Oct 4 (Reuters) – A recently recalled batch of Glucagon Emergency Kits, Eli Lilly and Co’s (LLY.N) therapy for diabetic patients in crisis, was manufactured at an Indiana factory cited by U.S. health regulators this year for quality-control violations, including several involving that product, according to the company and a Reuters review of federal inspection records.
The Indianapolis-based company on Sept. 24 issued a voluntary U.S. recall of one lot of the kits whose key ingredient is Glucagon, a drug used to treat dangerously low blood sugar in diabetes patients. The company issued a voluntary recall in Canada the following day.
Lilly’s recall notices said that the company had received a report of a patient who experienced seizures even after being injected with the drug, a sign that the treatment was not potent enough to work. The company said the product failure might be related to its manufacturing process, without elaborating.
In response to Reuters’ inquiries, Lilly told the news organization that the affected kits were produced at a company facility in Indianapolis, and that the kit that prompted the recall had been distributed in Canada. As Reuters reported in May, the Indianapolis plant had been cited by U.S. health regulators for substandard sanitation and quality control procedures.
Separately, Lilly is facing a federal criminal investigation into alleged manufacturing irregularities involving another of its U.S. factories in New Jersey, details of which were first reported by Reuters earlier this year. The recall of Glucagon kits made in Indianapolis is the first indication of potential patient harm due to recent manufacturing issues at the company’s plants.
“Lilly is deeply committed to manufacturing high-quality medicines for patients who need them—nothing is more important to us,” the company said in a statement. “We take our obligations seriously and have rigorous quality systems in place to ensure compliance with stringent regulatory requirements.”
In all, roughly 66,000 Glucagon Emergency Kits were affected by the recalls, Lilly spokeswoman Kathryn Beiser told Reuters. She said about 19,000 of those were distributed to U.S. customers and nearly all the rest in Canada. She said the kits were produced at the Indianapolis plant around May 2020. Beiser declined to say whether Lilly has received other reports of adverse events related to the Glucagon kits.
The recalled Glucagon Emergency Kit was designed for diabetes patients whose blood sugar is plummeting, and who need to raise it quickly to avoid complications that can include seizures or death. The kit consists of a vial, which is supposed to contain freeze-dried Glucagon powder, and a separate syringe filled with liquid.
Normally, a caregiver inserts the liquid-filled syringe needle into the Glucagon vial in order to dilute the powder before administering it. Lilly’s recall announcement said the vial used by the stricken patient contained liquid, instead of powder.
The company’s Indianapolis plant performs what is known in the industry as “fill and finish” – receiving raw drugs made at other facilities, putting them into vials and syringes, and shipping them to customers.
U.S. Food and Drug Administration inspection records from March 2021 viewed by Reuters cited numerous quality-control violations at that plant, such as staff failing to properly monitor environmental conditions where the finished drugs are made and failing to establish appropriate procedures to prevent contamination.
The FDA inspectors said they observed lapses in the manufacturing of the Glucagon kits as well as in Lilly’s COVID-19 antibody therapy bamlanivimab and several other drugs, according to the inspection records, dated March 16. They concluded that Lilly must take steps to remedy the lapses but did not recommend regulatory action on the part of the FDA.
Lilly spokeswoman Beiser said U.S. distribution of Glucagon Emergency Kits from the lot that was later recalled had ceased by March 25, a little more than a week after the FDA inspection report. Beiser said the distribution of the lot followed its regular process via wholesaler channels and was not related to the FDA report, adding that “any suggestion” it ended for other reasons is false.
Meanwhile, emergency kits from that same batch continued to be distributed in Canada, Beiser said. Distribution of 44,000 kits in Canada began in February 2021 and continued through the middle of September, she said. The patient complaint that triggered the late September recall involved a kit that had been shipped to Canada, Beiser told Reuters.
Beiser declined to comment specifically on why distribution of Glucagon Emergency Kits from the batch continued for another six months in Canada after distribution had ceased in the United States. She did not answer questions about whether the affected patient recovered.
