As 3D printing technology gains acceptance with pharmaceutical companies, clinical laboratories could see increased demand for pharmacogenomic testing
Will physicians someday “print” prescription drugs for patients in-office? It sounds like science fiction, but research being conducted at the University College London (UCL) indicates the capability may be closer than we think, and it could bring about a new type of collaboration between clinical laboratories, ordering physicians, and pharmacies.
UCL’s new 3D technique, which it calls “volumetric 3D printing,” is intended to enable the pharmaceutical industry to tailor drug dosage, shape/size, and release to an individual patient’s needs and preference. A key element of precision medicine.
According to GlobalData Healthcare, 3D printing also can “significantly reduce cost, wastes, and economic burden as printers only deposit the exact amount of raw materials required.”
3D printing may enable pharmaceutical companies to address gender and racial disparities in prescription drug manufacturing through a developing technology that could have implications for clinical laboratory testing. Fred Parietti, PhD (above), co-founder and CEO of Multiply Labs, a technology company that develops robotics for precision medicine pharmaceuticals, told 3D Natives, “Currently, medications are developed especially for white adult men, which means that all women and children have an excessive prescription for their bodies. This fact underlines the importance of the advent of personalized medicines, as well as highlighting the individuality of each patient, since the error in the dosage of certain active ingredients can even lead to the malfunctioning of some treatments.” (Photo copyright: Multiply Labs.)
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Increased Demand for Pharmacogenomic Testing
Though 3D printing of prescription drugs is not directly in the clinical laboratory/pathology space, it is noteworthy because it shows how technological advancements are progressing that actualize the ability to deliver precision medicine care to individual patients.
In turn, this could increase physician/patient demand for pharmacogenomic tests performed by clinical laboratories. The test results would be used by treating physicians to determine proper dosages for their individual patients prior to ordering 3D-printed drugs.
Being able to provide medication tailored to patients’ specific needs could bring about a revolution in pharmaceutical manufacturing. If 3D printed prescription drugs become mainstream, the demands could affect the clinical laboratory and pathology industries as well.
How Far Are We from Mass Production of 3D Printed Drugs?
The first and only 3D printed pharmaceutical drug on the American market is Spritam (levetiracetam) an anti-epileptic drug developed by Aprecia Pharmaceuticals, according to Medical Device Network. It received FDA clearance under the name Keppra in 1999.
Headquartered in Blue Ash, Ohio, Aprecia’s patented ZipDose manufacturing process allows 3D-printed pills to hold a larger dosage and dissolve rapidly. They currently have the only FDA process-validated 3D printing platform for commercial-scale drug production. They are leading the way on this new 3D technology and others are following suit.
FabRx, a start-up 3D printing company developed by academic researchers in 2014 at the University College London, released its first pharmaceutical 3D printer for personalized medicine called M3DIMAKER according to LabioTech.eu. The system is “controlled by specialized software, allowing the selection of the required dose by the pharmacist according to the prescription given by the clinician,” the company’s website notes.
The technology also allows for additional customization of pills, including the application of Braille for visually impaired patients, and printing of Polypills, which combine more than one drug into a single pill.
Other company’s developing 3D printing of pharmaceuticals, according to LabioTech.eu, include:
Germany’s Merck: currently in clinical trials of 3D printing medication with the goal of reaching large scale production.
China’s Triastek: which holds “41 patents that account for more than 20% of global 3D printing pharmaceuticals applications.”
We are still far away from large scale production of drugs using 3D printing, but that doesn’t mean it should not be on clinical laboratory leaders’ radar.
The rise of 3D printing technology for precision medicine could lead to big changes in the pharmaceutical world and alter how patients, providers, and clinical laboratories interact. It also could increase demand for pharmacogenomic testing to determine the best dosage for individual patients. This breakthrough shows how one line of technology research and development may, as it reaches clinical use, engage clinical laboratories.
University of Cincinnati researchers hypothesize that low levels of amyloid-beta protein, not amyloid plaques, are to blame
New research from the University of Cincinnati (UC) and Karolinska Institute in Sweden challenges the prevailing theory about the causes of Alzheimer’s disease, suggesting the possibility of new avenues for the development of effective clinical laboratory assays, as well as effective therapies for treating patients diagnosed with Alzheimer’s.
Scientists have long theorized that the disease is caused by a buildup of amyloid plaques in the brain. These plaques are hardened forms of the amyloid-beta protein, according to a UC news story.
