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Boston Scientific Loses Patent War with Cardium Therapeutics

Boston Scientific, a global medical device manufacturer based in Natick, Massachusetts, recently lost a patent war against Cardium Therapeutics, a healthcare company based in San Diego, California. The disputed patent is based on Cardium Therapeutics' gene therapy technology that is used in the treatment of coronary heart disease. According to a press release by Cardium Therapeutics, the company first filed a patent for its gene therapy technology with the European Patent Office. In 2006, the company's claim for its patent was upheld by the United States Court of Appeals for the Federal Circuit. The appeal upheld three of Cardium Therapeutics' patents. Cardium Therapeutics' technology employs the use of transient cardiac ischemia to enhance transfection and gene delivery efficiency after an intracoronary dosage of adenovector in a mammalian heart. According to information from the company, two back-to-back periods of coronary artery occlusion increased both transgene expression and adenovector presence (when combined with the administration of nitroglycerin). Adenovector presence was measured by PCR, and transgene expression was assessed by luciferase activity. Tyler Dylan-Hyde is the general counsel and chief business officer at Cardium Therapeutics. In a prepared remarks, he stated, "The resolution of these important reviews of our gene therapy patents, and the consistent decisions in our favor including rulings by the U.S. courts of appeal, underscore the value of our patent portfolio, which we believe reflects a breakthrough approach to the treatment of coronary heart disease." References

Medical Device Recalls Soar in Q3 2012

The total number of medical-device recalls in the third quarter of 2012 jumped by nearly 70% over the previous quarter. Image from SteriCycle ExpertRECALL report.    

There were 407 documented medical device recalls in the third quarter of 2012 compared with 242 recalls in the previous quarter. The number of recalls in Q3 2012 is the highest total in at least nine quarters, says Mike Rozembajgier, vice president of recalls for ExpertRECALL (Indianapolis). Approximately 26.5 million units were affected by the recalls in the third quarter of 2012; 40% of the companies named in the FDA Enforcement Reports had multiple products recalls. Class I recalls, the most serious type, saw a nearly threefold increase over the previous quarter. Class II recalls also saw a significant jump.  

Interestingly, the total of medical devices affected by the recalls fell compared with the second quarter of 2012, in which 123.5 million units were recalled. "Certainly the dynamic nature of recalls gives you this level of unpredictability in terms of how it is going to occur," Rozembajgier says.

Determining the reason behind the uptick in recalls is a subject worthy of debate, with increased scrutiny at FDA and growing supply-chain complexity each playing a role. Patient advocates and a number of politicians have criticized the 510(k) pathway, arguing that it does not prevent new medical devices from being based on faulty predicates.

"There is no doubt when we look at the trends that there is an increased [level of] scrutiny at the agency in a variety of different areas, and certainly medical device sees its share of oversight," Rozembajgier says. In terms of other FDA-related sectors, there was also a significant increase in the number of recalls related to food and pharmaceuticals. "From a percentage-wise basis, med device actually had the lowest increase among those segments."

Brian Buntz is the editor-at-large at UBM Canon's medical group. Follow him on Twitter at @brian_buntz.

Cream of the Crop: The Best Medtech Products and Services of 2012

The EC8 8-mm brushless dc motor from Maxon Precision Motors offers continuous torque as great as 0.95 mN•m, a nominal maximum speed of 80,000 rpm, and an efficiency rating of 70%. Available with or without Hall sensors and with 6-, 12-, and 24-V windings, this motor can be combined with a specified planetary gearhead. One-quadrant amplifiers serve as controllers, and users can choose between an amplifier directly connected via flexprint and a miniature plug-in module. Manufactured to ISO 13485 standards, the miniature motor is suited for a variety of medical device applications, including portable analyzers, metering systems, and analytical instrumentation.Maxon Precision MotorsFALL RIVER, MA

Each year, MPMN turns to its readers to select the top products and services of the year. As 2012 winds down, our readers have spoken. Starting on this page and continuing throughout the issue, we present a broad array of components, equipment, contract manufacturing services, materials, and more that enable medical device design and development. Click on the 'Continue to the Next Photo' button above to view the next slide.

