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Biosimilars could be brought to market much quicker in North America if a Trump administration proposal makes it into a new US-Canada-Mexico (USMCA) trade pact, according to press reports.

Citing people familiar with the matter, the Wall Street Journal says the US government is considering a reduction in the protections from competition for biologic drugs detailed in the USMCA from 10 years to five, to try to win support for the deal from Democrats in Congress.

Biologics have 12 years’ market exclusivity in the US, but the current wording of the trade agreement would reduce that to 10.

For comparison, Canada currently has eights years’ protection and Mexico five, so under the current wording patients would have to wait longer for biosimilars in the latter two countries.

Democrats and other groups have argued for the duration of the additional protection to be reduced to to allow cheaper copies of reference biologic drugs to get to market more quickly, as that would help cut spending on medicines by healthcare systems in all three countries.

Some have also argued for the provision to be dropped altogether, with the three countries retaining the status quo on biologics protection.

Companies that produce biosimilars in the US are also pushing for the reduction of course. The Association of Accessible Medicines – which represents generic and biosimilar manufacturers – argues that passing the USMCA with a five-year provision would prevent a biopharma monopoly from being expanded beyond the US and lower prescription drug prices for America’s patients.

Trump is keen to get the USMCA passed, as he has pledged a series of trade deals to boost the US economy in the build-up to the Presidential election next year. USMCA was agreed in principle by the US, Canada and Mexico a year ago, but still needs to be ratified by Congress.

The governments of Mexico and Canada would clearly need to agree any changes to the biologics’ exclusivity provisions in the trade deal if they do make it into the document.

Trump signed the USMCA in November 2018, shortly before the Democrats took control of the House of Representatives in the midterms. The shift in power has held up the treaty, which is the successor the North American Free Trade Agreement (NAFTA).

Last week, top Democrat Nancy Pelosi said that discussions with US Trade Representative (USTR) Robert Lighthizer were getting closer to an accord that could allow the USMCA to be tabled for a vote, with a few ‘wrinkles’ – such as enforcement of the provisions – still to be worked out.

Ireland’s medtech industry is importing more raw materials to keep pace with demand for its products, according to data published by the foreign exchange specialist Fexco International Payments.

The analysis, of more than 7,500 transactions made through Fexco International Payments, shows that since 2016 Irish Medtech firms have increased spending on material imports from the UK by a third (31%).

Imports have risen too, with spending on imports from the UK jumping by almost a fifth (18%) in the past 12 months alone.

The research, which compared import purchases made between January and October each year from 2016 to 2019, also found the number of transactions rose steadily after the UK’s Brexit referendum, before spiking this year.

Between 2016 and 2018, the number of transactions rose by 7%, while in the first 10 months of 2019 they surged by 20% compared to 2018 levels.

While the original increase in imports from the UK can be traced back to the fall in sterling after the 2016 Brexit referendum, 2019’s rapid growth in spending may be the product of a desire to stockpile materials ahead of what should have been Brexit Day, 31 October.

The rise in material imports also mirrors the progress of Ireland’s medtech sector, which now employs 38,000 people across 450 companies. According to Enterprise Ireland, the life sciences sector as a whole grew its exports by 7% in 2018. With export sales of €12.6 billion a year, medtech accounted for 11% of Irish goods exports in 2018, making Ireland the second biggest exporter of Medtech products in Europe.

By contrast, Britain’s medtech sector is faring less well. UK Government figures show the UK’s core Medtech sector has seen turnover stagnate or fall every year since 2010.

David Lamb, head of dealing at Fexco International Payments, said: “Medtech is a true Irish success story, and per capita, Ireland now has more people working in the sector than any other European country.

“While the UK is an important market for Irish medtech exports, it’s also a vital source of the raw materials Ireland’s medtech manufacturers need to make their products.

“Sterling’s weakness since the Brexit referendum has clearly spurred Ireland’s medtech firms into spending more, and more often, on raw materials from the UK. But the import boom accelerated sharply in 2019 as manufacturers stockpiled materials ahead of the scheduled Brexit date of Halloween.