“The paradox is that so many of us accrue plaques in our brains as we age, and yet so few of us with plaques go on to develop dementia,” said Alberto Espay, MD, one of the lead researchers of the study, in another UC news story. Espay is Professor of Neurology at the UC College of Medicine and Director and Endowed Chair of the Gardner Center for Parkinson’s Disease and Movement Disorders.
“Yet the plaques remain the center of our attention as it relates to biomarker development and therapeutic strategies,” he added.
“It’s only too logical, if you are detached from the biases that we’ve created for too long, that a neurodegenerative process is caused by something we lose, amyloid-beta, rather than something we gain, amyloid plaques,” said Alberto Espay, MD (above), in a University of Cincinnati news story. “Degeneration is a process of loss, and what we lose turns out to be much more important.” The UC study could lead to new clinical laboratory diagnostics, as well as treatments for Alzheimer’s and Parkinson’s diseases. (Photo copyright: University of Cincinnati.)
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High Levels of Aβ42 Associated with Lower Dementia Risk
In their retrospective longitudinal study, the UC researchers looked at clinical assessments of individuals participating in the Dominantly Inherited Alzheimer Network (DIAN) cohort study. DIAN is an ongoing effort, sponsored by the Washington University School of Medicine in St. Louis, to identify biomarkers associated with Alzheimer’s among people who carry Alzheimer’s mutations.
The researchers found that study participants with high levels of a soluble amyloid-beta protein, Aβ42, were less likely to develop dementia than those with lower levels of the protein, regardless of the levels of amyloid plaques in their brains or the amount of tau protein—either as phosphorylated tau (p-tau) or total tau (t-tau)—in their cerebral spinal fluid. P-tau and t-tau are proteins that form “tau tangles” in the brain that are also associated with Alzheimer’s.
One limitation of the study was that the researchers were unable to include Aβ40, another amyloid-beta protein, in their analysis. But they noted that this “did not limit the testing of our hypothesis since Aβ40 exhibits lower fibrillogenicity and lesser depletion than Aβ42, and is therefore less relevant to the process of protein aggregation than Aβ42.” Fibrillogenicity, in this context, refers to the process by which the amyloid-beta protein hardens into plaque.
While the presence of plaques may be correlated with Alzheimer’s, “Espay and his colleagues hypothesized that plaques are simply a consequence of the levels of soluble amyloid-beta in the brain decreasing,” UC news stated. “These levels decrease because the normal protein, under situations of biological, metabolic, or infectious stress, transform into the abnormal amyloid plaques.”
The UC News story also noted that many attempts to develop therapeutics for Alzheimer’s have focused on reducing amyloid plaques, but “in some clinical trials that reduced the levels of soluble amyloid-beta, patients showed worsening in clinical outcomes.”
New Therapeutics for Multiple Neurodegenerative Diseases
Eisai, a Japanese pharmaceutical company, recently announced phase three clinical trial results of lecanemab, an experimental drug jointly developed by Eisai and Biogen, claiming that the experimental Alzheimer’s drug modestly reduced cognitive decline in early-stage patients, according to NBC News.
Espay noted that lecanemab “does something that most other anti-amyloid treatments don’t do in addition to reducing amyloid: it increases the levels of the soluble amyloid-beta.” That may slow the process of soluble proteins hardening into plaques.
Beyond their findings about Alzheimer’s, the researchers believe similar mechanisms could be at work in other neurodegenerative diseases such as Parkinson’s disease, where the soluble alpha-synuclein protein also hardens into deposits.
“We’re advocating that what may be more meaningful across all degenerative diseases is the loss of normal proteins rather than the measurable fraction of abnormal proteins,” Espay said. “The net effect is a loss not a gain of proteins as the brain continues to shrink as these diseases progress.”
Espay foresees two approaches to treating these diseases: Rescue medicine, perhaps based on increasing levels of important proteins, and precision medicine, which “entails going deeper to understand what is causing levels of soluble amyloid-beta to decrease in the first place, whether it is a virus, a toxin, a nanoparticle, or a biological or genetic process,” according to UC News. “If the root cause is addressed, the levels of the protein wouldn’t need to be boosted because there would be no transformation from soluble, normal proteins to amyloid plaques.”
Clinical Laboratory Impact
What does this mean for clinical laboratories engaged in treatment of both Alzheimer’s and Parkinson’s patients? A new understanding of the disease would create “the opportunity to identify new biomarkers and create new clinical laboratory tests that may help diagnose Alzheimer’s earlier in the disease progression, along with tests that help with the patient’s prognosis and monitoring his or her progression,” said Robert Michel, Editor-in-Chief of Dark Daily and its sister publication The Dark Report.