5 Questions on Recall Strategy with Rita Hoffman

“Recall Strategy” is a planned course of action to be taken in managing and implementing a specific recall. This action is distinguished from the process a firm takes when deciding whether a product needs be recalled. The elements of this include communications with FDA on the depth of the recall, publicity, and process for effectiveness checks.

2. What should the recall strategy take into account?

  • Results of the firm’s health hazard evaluation (risk assessment).
  • Ease in identifying the product being recalled.
  • Degree to which the product’s deficiency is made clear to the user, consumer and consignees.
  • Degree to which the recalling product remains unused in the marketplace.
  • Continued availability of essential product.

3. What aspects of your recall strategy does FDA expect to discuss with you during your first contact with the district recall coordinator?

  • Information about the product being recalled including--the nature and scope of the problem, affected lots and labeling.
  • The proposed recall strategy (proposed action) availability of acceptable alternative product to address both patient risk and the customer’s needs, (if a medically necessary product is involved).
  • The current status of the firm’s investigation.
  • A draft of a well- developed public notification letter. (However be prepared to negotiate the type and content of your communication that your firm will be sending.)
  • The fact that you will be notifying international customers and authorities.

4. What will likely happen after you have implemented a properly executed recall strategy?

An FDA investigator will inspect your firm, either immediately, or after the recall is conducted. Some customers will refuse to return the product or discontinue using the equipment even after your sales people have explained the risk. To minimize incomplete effective checks you will have to develop and implement a well planned first and alternative course of action for receiving responses from users, consignees and customers. Also, some third parties will not properly dispose some of your products.

5. How can firm developed policies, training and procedures for effective implement a recall strategy?

Firms should consider developing in-house programs to training all staff on each aspect for implementation of an effective recall. The training should include recall readiness assessment, recall plan development, staging a mock recalls, recall execution and results. Having a recall management plan in place before it is needed will assist employees in the knowledge of their roles and responsibilities during the recall process and will avoid a “Management by Crisis” scenario.

Editor's Note: Rita Hoffman will be speaking on Devising a Recall Strategy: Dealing with Removals and Corrections at the upcoming MD&M West trade show and conference. Join her and other regulatory experts February 11-14, in Anaheim, CA. 


Rita Hoffman, RAC is managing partner at RHoffman, Inc. She has an intimate understanding of FDA regulatory and compliance issues from the perspective of both FDA and regulated industry. As an FDA compliance consultant, she provides clients with regulatory insight, advises on critical compliance deficiencies, performs compliance and new product audits, provides insight and guidance on recall strategies to the medical device industry, and advises on jurisdiction determinations for combination products. Until January 2011, Hoffman served as recall branch chief for CDRH, where she was responsible for oversight and review for all medical device recalls. Ms. Hoffman held several positions including the Center for Drug Evaluation and Research (CDER) Jurisdiction Review Officer (providing guidance on drug/device product designation, combination products and co-packaging), Acting Associate Ombudsman, Small Business Liaison, and was a Policy Analyst for eight years in the Office of the Commissioner.

EU Grants CE Mark Approval for Imagine Eyes Retinal Camera

Imagine Eyes, a medical device manufacturer based in Orsay, France, received CE Mark approval in the European Union for its new retinal imaging system. According to information released by the company, the product is the first clinically-approved adaptive optics platform system. The rtx1 retinal camera system is used to take images of the retina in the eye. Unlike other products on the market, the rtx1 can take images at the cellular level. This will allow opthamologists to observe vascular structures in the eye that are often affected by certain diseases that impact vision. To avoid burning, the retinal camera is focused at the cone photoreceptor layer in the eye. The rtx1 retinal camera system uses a flood illumination system for lighting. This illumination system is similar to those found in other cameras. However, flood illumination with cellular-level imaging allows the rtx1 to capture vascular patterns found in the eye. When combined with other diagnostic techniques, the rtx1 will allow opthamologists to quickly and easily diagnose a variety of eye diseases. In prepared remarks, global communications director Mark Zacharria said, "The technology is protected by 4 proprietary patents." He continued, "These cover different aspects of the device's optical architecture that enable its superior image quality." In addition to CE Mark approval in the European Union, the rtx1 received approval in Japan under the Shonin mark. The company hopes to receives FDA approval in mid-2013. References

FDA’s Registration List is Changing. Should You Be on It?

