ISO 80369: Frequently Asked Questions, Answered

ISO 80369: Frequently Asked Questions, Answered
The medical device industry is in the process of shifting from the adoption of ISO 594 to ISO 80369 as the preferred standard for qualifying luer connectors, as FDA will no longer accept ISO 594 in support of premarket submissions after December 31, 2019. Image courtesy of DDL Inc.

In the years since ISO 80369 was announced, the impact of the changes to the medical device industry have begun to sink in, and momentum has been steadily building as designers are adopting the changes. At DDL, we have observed a dramatic shift away from ISO 594 as the preferred standard for qualifying luer connectors, which is inevitable, but surprising in terms of the pace of adoption within the industry as a whole.

As with every new standard, there are certain changes that have more impact than the rest and generate the bulk of the questions that come up during new project discussions. Below are responses to the most common questions we receive from our customers. As implementation of the standard progresses throughout the industry, I would like to continue to update the audience by answering new questions as they arise in a future article.

What are the requirements for dimensional compliance?

Dimensional conformance to the figures and tables in Annex B of ISO 80369 (Part 3 for enteral connectors, Part 5 for limb cuff connectors, Part 6 for neuraxial connectors, and Part 7 for IV and hypodermic connectors) is a requirement. In your submission, you will be required to show objective evidence that your molded or machined connector meets the dimensional specifications for the connector style. If the connector does not meet the specs, then it is prohibited from being labeled as a connector per the intended application category (e.g., a luer connector).

Many different measurement techniques may be employed to fully and accurately assess a connector’s dimensions, including contact and vision CMM, CT scanning, potting and sectioning, calculation by interpolation, and using reproduction rubber to create casts of internal features. The specific techniques depend on the connector type and gender and the judgment of the inspection lab.

As manufacturing processes pass the design verification hurdle and get into commercial production, a different concern has started to arise – that of in-process checks. Commonly, the go/no-go gauging test using the plug or ring gauge per Figure 3A, 3B, or 3C in ISO 594-1 is used as a simple and effective means to monitor for process drift. However, as this requirement doesn’t exist in ISO 80369-7, the suitability of this method has been brought into question. The surprising fact is that the tolerances for the luer taper are actually looserin ISO 80369-7 than in ISO 594-1, so utilizing the go/no-go gauge provides an additional layer of assurance that the samples coming off the mold are within specification.

Is non-interconnectability testing a requirement?

There is an update pending to ISO 80369-1 that makes this point clear – if a connector meets the material (modulus), dimensional, and performance requirements of one of the existing application categories, then it is considered to be non-interconnectable by default. The non-interconnectability characteristics of the connector designs were validated by the ISO committee responsible for publishing the standards; so as long as the critical assumptions are adhered to, it is not required to perform the non-interconnectability test per ISO 80369-1 Annex B.

For non-standard geometries, there is a special case regarding luer access devices, or LADs. These are female lock connectors that are designed to mate to male luers but that have an internal valve, rather than a luer taper that is actuated by the male taper and opens the fluid path. LADs do not meet the definitions for a luer and are therefore outside the scope of ISO 80369-7. However, demonstrating conformance with the performance requirements and certain dimensional elements that support non-interconnectability characteristics are meaningful and help support claims of compatibility with male luer connectors.

Are variable test methods worth the effort?

Like many complex questions, the answer to this one is, “it depends.” The performance tests described in Annexes B through I in ISO 80369-20 are all set up as attribute analyses. Annex J in the standard describes ways in which the test procedures may be modified in order to perform them so as to permit variable analysis. The advantage to variable methods is that there is typically more power to each data point, meaning fewer samples need to be tested in order to achieve the required confidence and reliability intervals. Each method requires a different degree of modification, ranging from trivial to fairly complex, in order to make the conversion. In loose terms, here’s how I would rank the relative degree of difficulty for each test method:

Trivial

  • Leakage by pressure decay.
  • Sub-atmospheric pressure air leakage.
  • Disconnection by unscrewing.

Moderate

  • Resistance to separation from unscrewing.

Challenging

  • Positive pressure liquid leakage.
  • Resistance to separation from axial load.
  • Resistance to overriding.

The "Stress Cracking" method can’t be modified in order to obtain variable data, which is unfortunate, because that is the most time intensive test of the lot.

For the methods that I place in the “Trivial” category, the only modification necessary is in the data analysis, because the standard test output is a numerical value. The first step is to test for normality and transform the data to normal, if necessary. From there, the upper or lower specification limit can be determined on the sample group and compared to the limit prescribed in the standard for the connector application being tested.

For the "Resistance to Separation from Unscrewing" test, the main challenge is in ensuring that the equipment used to measure the unscrewing torque has the necessary control required for the test. For example, spring-loaded torque watches are not suitable because the torque reading can get distorted when the sample suddenly breaks loose from the reference connector. The reading is also sensitive to the torque application rate, so applying some measures to ensure consistency are important for repeatability and reproducibility.