“Though Brexit has been delayed once again, the threat of import tariffs being imposed in the event of a ‘no deal’ continues to concentrate Irish importers’ minds. And with a Euro still worth 10% more against the Pound than it was on the eve of the Brexit referendum, importing raw materials from the UK is an attractive way to mitigate rising wage bills at home.

“But with the UK election and the final course of Brexit hanging in the balance, the sterling exchange rate is likely to be volatile in coming months – and Irish firms that import regularly from Britain should consider locking in the current favourable exchange rate by using a forward contract.” 

Dive Brief:

• Healthcare-associated infections (HAIs) that are antibiotic-resistant resulted more frequently from use of temporary medical devices than from surgical procedures, according to an analysis of patient data from 5,626 sites reported to the Centers for Disease Control and Prevention’s National Healthcare Safety Network from 2015 to 2017.
• The report, published in the journal Infection Control & Hospital Epidemiology, examined devices like central lines, ventilators and urinary catheters at acute-care hospitals, long-term acute-care hospitals and inpatient rehabilitation facilities.
• Patients with antibiotic-resistant, device-associated HAIs were more likely to have been admitted to the hospital several days prior to contracting an infection and therefore were exposed to the pathogen during their stay. Surgical site infections, on the other hand, are often caused by contamination from the patient’s skin flora, the report said.
  

  Dive Insight:

  The CDC NHSN study looked at devices with a limited use in patients rather than permanent implants. The analysis covered HAIs from central line-associated bloodstream infections, catheter-associated urinary tract infections, ventilator-associated events and surgical site infections.

  Antimicrobial resistance was higher for device-associated HAIs than for the same bacteria identified after surgical procedures in all phenotypes analyzed except CRE E. coli. For example, the analysis determined that 48.4% of tested Staphylococcus aureus isolated from device-associated infections were methicillin resistant (MRSA), compared to 41.9% in surgical site infections.

  The three most frequently reported pathogens were E. coli at 17.5%, Staphylococcus aureus at 11.8% and Klebsiella at 8.8%.

  Among the various types of facilities analyzed in the report, long-term acute-care hospitals, which serve one of the most vulnerable patient populations, had significantly more cases involving antibiotic-resistant bacteria than did general hospital wards and short-stay acute care hospitals.

  The report also found that HAIs in adult healthcare facilities are more likely to be antibiotic-resistant than those in pediatric settings. The NHSN tracked antimicrobial-resistant pathogens associated with infections in children in 2,545 facilities during the same 2015-2017 period. It found the most common pathogens in pediatric HAIs were Staphylococcus aureus (15.4%), E. coli (12.3%) and coagulase-negative staphylococci (12.1%).

  CDC epidemiologist Lindsey Weiner-Lastinger said in a statement the data “serve as an urgent call for healthcare facilities and public health agencies to intensify their efforts to prevent the emergence and spread of antimicrobial resistance.”

  Separately, U.S. health regulators have stepped up scrutiny of infections tied to medical devices in recent months with efforts to reduce adverse events linked to duodenoscopes. The devices are used in minimally invasive procedures to diagnose and treat conditions of the pancreas and bile duct, and can transfer infection from one patient to another if not cleaned properly.

  Medical device reports to the FDA between Oct. 15, 2018, and March 31, 2019, showed three deaths, 45 patient infections and 159 cases of device contamination tied to inadequate reprocessing of duodenoscopes. In August, FDA issued a safety communication urging the development of new types of duodenoscopes with disposable parts due to the risk of infection from fixed endcap models. 

  The first duodenoscope with a sterile disposable elevator component, made by Pentax of America, was authorized earlier this month. It followed FDA’s clearance in October of GI Scientific’s adjunctive device designed to shield the distal end of a duodenoscope, and previous clearances for duodenoscopes with removable endcaps. 

Concerned about what the new EU MDR 2020 regulations mean to you? Volker Watzke, Domino Printing Sciences, offers advice on how to become compliant as quickly and efficiently as possible

The deadline for ensuring compliance with the European Union’s Medical Device Regulations (EU MDR) is looming. These new regulations are aimed at improving the traceability features and safety management of medical devices for sale within the EU. With less than nine months to go before the deadline, the countdown is on for medical device manufacturers to ensure they are compliant.