FDASIA was signed into law on July 9, 2012. This piece of legislation grants FDA the authority to collect user fees from industry to fund reviews of drugs, devices, and biologics. The changes to establishment registration went into effect on October 1, the beginning of the government’s fiscal year 2013. As a result of the changes to the establishment registration process, Title 21 CFR Part 807 has been revised. One of the salient changes influencing the device industry is the need for all registered medical device establishments to pay an annual registration fee—not just device manufacturers. The expanded scope, associated with the change in establishment registration, results in establishments previously not required to pay fees such as contract manufacturers and sterilization facilities to file and pay the annual establishment registration fee.

Summary of Changes to the Medical Device Establishment Database

Important Links for Medical Device Establishments


In August, FDA published to the Federal Register a requirement that medical device manufacturers, contract sterilizers, and contract manufacturers are now required to register their products electronically. Medical device establishments, as of October 1, 2012, must register devices on the FDA Unified Registration and Listing System (FURLS). Device manufacturers (foreign and domestic) should establish an account on the FURLS. The FURLS will be employed to update information regarding device establishment registrations and information pertaining to device listings. According to FDA, existing product listing from device manufacturers will be migrated into the FURLS.

As mentioned in the introduction, the expanded requirement for contract manufacturers and contract sterilizers results in establishments falling within these two categories to register and pay the annual establishment registration fees. The requirement applies to domestic and foreign establishments. Another significant regulatory change impacting the device industry is the requirement for contract manufacturers and contract sterilizers to collect and list client devices. Additional changes that went into effect on October 1 are as follows:

  • Proprietary device names that are employed to market a device must be listed.
  • Combination devices, devices employing a device and a biologic or drug component, must be listed as such.
  • Device importers are required to identify the manufacturers of devices they import.
  • Foreign establishments exporting devices into the United States must identify all of the known importers of their devices.
  • Devices are now required to be listed by the: (a) manufacturer; (b) specification developer; (c) device reprocessors; (d) remanufacturers; (e) device repackers; and (f) device relabelers; before listing by foreign exporters; contract manufacturers, or contract sterilizers.
  • Establishments dedicated to complaint management that were previously registered as manufacturers and specification developers, must change their establishment type to Complaint File Establishment (reference 21 CFR Part 820.198).
  • Establishments located in foreign trade zones are now required to register and list their devices. They must clearly identify themselves as residing in a foreign trade zone.
  • All establishments, required to register under these changes, must now pay the annual registration fee (per FDASIA).

Tables 1 (Domestic) and 2 (Foreign) contains specific establishment registration details associated with the changes going into effect on October 1st.

Table I. Requirements for domestic registration and listing by establishments:

Establishment Type: Domestic

Requirements for Fiscal Year 2013

All Establishments

Pay the annual registration user fee prior to registration.
All Establishments, Except Initial Importers

Identify all proprietary names for each device listed. Names may be marked as confidential to exclude them from the data published on the FDA web site if disclosure could identify confidential business relationship(s).
Proprietary names may be uploaded from Excel spreadsheets rather than manually typed, if preferred.
Identify combination products and the type of combination product (e.g., device/drug, device/biologic) during listing.
Initial Importers Identify manufacturers of products being imported. This may be done by listing number or searching and identifying the manufacturer in FURLS.
Contract Manufacturers
Register and list, regardless of whether the contract manufacturer puts the device into commercial distribution or returns the device to their customer.
For non-exempt devices, list only after the manufacturer, specification developer, single use device remanufacturer or remanufacturer has done so.
Contract Sterilizers
Register and list, regardless of whether the contract sterilizer puts the device into commercial distribution or returns the device to their customer.
For nonexempt device, list only after the manufacturer, specification developer, single use device remanufacturer or remanufacturer has done so.

