The complaint filed with the consent decree alleges that Ranier's manufactured and distributed purportedly sterile drug products, including injectable drugs for conditions such as erectile dysfunction and ophthalmic drugs for use as anesthetics, antibiotics, and cataract therapies, among others, that were adulterated under the FD&C Act because the drugs were made under insanitary conditions.  Under the consent decree, Ranier's and Ranier cannot resume sterile compounding operations for human and animal drugs until they complete required corrective actions and receive authorization from the FDA.

Invitation to participate in FDA's public workshop on generic drug regulatory science initiatives    The  Fiscal Year (FY) 2019 Generic Drug Regulatory Science Initiatives Public Workshopwill be held at FDA's main campus in Silver Spring, Maryland, on May 1, 2019, from 8:30 am-4:30 pm and will be webcast for those who cannot attend in person.  Please submit requests to make oral presentations during your online registration by April 1, 2019. You may also suggest generic drug research topics that you recommend be added to the FY 2020 regulatory science initiatives by emailing GDUFARegulatoryScience@fda.hhs.gov.   If you wish to attend in person or via webcast, please email GDUFARegulatoryScience@fda.hhs.gov  by April 1, 2019. The email should contain each attendee's name, title, affiliation, address, email address, telephone number, and whether attending in person or by webcast.

FDA finalizes new policy on treatments for opioid use disorder.    Today, the U.S. Food and Drug Administration  issued a final guidance, "Opioid Use Disorder: Developing Buprenorphine Depot Products for Treatment.,"  There are currently three FDA-approved drugs for MAT - methadone, buprenorphine, and naltrexone - that have been demonstrated to be safe and effective in combination with counseling and psychosocial support to treat opioid use disorder (OUD). Regular adherence to MAT with buprenorphine reduces opioid withdrawal symptoms and the desire to use opioids, without causing the cycle of highs and lows associated with opioid misuse or abuse. At proper doses, buprenorphine also blocks the pleasurable effects of other opioids, making continued opioid abuse less attractive.
February 5
NIH:  Sleep Loss Encourages Spread of Toxic Alzheimer's Protein  
In addition to memory loss and confusion, many people with Alzheimer's disease have trouble sleeping. Now an NIH-funded team of researchers has evidence that the reverse is also true: a chronic lack of sleep may worsen the disease and its associated memory loss.   It's long been recognized that Alzheimer's disease is associated with the gradual accumulation of beta-amyloid peptides and tau proteins, which form plaques and tangles that are considered hallmarks of the disease.  In the healthy brain, active neurons naturally release some tau during waking hours, but it normally gets cleared away during sleep.  The latest findings in studies of mice and people further suggest that sleep deprivation upsets this balance, allowing more tau to be released, accumulate, and spread in toxic tangles within brain areas important for memory. While more study is needed, the findings suggest that regular and substantial sleep may play an unexpectedly important role in helping to delay or slow down Alzheimer's disease.  Read more here.

February 1
FDA warns compounders not to use glutathione from Letco Medical, Decatur, Alabama, to compound sterile drugs.   Based on reported adverse events, the agency has concerns with use of the Letco distributed glutathione to compound injectable drugs due to potential endotoxins.  Letco supplied this glutathione powder to about 100 compounders in 30 states.  FDA is aware of seven patients who experienced various adverse events ranging from nausea and vomiting to difficulty breathing, which required one patient to be hospitalized immediately after receiving glutathione 200mg/mL intravenous injection.   Following these reports, FDA has received varying third-party test results on the levels of endotoxin that may be present in Letco's glutathione powder. FDA testing is underway.

Expiration Date Extension for North American Coral Snake Antivenin (Micrurus fulvius) (Equine Origin) Lot L67530 through January 31, 2020    Coral Snake Antivenom product was manufactured by Wyeth Pharmaceuticals, now a wholly owned subsidiary of Pfizer, Inc.  FDA has extended the expiration date on this lot of Antivenin (Micrurus fulvius) (Equine Origin), from January 31, 2019, to January 31, 2020.  The extension is based upon FDA evaluation of stability data, which determined that this lot of product will maintain stability and potency for an additional year.

FDA warns of recall of test strip devices used to monitor warfarin.    The FDA is warning patients and doctors, who use at-home or in-the-office medical devices to monitor levels of the blood thinner warfarin, that certain test strips used with the devices may provide inaccurate results and should not be relied upon to adjust the drug dosage. Medical product distributor Terrific Care/Medex Supply LLC issued a  voluntary recall of certain Roche Diagnostics test strip lots used with CoaguChek test meter devices last month. Today, the FDA classified this action as a Class I recall, the most serious type of recall, which means use of these devices may cause serious injuries or death. This recall is related to the November 2018 Roche Diagnostics Recall, the manufacturer of CoaguChek meters and test strips.