What is required from the EU MDR?

The EU MDR will come into force on 26 May 2020, replacing the EU’s current Medical Device Directive (93/42/EEC) and Directive on Active Implantable Medical Devices (90/385/EEC). Manufacturers of medical devices for sale within the EU must adhere to strict guidelines to ensure their products are safe to use.

From 26 May 2020, all medical devices will need to be assigned a unique device identification (UDI) code. Devices which fall under Class III and Class IIa/b will need to have their UDI recorded, indexed, and registered on a central EU database called EUDAMED – the European Database for Medical Devices.

Manufacturers of Class III and Class IIa/b products will be responsible for sharing product data according to Annex VI Part B of the regulation. Manufacturers of Class I products will also be required to collect and save product data but need only share this information if requested.

The introduction of the EU MDR obligates medical device manufacturers to invest in technology to enable the fast and accurate application of traceability coding to products and packaging at the individual item level. Failure to comply with these procedures may mean that devices are withdrawn from sale, with device manufacturers no longer able to supply their products to other EU member states. 

Where are we now?

The technical specification for EUDAMED is expected to be released by the end of 2019. So far, manufacturers have the benefit of a technical bulletin, available from the European Commission, which provides information on how data should be submitted. The technical bulletin is addressed to the different needs of each manufacturer.

Manufacturers will have approximately five to six months from the release of the technical specification of EUDAMED and the final date of registration. It is, therefore, advisable to begin collecting data as soon as possible. Manufacturers will need to collect data on each product according to the Annex VI, Part B of the EU MDR, and begin preparing the data for sharing on EUDAMED.

As well as preparing all data in advance of the May 2020 deadline, manufacturers should ensure that they have the right partners who support them through the process. To ensure that their devices comply with the new regulations, manufacturers should speak to their code issuing agency and notified bodies for advice.

At present, some large medical device manufacturers are utilising up to 25% of their employee base in bringing their procedures up to standard. Small and medium-sized manufacturers are unlikely to have the capacity to dedicate so much of their workforce and should consider options for external support.

Issuing agencies

In June 2019 GS1 became the first issuing agency for EU MDR compliant codes, meaning that 2D Data Matrix and GS1-128 codes can be used going forward. It is expected that other issuing agencies will follow suit, with potential for the use of HIBCC and ICCBBA coding in the future.

Notified bodies

As part of existing EU Directives (90/385/EWG) and (93/42/EWG) manufacturers audit and check their products on a regular basis to ensure compliance. Notified bodies support manufacturers in this process to ensure that new and existing products can be sold. Of the 57 notified bodies across Europe dealing with current legislation, only 38 have applied for accreditation to the EU MDR.

At the time of writing, only four notified bodies had achieved the new accreditation.

A global effect

The EU MDR covers all items sold within the EU, but this does not mean that only EU member states need to fulfil the requirements. All manufacturers that wish to sell their product in the EU need to ensure that they satisfy the EU MDR requirements, or they may see their products removed from sale.

The medical device industry lags behind in technology adoption and Quality-as-an-Asset mindset, according to a report.

The survey from the “State of Medical Device Product Development & Quality Management Report 2020” report, undertaken by Greenlight Guru, indicates that 81% of medical device companies are not using tools designed for the industry in their quality management processes.  

The report provides insights on survey findings from more than 500 medical device product development and quality professionals from across the world, giving a look into the strategies, tactics, and technologies they are using to accelerate product development, ensure compliance and promote quality. 

Key findings from the report identified several organisationally-inflicted challenges to improving product development processes, with a shortage of resources (55%), insufficient budget (37%) and lack of management buy-in (29%) cited as leading issues. Additionally, more than half of the respondents shared that their organisations are utilising tools that are not specifically designed for the medical device industry as it relates to design controls and risk management of their device(s).

David DeRam, CEO of Greenlight Guru, said: “To find that more than 80% of organisations are asking their quality and engineering teams to ‘make do’ with legacy tools and solutions is as an eye-opener. Quality isn’t a department, but a cultural mindset within a business. Quality cannot be treated as a check-the-box activity — unfortunately, even when mandated by law, we’re seeing companies do the bare minimum.”

