Felicity Thomas is Associate Editorial Director of Pharmaceutical Technology, Pharmaceutical Technology Europe, BioPharm International.

Felicity Thomas

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The government of the United Kingdom announced on March 20, 2024 that it is 

 that are considered highly addictive, dangerous, and pose a higher risk of accidental overdose (1). These substances will now be subjected to the strictest controls, in line with the controls placed on fentanyl.

As a result of these new government controls, if anyone is involved in the production or supply of the synthetic opioids, they will be subjected to the full force of the law. “We are highly alert to the threat from synthetic drugs and have been taking a range of preventative action, learning from experiences around the globe,” said James Cleverly, UK home secretary in a press release. “Our plan is working—the overall quantities of synthetic opioids reaching the UK remain lower than other countries, but we are not complacent.”

Synthetic opioids are a major contributor to preventable drug overdose deaths, particularly affecting the United States. However, Europe is also now fearing a crisis, as the availability of these drugs is increasing (2). Although opioids can be prescribed for pain relief, any regular non-medical use, prolonged use, misuse, or use without medical supervision can result in dependence on the drug and various related health problems (3).

Of the 15 synthetic opioids, 14 are nitazenes, which were developed by the pharmaceutical industry during the 1950s but were never approved for use as medicines and can cause fatal respiratory depression. Some nitazenes are known to be hundreds of times more potent than heroin, and these compounds are being detected in other products, meaning consumers may be using these substances without realizing (4).

“Synthetic opioids are significantly more toxic than heroin and have led to thousands of deaths overseas,” added Chris Philp, UK’s crime and policing minister. “We are determined to ensure these destructive and lethal drugs do not take hold in our communities in the UK.”

The opioids that have been made Class A drugs under the UK’s Misuse of Drugs Act 1971 are metonitazene; protonitazene; isotonitazene; butonitazene; flunitazene; metodesnitazene (metazene); etodesnitazene (etazene); N-pyrrolidino-etonitazene (etonitazepyne); N-piperidinyl-etonitazene (Etonitazepipne); N-pyrrolidino protonitazene; ethyleneoxynitazene; N-desethyl protonitazene; N-desethylisotonitazene; N-desethyl-etonitazene; and brorphine.

Additionally, the UK government has placed controls on five other substances on March 20, 2024. Of these substances, three are stimulants—diphenidine, ephenidine, and methoxyphenidine—that are now Class B drugs; one is a synthetic cannabinoid receptor agonist (cumyl-PeGaClone) that is also now a Class B drug; and the final one is a short-acting benzodiazepine (remimazolam), which is now a Class C drug.

1. UK Gov. More Synthetic Opioids Banned to Protect Communities. 

, News Story, March 20, 2024.
2. Bauer-Babef, C. Opioids on the Rise, Under Close Surveillance in Europe. 

, March 6, 2024.
3. WHO. Opioid Overdose. 

, Fact Sheet, Aug. 29, 2023.
4. Holland, A.; Copeland, C.S.; Shorter, G.W.; et al. Nitazenes—Heralding a Second Wave for the UK Drug-Related Death Crisis? 

Articles

More synthetic opioids have been placed under the strictest controls in the United Kingdom.

UK Government Bans 15 Synthetic Opioids

Global pharmaceutical company, AstraZeneca, has revealed its latest investment plans, which involve spending a total of £650 million ($828 million) within the United Kingdom. This influx of money is expected to boost the country’s life science sector and grow the economy.

In a press release, issued by the UK Government on March 6, 2024, it was announced that AstraZeneca’s investment will be used across Liverpool and Cambridge in the UK. The company’s manufacturing site in Speke, Liverpool will receive £450 million ($573 million), which will be used for the research, development, and manufacture of vaccines. Additionally, AstraZeneca will use the remaining £200 million ($255 million) to expand its presence in Cambridge with a facility that will be built adjacent to its R&D Discovery Centre (DISC), which is already located on the life sciences cluster site.

“We are sticking to our plan to make the UK one of the best places in [the] world to invest in developing and manufacturing new, innovative medicines—both protecting public health and growing our economy,” said Jeremy Hunt, the UK’s Chancellor of the Exchequer, in the press release. “AstraZeneca’s investment plans are a vote of confidence in the attractiveness of UK as a Life Sciences superpower and strengthen our resilience for future health emergencies.”

“AstraZeneca’s planned investment would enhance the UK’s pandemic preparedness and demonstrates our ongoing confidence in UK life sciences,” added Pascal Soriot, CEO of AstraZeneca in the press release. “We will continue to support the UK in driving innovation and patient access, building on the strong foundations which have been put in place.”

