Amazon lays off some employees in its Pharmacy unit

Amazon has let go of some of the employees in its Pharmacy business, the company confirmed to CNBC.

A “small number” of staffers in the Amazon Pharmacy division were informed Thursday they were being laid off, Amazon spokesperson Brad Glasser said in a statement. About 80 employees were laid off, according to Semafor, which previously reported the news.

“Like many businesses, we are always improving our processes, for both quality and efficiency, and identifying how we can deliver on the best customer experience,” Glasser said. “As a result, we have made the decision to adjust resources and a small number of roles have been eliminated on the Amazon Pharmacy Services team.”

The cuts come as Amazon recently wrapped up the largest layoffs in its 29-year history. The company laid off 18,000 employees over several months last fall and earlier this year, then announced an additional 9,000 employees would be let go in March. Amazon CEO Andy Jassy has been aggressively slashing costs across the company as the e-retailer reckons with an economic downturn and slowing revenue growth. Jassy has targeted some of Amazon’s more unproven bets such as grocery and devices, while freezing corporate hiring and slowing warehouse expansion.

Amazon’s health-care businesses were affected by the layoffs earlier this year. Some employees in the company’s pharmacy, digital health tools and Halo fitness band units were laid off, CNBC previously reported.

Amazon has spent years trying to crack the health-care market. The company launched its own online pharmacy in 2020, a service that was born out of its acquisition of PillPack in 2018. Amazon introduced, then shuttered, a telehealth service called Amazon Care, and announced in July it would acquire boutique primary care provider One Medical for $3.9 billion.

Mark Cuban's online pharmacy set to launch Humira biosimilar

Mark Cuban Cost Plus Drugs, an online pharmacy launched by the billionaire to sell drugs directly to customers at low prices, should soon begin selling Coherus BioSciences's (CHRS.O) biosimilar version of AbbVie Inc's (ABBV.N) blockbuster rheumatoid arthritis drug Humira, Cuban said on Wednesday. Cuban declined to make any projections on the size of the market the pharmacy will supply. "But we will be here and have it readily available to patients on costplusdrugs.com," he said. Coherus said last month it would sell the biosimilar, branded Yusimry, at $995 per carton, compared with the current list price of Humira of $6,922 per carton. Cost Plus Drugs will sell Yusimry for $569.27 plus dispensing and shipping fees.

Coherus introduced its Humira biosimilar in the U.S. market this month alongside offerings from other drugmakers such as Boehringer Ingelheim, Sandoz and Organon (OGN.N). Usually prices fall, often dramatically, when multiple generic versions of a widely used medication enter the market.

But manufacturers of Humira biosimilars - the name for copies of biologic drugs - are likely to keep prices high to compete with one another for leverage with pharmacy benefit managers (PBMs), which negotiate insurance coverage on behalf of their customers - large employers and health insurance plans, industry experts said. Sales of Humira, once the world's biggest-selling drug, are expected to drop 37% this year, AbbVie said in February.

Cuban's Cost Plus Drugs aims to drive down the cost of drugs broadly by selling them at a 15% markup over its cost, plus pharmacy fees. While some insured patients can use their benefits on the website, the biggest savings from the pharmacy are currently for uninsured and underinsured people.

Cuban said the company hopes to provide other biosimilar drugs as well. "Our mission is to be the low-cost provider of any and all medications we are able to carry," he wrote.

Narcan Nasal Spray Becomes an OTC Drug

The Food and Drug Administration (FDA) approved the Narcan® 4 mg naloxone hydrochloride nasal spray to be sold over the counter (OTC), making it the first naloxone product that will be available without a prescription. Naloxone is a life-saving medication that reverses the effects of opioid overdoses. The product will include instructions for consumers regarding how to use the drug safely and effectively without the supervision of a health care professional. While it may take months for the medication to transition from prescription status to OTC, the agency has plans to work with all stakeholders to ensure the continued availability of other naloxone nasal spray products during this time.

