In a May 19, 2014 Federal Register notice, FDA announces that it will hold a public workshop October 8-9, 2014, on the technical considerations of additive manufacturing, also known as 3-D printing.  "The purpose of this workshop is to provide a forum for FDA, medical device manufacturers, additive manufacturing companies, and academia to discuss technical challenges and solutions of 3-D printing. "  To permit the widest possible opportunities for public input, the agency is also soliciting electronic or written comments on all workshop topics.

 3-D printing is a fast-growing new manufacturing technique that builds devices from computerized blueprints or models, by laying material only where it is needed.  Through 3-D printing, designers can quickly create a medical device that is anatomically modeled to a specific patient. As discussed in a recent MedWarn Alert, 3D-printed medical devices have already been used successfully in patients.  As medical applications for 3D printing technology continue to grow, the regulation these devices pose important questions for regulators including: whether each device would be required to be registered with FDA; how to ensure process verification and validation for devices produced in individual or small batches; how small design changes could affect the safety of a device;  and whether materials used in the printing process might affect durability and strength of the device. 

To begin to address such issues, FDA's proposed list of discussion topics include:

• Preprinting considerations, including but not limited to:
  • material chemistry;
  • physical properties;
  • recyclability;
  • part reproducibility; and
  • process validation.
• Printing considerations, including but not limited to:
  • printing process characterization;
  • software used in the process;
  • post-processing steps (hot isostatic pressing, curing); and
  • additional machining.
• Post-printing considerations, including but not limited to:
  • cleaning/excess material removal;
  • effect of complexity on sterilization and biocompatibility;
  • final device mechanics;
  • design envelope; and
  • verification.

As the FDA receives an increasing number of submissions using 3D-printing for both traditional and patient-matched devices, how 3-D printed medical devices will be overseen by the FDA has become a pressing issue.  FDA hopes that ideas generated from the workshop will facilitate development of new draft guidances and/or standards.

[1] "Additive Manufacturing of Medical Devices: An Interactive Discussion on the Technical Considerations of 3-D Printing; Public Workshop; Request for Comments," Federal Register, May 19, 2014.
[2] "Growing Trend: 3D-Printing Medical Devices," MedWarn, April 2, 2014.

As part of a settlement, Minneapolis-based MedTronic has agreed to pay $22 million to plaintiffs in an estimated 950 lawsuits filed over its Infuse bone growth product, but does not admit to any wrongdoing.  An additional 750 cases brought by 1,200 plaintiffs are pending and more claims are expected to be brought.  

Infuse contains recombinant human Bone Morphogenetic Protein (rhBMP), which is a genetically engineered version of a protein found in the body.  Use of the protein causes bone growth in specific areas of the spine.  The FDA approved its use in 2002 as an alternative to conventional spinal fusion.  However, approval was limited to treat degenerative disc disease, open fractures of the tibia,  sinus augmentation, and localized alveolar ridge augmentation.  

Worldwide, more than one million people have received an Infuse implant.  Plaintiffs allege Medtronic promoted Infuse to spinal surgeons for off-label uses that caused patient injuries.  According to a report by the Senate committee investigating the product, the company's undisclosed manipulation of information through the medical literature included overstating its benefits and downplaying concerns about serious complications. Over the last 15 years, Medtronic reportedly has paid $210 million in royalties and other payments to a group of 13 doctors and two corporations linked to doctors to promote the off-label use of Infuse.

India's largest drug manufacturer Sun Pharmaceutical Industries Ltd., is recalling nearly 400,000 bottles of its generic form of the anti-depressant Effexor (Venlafaxine) and the antihistamine Cetirizine because the pills fail to dissolve properly.
[1] Basak, S. "Sun Pharma Recalls 400,000 Bottles of Drugs in U.S., FDA Says," Bloomberg News, May 8, 2014.

The FDA is warning that the sleep aid Lunesta (eszopiclone) can cause next-day impairment of driving and other activities that require alertness.  As a result, the FDA has decreased the recommended starting dose of Lunesta from 3 mg at bedtime to 1 mg at bedtime.  Lunesta is a sedative-hypnotic sleep medicine used to treat insomnia in adults.  A recent study found that the previously recommended starting dose of 3 mg can cause impairment of driving skills, memory and coordination that can last more than 11 hours after receiving an evening dose.  The new lower recommended dose will result in less drug in the blood the next day.  The FDA recommends that patients continue to take their prescribed dose and contact their doctors to ask about the most appropriate dose for them.

