Susan Haigney

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Syntegon, a processing and packaging company, announced on June 7, 2024 that it is acquiring Telstar, an equipment manufacturer located in Barcelona, Spain. The acquisition will add liquid pharmaceutical processing to Syntegon’s portfolio, including freeze-dryers and loading and unloading systems that will enhance the company’s vial filling and isolator solutions. The expanded portfolio will allow Syntegon to provide seamless line solutions from a single source and offer additional engineers, geographic coverage, proximity, and application expertise.

“Syntegon is world market leader in liquid vial filling. With the acquisition of Telstar, we will enhance our portfolio of innovative technologies and many successful references in the market. Our customers will benefit from even more comprehensive solutions, seamless processes, and lifecycle services,” said Torsten Türling, CEO of the Syntegon Group, in a press release. “At the same time, we can jointly capture growth opportunities and expand our market presence.”

Telstar was founded in 1963 and has been part of the Azbil Corporation since 2013. The company has four production plants located in Spain, China, and the United Kingdom; six technology centers; 10 consultancy and engineering centers; and commercial offices worldwide. Syntegon, headquartered in Germany, has 39 sites in 20 countries with 6300 employees.

“Azbil has been strengthening its product capabilities, particularly in loading systems, and enhancing the overall competitiveness of Telstar since the acquisition in 2013. Now Azbil has decided to transfer Telstar to the company we consider best to further drive Telstar’s business. We are convinced that Syntegon will make the best use of the accumulated technological capabilities and products and will achieve sustainable growth,” said Kiyohiro Yamamoto, president and Group CEO of Azbil, in the release.

“For Telstar, the incorporation into the Syntegon Group represents a great opportunity to ensure stable business development and future growth. We look forward to bringing our knowledge, expertise, and high-value technologies for aseptic manufacturing to the joint portfolio and to becoming part of the Syntegon team, backed by a shared business culture,” said Jordi Puig, CEO of Telstar.

The transaction is subject to approval by regulators. “After leading the Life Science Engineering business division of Azbil during more than 11 years, Telstar also expresses its gratitude to the Japanese Corporation for their support throughout this time, during which Telstar has reached a more solid and stable structure, in addition of reinforcing innovation activity arised from solid synergies experienced in the R&D field,” Telstar stated in a press release (2).

Syntegon also announced on June 10, 2024 that its subsidiary, Pharmatech, is launching a new Modular Bioprocessing Platform (MBP) at the Achema 2024 conference. The MBP is a flexible, fully integrated automated solution that can be configured for a full range of microbial and mammalian cell culture applications.

“Its innovative, modular design allows our customers to profit from shorter lead times and lower costs, without compromising on functionality or the accustomed ‘made in Germany’ quality,” said Christian Lavarreda, global product manager at Pharmatec, in a press release (3). “Biopharmaceutical manufacturers can now turn to Syntegon for seamless, complete solutions along the entire production chain.”

1. Syntegon. Set for Future Growth: Syntegon Announces Acquisition of Testar. Press Release. June 7, 2024.


https://www.syntegon.com/press/set-for-further-growth-syntegon-announces-acquisition-of-telstar


2. Telstar. Telstar Starts a New Stage. Press Release. June 7, 2024.


https://www.telstar.com/en/about-telstar/news-events/news/telstar-starts-a-new-stage/


3. Syntegon. Syntegon Launches Modular Bioprocessing Platform at Achema. Press Release. June 10, 2024. 

https://www.syntegon.com/press/syntegon-launches-modular-bioprocessing-platform-at-achema/

Articles

Syntegon will expand its processing and packaging by acquiring the Spanish equipment supplier.

Syntegon Acquires Telstar

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On June 10, 2024, FDA’s Center for Drug Evaluation and Research (CDER) announced that it is publishing a notice in the 

 on June 11, 2024 (1) introducing the Emerging Drug Safety Technology Meeting (EDSTM) program. The meetings, which will be administered through CDER’s Emerging Drug Safety Technology Program (EDSTP), will provide those involved in pharmacovigilance activities (e.g., manufacturers, academia, contract research organizations, vendors, software developers) the ability to interact with CDER staff regarding the use of artificial intelligence (AI) in the advancement of pharmacovigilance.

The EDSTM program will facilitate learning and discussion regarding the application of emerging pharmacovigilance technologies and the verification and validation of these models. The EDSTP is a central point of contact for these discussions between industry and FDA that will enable knowledge management and transfer within the agency. EDSTP will also work to understand the scope of the use of AI and other technologies in pharmacovigilance and look for regulatory policies.