Furthermore, adding to the boost that the investment will afford the UK to improve resilience to potential future pandemics and health threats, AstraZeneca and the UK Health Security Agency (UKHSA) are planning to partner on advancing science for the development and evaluation of vaccines. This partnership will take advantage of the technology at AstraZeneca’s Speke site in Liverpool and also the UKHSA’s Vaccine Development Evaluation Centre at the Porton Down site in Salisbury, UK.

“This investment will bolster the development of the UK’s vaccine capabilities and life sciences sector—critical components of the country’s resilience to future health threats,” explained Dr. Isabel Oliver, chief scientific officer at UKHSA, in the press release. “UKHSA majors on researching and developing new ways to strengthen the country’s defences against all health hazards—including future pandemics—and works routinely with a range of commercial and academic partners. We are looking forward to working with AstraZeneca to collectively protect the population’s health.”

“The UK is a global leader in the research and development of life saving vaccines. Today’s announcement is testament to this country’s Life Science capabilities—and our continued commitment to pandemic preparedness and global health,” stated Victoria Atkins, Secretary of State for Health and Social Care of the United Kingdom, in the press release. “As well as creating new highly skilled jobs, this investment will help maintain the UK’s position at the forefront of tackling emerging diseases, and support our work to make our healthcare system faster, simpler, and fairer.”

New plans laid out by AstraZeneca will see £650 million ($828 million) be invested into the UK.

AstraZeneca Set to Boost the UK’s Life Sciences Sector with Investment Plans

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All drugs are subjected to regulatory scrutiny during the full development lifecycle because, whichever way a drug is administered, it should always be effective and, most importantly, safe for the end-user. The requirement for safety, however, is ever more pressing for parenteral products, as these drugs are administered either directly into the bloodstream or into other delicate mucus membranes.

Focusing on parenteral drug manufacturing in particular, a critical step that ensures sterility and contaminant-free results is fill/finish. “Following drug development and production, fill/finish is the next step in the process—and crucial for getting the drug into the required container and making it ready for distribution,” confirms Andreas Mattern, vice-president Strategy and Global Product Management Pharma at Syntegon.

“Fill/finish manufacturing entails the process of aseptically filling and sealing products, in this case pharmaceutical products, ensuring that precision, sterility, and compliance with regulatory standards are meticulously followed,” concurs Carlos Quintero, director, Industry Services—PMMI (the Association for Packaging and Processing Technologies). “This is critical to ensure safety, efficacy, and shelf life.”

It is imperative for both bio/pharma manufacturers and any contract service providers, such as contract manufacturing organizations, to pay close attention to fill/finish processes, making sure there is the utmost sterility while also being robust and reliable, notes Mattern. “Filling and closing are especially demanding [because] the drug and its container come into contact with many different parts of equipment,” he adds. “To date, some of these processes still require manual intervention from operators, which makes them even more prone to contamination.”

In 2022, a key regulatory revision was released—the European Union’s Good Manufacturing Practice Annex 1 revision (1)—that has far-reaching consequences for sterile filling operations, not just within the EU but for the global bio/pharma industry, Mattern reveals. “The specifications affect the manufacturing processes of all drugs imported into the EU,” he says.

“Among the major challenges of the new Annex 1 is the separation of the aseptic process area from the operator environment,” Mattern continues. “Pharmaceutical manufacturers therefore require at least restricted access barrier systems (RABS) for the approval of new products.”

As a result of these new regulatory requirements, there is now high demand for new machines and barrier technology upgrades, Mattern explains. “In the case of older machines, the question is whether to upgrade or invest in a completely new line with pre-installed barrier technology,” he says.

The revised Annex 1 also clearly sets out the requirements for air flow, Mattern specifies. “Unidirectional air flow is mandatory for open isolators and RABS in all class A areas and should not be interrupted between the air inlet and the open product. Yet this uninterrupted flow is not possible everywhere,” he says.

“A typical exception is the filling needle together with the filling needle holder, which must be positioned exactly above the open, sterilized packaging material in order to achieve loss-free filling,” Mattern states. “It is expected that these components are aerodynamically designed to minimize turbulences and that these items can be sterilized separately and installed aseptically.”

As alluded to earlier, the revised regulatory requirements are leading to the need for new technologies to be used in fill/finish processes. A further elaboration on this matter is highlighted in the second chapter of Annex 1 (1), where automation and robotic systems are penned as appropriate technologies, confirms Mattern. “By using these technologies, gloves and human intervention in barrier systems can be reduced to an absolute minimum or even eliminated,” he says.

Just a decade ago, the primary focus for bio/pharma research companies and manufacturers was large-batch blockbusters or traditional drugs, remarks Andreas Mattern, vice-president Strategy and Global Product Management Pharma at Syntegon. “Today, these medicines continue to make an important contribution to human health. Some of them, such as blood thinners, painkillers, or insulin, have become an indispensable part of the drugstore shelf. They are produced on lines in 24-hour operations,” he says. “Further new drugs in this realm (e.g., a high-dose injectable version of the incretin mimetic semaglutide) will continue to push the need for high-speed production.”

