Susan Haigney

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On Jan. 24, 2024, Azurity Pharmaceuticals, a Woburn, Mass., company, issued a voluntary recall of one lot of Zenzedi CII (dextroamphetamine sulfate tablets, USP) 30 mg because the incorrect product was found in the bottle. Tablets of Carbinoxamine Maleate, an antihistamine drug, were found in the Zenzedi bottle by a pharmacist in Nebraska.

The recalled lot, F230169A, was shipped to wholesalers from Aug. 23, 2023 to Nov. 29, 2023 and has an expiration date of June 2025. It is marketed under the Arbor Pharmaceuticals brand. Zenzedi 30 mg tablets are a light yellow, hexagonal tablet debossed with “30” on one side and “MIA” on the other side and distributed in a white bottle with black writing and “30 mg” highlighted in yellow. Carbinoxamine Maleate Tablets USP, 4 mg, are white round tablets with imprints of “GL” on one side and “211” on the other side.

Zenzedi is used to treat narcolepsy and attention deficit hyperactivity disorder. According to the company, patients may experience symptom undertreatment and increased risk of accidents if they take carbinoxamine instead of Zenzedi. Unknowingly consuming carbinoxamine may result in drowsiness, sleepiness, central nervous system depression, increased eye pressure, enlarged prostate urinary obstruction, and thyroid disorder, according to the company. Carbinoxamine may also cause sedation, which could lead to disability or accidents.

The company has sent recall notifications to wholesale distributors. Consumers should stop using the recalled product and return it to where it was purchased. Azurity has not received reports of adverse events as a result of the recall. Adverse events may be reported to FDA via its MedWatch program.

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The company issued the recall because of a package mislabeling problem.

Azurity Recalls Zenzedi

The European Medicines Agency (EMA) published 

on Jan. 16, 2024, which gives an overview of the medicines that received recommendations for marketing authorization in 2023. The agency recommended 77 medicines, 39 of which were new active substances to the European Union. Two vaccines were recommended to protect respiratory syncytial virus (RSV). In addition, a new drug that uses clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 was recommended to treat two rare blood disorders.

Recommended approvals of specific note include the following:

Nine cancer treatments including Omjjara (momelotinib), the first treatment for myelofibrosis; Columvi (glofitamab) and Tepkinly (epcoritamab) for the treatment of diffuse large B-cell lymphoma; and Elrexfio (elranatamab) for the treatment of adult patients with relapsed or refractory multiple myeloma

Aqumeldi (enalapril maleate), which treats heart failure in children up to 18 years

Skyclarys (omaveloxolone) for the treatment of Friedreich’s ataxia

Arexvy (recombinant, adjuvanted) to protect adults aged 60 years and older against lower respiratory tract disease caused by RSV.

Seventeen orphan medicines were recommended for authorization that included treatments for cancer, chronic hypoparathyroidism, sickle cell disease, Duchenne muscular dystrophy, and a variety of other conditions.

Three medicines were recommended under the agency’s Priority Medicines (PRIME) program: cancer treatments, Elrexfio and Talvey; and Casgevy for the treatment of sickle cell disease.

There were 77 extensions for indications, which included 38 drugs for pediatrics.

Three medicines received negative approval from the agency in 2023: Albrioza (sodium phenylbutyrate/ursodoxicoltaurine) for the treatment of amyotrophic lateral sclerosis; Lagevrio (molnupiravir) for the treatment of COVID-19 in adults; and Sohonos (palovarotene), to treat fibrodysplasia ossificans progressive.

The agency monitors authorized medications after approval for quality and safety and provides industry with advice. Agency advice given in 2023 includes, but is not limited to, the following:

It was recommended that Adakveo (crizanlizumab) no longer be used to “prevent painful crises in patients aged 16 years and older with sickle cell disease, a genetic condition in which the red blood cells become rigid and sticky and change from being disc-shaped to being crescent-shaped (like a sickle).”