Health Canada, a regulatory agency similar to the U.S. FDA, declined to comment about Lilly’s voluntary recall of the Glucagon Emergency Kits, or why kits from the batch continued to be distributed in Canada for months after they had ceased to be distributed in the United States.
The FDA declined to comment on distribution of the kits, whether it had received other reports of adverse events, had re-inspected Lilly’s Indianapolis facility or if it planned additional actions related to the recall.
“It is important to note that this recall was a voluntary action taken by the company,” FDA spokesman Jeremy Kahn said, without elaborating. “We have been closely evaluating this event and will continue to monitor the marketplace and manufacturing efforts to help ensure the availability of safe products for U.S. consumers.”
The recall comes as Lilly faces a criminal investigation by the U.S. Department of Justice into alleged manufacturing irregularities and records-tampering at a separate factory in Branchburg, New Jersey, that produces bamlanivimab and other drugs.
The Justice Department has not accused Lilly of any wrongdoing, and the company said earlier this year that it is cooperating in the probe. Lilly did not respond to a question from Reuters about the status of that investigation. The Justice Department did not respond to a request for comment.
Bamlanivimab, the COVID-19 antibody, manufactured at the Branchburg facility has been sent to the Indianapolis fill-and-finish plant to be put into vials and shipped.
A group of FDA inspectors arrived at the Indianapolis plant in mid-February and stayed for more than two weeks, according to a redacted version of their report, which Reuters obtained via a Freedom of Information Act request.
In their report, the inspectors listed Glucagon as among the drugs where Lilly “failed to establish an adequate system for monitoring environmental conditions,” and noted that Lilly failed to establish and follow appropriate written procedures “to prevent microbiological contamination of drug products purporting to be sterile.”
In addition, the inspectors said Lilly did not properly conduct quality-control sampling of glass components like vials and pharmaceutical ingredients for drugs including Glucagon, bamlanivimab and the cancer drug Cyramza.
In Lilly’s April 6 response to the FDA obtained by Reuters through an open records request, the company said it takes the inspectors’ findings “very seriously” and is implementing actions to resolve concerns “on aggressive timelines.”
Lilly said it has established a comprehensive environmental monitoring program designed to assess microbiological control of manufacturing spaces, the redacted response said. The company did not respond to questions about the status of its efforts to rectify violations noted by the FDA at the Indianapolis plant.
Reporting by Dan Levine in San Francisco and Marisa Taylor in Washington, DC; Additional reporting by Allison Martell in Toronto; Editing by Michele Gershberg and Marla Dickerson
Our Standards: The Thomson Reuters Trust Principles.
Taking next-generation motion from concept to reality
~ How free motion can address challenges in the pharmaceutical industry ~
If companies were to take home one lesson from the COVID-19 pandemic, it should be that flexibility is key. This statement is no less true for the pharmaceutical industry, which has been pushing for flexibility for years. With a pandemic almost behind us and the challenges of a rapidly ageing population, flexible manufacturing is needed now more than ever. In this article , Adnan Khan, manager of pharma industries at Beckhoff UK, discusses the challenges of pharmaceutical production lines and how next-generation motion can help.
While there are many tips for creating a more flexible manufacturing process, from plug-and-play robotics to single-use manufacturing, few tips focus on motion control in production lines. Motion control has the power to make production lines more flexible and efficient, but few motion control systems provide the freedom and range to maximise their benefits.
From concept to reality
In interviews conducted by Donna Ritson, president of DDR communications and Paula Feldman, senior director of Business Intelligence, 75 per cent of pharmaceutical manufacturers said they were increasing their level of automation going forward. So for those wanting to invest in optimising their production lines, where should they spend their money?
Over the years, technology has advanced, allowing the pharmaceutical industry to advance with it. However, despite the introduction of sophisticated technology, challenges still occur in the production of pharmaceutical products, such as flexibility and efficiency. The XPlanar, a first-of-its-kind planar motor system, can help address these challenges.
The XPlanar system comprises the mover, tile and control software. The magnetically driven mover is wireless, with six degrees of jerk-free movement, allowing for the technology to effortlessly levitate over the tiles, which can be moved and placed as a facility needs. With each singular mover having a bare load of up to 4.2 kg, a maximum speed of 2 m/s and an easily wipeable surface, the XPlanar is bringing the reality of next-generation motion to the pharmaceutical industry.