However, there is an apparent drive towards more niche areas. “Special and often personalized medications are now available to cure or at least delay some life-threatening illnesses. Cellular and molecular biotechnology has been accompanied by a revolution in pharmaceutical manufacturing: while high-speed, high-throughput lines used to be in the greatest demand, more and more pharmaceutical companies are now investing in the development and commercialization of small-volume medicines, which have very different production and filling requirements,” Mattern asserts.

“The increasing prevalence of advanced therapy medicinal products, such as cell and gene therapies and bioengineered tissue products, shows that the industry is specializing steadily,” Mattern continues. “These drugs are not manufactured on huge lines. Instead, the focus is on what is commonly known as small batch production.”

“The issue of gloves presents many challenges, which are acknowledged in separate paragraphs,” Mattern continues. “For example, gloves are to be additionally tested in operation during longer campaigns—which is not possible with the glove testing equipment used to date without risking the integrity of the sterile room. A switch to gloveless systems with robotics that handle these manipulations is already possible.”

Additionally, in conjunction with robotic filling lines, artificial intelligence (AI)-influenced line controls and automation will be able to offer faster scalability and increased flexibility for manufacturers, remarks Quintero. “Automation and AI are always accelerating the rate of precision, quality control, and efficiency of the fill and finish-seal process in manufacturing,” he says. “This has a huge impact on reducing contamination risks and the overall effectiveness and performance of the lines.”

Another pressing issue for the bio/pharma industry and its stakeholders is sustainability. More sustainable equipment and processes are needed across the board in bio/pharma manufacturing to ensure various reporting requirements can be met, which is something that technology providers, such as Syntegon, can help with, notes Mattern.

In terms of the sustainability of fill/finish manufacturing, Quintero anticipates a marked and quick change in the coming years. “Fill/finish manufacturing most likely will rapidly evolve into a zero-waste process and will incorporate more and more, sustainable renewable energy sources,” he states.

Furthermore, the drive towards automation of fill/finish processes will continue into the future as humans remain to be the main source of contamination, Mattern adds. “While drugs are becoming more and more complex, and as such expensive, separating pharmaceuticals from operators has been gaining attention throughout the industry for some years—a topic that is still becoming more pressing when considering small and even micro batch filling of highly potent substances,” he says. “Hence, automation and digitalization will play an increasingly crucial role.”

“While it is not easy to integrate what is known as ‘Industry 4.0’ into complete pharmaceutical manufacturing operations, many individual solutions are already available,” he summarizes. “The main question here is how to make use of the enormous amounts of data generated by fill/finish (and other pharmaceutical) processes every day.”

1. EC. Annex 1 Manufacture of Sterile Medicinal Products, 

Felicity Thomas is the European/senior editor for Pharmaceutical Technology Group.

When referring to this article, please cite it as Thomas, F. Automating the Future of Fill/Finish. 

Given the criticality of fill/finish processes, it is clear that automation is the next technological step.

Automating the Future of Fill/Finish

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Springtime is upon us once again, as the colder weather makes way for more warmth and the dark mornings and evenings start to recede, what better time of year than this to receive positive financial tidings! For the life sciences industry in the United Kingdom, the Spring Budget, announced by the Chancellor of the Exchequer, Jeremy Hunt, on 6 March 2024 (1), is giving rise to optimism and opportunities in the coming months.

In the latest budget, Hunt revealed further support for the life sciences industry, expanding upon the investment laid out in the Autumn Statement in 2023 (2), including an additional £45 million (€53 million) in funding aimed at supporting the next generation of medical researchers and boosting medical charities’ research agendas (1). “I also want to mention our life sciences sector where we will support research by medical charities into diseases such as dementia, cancer, and epilepsy with an additional £45 million including £3 million for Cancer Research UK,” said Hunt in his speech to the Houses of Parliament about the budget (3).

Hunt also confirmed greater backing for the advanced manufacturing sector with plans for a £50 million (€59 million) Apprenticeship Growth Pilot and iterated the importance of manufacturing medicines in the UK, something that is experiencing a boost through investment from AstraZeneca (4). “… because of the government’s support for the life sciences sector, [AstraZeneca] announced plans to invest £650 million in the UK to expand their footprint on the Cambridge Biomedical Campus and fund the building of a vaccine manufacturing hub in Speke in Liverpool,” Hunt added (3).

And it isn’t just the UK’s industry that is gaining financial support from governing bodies, the European Union has also specified increased spending on the Horizon Europe research programme in its 2024 budget (5,6). The level of this increase was unexpected, as there had initially been an agreement to cut the funding for the programme by €2 billion; however, European Parliament members are now promoting the position of making the research programme a priority for the bloc in 2025 (7).