The tests in the “Challenging” category require equipment that is substantially different than what is commonly used for the attribute methods. The "Resistance to Separation from Axial Load" and "Resistance to Overriding" tests commonly require special fixturing in order to securely grip the sample in tensile or rotational test systems, adding time and expense to the project for design and qualification work. Also of great concern is the prospect of damage to the reference connectors. A sufficiently robust sample connector design could require application of forces that cause localized yielding of the stainless steel.

All in all, variable methods can be a great option in situations where high risk attributes mandate very high confidence and reliability, or when the sample connectors are expensive or in limited supply, but there are also significant complications that need to be addressed. In many cases, the value of performing variable analysis is more difficult to realize than it initially appears.

DDL will be exhibiting at Booth #1832 at the upcoming MD&M Minneapolis October 31 to November 1.

Alcon Pulls CyPass Micro-Stent from Market Based on Long-Term Safety

Alcon Pulls CyPass Micro-Stent from Market Based on Long-Term Safety

One company's loss is another company's gain today in the increasingly competitive microinvasive glaucoma surgical (MIGS) market. 

Alcon, a division of Novartis, said it is voluntarily removing all versions of the Cypass Micro-Stent from the global market based on a new analysis of five-year post-surgery data. The COMPASS-XT long-term safety data showed that at five years, patients in the CyPass Micro-Stent group experienced statistically significant endothelial cell loss compared to patients who underwent cataract surgery alone.

The news sent shares of Glaukos, one of the main competitors in the MIGS space, soaring today. Glaukos' stock was trading at about $61 a share at midday, up 36.16% ($16.20), and reached as high as $70 a share in morning trading. FDA approved Glaukos' iStent inject Trabecular Micro-Bypass System in June. Another competitor, Ivantis, received FDA approval earlier this month for its Hydrus Microstent.

FDA approved the CyPass Micro-Stent in July 2016 for use in conjunction with cataract surgery in adult patients with mild-to-moderate primary open-angle glaucoma based on the results of the landmark two-year COMPASS study, which demonstrated a statistically significant reduction in intraocular pressure at two years post-surgery in patients implanted with the CyPass Micro-Stent at the time of cataract surgery, compared to patients who just had cataract surgery.

At two years post-surgery, there was little difference in endothelial cell loss between the two groups, the company noted, but the study was designed to follow patients for an additional three years, with analysis at the five-year mark. That's where the difference in cell loss was revealed.

Novartis acquired the device for its Alcon business in early 2016 when the company bought Transcend Medical.

"We believe that withdrawing the CyPass Micro-Stent from the market is in patients' best interest and is the right thing to do," said Stephen Lane, MD, Alcon's chief medical officer. "Although we are removing the product from the market now out of an abundance of caution, we intend to partner with the FDA and other regulators to explore labeling changes that would support the reintroduction of the CyPass Micro-Stent in the future."

Alcon said it will communicate directly with ophthalmic surgeons about how to manage patients who have already received a CyPass Micro-Stent, and instructions for returning unused devices.

Why a Texas Man Wants Boston Scientific to Stop Calling Him

Why a Texas Man Wants Boston Scientific to Stop Calling Him

A man in Texas became so fed up after receiving two prerecorded sales calls from Boston Scientific, that he decided to take the Massachusetts company to court. 

According to the class action complaint, Steven Sandoe is asking for a jury trial to stop Boston Scientific from making these types of calls to consumers and to stop calling consumers whose phone numbers are registered on the National Do Not Call (DNC) list. Sandoe registered his phone number on the DNC list on July 25, 2015, according to the filed complaint.

Sandoe's lawsuit claims that these calls harmed him in the form of "annoyance, nuisance, and invasion of privacy," and disturbed his use and enjoyment of his phone, in addition to the wear and tear on the phone's hardware (including the phone's battery) and the consumption of memory on the phone.

Boston Scientific has not yet commented on the lawsuit.

Sandoe said he received the first of two prerecorded sales calls from Boston Scientific sometime in or around June 2018, and the second call on July 6, 2018. Both calls were a prerecorded message on behalf of a practicing pain management doctor at Richland Hills, TX-based Spine Works Institute promoting an educational seminar scheduled for July 10 to discuss non-medication treatment options for chronic pain. Both messages allegedly directed consumers to this Boston Scientific marketing website for more information and to register for the event.

Sandoe said he does not have a relationship with Boston Scientific or any of its affiliated companies. 

"Simply put, Boston Scientific did not obtain plaintiff's prior express written consent to place any solicitation telephone calls to him using a prerecorded voice message," the complaint states.