Given the incidence of Alzheimer’s disease in the population, any clinical laboratory test cleared by the FDA would be a frequently-ordered assay, Michel noted. It also would create the opportunity for pathologists and clinical laboratories to provide valuable interpretation about the test results to the ordering physicians.
Company also launches Amazon Clinic virtual healthcare services and announces it will terminate Amazon Care by end of year
Clinical laboratory leaders and pathologists may understandably struggle to keep abreast of Amazon’s moves in the healthcare space. For years, Amazon has tried to develop medical services that disrupt the US healthcare industry in the same way its digital book business upended traditional book publishing. It is clear that Amazon is heavily investing in healthcare ventures that deliver what it believes are better alternatives to existing primary care, clinical laboratory, and retail pharmacy options.
Now, the Seattle-based global e-commerce company has announced plans to acquire One Medical, a membership-based primary care organization, for $3.9 billion according to a news release.
Headquartered in San Francisco, One Medical has primary care offices in 12 major US markets and offers its members 24/7 virtual care, according to the company’s website.
“We think healthcare is high on the list of experiences that need reinvention,” said Neil Lindsay (above), SVP of Amazon Health Services, in a news release announcing the planned acquisition of One Medical. “We love inventing to make what should be easy easier, and we want to be one of the companies that helps dramatically improve the healthcare experience over the next several years,” he added. However, clinical laboratory leaders have watched Amazon’s efforts to disrupt healthcare come and go. (Photo copyright: Advertising Age/Daniel Berman.)
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As One Medical Grows, Amazon Launches Virtual Care Clinic
“One Medical’s philosophy is rooted in quality care, patient-centered design, and a smart application of technology,” Greg Hayes, MD, District Medical Director for One Medical, Preston Center, Dallas, told Texas News.
For its part, One Medical, which currently has more than 125 clinic locations, sees opportunity to grow its services as part of Amazon (NASDAQ:AMZN). “Joining Amazon is a tremendous next step in innovating and expanding access to high-quality, high-value healthcare,” said Amir Dan Rubin, One Medical Chief Executive Officer, in a blog post.
One Medical (NASDAQ:ONEM) is the operating name for 1Life Healthcare, Inc., a chain of primary care clinics that has 815,000 members, a 14% increase over last year. According to a news release on the company’s third quarter 2022 financial results, its revenue was $261.4 million, up 73% over the same period last year. More than 8,000 companies and organizations work with One Medical, the company’s website notes.
Meanwhile, Amazon is also launching Amazon Clinic, a virtual health service “that delivers convenient, affordable care for common conditions” to people in 32 states, an Amazon news release states.
Amazon Clinic offers virtual care services for 20 common conditions including allergies, acne, migraines, and urinary tract infections. Patients complete a questionnaire through a message-based portal prior to meeting with clinicians.
Clinical laboratory managers and pathologists will want to note that Amazon Clinic will need medical laboratory testing performed to properly diagnose patients and determine the best treatments. Since Amazon Clinic will be a virtual care service, Amazon can be expected to explore such options as sending collection kits directly to individuals using the virtual care service, allowing them to collect needed samples that can be returned to traditional clinical laboratories for testing. Amazon’s existing courier and delivery service would make it easy for the internet giant to deliver either specimen collection kits or home-test kits to obtain the necessary diagnostic data.
“Amazon Pharmacy and One Medical (once the deal closes) are two key ways we’re working to make care more convenient and accessible. But we also know that sometimes you just need a quick interaction with a clinician for a common health concern. … That’s why today were also introducing Amazon Clinic, a message-based virtual care service,” Amazon said in its news release.
What’s Next for Amazon?
Separately, Amazon announced it will terminate Amazon Care at the end of 2022. Amazon Care is a virtual and in-home care service it launched in 2019.
However, in a 2022 internal email, senior vice president of Amazon Health Services Neil Lindsay said Amazon Care wasn’t a sustainable, long-term solution for its enterprise customers, according to Fierce Healthcare.
“This decision wasn’t made lightly and only became clear after many months of careful consideration,” he said. “Although our enrolled members have loved many aspects of Amazon Care, it is not a complete enough offering for the large enterprise customers we have been targeting and wasn’t going to work long-term.”
Will Amazon Provide Clinical Laboratory Services?
Now that Amazon is set with primary care, pharmacy, and virtual health services, might it next explore medical laboratory testing or other diagnostics relationships?
But this apparently has not slowed Amazon’s drive to gain a foothold in the primary care and virtual health services market. Therefore, clinical laboratory leaders should advance their outreach to healthcare providers who are caring for Amazon employees, customers, and soon patients, in new ways and offer their lab services.