[1] FDA Safety Announcement, "FDA Drug Safety Communication: FDA warns of next-day impairment with sleep aid Lunesta (eszopiclone) and lowers recommended dose" May 15, 2014. 

In a regulatory filing, the maker of implantable heart devices, St. Jude Medical Inc., reported that the Department of Justice is investigating whether St. Jude violated the False Claims Act by paying  doctors and health care facilities to implant its heart devices.  St. Jude is reportedly cooperating with the investigation.  

In 2011, St. Jude paid $16 million to settle a civil suit alleging that the company used a postmarket study to pay participating doctors as much as as $2,000 per patient in an effort to increase sales of its implantable cardioverter defibrillators (ICDs) and pacemakers.  

[1] United States Securities and Exchange Commision Form 10-Q, St. Jude Medical, Inc., File No: 1-12441, May 6, 2014.
[2] Wood, S. "DOJ Investigating St Jude Cardiac 'Kickback' Scheme," Medscape, May 8, 2014.
[3] Wood, S. "St Jude Pays $16M to Settle Kickback Claims Relating to ICD, Pacemaker Use," Medscape, January 21, 2011.

Boston Scientific has received a subpoena from the U.S. Health & Human Services Department seeking information regarding its Cognis and Teligen line of implantable cardiac defibrillators (ICDs).   In 2009, the company warned of problems in some 8,000 of the ICDs related to 15 cases of inappropriate shocks to patients.  Another company warning soon followed over potential problems between the ICD's header and case.  By the end of 2009, Boston Scientific stopped making the devices.  In 2013, the company issued a new warning about premature battery depletion in older models.

Seattle-based Jintronix has announced that it received 510(k) clearance from the FDA for its rehabilitation software.  Jintronix's system is a set of games and exercises designed for Microsoft's Xbox Kinect system to stimulate recovery in stroke victims.   The Kinect's motion-sensing camera allows players to interact with what they see on the screen, providing  immediate feedback for patients. 

Jintronix sells the Kinect for $250 and charges $50 a month for its software, which lets physical therapists track patient progress, program routines for patients, and adjust the exercises as mobility improves.

According to the company, the FDA clearance is the first time that the Microsoft Kinect has been approved for use directly by patients in a healthcare setting.

FDA has approved a new drug made by Merck & Co., Zontivity (vorapaxar), to decrease the formation of blood clots in patients with a previous heart attack or blockages in the arteries to the legs.  Zontivity is an anti-platelet agent designed to decrease the tendency of platelets to clump together to form a blood clot.  By decreasing the formation of blood clots, Zontivity decreases the risk of heart attack and stroke.  

“In patients who have had a heart attack or who have peripheral arterial disease, this drug will lower the risk of heart attack, stroke, and cardiovascular death. In the study that supported the drug’s approval, Zontivity lowered this risk from 9.5 percent to 7.9 percent over a 3-year period – about 0.5 percent per year,” said Ellis Unger, M.D., director of the Office of Drug Evaluation I in the FDA’s Center for Drug Evaluation and Research. 

As in other drugs that inhibit blood clotting, bleeding is the most commonly reported adverse reaction.  The drug's label information includes a Boxed Warning to alert health care professionals about this risk.  Zontivity must not be used in people who have had a stroke, transient ischemic attack (TIA), or bleeding in the head, because the risk of bleeding in the head is too great.

[1] FDA Press Release, "FDA approves Zontivity to reduce the risk of heart attacks and stroke in high-risk patients," May 8, 2014.  

The first federal lawsuit involving laparoscopic power morcellators was filed in the Eastern District of Pennsylvania against LiNA Medical on March 14, 2014 by the family of Donna Burkhart.  The lawsuit alleges that the morcellator manufacturer failed to adequately warn surgeons of the risk of disseminating cancer following the use of the device, failed to design a safer "closed" system that would prevent the spread of cancer cells, and failed to  act when studies revealed that disseminating cancer was occurring.  In 2012 Mrs. Burkhart had a hysterectomy in which a power morcellator was used and she died of uterine cancer less than a year later.  