AtriCure Makes Significant Progress with Afib Therapy

Pixabay AtriCure Makes Significant Progress with Afib Therapy

AtriCure is one step closer to getting its Convergent atrial fibrillation (Afib) treatment approach a nod from FDA. The Mason, OH-based company said it has fully completed enrollment of the full cohort of 153 patients in the CONVERGE IDE clinical trial.

AtriCure said the trial will compare the Convergent approach to endocardial catheter ablation for patients with persistent or long-standing persistent Afib.

“The full enrollment of the CONVERGE clinical trial is a significant milestone for AtriCure,” Mike Carrel, president and CEO of AtriCure said in a release. “This study is the first of its kind, evaluating the multi-disciplinary Convergent approach against catheter ablation for patients who suffer from the most serious forms of Afib. We believe that once concluded, this study will be a meaningful step forward in demonstrating the safety and effectiveness of the Convergent approach.”

The CONVERGE study’s primary efficacy endpoint is for enrolled patients to be Afib, atrial tachycardia, and atrial flutter free, absent class I and III AADs except for a previously failed or intolerant class I or III anti-arrhythmic drugs, with no increase in dosage following the 3-month blanking period through the 12 months’ post procedure follow-up visit. The last patient follow-up is expected to be sometime in 3Q19, after which the company will submit final documentation to FDA and seek a PMA.

AtriCure has had a lot of momentum recently. In July the company was listed as one of the 25 most attractive medtech companies on the M&A radar.

Protecting and Enforcing the Intellectual Property Behind Medical Diagnostics

Protecting and Enforcing the Intellectual Property Behind Medical Diagnostics
Image source: Shutterstock/master_art

Medical diagnostic devices detect and measure biological events and structures in the human body. This specific class of medical device derives value from the prevention, diagnosis, monitoring, treatment, and alleviation of human disease and other conditions. The commercialization of a diagnostic device is often a lengthy, multi-step process that requires significant investment in research, design, manufacturing, clinical trials, and regulatory approval. In each stage of the product life-cycle, a company can protect and enforce intellectual property flowing from technical and functional attributes of the medical diagnostic device. Determining the appropriate form of intellectual property protection and implementing an internal IP assessment policy will help corporations maximize the competitive advantage of the innovation and return on investment.

PATENTS VERSUS TRADE SECRETS

From conception to commercialization of a diagnostic medical device, engineers and product design teams develop new components, features, and functionality. Isolating and protecting innovation throughout the product life-cycle requires a balance between patent and trade secret protection.

A. Patent Protection for Diagnostic Devices

“Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof” may obtain a utility patent.[1] Corporations developing medical diagnostic devices rely heavily on utility patents to preclude competitors from using valuable and competitive improvements in diagnostic technology. Patent protection applies to many aspects of a diagnostic device, including the device functionality, device configuration, method of detection, and other novel device features.

Prior to issuance, patent applications undergo an extensive examination process at the United States Patent and Trademark Office. The examination process can take 2 to 2.5 years from filing to grant.[2] The term of a patent begins on the date the patent issues and ends 20 years from the effective filing date.[3] The limited patent term is a constitutional right granted to promote the “progress of science and useful arts” in exchange for disclosing the process of making and using the claimed invention to the public.[4]

A patent owner has the right “to exclude others from making, using, offering for sale, or selling the invention throughout the United States or importing the invention into the United States.”[5] This bundle of patent rights is enforced by filing a patent infringement lawsuit in federal district court.[6] The average time to trial for a patent lawsuit across all jurisdictions in the U.S. has increased to approximately 2.5 years, although some jurisdictions move faster.[7] Upon a finding of infringement, a jury or court may award a patent owner lost profits, a reasonable royalty, or an injunction precluding the acts of infringement.[8]

In addition to blocking competitors from using intellectual property, patents are offensive assets that generate revenue. A tactical enforcement campaign against strategic targets can increase market share in areas where the company has invested sweat equity to develop new diagnostic technology. The median damages awarded for patent infringement between 1997 and 2016 ranged from $2.0 million to $17.0 million per case, depending on the year.[9] In many cases, a successful enforcement campaign generates royalties from a competitor’s sales after the lawsuit has settled and through the life of the patent.

B. Trade Secret Protection for Diagnostic Devices

A trade secret is any type of proprietary financial, business, scientific, technical, economic, or engineering information that has been kept secret through reasonable measures.[10] The proprietary information must not be generally known or readily ascertainable through proper means by another person who can obtain economic value from disclosure or use.[11] This powerful and expansive form of intellectual property protects the company’s most valuable and competitive secrets. For diagnostic devices, proprietary detection methods, software, data processing techniques, sensor functionality, internal circuitry, clinical data, customer lists, and other technical, economic, and competitive information can qualify as trade secrets.