Experts cite high vaccination rates and behavioral changes among at-risk groups, but warn about complacency; clinical laboratories should remain vigilant
In July, Scott Gottlieb, MD, Commissioner of the US Food and Drug Administration (FDA) from May 2017 to April 2019, wrote an op-ed in The New York Times titled, “Monkeypox Is About to Become the Next Public Health Failure.” In it, he wrote, “Our country’s response to monkeypox has been plagued by the same shortcomings we had with COVID-19.” But has it improved? Clinical laboratory leaders and pathology group managers will find it informative to find out what has taken place since Gottlieb made his stark prediction.
The global monkeypox outbreak that emerged last spring appears to have subsided in the US and Europe, though it remains to be seen if the disease can be completely eradicated, according to multiple media reports. As of Oct. 26, 2022, the Centers for Disease Control and Prevention (CDC) reported a 7-day rolling average of 30 cases per day in the US, down from a peak of nearly 440/day in early August.
Cases are also down in cities that earlier reported heavy outbreaks. For example, the New York City Health Department reported a 7-day average of just two cases per day on Oct. 25, compared with 73/day on July 30.
And the San Francisco Department of Public Health announced on Oct. 20 that it would end the city’s public health emergency on monkeypox (MPX) effective on Oct. 31. “MPX cases have slowed to less than one case per day and more than 27,000 San Franciscans are now vaccinated against the virus,” the agency stated in a press release.
“Once again, we caution that a declining outbreak can be the most dangerous outbreak, because it can tempt us to think that the crisis is over and to let down our guard,” said World Health Organization (WHO) Director-General Tedros Adhanom Ghebreyesus, PhD, in an Oct. 12 global press briefing. “That’s not what WHO is doing. We are continuing to work with countries around the world to increase their testing capacity, and to monitor trends in the outbreak.” Clinical laboratories should not assume the outbreak has passed but continue to be vigilant and prepared for increased demand in monkeypox testing. (Photo copyright: ITU Pictures.)
Changing Behavior Lowers Infection Rates
In addition to high vaccination rates, public health experts have attributed the decline to behavioral changes among at-risk groups. “There were really substantial changes among men who have sex [with] men,” infectious disease physician Shira Doron, MD, of Tufts Medical Center in Boston, told ABC News.
On September 2, the CDC published the results of a survey indicating that about half of men who have sex with men “reported reducing their number of sex partners, one-time sexual encounters, and use of dating apps because of the monkeypox outbreak.”
Another likely factor is the disease’s limited transmissibility. “Initially, there was a lot of concern that monkeypox could spread widely at daycares or in schools, but, overall, there has been very little spread among children,” NPR reported.
But citing multiple studies, the NPR story noted “that often there isn’t very much virus in the upper respiratory tract,” where it might spread through talking or coughing. “Instead, the highest levels of virus occur on sores found on the skin and inside the anus.”
These studies, along with earlier research, “explain why monkeypox is spreading almost exclusively through contact during sex, especially anal and oral sex, during the current outbreak,” NPR reported.
Monkeypox Could Mutate, experts say
Despite the promising numbers, public health experts are warning that monkeypox could remain as a long-term threat to public health. According to an article in Nature, “At best, the outbreak might fizzle out over the next few months or years. At worst, the virus could become endemic outside Africa by reaching new animal reservoirs, making it nearly impossible to eradicate.”
In addition to the limited transmissibility of the virus, Nature noted that the outbreak stems from a relatively mild form of the pathogen and is rarely fatal. As of Oct. 28, the CDC reported a total of just six confirmed deaths in the US out of a total of 28,302 confirmed cases since the first infections were reported in May.
It is possible that the virus could mutate into a more contagious form, but Nature noted that monkeypox is a DNA virus, and that they tend to mutate more slowly than RNA viruses such as SARS-CoV-2 and HIV. Nevertheless, University of Alabama at Birmingham School of Medicine bioinformatician Elliot Lefkowitz, PhD, warned that a “worrisome mutation” could arise if the outbreak continues for much longer.
“I have no confidence that all the people who need to be tested are being tested,” she told Nature. She expressed concerns that people could resume risky behavior if they think the danger has passed.
Another question is whether currently available vaccines offer long-lasting protection. And though reported case numbers are down in the US and Europe, they are rising in parts of Africa and South America, Nature noted.
