Alivia Leon

Sumitovant Biopharma announced on March 10, 2023 that it has completed its acquisition of Myovant Sciences. Sumitovant has acquired all outstanding shares of Myovant not already owned by Sumitovant in an all-cash deal with a total transaction value of approximately $1.7 billion. Myovant will now be delisted from the New York Stock Exchange, and its shares will no longer by publicly traded.

“We are excited to have officially completed our acquisition of Myovant and look forward to working together to address unmet needs in women’s health and prostate cancer,” said Myrtle Potter, CEO of Sumitovant, in a company press release. “By combining our unique expertise, platforms, and resources, we will be better positioned to drive the growth of Myovant’s products and accelerate the development of our robust combined pipeline.”

“I am confident that bringing together the capabilities and strengths of Sumitovant and Myovant will best position us to continue delivering innovative therapies to patients sooner and accelerate the potential opportunities for ORGOVYX and MYFEMBREE,” said Hiroshi Nomura, CEO of Sumitomo Pharma, in the release.

“I look forward to all we will be able to achieve with the support of Sumitovant and Sumitomo Pharma to expand the impact of our differentiated therapies and advance our clinical programs,” said David Marek, CEO of Myovant, in the release. “We remain steadfast in our commitment to advance life-changing medicine and health equity for the patient communities we serve.”

Articles

Sumitovant Bipharma has completed its acquisition of Myovant Sciences for approximately $1.7 billion.

Sumitovant Acquires Myovant for $1.7 Billion

On March 10, 2023, Silicon Valley Bank (SVB) was closed by the California Department of Financial Protection and Innovation, with the Federal Deposit Insurance Corporation (FDIC) as appointed receiver. Biotechnology companies made up a substantial part of the bank’s client base, with 12% of the bank’s $173 billion in deposits coming from life sciences and healthcare, according to SBV’s 

SVB was also a critical partner for many startups and young biotechnology companies. Many companies have issued statements regarding their lack of affiliation with the bank. ONWARD Medical N.V. issued a 

 statement on March 13, 2023, stating, “ONWARD has no business arrangements nor known exposure to SVB. All banks currently holding cash deposits and securities on behalf of ONWARD carry Moody’s Investors Service ratings of A1/P-1 or higher on long/short-term deposits,” (2).

 statement on March 13, 2023, stating, “Autolus Therapeutics…following recent events with Silicon Valley Bank, announced that the company has no business relationships with Silicon Valley Bank past or present,” (3). 

 from the FDIC, “all deposits—both insured and uninsured— … [have been transferred] to a newly created, full-service FDIC-operated ‘bridge bank’ in an action designed to protect all depositors of Silicon Valley Bank. Depositors will have full access to their money beginning this morning, [March 13, 2023], when Silicon Valley Bank, N.A., the bridge bank, opens and resumes normal banking hours and activities, including online banking.”

Some biotechnology companies who have had relations with SVB are beginning to reassess their approach, with Agenus announcing in a 

 that “it has cancelled its conference call on Monday, March 13 to discuss its minority cash holdings at Silicon Valley Bank in light of the government’s SVB deposit access announcement,” (4).

Ventyx Biosciences provided an update in a 

, stating, “A portion of our cash is deposited in accounts with SVB and custodial accounts managed by SVB, and Ventyx may not have full access to these funds in the near-term. We do not see a material impact to our liquidity position or our ongoing operations as a result of this event,” (5).

1. SVB. Q4 2022 Financial Highlights. Jan. 19, 2023.

2. ONWARD. ONWARD Does Not Hold Cash Deposits at Silicon Valley Bank. Press release. March 13, 2023.

3. Autolus Therapeutics. Autolus Therapeutics Has No Business Relationship with Silicon Valley Bank. Press release. March 13, 2023.

4. Agenus. Agenus Cancels Conference Call to Discuss the Company’s Minority Cash Holdings at SBV in Light of Government’s SBV Deposit Access. Press release. March 12, 2023.

5. Ventyx Biosciences. Ventyx Biosciences Provides Update on Silicon Valley Bank Financial Exposure. Press release. March 11, 2023.

Silicon Valley Bank has collapsed, leaving many biotechnology companies unsure of the future. 

Biotech Companies Deal with Silicon Valley Bank Collapse

Catalent announced on March 9, 2023 the expansion of its UpTempo platform process for the development and current good manufacturing practice manufacturing of adeno-associated viral (AAV) vectors. The platform now includes an in-house clonal HEK293 cell line, and off-the-shelf plasmids to support a robust supply chain for the development and manufacture of gene therapies and the reduction of timelines to first-in-human clinical evaluation.