Unlike patents, trade secrets are created and protected independent of an agency examination or public disclosure process. Once a company institutes reasonable measures to guard the proprietary information or technology, it becomes a trade secret. As long as reasonable measures are in place, a trade secret is perpetual.

Recently, Congress passed the Defend Trade Secrets Act (DTSA), which introduces a new federal cause of action for trade secret misappropriation.[12] Under the DTSA, reverse engineering and independent derivation constitute proper means of discovering a trade secret and are not actionable.[13] Theft, bribery, misrepresentation, breach of a duty to maintain secrecy, and espionage are all improper means of discovery that give rise to misappropriation.[14] A trade secret owner has the right to preclude misappropriation through improper acquisition, disclosure, or use of the trade secret.[15]

A trade secret is enforced by filing a lawsuit in federal district court under the DTSA or in state court under the applicable state law. Upon a finding of misappropriation, a jury or court may award a trade secret owner an injunction to prevent any actual or threatened misappropriation and damages in the form of actual loss, unjust enrichment, or a reasonable royalty.[16] A federal jury recently awarded $940 million in damages to an electronic health records vendor that filed suit against an India-based consultant for theft of password protected software while under contract.[17] When misappropriation rises to the level of espionage or bad faith, it can also carry stiff criminal penalties.[18]

BEST PRACTICES

A. Invention Disclosure and Documentation

Implementing a company policy is the first step in identifying and securing valuable intellectual property. An invention disclosure report is a form used by scientists and engineers to document and describe inventions at the time of conception. The form may require (1) name, contact information, and citizenship of inventors; (2) identification of principal inventor; (3) description of the invention; (4) funding source; (5) signature of inventors; and (6) date. This confidential disclosure form documents inventorship and provides in-house and outside counsel with information necessary to decide whether to pursue IP protection and the type of protection to pursue.

B. Selecting Appropriate IP Protection

Because of publication requirements, patent protection is better reserved for inventions that the company is comfortable disclosing to the public. The process of obtaining and maintaining a utility patent is typically more expensive than the process of obtaining and maintaining a trade secret. For diagnostic devices, features and functionality of the device that are not discoverable through reverse engineering, such as software, diagnostic methods, signal processing, internal circuitry, and processor functionality, should be targeted for trade secret protection. If it is not feasible to keep the technical information or product feature secret, a utility patent is a more appropriate form of IP protection.

C. Patent Eligibility Standards for Diagnostic Devices

“Phenomena of nature, though just discovered … are not patentable, as they are the basic tools of scientific and technological work.”[19] In a series of recent decisions, federal courts have shaped the law governing patent eligibility of diagnostic devices. Detecting naturally occurring events in the human body with a known method of detection alone is not patent eligible.[20] Inventors and attorneys must now focus on securing patents for improved and unconventional equipment and methods of detection, diagnostics, signal processing, and imaging.

D. Reasonable Measures

Once a proprietary feature or method is deemed appropriate for trade secret protection, it should be earmarked and protected through reasonable measures. Reasonable measures can include: (1) executing employee confidentiality and non-disclosure agreements, (2) implementing password protection and network security for proprietary software and diagnostics, (3) requiring security badges for access to sensitive areas, (4) conducting exit interviews to verify that all proprietary and company information and devices are returned, (5) creating and enforcing a written policy, (6) auditing the policy, and (7) executing third-party confidentiality and non-disclosure agreements with vendors and contractors.

CONCLUSION

A successful IP assessment policy creates a framework for identifying new inventions, documenting the invention disclosure process, determining the appropriate IP protection, and educating employees.

REFERENCES

[1] 35 U.S.C. § 101.

[2] USPTO Performance and Accountability Report, FY 2017 at p. 15 (The average first USPTO action pendency is between 1.2 and 1.5 years.).

[3] 35 U.S. Code § 154.

[4] U.S. Const. art. I, § 8, cl. 8; see also 35 U.S.C. § 112.

[5] 35 U.S. Code § 154(a)(1).

[6] 28 U.S. Code § 1338 (“The district courts shall have original jurisdiction of any civil action arising under any Act of Congress relating to patents.”).

[7] PwC’s Forensic Services, 2017 Patent Litigation Study, Change on the Horizon?, p. 7; see also DocketNavigator analytics (Since 2008, the Eastern District of Virginia has maintained an average time to trial of approximately 1.3 years).

[8] See 35 U.S. Code § 284; see also eBay Inc. v, MercExchange, L.L.C., 126 S. Ct. 1837 (2006).

[9] PwC’s Forensic Services, 2017 Patent Litigation Study, Change on the Horizon?, pp. 5, 9 (“The largest patent-infringement verdict in U.S. history was granted in 2016 in Idenix Pharmaceuticals LLC v. Gilead Sciences Inc. Idenix, a subsidiary of Merck, was awarded $2.5 billion by a jury for its patent related to a hepatitis C drug.”).