Gottlieb’s Dire Prediction
The decline in new infections followed dire warnings last summer about the possible consequences of the outbreak. In his New York Times op-ed, former Gottlieb criticized the CDC for being slow to test for the virus. He wrote, “[I]f monkeypox gains a permanent foothold in the United States and becomes an endemic virus that joins our circulating repertoire of pathogens, it will be one of the worst public health failures in modern times not only because of the pain and peril of the disease but also because it was so avoidable.”
At the time of his writing, Gottlieb was right to be concerned. On July 29, the CDC reported a seven-day moving average of 390 reported cases per day. According to the federal agency, a reported case “Includes either the positive laboratory test report date, CDC call center reporting date, or case data entry date into CDC’s emergency response common operating platform, DCIPHER.”
Quashing the outbreak, Gottlieb estimated, would have required about 15,000 tests per week among people presenting symptoms resembling monkeypox. But between mid-May and the end of June, he noted, the CDC had tested only about 2,000 samples, according to the federal agency’s July 15 Morbidity and Mortality Weekly Report (MMWR).
As a remedy, Gottlieb called on the Biden administration to re-focus the CDC’s efforts more on disease control “by transferring some of its disease prevention work to other agencies,” including the FDA.
Regulators and lawmakers are considering proposed changes to CLIA and PAMA involving medical laboratory services
Clinical laboratories and pathology groups should monitor a series of federal regulatory developments underway this fall. The proposals and documents will potentially affect how lab managers and staff do their jobs and how much Medicare reimbursement medical laboratories receive for certain diagnostic tests next year.
Among the initiatives under consideration are the following:
Below are details about these laboratory-related federal bills and regulatory documents that observant laboratory managers will want to track in the coming months.
“Clinical laboratories need to make sure that they have proper requisitions and documentation for genetic testing that involves telemedicine.” Danielle Tangorre, JD (above), a partner at law firm Robinson and Cole LLP in Albany, NY, told Dark Daily. (Photo copyright: Robinson and Cole LLP.)
CLIA Fee Increases and Testing Personnel Changes
The federal Centers for Medicare and Medicaid Services (CMS) is examining fee and personnel changes for CLIA. Officials from CMS are reviewing public comments on the proposal ahead of publishing a final rule.
Among other changes, the proposal would:
Institute a 20% across-the-board increase on existing fees.
Establish a biennial increase of CLIA fees for follow-up surveys, substantiated complaint surveys, and revised certificates.
Add doctoral, master’s, and bachelor’s degrees in nursing to qualify testing personnel for high and moderate complexity testing.
“The Practitioner does not have sufficient contact with or information from the purported patient to meaningfully assess the medical necessity of the items or services ordered or prescribed.
“The Telemedicine Company compensates the Practitioner based on the volume of items or services ordered or prescribed, which may be characterized to the Practitioner as compensation based on the number of purported medical records that the Practitioner reviewed.
“The Telemedicine Company only furnishes items and services to Federal health care program beneficiaries and does not accept insurance from any other payor.
“The Telemedicine Company does not expect Practitioners (or another Practitioner) to follow up with purported patients nor does it provide Practitioners with the information required to follow up with purported patients (e.g., the Telemedicine Company does not require Practitioners to discuss genetic testing results with each purported patient).”
And more.
“In the telehealth space, the issue the OIG has flagged is that genetic tests are being ordered without patient interaction or with only brief telephonic conversations,” Danielle Tangorre, JD, a partner at law firm Robinson & Cole LLP in Albany, N.Y., told Dark Daily.
New Bill May Eliminate 2023 Medical Laboratory Payment Cuts Under PAMA
Medical labs and pathology groups face payment cuts of up to 15% for 800 lab tests on the Medicare Clinical Lab Fee Schedule (CLFS) on Jan. 1, 2023, as part of PAMA.
The bill proposes to move regulatory oversight of LDTs from CLIA to the federal Food and Drug Administration (FDA). Champions of the bill argue that FDA regulation is needed for in vitro clinical tests (IVCTs) because they are similar to medical devices and bring with them patient safety concerns.
The bill seemed ready for a Senate vote over the summer but stalled. On Sept. 30, Congress passed a short-term resolution to keep the federal government funded. During negotiation, the VALID Act was removed from the larger spending package, according to Boston law firm Ropes and Gray.
Expect discussion to renew in Congress about the VALID Act after the mid-term elections.
Clinical laboratory leaders and pathology group managers will want to closely monitor the progress of these four federal legislative and regulatory developments. Each of the possible actions described above would significantly change the status quo in the compliance requirements and reimbursement arrangements for both clinical laboratory testing and anatomic pathology services.