FDA authorizes 503Bs to assist liquid pain reliever shortage

As the “triple-demic” of COVID-19, influenza, and respiratory syncytial virus raged through the fall and winter, drug manufacturers found themselves unable to keep up with increased demand for children’s liquid ibuprofen and other liquid pain relievers and fever reducers. In response to the shortage, FDA released new guidance in February 2023 outlining how 503B outsourcing facilities could offer some assistance. The FDA guidance allows for 503B outsourcing facilities to compound liquid ibuprofen to make available for sale to hospitals and health systems for administration within the facility and to state-licensed pharmacies, including those within hospitals and health systems, and applicable federal facilities to dispense for home use to patients who have a valid, patient-specific prescription.

“I think this will play an active role in helping satisfy the shortage,” says Lee Rosebush, PharmD, JD, chairman and general counsel, Outsourcing Facility Association (OFA).

By law, outside of the setting of an FDA-recognized drug shortage, neither 503As nor 503Bs can compound essential copies of commercial products made by drug manufacturers. Without adding ibuprofen suspension to the FDA drug shortage list, the recent guidance allows 503Bs to produce essential copies of the drug, in certain circumstances, until manufacturers are once again able to meet consumer demand. It makes no such allowance for 503As, who are still limited to “four or fewer prescriptions for the relevant compounded drug product in a calendar month.”

“It would have been more valuable for FDA to officially put ibuprofen on the shortage list so that 503A pharmacies could help patients in their local communities,” says Matt Martin, PharmD, coordinator-elect for APhA’s Compounding Special Interest Group.

FDA has added an additional unnecessary barrier to getting the compounded ibuprofen, Martin added, by requiring a prescription for a product that is usually sold over-the-counter.

Global Pharmaceutical Packaging Market is Expected to Witness a Market Value of US$ 310.5 Billion by the end of 2033

According to Fact.MR, the demand for pharmaceutical packaging will increase globally between 2023 and 2033 at a compound annual growth rate (CAGR) of 9%. By the end of 2033, the size of the worldwide pharmaceutical packaging industry is expected to increase from its present value of US$ 131 billion to US$ 310.5 billion. In the upcoming years, increased healthcare costs and a strong emphasis on wellness are projected to propel sales of pharmaceutical packaging goods. In the upcoming years, it is anticipated that the growing popularity of retail pharmacies around the world would play a significant role in increasing demand for custom medicine packaging goods among pharmaceutical producers.

 FDA Changes Opioid Label to Include Warnings

As part of implementing its Overdose Prevention Framework, the FDA updated its prescribing information for opioids to include not only warnings for patients about the risks for opioid misuse, overdose, addiction and death but also the risk for opioid-induced hyperalgesia (OIH), according to the agency.  The FDA noted that although the OIH can occur at any dosage, the increase in pain or increased sensitivity to pain associated with the condition occurs more frequently with higher opioid doses. The new guidelines require that the following information is included with safety labeling:

Overdose risk increases as dosage increases for all opioid pain medicines.

Immediate-release opioids should not be used for an extended period unless a patient’s pain remains severe and alternative treatment options continue to be inadequate.

Many acute pain conditions treated in an outpatient setting require no more than a few days of opioid pain medicine to be successful.

Extended-release/long-acting opioid pain medicines should be reserved for severe and persistent pain that requires daily opioid administration and for which alternative treatment options are inadequate.

Global pharmaceutical companies have long been under the spotlight for a variety of reasons, including cyclical and uneven availability; a lack of environmental, social and governance (ESG) transparency; and skyrocketing incidents of counterfeit medications.

This rising and widespread scrutiny means that Industry 3.0, which is the foundation of the manufacturing and distribution processes of the vast majority of today’s pharmaceutical companies, is no longer sufficient.  

A recent report in the International Journal of Pharmaceutics, titled "Industry 4.0 for pharmaceutical manufacturing: Preparing for the smart factories of the future," states that pharma companies will need to evolve to achieve an unprecedented level of data digitalization to include "supply chain-related information such as raw materials variability and global tracking of materials across facilities."

The reasons for more digitally mature pharmaceutical supply chains are multiple—and go beyond "simply" supply chain resilience and data-driven decision-making. End-to-end traceability also improves compliance with current and looming regulatory standards, helps to meet ESG targets and, inevitably, safeguards patients. 

Governments and regulatory agencies worldwide are imposing stricter regulations on the pharmaceutical industry to ensure drug safety and quality.

One example is the Drug Supply Chain Security Act (DSCSA) in the United States, which will require pharma businesses to implement a serialized, electronic and interoperable system to track and trace prescription drugs throughout a company’s supply chain and among all stakeholders. The deadline is coming up fast: November 27, 2023. 