Catalent launched its UpTempo platform in 2022 to standardize protocols for cell culture, transfection, and downstream purification, as well as implement a single, uniform bill of materials to simplify the critical supply chain and material qualification. The new additions aim to increase consistency and efficiency, potentially reducing the time to manufacture clinical-quality drug product to just nine months.

“Speed to patients is paramount for gene therapy innovators, and as such, we’ve seen multiple customers requesting and signing up for the UpTempo platform. We are pleased to now include HEK293 producer cell line and off-the-shelf plasmids as part of the platform, enabling improved efficiency and simplicity for our customers as they prepare to enter clinical trials,” said Manja Boerman, president, BioModalities (cell, gene, and protein therapies) at Catalent, in a company press release. “Having a partner that offers end-to-end solutions provides security of supply, can eliminate time-consuming tech transfers between companies, optimizes the development steps, and ensures seamless transition from development through to commercial-scale manufacturing.”

Catalent is expanding its UpTempo AAV platform to accelerate the development of gene therapies. 

Catalent Expands UpTempo AAV Platform 

Vetter announced on March 6, 2023 that is has become a participant of the UN Global Compact Network. The UN Global Compact was launched in 2000 and is the largest corporate initiative on sustainable business worldwide. More than 15,000 companies and 3000 non-profit organizations from over 160 countries have signed the initiative to date.

A main focus of the UN Global Compact is on the enforcement and implementation of human and employee rights, environmental protection, and the prevention of corruption. By becoming a participant, Vetter gains access to the large network of companies and organizations that are committed to the same corporate goals. Vetter will submit a publicly viewable annual progress report, which will serve as evidence of transparency and accountability.

"As a family-owned business in the healthcare sector, we bear great responsibility,” said Henryk Badack, senior vice president, technical service and internal project management, in a company press release. “And we believe in the power of cooperation. The UN Global Compact combines these two approaches very well and is also a strong commitment to shared values and goals across business sectors and national borders."

Vetter has become a participant of the UN Global Compact Network.

Vetter Joins United Nations Global Compact

Janssen announced on Feb. 24, 2023 that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended marketing authorization for AKEEGA (niraparib and AA) in the form of DAT, given with prednisone or prednisolone, for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) and BRCA1/2 mutations (germline and/or somatic) in whom chemotherapy is not clinically indicated.

If approved, the treatment will be the first dual action tablet (DAT) available in the European Union for first-line treatment of adult patients with mCRPC with BRCA1/2 mutations. Niraparib is a highly selective poly adenosine diphosphate-ribose polymerase (PARP) inhibitor. Alongside AA, a cytochrome P450 17α-hydroxylase (CYP17) inhibitor, the combination DAT regimen targets two oncogenic drivers in patients with mCRPC.

“Metastatic castration-resistant prostate cancer remains a lethal disease, with high unmet needs in terms of treatment options, particularly for patients with BRCA1/2 gene mutations,” said Elena Castro, consultant oncologist, Hospital Universitario 12 de Octubre, in a company press release. “We’ve seen that in these patients, niraparib combined with abiraterone acetate and prednisone significantly reduces the risk of disease progression or death compared to AAP. This niraparib-based regimen is a welcomed targeted treatment option and, if approved, has the potential to impact the standard of care for men with mCRPC BRCA who are treated with first-line therapy.”

Janssen has received a positive opinion from EMA for AKEEGA plus prednisone or prednisolone for the treatment of BRCA1/2 gene-mutated metastatic castration resistant prostate cancer.

Janssen Receives Positive Opinion for AKEEGA Plus Prednisone or Prednisolone 

When it comes to solid vs. semi-solid drugs, there are many 
considerations for manufacturers to take in regards to the process in which the end product is made. While solid dosage drugs may be easier to manufacture, they present more challenges regarding regulatory requirements. While semi-solid dosage drugs are more challenging to manufacture, they are subject to fewer regulatory obstacles.

To learn more about the manufacturing processes for solid and semi-solid dosage drugs, 

 spoke with Shankar Gupta, chief sales officer at ACG.

 What are the pros and cons of solid dosage versus semi solid dosage, or capsules vs. soft gels?

 Each of them have their own pros and cons. On the one hand, from a manufacturing standpoint, capsules are fairly straightforward. The capsules are filled using a filling machine,
and the product is ready. However, there are a number of standard and regulatory requirements that need to be met before they are approved for consumption and marketing.

Although soft-gel capsules are subject to fewer regulations, the manufacturing process is both longer and more complex, requiring a larger manufacturing space. Additionally, the processes require greater numbers of staff with a wide range of skills. Also, processes result in more wastage. Before they can be packed, they [also] need to be dried, which adds to the time, complexity, and cost.

 How can the formulation of a drug impact the quality of the resultant oral solid dosage form and the tableting process altogether?