In April, the FDA issued a strong warning against using power morcellators during laparoscopic uterine surgery because of the risk of inadvertently spreading uterine cancer cells throughout the abdominal cavity (MedWarn, 4/17/2014).  Morcellators are used in about 10% of the 600,000, hysterectomies performed in the U.S. each year. 
 
A state lawsuit filed in New York on May 1, 2014, accuses Johnson & Johnson subsidiary Ethicon of substandard testing of its Morcelex morcellation device.  The plaintiff in that case was diagnosed with cancer after a hysterectomy assisted by the laparoscopic power morcellator in 2012.  According to the plaintiff, Ethicon knew about the risk of dissemination of cancer but failed to provide hospitals with potential safety precautions such as a reinforced intra-peritoneal bag to avoid spillage of unsuspected cancer cells.  

Johnson & Johnson  suspended sales of its laparoscopic power morcellators, but did not recall the devices because it maintains the devices may be the best option for some patients after risk evaluation and informed consent (MedWarn, 5/02/2014).  

While the trouble with power morcellators continues, another company is poised to market what could be a better option for uterine surgeries.  On May 8, Boston Scientific announced a $65 million acquisition of loGyn, a company that makes Symphion, an FDA-approved system for hysteroscopic intrauterine tissue removal.  The recirculating Symphion system evacuates the tissue under suction, which may prove to be a safer alternative to power morcellators.

[1]  J&J Stops Sale of Laparoscopic Power Morcellators Used in Fibroid Surgery, MedWarn Alerts, 05/02/2014.
[2] FDA Safety Communication, "Laparoscopic Uterine Power Morcellation in Hysterectomy and Myomectomy: FDA Safety Communication," April 17, 2014
[3] FDA Warns That Laparoscopic Power Morcellators Used in Hysterectomy and Fibroid Removal May Spread Cancerous Tissue, MedWarn Alerts, 04/17/2014.[4] Burkhart v. LiNA Medical US et al., No. 5:14-cv-1557, complaint filed (E.D. Pa., Allentown Mar. 14, 2014).
[5] Baker, R., "Woman died of cancer spread by surgical tool, husband says," Thomson Reuters, March 26, 2014.
[6] Leuzzi et al. v. Ethicon Endo Surgery, Inc., d/b/a Ethicon Womens Health and Urology et al., No. 6:14-cv-06218 (N.Y. Western, May 1, 2014).
[7] Sarvestani, A., "FDA morcelator warning spurs lawsuit against J&J," MassDevice, May 7, 2014.
[8] Boston Scientific Press Release, "Boston Scientific to Acquire Iogyn, Inc.," May 6, 2014.

The FDA has granted approval to Zykadia (ceritinib) to treat patients with late-stage (metastatic) non-small cell lung cancer (NSCLC).  Zykadia is an anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor that blocks proteins that promote the development of cancerous cells. It is intended for patients with metastatic ALK-positive NSCLC who were previously treated with crizotinib, the only other approved ALK tyrosine kinase inhibitor.  Zykadia is marketed by Novartis.

Lung cancer is the leading cause of cancer-related deaths in the US. According to the National Cancer Institute, an estimated 224,210 men and women in the US will be diagnosed with lung cancer, and 159,260 will die from the disease this year. About 85 percent of lung cancers are NSCLC, making it the most common type of lung cancer. However, only 2-7 percent of patients with NSCLC are ALK-positive.

The FDA is approving Zykadia under the agency’s accelerated approval program, which allows approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients. This program provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials.  Results of Zykadia's clinical trials showed that about half of the 163 participants had their tumors shrink, and this effect lasted an average of about seven months.
 
Common side effects of Zykadia include gastrointestinal symptoms such as diarrhea, nausea, vomiting and abdominal pain. Laboratory abnormalities such as increased liver enzymes, pancreatic enzymes and increased glucose levels were also observed.
 
[1] FDA News Release, "FDA approves Zykadia for late-stage lung cancer," April 29, 2014.