Making ionocytes: A step toward cell or gene therapy for cystic fibrosis

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators were a breakthrough for cystic fibrosis, improving the movement of chloride and water and moistening mucus secretions. But these drugs are expensive, don't work in all patients with cystic fibrosis, and have side effects and interactions with other drugs. People who do respond to CFTR modulators must take them for a lifetime.  Researcher Ruby Wang, MD, and Benjamin Raby, MD, MPH, chief of the Division of Pulmonary Medicine at Boston Children's Hospital, envision an alternative approach: cell therapy or gene therapy targeting a cell type that's only recently been discovered.  

In 2018, two studies published in Nature rocked the cystic fibrosis scientific community. They found that the CFTR gene mutation primarily affects ionocytes—previously unknown cells that make up just 1% of the airway's cells. Surprisingly, more than 90% of the CFTR protein was being made by these rare cells.

Now, in the American Journal of Respiratory and Critical Care Medicine, Wang and colleagues at Boston University report creating ionocytes from patients for the first time using stem cell technology. Collaborators at Boston Children's include Thorsten Schlaeger, Ph.D., and Yang Tang from the Stem Cell Research Program and Stuart Rollins, MD, and Chantelle Simone-Roach in Pulmonary Medicine.

The accomplishment means that ionocytes can now be studied in a dish to understand their biology—and their possible use as a treatment vehicle.

"Maybe we could correct patients' ionocytes and put them back in the lungs," Wang says. "This is why it's exciting."

For cell and gene therapies, all stages of the drug development life cycle are complex. The patient, product and supply chain require specialized sets of capabilities, as standards and protocols differ from more traditional therapy areas.

Specifically, cell and gene therapy development presents unique chemistry, manufacturing and controls (CMC) challenges because of inherent properties such as shorter shelf life, variability in starting and ancillary materials, manufacturing and logistical complexities and cost. 

Below is a case study in which strategic regulatory and CMC expertise from Cardinal Health Regulatory Sciences helped guide a biopharmaceutical company’s regulatory and development strategy for a cell and gene therapy product.

Avoiding a clinical hold

A biopharmaceutical company focused on developing novel autologous T cell therapies had promising findings targeting a rare-disease tumor type. The product had reached the stage in the development pipeline where the company was ready to assemble their Investigational New Drug application (IND). The company referenced a drug master file (DMF) filed by their contract manufacturer in order to provide required information for the IND, but upon submission, the FDA indicated that there was insufficient data within the master file. The company had only a matter of days to provide the required additional data to ensure that their IND review would continue and not lead to a clinical hold. Experts from Cardinal Health Regulatory Sciences were selected to quickly advise on next steps.

Additional submissions to advance IND review

The Cardinal Health Regulatory Sciences team began auditing the information that was originally submitted. They quickly recognized that insufficient process specific DMF information for this type of manufacturing process had been provided in the submission. Experience and fluency with these types of submissions allowed the team to quickly identify the issue. They realized that specific product quality information was needed on ancillary materials used in the manufacturing process as well as additional information about the manufacturing equipment to ensure that the product would not be contaminated during manufacturing. Within days, the team formulated a strategy and assembled all outstanding information required, ultimately receiving notification that the IND could proceed.

Recovering at-risk clinical batches

The biopharmaceutical company continued to partner with the Regulatory Sciences team to help address significant incidents or amendments that required a timely, strategic response. Some early clinical batches failed release specifications, so the team worked with the company to craft a package for review, to ensure that the batches could be used. The information packages included a summary of the investigation into the manufacturing process and analytical testing, the failed test result, justification and corrective actions as needed and a patient risk/benefit statement. As patients awaiting these therapies are often in dire need and the shelf life of autologous T cell therapies is extremely short, the submission was extremely time sensitive. The prompt and thorough submissions from the Regulatory Sciences team convinced the FDA to grant an exception for product release and ensured that the custom products were delivered.