[10] See e.g., 18 USC §§ 1836; 1839(3) as amended by the Defend Trade Secrets Act (DTSA).

[11] 18 USC § 1839(3).

[12] 18 U.S.C. § 1836.

[13] 18 U.S.C. § 1839(6)(b).

[14] 18 U.S.C. § 1839(6)(a).

[15] 18 U.S.C. §§ 1836(b)(3); 1839(5).

[16] 18 U.S.C. § 1836.

[17] See Epic Systems Corp. v. Tata Consultancy Svcs. Ltd., 2016 WL 4976632 (W.D. Wis. 2014).

[18] https://www.justice.gov/usao-cdca/pr/irvine-engineer-named-new-indictment-alleging-theft-trade-secrets-two-medical-device. (A California federal grand jury issued a 12-count indictment charging a California resident with stealing and possessing trade secret devices used to treat cardiac and vascular ailments. The counts carry a statutory maximum sentence of 10 years in federal prison and a fine of up to $5 million.)

[19] Gottschalk v. Benson, 409 U.S. 63, 67 (1972).

[20] See e.g., Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66 (2012) (method of administering a drug and measuring naturally occurring metabolites was not patent eligible); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371 (Fed. Cir. 2015) (detecting cell-free fetal DNA in maternal plasma or serum with some common preparation and amplification steps was not patent eligible); Genetic Technologies Ltd. v. Merial L.L.C., 818 F.3d 1369 (Fed. Cir. 2016) (method of detecting coding region of person’s genome by amplifying and analyzing linked non-coding regions was not patent eligible); Exergen Corporation v. Kaz USA, Inc., 172 F.Supp.3d 366 (D. Ma 2016) (new radiation detector capable of taking three temperature readings per second over the skin surface, above the temporal artery to more accurately detect deep body temperature was patent eligible).

Taking a Deeper Look at Device Certification and Recertification

Pixabay Taking a Deeper Look at Device Certification and Recertification

The new Medical Devices Regulation (MDR) and In Vitro Diagnostic Regulation (IVDR) approved by the European Union in May 2017 tightens requirements in an effort to create a more transparent and uniform process for certifying new medical and IVD devices, and recertifying existing ones. Manufacturers have three years and five years to comply with the MDR and IVDR respectively. Some of the challenging questions facing manufacturers are:

  • Is it cost-effective to recertify our entire product portfolio, when the investment for some may outweigh the benefit?
  • How will we expand our data collection resources and post-market surveillance/performance assessments required under the new laws?
  • What is the new role of Notified Bodies (NBs) and how will our relationship with them change?
  • Are any of our products Class III implantable devices or Class IIb active devices intended to administer and/or remove a medicinal product that may be required to undergo further scrutiny during the conformity assessment procedure?
  • What is the best timeframe to begin implementation, and how long will it take?

This article will outline a three-step approach to identifying your products with the highest commercial value, helping you prioritize your medical and IVD devices for compliance with the new MDR and IVDR.

Internal assessment

First, manufacturers need to inventory their entire pipeline and portfolio to determine the category for each product. At the same time, they need to note which devices have been newly classified as medical devices, such as disinfection and sterilization products, or up classified as Class III medical devices, such as surgical meshes and joint replacements. New additions to the IVDR are genetic tests and companion diagnostics that predict treatment response or individual patient reactions.

The investment will vary greatly among products, from a standard regulatory submission to the need for clinical trials with patient data. Ask yourself which ones are worth carrying forward, based on the difference between additional compliance costs and future revenue potential. Take into consideration that payers may prefer devices certified under the new rules. In some cases, it may be more cost effective to renew certain products under existing directives, then discontinue them when their certificates are voided in 2024. Review how you will meet the increased data collection and reporting requirements, such as post-market surveillance, under MDR and IVDR. Then create gap assessment and closure plans, with the future steps you will take to be in compliance with the new regulations.

External validation

Second, it’s important to interview customers to receive feedback on how your products are regarded in the marketplace. This process helps you validate internal hypotheses, especially for strategic drivers, and identify your portfolio’s contribution to company and brand value position. Further, you can assess the implications of removing different products from the portfolio from a business, regulatory, and compliance perspective. You’re then prepared to create a product priority list, with each device and diagnostic tool ranked by level of commercial importance.

Prioritization and implementation

Lastly, by integrating the findings from the internal and external work streams, you can prioritize your portfolio. By this stage, you’re equipped to make decision on which products to de-prioritize and potentially withdraw/sunset. During this third step you need to conduct financial calculations/simulations, including net present value (NPV), to understand the financial impact of your portfolio adjustments. You’ll need to assess resource requirements, including return on investment (ROI) for regulatory re-filing.