The formulation of a drug is governed by a number of key factors. For a contract manufacturer, this would be determined by the customer’s preference or need. Otherwise, the formulation of a drug is generally dictated by the patient’s experience, compliance, and the appropriate packaging for the product.

In the case of needing to taste mask to achieve a neutral product or to add color, capsules would be the preferred choice.

Although capsules have a good shelf life, when exposed to humidity, temperature fluctuations, or if they are subjected to prolonged light exposure, they can become brittle. Despite these variances, the packaging for capsules is quite simple.

[On the other hand,] tablet packaging has a higher degree of complexity due to varied shapes, sizes, and consistency of the end product.

 What processes can be used to ensure uniformity/equal distribution of ingredients in capsules/tablets during manufacturing?

 From a mechanical perspective, the machinery utilized to ensure the uniformity or equal distribution of ingredients depends on the requirement of the formulation, and also determines the process. For example, in cases of a high degree of content uniformity, the processes may rely on the utilization of a fluid bed drier, processor, or a high-shear mixer.

Other dependencies include the dissolution time, [need] for fast delivery, or the disintegration requirement.

 Can you explain tablet tooling and provide some considerations to make when deciding what methods to use?

 Tablet tooling refers to a tooling method that uses upper and lower punches, and compression force with a die and cup to shape granules or powder into a tablet. The die is used in conjunction with the punches to accept the granules or powder for compression and creates the tablet’s perimeter size. The cup depth determines the tablet’s depth.

The end product will influence the tooling parameters including the tablet size, based on economies and end-user price point. This goes from low-cost packaging through to the creation or innovative shapes to drive product differentiation and competition in a particular category and market.

What are some of the main challenges drug manufacturers face when trying to process oral solid dosage forms/tablets quickly and cost-effectively while also maintaining high quality?

 It is widely known that efficiencies in pharmaceutical productivity are not comparable to productivity gains in other manufacturing sectors. Running at an efficiency of 60–65%, the biggest challenge across the sector is by far productivity.

Also, as accuracy and quality are vital in cases where products are exported to regulatory markets, the levels of inspection are hugely increased. This, in turn, can hamper the ability to streamline and drive efficiencies.

The other challenges facing pharmaceutical manufacturing are varied, from API variations to labor shortages, speed of product inspection, production timelines, and speed of adopting new technology. However, the industry is accelerating its digital Industry 4.0 transformation in pursuit of data-controlled processes, which should help the sector to increase efficiencies, as well as speed to market.

 Have you witnessed any significant trends in tableting over the past decade that have had a positive/negative impact on the industry?

 We are seeing a rise in multi-unit pellet system tablets. This is a solid dosage form that is the outcome of compressing a mixture of pellets that contain drugs and powder excipients [in order] to control drug release.

We have also seen a significant change in the adoption of inspection technology. The COVID-19 pandemic made it more evident that human inspection regarding the quality of products must be reduced, for example, by removing processes such as hand-picking products to test. Companies that focus on cost control, through the use of more efficient equipment and less onerous inspection processes, will not only reduce waste and the need for costly labor, but will also benefit from a reduction in costly product recall.

Manufacturers who adopt inspection technology benefit from microlevel distinction differentiation of the product; inside and outside. These inspections are efficient performing at high speed and in real-time, meaning samples do not have to be taken off the line to be tested. Inspection technology assesses every single product and provides real-time intelligence regarding rejections so the quality of the products in the batch that haven’t been rejected can be guaranteed.

Where as the sample method of testing means the entire batch quality is based on the test results of a subset of the batch and the remaining products in the batch are assumed to be of the same quality but can’t be guaranteed.

 Could you give us your predictions on the trends within tableting for the coming decade?

 A growing and ageing global population, along with new emerging markets, are creating high demand in the pharmaceutical sector globally. With an increase in competition, speed to market is vital. Those who are customer-centric, provide safety assurance, and deliver faster will ultimately win.

We are seeing the nascent signs of demand for high-output machines. This is coupled with the need to drive efficiencies in the sector. The combination of advancements in Industry 4.0 and the need for leaner workforces will drive the analysis of multiple sources of data to provide information such as predictive maintenance and even remote maintenance. Where machine uptime and efficient running costs are improved, cost savings will be achieved without compromising the quality of the product.

Additionally, we are starting to see a greater uptake in 3D printing in the sector. Being able to print in small batches results in waste reduction, coupled with reliable outputs and efficiencies. It will have a useful place in the set-up of new product development and has the potential to revolutionize the delivery of personalized medicine.

When referring to this article, please cite it as A. Leon, "Considerations for Manufacturing Solid Versus Semi-solid Drugs," 

Manufacturers must consider key components of manufacturing solid versus semi-solid drugs to create a successful end product. 