Support during clinical development

CMC requirements are very complex for cell and gene therapies, with no room for error or contamination. The Cardinal Health Regulatory Sciences team continued to work with the company throughout the clinical trial and provided multiple follow-up IND amendments with improvements in analytical methods, including rapid microbiology methods and manufacturing processes. The Regulatory Sciences team advised on comparability protocols and data required to support changes in manufacturing sites, while still ensuring proper maintenance of product quality attributes. Their CMC expertise ensured that the company continuously provided improvements and amendments to their IND as advances were made throughout the development process. The orphan drug is currently in phase 1 clinical trials and multiple lots have been successfully administered.

At the beginning of the pandemic, some in-person inspections of drug manufacturing facilities were paused by the FDA – especially those conducted internationally. Over the past few months, these “Good Manufacturing Practices” (GMP) evaluations have resumed. In Digwal, India, the FDA conducted one of these physical surveys from March 27th to the 31st at a factory owned by Piramal Pharma LTD. The FDA found that the building’s operations were compliant as there were no “form-483 observations” – which represent failures to comply with industry standards.  

On the business side of things, this was welcomed news by the manufacturer. After the inspection results were made public, the corporation’s stock grew over 6% on April 3rd. Piramal Pharma has a 5-year loss of almost 75%* but the short-term boost and the positive report from the FDA could indicate things are looking up for the international company.

Also on Monday, April 3rd, a report from the FDA had the opposite impact for another company in the medicinal field, a Denmark company called Ascendis Pharma. The US federal agency reported that “deficiencies” were observed when studying the application of a possible treatment, developed by Ascendis, for a condition known as hypoparathyroidism. The pending drug under scrutiny is named TransCon PTH. Although the report did not go into detail regarding the deficiencies, the FDA did note that the findings were not reflective of a “final regulatory decision.” The company’s stock, which is traded on the NASDAQ, fell over 30% in a day* after the news became public on Friday March 31st. Over the past years, however, Ascendis has posted a gain of almost 25% over that last five years*.

 * as of 4:30 PM EST on 4/3/23 

While not surprising, the delay is a disappointment for BioMarin, which has already spent years trying to win U.S. approval of its gene therapy known as Roctavian.

The company appeared on track to bring a long-lasting therapy to patients who suffer from the genetic bleeding disease back in 2019, when it first sought approval for Roctavian. The next year, the FDA surprised the gene therapy world by rejecting it, saying the agency needed more evidence that the one-time treatment would provide lasting benefit.

BioMarin collected additional two-year follow-up data and resubmitted its application in 2022, later adding the information on patients tracked for three years. The company has also been working with the FDA on other fronts to get ready to sell Roctavian in the U.S. In December, the agency finished a pre-license inspection of its manufacturing facility.

The treatment is already approved in Europe, and BioMarin last month forecast $100 to $200 million in Roctavian sales this year, depending on U.S. approval and reimbursement in Germany.

Two antivirals added to list of drugs that cannot be exported or hoarded

Two antiviral drugs used to treat flu have been added to the list of medicines that cannot be exported or hoarded.

Oseltamivir (Tamiflu; Roche) and zanamivir (Relenza; GSK) were added to the list by the government on 20 December 2022, along with the antibiotic flucloxacillin.

On 14 December 2022, the antibiotics amoxicillin, cefalexin, phenoxymethylpenicillin (Penicillin V) and azithromycin oral suspension were added to the list, in response to rising demand as a result of an increase in Strep A infections.

Antibiotic shortages have been widely reported, but despite the addition of the antiviral flu drugs to the no-hoarding list, Leyla Hannbeck, chief executive officer of the Association of Independent Multiple Pharmacists, said her members had not reported shortages of flu drugs.

“These medicines [oseltamivir and zanamivir] are not very commonly used, so if there was an issue we wouldn’t notice immediately,” she said.

She said that the “precautionary measures” relating to flu drugs were “welcome” but added that there is still a need for “transparency across the supply chain”.

The Pharmaceutical Services Negotiating Committee said its dispensing and supply team had not received reports from contractors about shortages of oseltamivir or zanamivir.

Primary care surveillance reports  showed influenza-like illness rose in the week of 5 December 2022 to 11 December 2022 to 15.5 per 100,000 population, compared with 9.4 per 100,000 population the previous week. Laboratory data showed an increase in samples testing positive for influenza, from 16.2% in the week beginning 29 November2022 to 20.2% in the week beginning 5 December 2022. The highest positivity rate was among children aged 5 to 14 years.