Manufacturers, Specification Developers, Single Use Device Manufacturers, Remanufacturers,

For nonexempt devices, list prior to contract manufacturer or sterilizer, if one is used.
Complaint File Establishment Register and list as a new establishment type and identify facility who maintains complaint files only (per 21 CFR 820.198).
Establishments Located in Foreign Trade Zones
Register and list.
Identify the establishment as located in a foreign trade zone.

Table 2. Requirements for foreign registration and listing by establishment type:

Establishment Type: Foreign

Requirements for Fiscal Year 2013

All Establishments

Identify all proprietary names for each device listed. Names may be marked as confidential to exclude them from the data published on the FDA web site if disclosure could identify confidential business relationship(s). Proprietary names may be uploaded from Excel spreadsheets rather than manually typed, if preferred.
Identify combination products and the type of combination product (e.g., device/drug, device/biologic) during listing.
Identify all importers known to the foreign establishment, including agents, brokers, or other parties used by the foreign establishment to facilitate the import of its device into the United States.

Manufacturers, Specification Developers, Single Use Device Manufacturers, Remanufacturers, Relabelers

For non-exempt devices, list prior to contract manufacturer or sterilizer, if one is used.
Complaint File Establishment Register and list as a new establishment type and identify facility who maintains complaint files only (per 21 CFR 820.198).
Contract Manufacturers For nonexempt devices, list only after the manufacturer, specification developer, single-use device remanufacturer or remanufacturer has done so.
Contract Sterilizers For non exempt devices, list only after the manufacturer, specification developer, single-use device remanufacturer or remanufacturer has done so.

Impact on the Medical Device Industry

Effective October 1, 2012, all registered medical device establishments are required to pay an annual registration fee. The fee for FY 2013 is $2,575.00. Medical device establishments have until December 31, 2012 to register their establishments and pay the 2013 registration fees. FDA estimates that this revised requirement will result in the addition of approximately 750 contract manufacturers being required to register with the agency. 

For contract manufacturers and sterilizers located outside of the United States and not having a business address within the United States, these foreign entities are required to contract with an agent located within the United States. The US agent must have a valid business address (note: a post-office box is not acceptable). US agents have no adverse event reporting responsibilities, in accordance with 21 CFR Part 803. Additionally, foreign establishments must identify all importers of their devices.   

According to FDA, on February 1, 2012, the agency reached an agreement in principle, with the medical device industry. A draft of MDUFA III was posted on FDA’s website. The 30-day review and comment period ended in April. In July, congress passed legislation allowing MDUFA III to become law, thereby sparing layoffs imminent at FDA had this legislation not passed. Considering the budgetary challenges of the federal government, and the need to reduce federal deficits, FDA badly needed the increase in fees and the expansion of establishments required to pay fees to offset part of the agency’s FY 2013 requested budget of $4.5 billion. According to the initial draft proposal from FDA, the device establishment user fee changes would result in an increase from 16,000 to approximately 22,000 establishments required to register and pay the $2,575 registration fee. This should result in the collection of approximately $57 million to support FDA operational expenses. Some of this addition funding will be used to add FDA headcount (projected 196 FTEs) to improve the agency’s efficiency. These resources will be used to improve the current device application review process and hopefully, a reduction in review times.


Effective October 1, 2012, changes to facility medical device establishment registration requirements will result in a significant expansion of organizations (worldwide) required to register with the agency. Establishments will be required to pay fees, register, and list products on the FURLS prior to December 31, 2012. The expansion of the establishment registration process will result in approximately $57M in registration fees collected by the agency. These fees are needed to support ongoing operations at the agency, including improvements to the device review process. It is the hope of the medical device industry, the addition of FDA headcount will result in a substantial improvement of the application review times, especially review times associated with Class II devices (510(k)). Device establishments that fall under the regulatory umbrella of FDA must visit the FDA’s website and learn as much as possible about these significant changes. One final note: for establishments failing to register and pay establishment registration fees prior to December 31, 2012, these establishments risk delisting by FDA. 