In terms of personnel, it’s useful to develop a roadmap for roles and responsibilities for activities and implementation planning. Under the new rules, you’ll need to appoint a “responsible person,” someone with the necessary credentials and training, to oversee that clinical evidence, quality data, and post-market surveillance are properly collected. That same person is responsible for making sure safety and performance issues are adequately addressed.

Be advised that NBs will now be in the role of regulatory enforcers, instead of industry partners. With the new rules, NBs are responsible for having sufficient, suitable qualified personnel and must be authorized to review specific classes and types of devices. We anticipate that there will be shortages of NBs to certify some types of devices, which could lead to delays and higher costs. Assess how the limited availability of NB services will affect your development and certification timelines, and lock in services in advance as needed.

Further, it is critical to develop a plan for the new regulatory documentation requirements, comparing them with what you’re already doing to discover any gaps and determine how to address them. Technical documentation for MDR and IVDR includes extensive requirements on what should be included in precertification and post-market surveillance reports, how often to file them, how they should be written, and who is responsible for them.

In addition, you’ll need to assess the resources you have to meet the new product labelling laws. There are significant changes to labelling, including simpler language and consistency across all languages on the label, as well as a requirement for implant cards to be given to patients who receive implantable devices. Further, Unique Device Identifiers (UDIs) must be included in labels and other documents to help trace medical devices for performance monitoring, safety alerts, or product recalls throughout the product’s lifecycle.

Smooth transition

To smoothly transition to the new MDR and IVDR as a successful player requires early intervention, forethought, and setting an action plan in motion. ICON and Simon-Kucher & Partners have teamed up to offer an integrated regulatory and commercial assessment of existing and pipeline medical devices and in vitro diagnostic devices. Jointly, we help our clients prepare the business case for which products to certify or recertify, based on revenue and profit, and which products should be withdrawn. We also help you create the substantial body of real-world evidence (RWE) required to conform to the new regulations. In addition, we help you save money in the long run through electronic health record-driven data collection and automated site management for ongoing product surveillance and performance assessment. Also, ICON’s medical device regulatory group can assist you in remediating technical documentation deficiencies by updating existing documentation or preparing new reports.

Can a New Radiopharmaceutical Company Unlock the Power of PET?

Can a New Radiopharmaceutical Company Unlock the Power of PET?

Since its invention and development in the 1970s, positron emission tomography (PET) has made an undeniable impact on cancer, neurology, and cardiology diagnosis. But the full potential of PET has been limited, primarily by cost and because the imaging technique relies on the use of radioactive isotopes to visualize physiological processes of the body and these isotopes tend to have short half-lives.

Now, a new company based in Pasadena, CA, is trying to unlock the full power of PET with its radiolabeling platform that launched today. Fuzionaire Dx's technology is based on a breakthrough discovery by Anton Toutov during his PhD studies under Nobel Laureate Robert Grubbs at the California Institute of Technology (Caltech) creating a new branch of catalysis based on Earth-abundant alkali metals like potassium and sodium.

"What we have is a radiolabeling platform that can radiolabel any ligand at record rates of speed," Fuzionaire Dx CEO Nick Slavin told MD+DI.

Not only is it the first platform that can radiolabel any ligand, Slavin said, but the speed matters a lot because of the half-life issue of radioisotopes. For example, fluorine-18, the most commonly used radioactive isotope in PET has a half-life of just 109.8 minutes.

"With our radiolabeling platform, labeling happens seemingly instantaneously, in seconds, and that shaves a lot of time off the current state of the art, which is 20 minutes on up to sometimes hours ..." Fuzionaire Dx CEO Nick Slavin told MD+DI. "We can unlock the potential of PET for disease diagnosis, but also as a tool for drug discovery. "

Until now, producing a catalytic reaction has generally required either the use of rare, expensive metals or high temperature and pressures. According to Fuzionaire Dx, this discovery makes it possible to initiate chemical processes at ambient temperatures and pressures without using precious metals, lowering cost, improving efficiency, and unlocking previously unthinkable chemical reactions.

The new method makes it possible to create fluorine-18 radiopharmaceuticals that contain a novel class of stabilized silicon-fluorine bond, a process that is much more efficient and uses existing radiochemistry infrastructure. These efficiency gains not only lower costs, they dramatically reduce the time it takes to prepare radiotracers.

As a result, molecular imaging techniques like PET will be able to image a much broader range of biological targets and a greater breadth of diseases. This radiolabeling method also reduces the amount of off-target imaging and produces images with greater specificity and image clarity, the company noted.

But, Is This New Platform Adoptable?

"The answer is yes, that's actually one of the most exciting aspects of this," Slavin said. "In a lot of industries, people say 'we have this breakthrough and it's better than the current way of doing things,' but the cost of learning this new method or switching over to this new process, or buying new equipment is a lot, so practically this new, better process just isn't used."

That's not the case with Fuzionaire Dx's platform, Slavin said.