Flexible and efficient
Flexibility has always been an issue in the pharmaceutical industry, as traditional plant layouts make it hard to switch over or adjust equipment to produce different products. Due to a large number of sensitive chemical processes in pharmaceutical manufacturing, moving equipment around requires equipment recalibrations and strategic positioning. However, with new methods such as modular manufacturing, allowing for multiple different drug productions in one facility, these challenges are slowly being addressed.
Modular manufacturing refers to a type of manufacturing where there is no fixed equipment, meaning facilities can be broken down and rearranged as needed. As modular manufacturing is embraced, new techniques will be needed to achieve a modular facility. The XPlanar system elevates this manufacturing method to a more efficient, flexible and long-lasting one. Like with many of the equipment used for modular manufacturing, the XPlanar system can be laid out freely in a multitude of arrangements to suit the pharmaceutical facilities’ requirements.
The XPlanar system provides the pharmaceutical industry with the production flexibility needed to not only create a modular manufacturing facility but a more efficient manufacturing facility. The XPlanar system allows manufacturers to create a flexible production line with movements of 360 degrees, allowing for easy and efficient product inspection, alignment or processing.
The easy adaptability of the movers and tiles ensures the technology can last in an ever-evolving technological landscape. Using this free-moving system the pharmaceutical industry can see the benefits of next-generation motion becoming reality.
Keeping pets protected during heatwaves this summer
We’ve been lucky to have been hit with some great weather this summer, however, some days have been exceptionally hot and causing us discomfort to the point where we don’t want to leave the house! Our pets can also struggle in this heat and if not looked after correctly, can lead to life threatening issues for them.
Dr. Sarah Machell, Medical Director for Vetster, has shared her top five top tips to ensure that our pets can enjoy the summer days as much as we can.
Vetster, is a digital platform that connects licensed vets with pet owners virtually, with 24/7 online appointments, launches in the UK this summer.
1. Provide adequate rest, shade, and ventilation
Coping with high temperatures and humidity is tough enough on its own, but it’s even more difficult for pets who are exercising in direct sunlight and don’t have adequate ventilation. Limit outdoor activities to early mornings and late evenings when it’s cooler. When walking your pet, choose shady routes off the pavement. Ensure outdoor pets have shady, ventilated places to escape the heat. Keep in mind that pets also rely on evaporation for cooling, regardless of if they sweat like horses or pant like dogs, and high humidity decreases the effect of evaporation. This means your pet needs you to keep an eye on the heat index for them as well as for you. Be sure your pets have easy access to a steady supply of clean water. Pets are naturally wired to stay hydrated as long as they are healthy and avoid heavy exercise in the heat, so there’s no need to try to encourage your pet to drink more. Just make sure the water supply is in easy reach and doesn’t run dry.
2. Be wary of paws on the hot pavement!
When the weather gets extremely hot, so does the pavement—asphalt, in particular. If you’re taking your dog out for a walk, try to remember that they don’t have shoes to protect against the heat. Even though paw pads are extremely tough, hot surfaces can burn them. Consider using padded booties for their paws to create a barrier between paw pads and the hot concrete. Better yet, try to steer clear of the streets and walk on the cool grass instead. If there’s an opportunity to wade through some clean water or catch the spray from a sprinkler, that’s even better. Remember that pavement retains heat and you still need to be aware of the risks when you go for walks in the evening.
3. Look out for signs of heatstroke
Heatstroke is a very serious condition and one to look out for in your pets. As a pet parent, it’s important to be aware of your pet’s fitness level and avoid overexertion when the weather’s too hot or humid. Less athletic dogs, dogs with underlying illnesses, and brachycephalic breeds are at higher risk for developing heatstroke, so keep an extra close eye on them. Heatstroke is life-threatening, but it can be avoided if you take action to cool your pet when they show early signs of heat stress. If your dog doesn’t want to keep walking, lies down in the shade, or digs up cool dirt to lie in, those are clues they’re getting too hot. Excessive panting that doesn’t improve after a short rest is another indicator. Get out of the heat and offer water to keep the threat of heatstroke from escalating. Splash down hot ears, paws, and bellies with water to achieve more rapid cooling.