EMA reminded industry to use measures to reduce the risk involved in the use of fluoroquinolone antibiotics.

A lower dose of Olumiant (baricitinib) was recommended for patients “at higher risk of blood clots, cardiovascular conditions, and cancer in line with the dosing recommendations for other JAK [Janus kinase] inhibitors used to treat several chronic inflammatory disorders.”

EMA also suspended marketing authorization for more than 350 generic drugs that were tested by the contract research organization, Synapse Labs Pvt. Ltd., after a good clinical practice inspection found that supporting data were lacking or insufficient to show bioequivalence.

The agency recommended 77 drugs for marketing authorization in 2023, including 39 new APIs.

EMA Looks Back at Medicines Approved in 2023 

FDA’s Center for Drug Evaluation and Research (CDER) published its 

 report on Jan. 16, 2024 highlighting new drugs approved in 2023. CDER approved 55 novel drugs during the year and expanded indications or patient populations for previously approved products.

The approved drugs treat a variety of diseases including COVID-19, respiratory syncytial virus (RSV), HIV, neurological conditions, anemia, weight management, type 2 diabetes, and endocrine disorders. Drugs were also approved that treat opioid addiction, three of which were over-the-counter opioid overdose reversal drugs.

More than half of the novel drugs approved were done so under the orphan drug designation program for rare diseases. Rare disease treatments include those for Friedreich’s ataxia, paroxysmal nocturnal hemoglobinuria, and activated phosphoinositide 3-kinase delta. Treatments were also approved for rare cancers such as mantle cell lymphoma and nasopharyngeal carcinoma.

There were five biosimilars approved in 2023 that included three for reference products that did not yet have a biosimilar. This brings the total of biosimilars approved by the agency to 45.

CDER also details in the report initiatives taken to create efficiencies in its review process. The center met or exceeded its Prescription Drug User Fee Act goal dates for89% of drug approvals. It also approved 84% of approvals on the “first cycle” and approved 35 of the 55 novel drugs before other countries. Thirty-six of the 55 drugs were approved using one of the agency’s expedited programs.

 CDER Director Patrizia Cavazzoni stated, “Deciding whether to approve a drug is a collaborative, well-coordinated process. It often involves expertise from throughout our center and agency, as well as external parties. We take our regulatory decision-making seriously, because we know our drug approval actions affect the health and well-being of patients and consumers nationwide. I want to thank my colleagues for their dedication to reviewing and approving these drugs, which will benefit many people in years to come.”

FDA’s Center for Drug Evaluation and Research released its report on new drugs approved in 2023.

CDER Approved 55 Novel Drugs in 2023

The European Medicines Agency (EMA) announced on Jan. 12, 2024 that its Pharmacovigilance Risk Assessment Committee (PRAC) was beginning a review of data on secondary malignancies related to T-cells for six approved chimeric antigen receptor (CAR) T-cell medicines. The committee is reviewing data from 23 cases of T-cell lymphoma or leukemia in the European Union’s EudraVigilance adverse event database.

According to EMA, secondary malignancies are those that develop when a cancer patient develops a second cancer that is different from the original cancer. This risk was considered at the time of authorization of the impacted drugs and included in risk management plans. The drugs have been monitored, and the marketing authorization holders are required to submit interim results from long-term and efficacy studies.

The impacted drugs—Breyanzi, Carvykti, Kymriah, Tecartus, and Yescarta—are approved in the EU and are used to treat blood cancers such as B-cell leukemia, B-cell lymphoma, follicular lymphoma, multiple myeloma, and mantle cell lymphoma in patients whose cancer has relapsed or has stopped responding to previous treatment. They are “personalized cancer immunotherapies where patients' white blood cells (T-cells) are reprogrammed and reinjected to attack the cancer.”

The agency is reviewing data on secondary malignancies related to T-cells for approved CAR T-cell medicines.