"It fits perfectly into the existing manufacturing paradigm, no new equipment is needed, it goes along the steps already taken to manufacture PET probes, some steps are actually cut out, but it just does everything a lot faster," he said. "That's exciting because I think it means we can become the go-to radiolabeling platform for disease diagnosis and drug discovery pretty quickly."

How Fuzionaire Dx Attracted Michael Phelps

Fuzionaire Dx has managed to attract support from leading experts in the field, including Michael Phelps, the original inventor of PET, and a professor and chair of the Department of Molecular and Medical Pharmacology at the University of California, Los Angeles (UCLA).

"Mike Phelps is just a remarkable person and, obviously, a luminary scientist, much like Bob Grubbs, and they've been friends for some time,"  Toutov, the co-founder and chief scientific officer at Fuzionaire Dx, told MD+DI. "Bob, of course, knew very intimately of this work because I was in his lab when these breakthroughs occurred."

Given that chemistry has historically been such a fundamental limitation in PET's potential in healthcare, it wasn't long before Phelps caught wind of Toutov's work in Grubbs' lab at Caltech.

"Given that Mike Phelps' legacy really is to make PET as available and as powerful and meaningful to patients as possible, any big chemistry discoveries, especially if they apply to that space, are exciting to think about, and I think that's how that interaction between Bob Grubbs and Mike Phelps happened," Toutov said. "And that has led, over subsequent years, to what we have now, which I think is really exciting."

The company's other advisors are Jason Lewis, former president of the World Molecular Imaging Society, and Kristin Swanson, a mathematical oncologist at the Mayo Clinic.

Does This Tech Play a Role in Precision Medicine?

As the diagnostics space continues its push toward early detection using technologies like liquid biopsy and even artificial intelligence-based genomic testing, 

Fuzionaire Dx's platform could be a natural fit with that paradigm shift. If, for example, a patient has a blood test and finds out they have prostate cancer, a PET scan can help track and image the disease and further inform the patient's doctors decide how to treat it.

"The precision medicine element is just a really clearcut case for us," Toutov added. "As new molecules and ligands are developed to target certain specific things ... we should be there ready to label any of those materials and help them be used for PET, so this falls in perfectly with precision medicine."

Edison Honored in 3D Printed Titanium

3D printing, GE Additive, Edison, Titanium
Normal view of the Edison statue. (Image source: GE Additive)
3D printing, GE Additive, Edison, Titanium
Twisted view of the Edison statue showing the internal filigree of electron beam melting. (Image source: GE Additive)

GE Additive R&D tech Oskar Zielinski has created a 3D printed Titanium statue of GE's founder, Thomas Edison. Zielinski works at Arcam EBM—a GE Additive company in Gothenburg, Sweden, where he's responsible for the maintenance, modification, and repair of electron beam melting systems. He recently decided to put an Arcam Q20plus electron beam machine through its paces by creating a statue of Edison using Titanium (Ti64). The whole build took 90 hours and stands 1.25 feet tall.

3D printing, GE Additive, Edison, Titanium
Oskar Zielinski hold his Titanium Edison statue. (Image source: GE Additive)

Zielinski created 25 pieces and generated different net structures inside each layer to test the capabilities of the machine. All 4,300 of the 90-micron layers were printed in one go, with only a little support between the outer skins of the slices. The nets were all free floating without supports. The different net structures inside show the filigree work of electron beam melting.The Arcam EBM creates dimensionally accurate parts by utilizing a high-power electron beam with high melting capacity. The process takes place in a vacuum at a high temperature, resulting in stress-relieved components with material properties comparable to wrought material.

This time-lapse video shows the statue being printed layer by layer. The video was captured from inside the machine using an Arcam LayerQam that is normally used for defect detection in printed parts.

In a statement, Zielinski noted, “I am really happy with the result; this final piece is huge. I keep wondering, though, what Thomas Edison would have thought if someone would have told him during the 19th century about the technology that exists today.”

Rob Spiegel has covered automation and control for 17 years, 15 of them for Design News. Other topics he has covered include supply chain technology, alternative energy, and cyber security. For 10 years, he was owner and publisher of the food magazine Chile Pepper.

Pacific Design and ManufacturingSAVE THE DATE FOR PACIFIC DESIGN & MANUFACTURING 2019!   
Pacific Design & Manufacturing  , North America’s premier conference that connects you with thousands of professionals across the advanced design & manufacturing spectrum, will be back at the Anaheim Convention Center February 5-7, 2019! Don’t miss your chance to connect and share your expertise with industry peers during this can't-miss event.   Click here to pre-register for the event today!

 

Exciting Keynotes Announced for ESC Minneapolis 2018

We are just weeks away from the Minneapolis edition of the Embedded Systems Conference, and if you are on the fence about attending, this may change your mind. Design News and UBM have announced two exciting keynotes: VSI Labs’ Phil Magney and Michael McAlpine, associate professor of mechanical engineering at the University of Minnesota.