Bob Mehta is principal consultant of GMP ISO Expert Services, a Los Angeles/Orange County-based consulting firm specializing in global supplier quality management, supporting quality systems for FDA and ISO regulated companies and helping with remediation of quality systems as a result of FDA’s warning letters to make the system compliant to regulatory requirements. Mehta has more than 22 years of experience in the fields of quality, regulatory compliance, regulatory and notified body inspections, supply management, and risk management. Mehta holds MSQA, MBA, B.S. (Chem), and ASQ - CSSBB, CQE, CRE, CSQE, CBA, CQA, CPA certifications. He serves on the committee of the Industry Board of Advisor for Medical Device Industry Education Consortium (MDIEC). He is heavily involved in remediating and implementing the risk-based quality systems and supplier audit program for Fortune 500 clients in a variety of industries, including medical device, pharmaceutical, biotech and neutraceutical. 

Implantable Polymer Composite From Invibio

A provider of biomaterial products for the surgical and medical device markets has released an implantable polymer engineered to deliver strength and performance in high-load applications. Endolign composite is a radiolucent, nonmetallic biomaterial capable of replacing cobalt-chromium alloys, titanium alloys, and stainless steel in many applications that traditionally have employed these or other metals. It features good fatigue behavior, biocompatibility, biostability, and is supported by FDA drug and device master files. An inherently pure and inert composite made up of continuous carbon fibers in a PEEK-polymer matrix, the material is offered as an option for providing structural support or sustained or cyclic load-bearing capability in applications involving implantation or blood, bone, or tissue contact exceeding 30 days. Applications include such devices as translaminar fixation pins, spinal-fusion cages, bone fracture plates and screws, and intermedullary nails and screws.

Invibio Inc.
West Conshohocken, PA


R 145 Thermoforming Packaging Machine

A supplier of packaging products to the medical industry has engineered a thermoforming packaging machine to meet the special requirements of the medical device and pharmaceutical industries. The compact R 145 Clean Design thermoforming packaging machine features a precision feeding system, optimized lifting units, and cleanroom-compliant construction and materials that are designed to ensure that the system packages medical sterile products in compliance with GMPs. With forming and sealing dies configured for fast format changes, the system can efficiently package sterile devices in virtually any batch size. It packages products within a modified atmosphere with a controlled oxygen content and accommodates diverse packaging materials. The machine also offers process reliability and reproducibility, process and access control through user identification, and traceability of parameter changes. Designed for ease of use, the system provides process visualization on the touch screen control.

Multivac Inc.
Kansas City, MO

CeraTek Medical Pouch Sealer

A manufacturer of sealing and thermoforming machines offers constant heat sealer and cutter systems for medical pouches. Available in two models, these CE- and ISO 11607–compliant systems allow medical device manufacturers to combine medical pouch sealing and cutting processes into a single step following sterilization. The cut-off knife and sealing die operate independently, so the user can operate the system as a sealer only, cutter only, or combined sealer and cutter. The CeraTek 12-MPK/2 features a 12-in.-long seal die and can accommodate a pouch up to 11.5-in. wide, while the 24-MPK/2 model has a 24-in.-long seal die and can accommodate pouches up to 23.5-in. The minimum distance from the outer edge of the applied seal to the cut location is 0.25 in.
SencorpWhite Inc.
Hyannis, MA

FDA Grants PMA for Cook Medical's Zilver PTX Stent

Cook Medical, a healthcare device manufacturer based in Bloomington, Indiana, recently received premarket approval (PMA) from the United States Food and Drug Administration (FDA) for its Zilver PTX stent. The Zilver PTX stent is the first drug-eluting stent for peripheral artery disease that has received approval in the U.S. The PMA for the device comes approximately one year after the Circulatory Systems Devices Panel at the FDA recommended the device for approval. The Zilver PTX stent is a drug-eluting, self-expanding stent that comes coated in a layer of paclitaxel, a mitotic inhibitor used in chemotherapy. In a prepared statement, Cook Medical VP Rob Lyles said, "This approval marks the start of Cook's program to bring the benefits of drug elution to U.S. physicians treating the peripheral arteries." He continued, "We expect to have a full suite of drug-eluting peripheral stents in the most commonly used lengths and diameters available to U.S. physicians." References