Survey data also identified risk as a significant challenge for leadership, particularly in regard to data and visibility. More than half of respondents stated that risk management was not fully integrated into their quality management systems. On top of this, 43% of respondents identified access to adequate risk information for device design and development as a top challenge in risk management.

Jon Speer, VP of QA/RA at Greenlight Guru, said: “Medical device manufacturers are taking huge gambles with their risk management; if management teams lack adequate insights into device risk, auditors lack sufficient insights, too. Revisions to ISO 14971 are coming soon, meaning issues with risk management now will create larger risk management issues in just a few months.”

Additional findings from the survey include:

●      75% of medical device professionals said that they would not be prepared for an unannounced audit by the FDA or other Notified Body. Of these professionals, even fewer (20%) said they are currently ready for an EU MDR audit. 

●      Of the organisations that say they use legacy products such as Excel or paper-based record-keeping systems, less than half (41%) agree that quality is woven into the organisation’s culture (compared to 56% using best-in-class tools). 

●      71% report the data collected by their company’s quality system is not easily accessible in real-time. And nearly 60% indicated the data generated by their quality system was not consistently reliable. 

Results from the “State of Medical Device Product Development & Quality Management Report 2020” were developed from an online survey fielded between September 11 and September 27, 2019. Survey respondents consisted of 524 participants, 93% of whom represented quality, regulatory, engineering and operations professionals from small and enterprise-size device makers.

Global Blood Therapeutics has seen its sickle cell disease drug approved by the FDA, promising to be the first treatment targeting the root cause of the condition.

The FDA has approved Oxbryta (voxelotor), a daily tablet for the treatment of sickle cell disease in adults and children aged 12 years and older.

GBT said the drug will be available within two weeks and will cost around $125,000 per patient annually.

Oxbryta was approved well ahead of a February 2020 decision deadline, and the company said the approval is a milestone for people living with sickle cell disease.

Until now doctors could only treat the symptoms of the inherited blood disorder that particularly affects people whose ancestors are from sub-Saharan Africa, while Oxbryta tackles the biological mechanism that causes the potentially fatal disease.

Also affecting people of Hispanic, South Asian, Southern European and Middle Eastern ancestry, the disease causes formation of abnormal haemoglobin.

This abnormal haemoglobin polymerises and causes red blood cells to become sickled, deoxygenated, crescent-shaped and rigid.

This causes anaemia and blocks capillaries and small blood vessels that impede the flow of blood and oxygen in the body.

The resulting damage to tissues and organs can lead to life-threatening complications including stroke and irreversible organ damage.

Oxbryta works by inhibiting the polymerisation process and had been granted a faster six-month priority review after tagging it as a Breakthrough Therapy that could represent a significant improvement over approved treatment options.

The accelerated approval of Oxbryta is based on clinically meaningful and statistically significant improvements in haemoglobin levels, accompanied by reductions in red blood cell destruction.

Data from the phase 3 HOPE study of 274 patients 12 years of age and older with SCD showed that, after 24 weeks of treatment, 51.1% of patients receiving Oxbryta achieved a greater than 1 g/dL increase in haemoglobin compared with 6.5% receiving placebo.

Earlier this month Novartis saw its Adakveo (crizanlizumab) approved to reduce frequency of vaso-occlusive crises in sickle cell disease.

bluebird bio is also working on LentiGlobin, a gene therapy for sickle cell disease which is in the early stages of clinical development.

Chronic obstructive pulmonary disease (COPD) is a group of diseases that causes breathing difficulties in nearly 16 million Americans and more than 250 million people around the world. It is estimated that COPD, which includes emphysema and chronic bronchitis, causes the deaths of about 3 million people annually. In the United States, it is the third leading cause of death.

There are many risk factors associated with COPD and, according to the World Health Organization, the number of confirmed diagnoses of the disorder is climbing across the globe, particularly in areas of low and middle income. In the United States, the Centers for Disease Control and Prevention, along with the National Institutes of Health, released a national action plan as a road map to address what it considers one of the most urgent health concerns facing the nation. COPD causes a narrowing of the airways, which in turn causes breathing problems that is often accompanies by a persistent cough and chest infections.