Michael McAlpine, ESC, Embedded Systems Conference, University of Minnesota
Michael McAlpine

McAlpine, who will speak at 1 pm on Wednesday, Oct. 31, said his keynote, “will introduce the audience to the concept of 3D printing functional materials and devices, which is enabled by our group's custom-built 3D printers, which allow us to print a broad range of materials and devices, including fully 3D printed semiconducting devices and 3D printed neural regeneration devices.”

McAlpine was previously an assistant professor of mechanical and aerospace engineering at Princeton University. He received a B.S. in chemistry with honors from Brown University (2000) and an M.A. (2002) and PhD (2006) in chemistry from Harvard University. In addition to his distinguished academic background, he has received several awards including the George W. Taylor Award for Distinguished Research and the Presidential Early Career Award for Scientists and Engineers (PECASE).

Click here for more information about McAlpine’s planned keynote, “3D Printing Functional Materials & Devices.”

Phil Magney has more than 25 years of experience in active safety systems, automated vehicle systems, and telematics. He is the founder and principal advisor of VSI Labs, which does research and advises engineering for autonomous vehicle technologies. Magney’s keynote presentation, "The Future of Automated Driving," will dissect all things associated with the “Automated Vehicle Stack.” In addition, VSI Labs will examine the technologies outside the car including intersections and supporting infrastructure supplementing deployment. Magney will be speaking Thursday, Nov. 1.

Click here for more information about Magney’s planned keynote, “The Future of Automated Driving.”

Phil Magney, VSI Labs, autonomous, ESC, Embedded Systems Conference
Phil Magney

Supporting Magney’s keynote presentation, VSI Labs will feature a Ford Level 2 (L2) automated vehicle, where attendees can experience a ride with a VSI employee and get a glimpse into the future of self-driving vehicles. Additionally, on-site demonstrations will discuss current capabilities of the L2 vehicle, including but not limited to Point Cloud Localization and Path Following.

“The medical and automotive industries are prime examples of the application of exciting advances in design and manufacturing today,” said Amy Sklar, group senior vice president, UBM. “When we gather at the Minneapolis convention center, we will explore these innovative themes, aiming to engage, inspire, and educate engineers across the design-to-build supply chain. With their wide breadth of knowledge and insight, Michael McAlpine and Phil Magney will bring tremendous value to our attendees’ experience.”

ESC Minneapolis is co-located with five other shows that span across medical technology and advanced design, including Medical Design & Manufacturing (MD&M), Minn Pack, Automation Technology Expo (ATX), Design & Manufacturing Minneapolis, and PLASTEC Minneapolis.

Click here to register for the event, and then click here to review the full schedule of events at ESC.

If you have questions that cannot be answered by visiting the event website, email technical content producer Jennifer Campbell.

U.S. and Mexico reach preliminary deal in revised NAFTA agreement

U.S. and Mexico reach preliminary deal in revised NAFTA agreement

NAFTA Rubik's cubeU.S. manufacturers breathed a collective sigh of relief and the stock market jumped more than 200 points at news today that the U.S. and Mexico have reached a preliminary trade deal to replace NAFTA that would benefit both countries. The deal, which President Trump wants to rename the U.S.-Mexico Trade Agreement, gives him a “win” in this particular trade dispute. Inclusion of Canada in the new agreement remains iffy, as it was not present at the table.

According to the New York Times, “many of the most significant changes agreed to by Mexico and the United States simply update the pact to take into account the rise of the internet and the digital economy since the agreement was negotiated. But Mr. Trump’s advisers have also pressed for big alterations to the rules governing automobile manufacturing, in an effort to bring more car production back to the United States from Mexico.”

Qualifying for zero tariffs under the renegotiated agreement would require that car companies “manufacture at least 75% of an automobile’s value in North America,” an increase from 62.5% in the previous trade agreement. “They will also be required to use more local steel, aluminum and auto parts, and have a certain proportion of the car made by workers earning at least $16 an hour, a boon to both the United States and Canada,” said the New York Times article.

Mexico’s automotive and aerospace manufacturing sectors are huge and growing as global companies, particularly from the U.S., have invested in manufacturing plants in that country over the past 30+ years. Foreign companies in Europe and Asia also see Mexico as a conduit for goods to North America as well as Central and South America. Mexico’s manufacturing infrastructure has risen to meet the demand for these companies, including demand for skilled workers through numerous large trade schools in major manufacturing hubs.

While many manufacturing businesses and others in agriculture have had—and still have—their doubts about Trump’s trade policies in an attempt to give the United States a “fair” global playing field, perhaps this proves that U.S. leadership can be tough and win. After all, it involves the “art of the deal.”