4 Never leave your pet unattended in a hot vehicle
Heatstroke can happen in the blink of an eye—it cannot be stressed enough that you should never, ever leave your pet unattended in a vehicle. This is true even if you leave the windows down for fresh air or if you think you’ll only be gone for a few minutes. Studies show that even if the outdoor temperature is 72℉ (22°C), a car can rise up to 117℉ (47°C) in only an hour. Imagine how quickly a car can become dangerously hot when outdoor temperatures are a balmy 86℉ (30°C). Even if you’re leaving your car unattended for a minute or think that leaving a window open will help – the life-or-death gamble you’re taking isn’t worth it.
Why dosage matters in menopause treatment
By Rizvan Faruk Batha MPharm, PGDip GPP, IPresc, MRPharmS, Superintendent Pharmacist of Specialist Pharmacy.
Bioidentical Hormone Restoration Therapy (BHRT) is an alternative option to traditional synthetic HRT, using bioidentical hormones to treat hormonal conditions in both men and women. BHRT is compounded medicine and put simply, means that the individualised ingredients are mixed together under the direction of a qualified prescriber’s prescription to meet the tailored needs of a patient.
For women going through menopause, compounding treatments are often prescribed later down the line, when a woman has been unable to settle on the appropriate dose of HRT with a General Practitioner, often experiencing severe side effects from either too much or too little HRT. In short, compounded menopause medication offers another route for those patients where the licensed preparation is not appropriate or hasn’t worked.
Patient-led care plays an important role in compounded menopause medicine because the patient is involved throughout the process; during the consultation with the prescribing practitioner, and with the pharmacist developing the customised dosage.
One of the biggest challenges faced by compounding pharmacies is the drugs being classified as unlicensed. For drugs to be licensed, it involves research and clinical trials to assess the efficacy, quality, and safety of the medicines, and because of this process, more often than not it is the recommended route to prescribe licensed medicines. That being said, prescribing unlicensed compounded menopause medicines may be necessary, especially when it comes to the patient’s specific need and interests and where licensed medicines have been unable to satisfactorily meet the needs of the patient or are unsuitable for them.
Utilising compounded menopause medicine as a method to enhance patient care could be beneficial for the many patients that need specific dosing or formulation requirements, but sadly more often than not we see delays to patient needs and treatment, as the rise of mass manufactured licensed medicines have grown in popularity. Compounding menopause medicine could offer huge potential for many, but prescribing practices have moved towards evidence-based medicines because of the responsibility imposed on prescribers for prescribing compounded therapies. Clinicians need to understand that even licensed products are not safe or effective for all patients particularly if the product is being used in a population that were not part of the original clinical trials for the drug.
It is important to know that compounding pharmacies and pharmacists in the UK are also regulated and licensed by the General Pharmaceutical Council (GPhC). The GPhC set standards for pharmacists and pharmacies to meet to remain on their register with the aim to protect the public and give them assurance that they will receive safe and effective care when using pharmacy services.
So even though compounded medicines are ‘unlicensed’, there is a lot of due diligence exercised by the pharmacists to ensure the products meet the safe and effective care criteria. This is generally demonstrated through the purchase of medical grade active and inactive pharmaceutical ingredients (with certificates of analysis and safety data sheets), trained staff, following and updating SOPs, audits, traceability of ingredients and products during recalls, as well as continuous learning and error reporting being supported in the pharmacy.
Ultimately, how compounded menopause medicine is viewed will depend on the knowledge and experience of the patients and professionals involved. Although the medicine is unlicensed it is important to understand that experienced clinicians and pharmacists involved in the process of making the decisions are regulated, and patients are consistently monitored during their response to the medicine. If compounded menopause medicine was integrated in the healthcare system, it could change and improve the quality of life of many patients suffering with debilitating menopause symptoms, and we hope as a pharmacy that in the future we will see a shift in how compounded medicine is viewed.