While there is no cure for the disease, there are a number of drugs that have been approved to treat the illness. And with the growing number of cases, the drug market for COPD is expected to dramatically increase as well. According to research composed by GlobalData, the COPD market is expected to increase from $9.9 billion to about $14.1 billion by 2025. Some of that growth will be from popular COPD drugs already on the market, such as Advair, Symbicort, Spiriva, Breo Ellipta, Trelegy Ellipta and more, but also due to the growing number of potential treatments currently in the developmental pipelines of pharma companies. With November being COPD Awareness Month, BioSpace takes a look at some of these clinical candidates, as well as some recently approved drugs.

Duaklir – This COPD drug won approval for from the U.S. Food and Drug Administration this year. Circassia Pharma’s Duaklir won approval for the maintenance treatment of COPD in April. Duaklir is a fixed-dose combination treatment of the long-acting muscarinic antagonist (LAMA) aclidinium bromide and long-acting beta-agonist (LABA) formoterol fumarate.

Breztri Aerosphere – AstraZeneca’s Breztri Aerosphere, formerly known as PT0101, was rejected by the FDA in October despite the medication having hit its endpoints in the Phase III KRONOS trial. In its announcement, AstraZeneca did not share the FDA’s concerns but noted that it will work with the regulatory agency as it moves forward. It is likely that the company will seek to use additional Phase III results from the ETHOS trial, PT0101 demonstrated a statistically-significant reduction in the rate of moderate or severe exacerbations compared with dual-combination therapies Bevespi Aerosphere (glycopyrronium/formoterol fumarate) and PT009 (budesonide/formoterol fumarate).

Nucala – GlaxoSmithKline has been positioning its IL-5 inhibitor Nucala as a possible treatment for COPD, but last year, the FDA raised doubts over the drug’s efficacy for that indication. An FDA staff report raised concerns over the drug’s “failure to meet a statistical threshold for effectiveness in one of the clinical trials.” The FDA staff report pointed to another IL-5 inhibitor, AstraZeneca’s Fasenra, which failed in a Phase III trial as a treatment for patients with moderate to very severe COPD. Nucala was initially approved in 2015 by the FDA to treat patients age 12 years and older with severe asthma with an eosinophilic phenotype.

Yupelri – In November 2018, the FDA approved Mylan and Theravance’s Yupelri, the first nebulized bronchodilator approved for the treatment of COPD in the United States. Yupelri, a long-acting muscarinic antagonist, was approved for the maintenance treatment of COPD. The approval was supported by Phase III data that showed Yupelri demonstrated statistically significant and clinically meaningful improvements as compared to placebo in trough forced expiratory volume in one second.

The U.S. Food and Drug Administration (FDA) approved an expanded indication for Sanofi’s Toujeo (insulin glargine injection) for blood sugar control in adult and pediatric patients who are ages six years and older. Previously, Toujeo was approved only for adults aged 18 years and older.

The company announced the results of the EDITION JUNIOR clinical trial earlier in the month. It was the first randomized, controlled trial to compare Toujeo to Gla-100 in this patient population. The trial met its primary endpoint, demonstrating comparable decreases in average blood sugar over six months with both treatments and similar risk of low blood sugar events (hypoglycemia). In fact, the proportion of patients experiencing severe low blood sugar events and high blood sugar (hyperglycemia) with ketosis was numerically lower with Toujeo.

Based on the data, the European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use recommended the expanded label in Europe.

“Across the globe, between 50 and 80% of young people living with type 1 diabetes need more treatment options to help them achieve an average blood sugar level below 7.5%,” said Dietmar Berger, Global Head of Development at Sanofi, at the time. “By taking this step toward investigating an additional option for children and adolescents living with diabetes, we hope to provide another treatment for them and their physicians, to develop an individualized treatment plan that helps patients better manage their disease.”

The EDITION JUNIOR study compared Toujeo to Gla-100 in 463 children and adolescents aged six to 17 years who had type 1 diabetes. They were evaluated for at least one year. They had HbA1C levels between 7.5% and 11.0% at the time of screening. The patients continued to use their existing mealtime insulin throughout the study.