. Policy Paper, 6 March 2024.
2. UK Gov. 

. Policy Paper, 22 Nov. 2023 (updated 30 Nov. 2023).
3. UK Gov. Spring Budget 2024 Speech. 

, 6 March 2024.
4. Thomas, F. AstraZeneca Set to Boost the UK’s Life Sciences Sector with Investment Plans. 

, Industry News, 7 March 2024.
5. European Council. EU Budget for 2024. 

 (accessed 8 March 2024).
6. Naujokaityte, G. Horizon Europe Gets a Small €85M Boost Next Year to Reach €12.9B. 

, 14 Nov. 2023.
7. Magee, R. MEPs Say Horizon Europe Should be a 2025 Budget Priority. 

When referring to this article, please cite it as Thomas, F. Budget Benefit. 

Wider life sciences industries in the UK and Europe are receiving favourable financial support from governing bodies.  

Budget Benefit

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AstraZeneca, a global science-led biopharmaceutical company, has successfully completed its acquisition of US-based clinical-stage biopharmaceutical company, Icosavax, which will become a subsidiary of AstraZeneca. The completion of the acquisition was announced in a Feb. 19, 2024 press release.

Through this acquisition, AstraZeneca will be able to expand its expertise in respiratory syncytial virus (RSV) thanks to Icosavax’s lead investigational vaccine candidate, IVX-A12—a combination protein virus-like particle (VLP) platform vaccine that targets RSV and human metapneumovirus (hMPV). The vaccine, IVX-A12, is ready for Phase III studies and has been granted Fast Track Designation from FDA.

According to Phase II clinical data, IVX-A12 elicits a robust immune response against both RSV and hMPV only one month after vaccination. These data reconfirm previous immunogenicity data seen during the Phase I trial. Currently, there are no treatments or preventative therapies available for hMPV and no combination vaccines available for RSV.

Completion of the acquisition was made through a tender offer for the purchase of all outstanding shares of Icosavax for $15 per share in cash. Additionally, in the event of specified regulator and sales milestones being met, AstraZeneca will pay a non-tradable contingent value of up to $5 per share in cash. In combination, the deal is expected to reach a value of $1.1 billion.

The definitive acquisition agreement between the two companies was announced back in a 

, when Iskra Reic, executive vice-president, Vaccines & Immune Therapies, AstraZeneca commented: “With the addition of Icosavax’s Phase III-ready lead asset to our late-stage pipeline, we will have a differentiated, advanced investigational vaccine, and a platform for further development of combination vaccines against respiratory viruses. This aligns with our strategy to deliver a portfolio of therapies to address high unmet needs in infectious diseases, and our ambition to protect the most vulnerable patients who have high risk of severe outcomes.”

AstraZeneca has completed its acquisition of Icosavax, gaining the IVX-A12 vaccine candidate that targets RSV and hMPV.

AstraZeneca Completes Acquisition of Icosavax

Global biopharma company, GSK, has announced its acquisition of Aiolos Bio, which is a clinical-stage biopharmaceutical company that is focused on addressing unmet treatment needs in the respiratory and inflammatory conditions space.

The acquisition, which was announced in a Feb. 15, 2024 press release, includes Aiolos’ long-acting anti-thymic stromal lymphopoietin (TSLP) novel monoclonal antibody, AIO-001, which is already set to start Phase II clinical development for the treatment of adults with asthma. AIO-001 works by binding to the human TSLP ligand and inhibiting its ability to signal, which will help to improve lung function and control asthma in patients.

With the addition of this novel therapy, expanding its respiratory biologics portfolio, GSK would have the potential to be able to reach 40% of severe asthma patients that have a type of overactive immune response associated with the respiratory condition—low T2 inflammation.

“Given the limited treatment options for asthma patients with low T2 inflammation, we look forward to using our deep respiratory expertise to potentially offer a long-acting biologic to a broader portion of the 315 million patients living with asthma,” said Tony Wood, chief scientific officer, GSK, in the press release.

Per the terms of the agreement, GSK will make a $1 billion payment upfront for the acquisition and will also make success-based regulatory milestone payments of the value of up to $400 million. Furthermore, GSK will be responsible for payments, based on reaching certain success milestones, to Jiangsu Hengrui Pharmaceuticals Co., Ltd., which is the company that provided Aiolos with an exclusive licence to AIO-001 outside of the Greater China area.

This acquisition announcement comes just over one month after the companies entered into the agreement for the buyout, which had been revealed in a 

GSK is expanding its respiratory biologics portfolio with its acquisition of Aiolos Bio and its novel therapy, AIO-001.