EMA Starts Safety Review of CAR T-Cell Medicines

On Jan. 12, 2024, the European Medicines Agency (EMA) announced that its Pharmacovigilance Risk Assessment Committee (PRAC) is recommending that precautionary measures be taken in the use of valproate medicines in male patients. According to PRAC, there is a potential increased risk of neurodevelopmental disorders in children born to men who used valproate medicines during the three months before conception. Male patients receiving valproate treatments should be supervised by a specialist in the management of epilepsy, bipolar disorder, or migraine, PRAC says.

The recommendation comes after the committee reviewed data from a retrospective observational study conducted by companies that market the drugs after a previous review of valproate used during pregnancy using registry databases in Denmark, Norway, and Sweden. The study focused on birth outcomes in children born to men that took valproate, lamotrigine, or levetiracetam around the time of conception. Data was also considered from non-clinical studies, scientific literature, and consultations with patients and clinical experts.

According to the data, approximately five out of 100 children whose fathers were treated with valproate had a neurodevelopmental disorder compared with around three out of 100 children born to fathers treated with lamotrigine or levetiracetam. The risk to children born whose fathers stopped using valproate more than three months before conception was not studied.

“The possible risk in children born to men treated with valproate in the [three] months before conception is lower than the previously confirmed risk in children born to women treated with valproate during pregnancy. It is estimated that up to 30 to 40 out of 100 preschool children whose mothers took valproate during pregnancy may have problems with early childhood development, such as being slow to walk and talk, being intellectually less able than other children, and having difficulty with language and memory,” EMA stated in a press release.

“The study data on male patients had limitations, including differences between the groups in the conditions for which the medicines were used and in follow-up times. The PRAC could therefore not establish whether the increased occurrence of these disorders suggested by the study was due to valproate use. In addition, the study was not large enough to identify which types of neurodevelopmental disorders children could be at increased risk of developing. Nonetheless, the Committee considered precautionary measures were warranted to inform patients and healthcare professionals,” EMA clarified in the release.

The European Medicines Agency safety committee says there is a potential risk of neurodevelopment disorders in children born to men treated with valproate. 

Precautionary Measures Recommended in Use of Valproate Medicines

Cherwell announced on Jan. 8, 2024 that it is joining AnalytiChem’s group of companies. Cherwell, founded in 1971, offers cleanroom microbiology solutions to customers in the United Kingdom and internationally. Its products focus on environmental and process monitoring in pharmaceutical manufacturing. Cherwell will continue to operate from Bicester, UK under its current managing director, Andy Whittard.

“AnalytiChem shares our vision for growth, philosophy, culture, market approach and guarantees the continuity of Cherwell as a provider of ultra-high-quality products and services. Within the AnalytiChem group, Cherwell will be able to leverage collaboration opportunities, especially with our new sister company bioTrading, alongside our focused offering of environmental and process monitoring products to the pharmaceutical manufacturing sector. Together with the great team at Cherwell we look to forward to the exciting next stepsin the development of the company,” said Whittard in the press release.

“[At] AnalytiChem, we are focused on highest quality capabilities for the benefit of our customer base, something Cherwell clearly demonstrates with its focused portfolio manufactured in Bicester and services provided remote as well as on-site,” said Raoul Biskupek, Group CEO at AnalytiChem, in the press release. “With the addition of Cherwell to our group we can offer an even broader, while specialized portfolio across the geographies we are active in. This complementary offering opens exciting growth opportunities for our subsidiaries in the adjacent countries and our strong distribution partners network.”

AnalytiChem, formed in 2021, contains a group of companies across Europe, North America, and Australia that provide quality control products and services that include off-the-shelf and customizable chemicals, high-quality standards, certified reference materials, laboratory, and analytical equipment.

Cherwell manufactures a range of prepared media products in a ISO9001-registered facility. The company has in-house engineering facilities to support bespoke solutions and supply, service, and calibrate environmental air monitoring equipment.

Cherwell Laboratories’ cleanroom microbiology solutions will join AnalytiChem’s group of seven companies across Europe, North America, and Australia.