The primary endpoint was non-inferior reduction of HbA1C after 26 weeks.

Insulin glargine injection is a long-acting, manufactured insulin. The injection holds three times as much insulin in 1ml as a standard 100 units/ml insulin.

Toujeo was originally approved for adults by the FDA in February 2015. Its primary competition is Novo Nordisk’s ultra-long-acting degludec, marketed as Tresiba. Both Toujeo and Tresiba are dosed once daily. The original insulin glargine is marketed by Sanofi as Lantus. It is facing competition from Boehringer Ingelheim’s Basaglar, the first insulin glargine follow-on approved by the FDA. It launched in 2016 after a patent battle with Sanofi.

In 2018, Toujeo brought in $840 million, while its Lantus sales dropped from $4.63 billion to $3.57 billion. Novo Nordisk’s Tresiba brought in $1.22 billion in 2018.

“We know that living with type 1 diabetes means dealing with highs and lows in blood sugar, which are worrying and present substantial challenges for young people,” said Thomas Danne, director of the Department of General Pediatrics and Endocrinology/Diabetology at the Children’s Hospital on the Bult, Hannover Medical School, Germany. “In addition to the trial demonstrating safety and efficacy, the percentage of patients with severe hypoglycemia, and the percentage with hyperglycemia with ketosis, were numerically lower with Toujeo.”

Buying top-quality excipients is now as easy as ordering pizza

Guaranteeing the quality of your products is extremely important in our branch. The same applies to excipients. The rules associated with this ensure that they shouldn’t simply be bought from any online retailer. But that’s good, really. Still, in an age where you can order anything online, ordering excipients seems an unnecessarily cumbersome process. Especially when you consider aspects like ease and delivery times. In this article, we explain how it can be done differently. 

Quality products from a reliable producer

In the eStore of DFE Pharma, it is possible to order top-quality pharma grade excipients online. Because DFE Pharma is a certified producer and supplier, the products are always delivered with the right documentation. These could be documents about the use of GMOs, a GMP statement and MSDS documentation.

Another important fact is that DFE Pharma was established over 100 years ago and works with pharmaceutical companies around the world to offer the best solution for each specific medicine. This allows DFE Pharma to offer specialist knowledge to answer any questions.

In August, Torrent Pharmaceuticals recalled dozens of lots of over-the-counter cough syrups, nasal sprays and rectal suppositories that put children and adults at risk of bacterial infection. Now, the FDA has lambasted the Indian drugmaker for a poorly designed water system that it said was the source of the bacteria. 

 

In a warning letter posted Tuesday, the FDA said the water system at the plant in Levittown, Pennsylvania tested positive for Burkholderia cepacia after the bacteria was discovered in manufacturing equipment rinse samples. 

RELATED: FDA tags Torrent as key offender in production of tainted blood pressure meds

The drugmaker blamed the problem on the multiple dead legs and poor fittings of the system. It said it would replace it, but the FDA said it had not shown that the temporary system it intended to use in the meantime would meet FDA standards. 

In addition, the FDA warning letter said the drugmaker was selling a phenobarbital oral solution USP and hydrocortisone acetate suppositories that had not been approved by the agency.  

Torrent in August recalled dozens of medicines, including children’s cough medicines and adult suppositories and nasal sprays. Torrent did not receive any reports of infections but the FDA said the company would do well to get an outside consultant to help it with its upgrades.  

In 2016, the FDA blamed an outbreak of Burkholderia cepacia on the water system of Florida-based CMO PharmaTech. In all, 60 people in eight states became infected, including ventilated cystic fibrosis patients after they were given a constipation drug made by the CMO.

RELATED: Feds blame multistate B. cepacia outbreak on PharmaTech plant’s water syste

This was the second warning letter issued to Torrent in one month. In October, the FDA also cited a Torrent plant in India as one of the central figures in the production of blood pressure meds that were found to contain unacceptable levels of NDMA and other suspected carcinogens. The discovery led to the global recall of angiotensin II receptor blockers (ARBs) such as valsartan, losartan and irbesartan.

The FDA said Torrent was one subject of an ongoing global investigation into the production of tainted meds. Since then, the FDA has cited a Mylan plant for many of the same problems.