“FDA expects increased communication with industry and/or other relevant parties during EDSTMs will accelerate our understanding of how AI-enabled tools are being used for PV, their associated risks and benefits, and barriers to implementation. We encourage interested parties to visit the 

 for more information about the program, including information on eligibility and selection criteria and how to request a meeting,” the agency stated in a press release.

“FDA plans to leverage these learnings to help inform potential regulatory and policy approaches, within the use of emerging technology in PV. The EDSTM program is not an avenue to seek regulatory advice on compliance with pharmacovigilance regulations. Rather, we expect that the information gained during this program will help CDER consider providing regulatory advice on specific technologies to facilitate their adoption when appropriate,” the agency states in the unpublished document (2).

Applicants may request EDSTMs on a rolling basis if they have at least one approved application with CDER, such as a new drug application, abbreviated new drug application, or biologics license application. Other individuals supporting industry pharmacovigilance activities may also request an EDSTM. These EDSTMS will be reviewed quarterly, and CDER will select up to nine participants that meet submission eligibility criteria.

“FDA has a longstanding commitment to ensure medicines marketed in the United States are safe through continued surveillance and research following approval. In the postmarket setting, regulated industry is obligated to review all adverse drug experience information received or otherwise obtained and submit timely reports to FDA,” the agency states in the document (2). “Both industry and regulatory authorities face challenges with timely and efficient collection, processing, and evaluation of single and aggregate patient safety data compounded by ever-increasing case volumes. Advances in emerging technology have the potential to address some of these challenges by creating more efficiencies within a PV system. For example, early adopters of AI are leveraging these emerging technologies to automate fundamental tasks (e.g., adverse event intake, data entry, and processing) with the intention to drive down associated administrative burden and costs. These technologies can also make safety surveillance more efficient and effective by capturing, aggregating, and analyzing larger and more diverse data sets.”

1. FDA. Hearings, Meetings, Proceedings, etc.: Emerging Drug Safety Technology Meetings, Program Announcement. 

https://www.federalregister.gov/public-inspection/2024-12770/hearings-meetings-proceedings-etc-emerging-drug-safety-technology-meetings-program-announcement


2. FDA. Emerging Drug Safety Technology Meetings; Program Announcement. [Docket No. FDA-2024-N-2332]. June 10, 2024. 

https://public-inspection.federalregister.gov/2024-12770.pdf

The new meeting program will create a dialogue around AI and be administered through CDER’s Emerging Drug Safety Technology Program.

CDER Announces Emerging Drug Safety Technology Meeting Program

In early June 2024, FDA and the US Pharmacopeial Convention (USP) both published reports on drug shortages as of the end of 2023. The Center for Drug Evaluation and Research at FDA published its 11th annual report to Congress on drug shortages on June 6, 2024, in which the agency stated it had worked with manufacturers to prevent 236 drug shortages in 2023 (1). According to FDA, drug shortages decreased from 251 in 2011 to 55 in 2023.

“Although the number of new drug shortages has declined since 2011, shortages continue to pose a real challenge to public health, particularly when the shortage involves a critical drug, such as those used to treat cancer, to provide parenteral nutrition, or to address other serious medical conditions,” the agency stated in the Executive Summary of the report.” In the past calendar year, FDA has seen manufacturers in the United States and abroad continue to experience quality issues as well as struggle with capacity constraints. Additionally, as demand increased for numerous drugs over the last several years as a result of the COVID-19 pandemic, the flu season, and the respiratory virus season, FDA has seen further strain on drug availability and the pharmaceutical supply chain.”

The USP report released on June 4, 2024, 

USP Annual Drug Shortages Report: Economic Factors Underpin 2023 Shortages, 

includes drug shortage trends up to the end of 2023 in the US (2). These trends were based on use of USP’s Medicine Supply Man tool, which uses artificial intelligence and predictive analytics to predict supply chain risks. One such trend found by USP is that shortages are lasting more than three years compared to two years in 2020. Shortages are also impacting a variety of therapeutic classes with 53% being new generic sterile injectable drugs. 

According to the USP report, the supply of a medicine is at risk when one or more of the following factors are in play: low prices, complexity of manufacture, geographic concentration, and quality problems. Drugs with lower prices had an increased discontinuation rate of 40% in 2023 for one year. Sterile injectable drugs that were in shortage were almost 8.5 times lower in price than those not in shortage.

Sterile injectables also have a higher manufacturing complexity, making them even more vulnerable to shortages. Antibiotics, which sometimes require separate dedicated facilities, and APIs that require complex chemical synthesis are also at risk.

Limited locations for API and finished dosage production also contribute to shortages according to USP, but it is quality concerns that can plague manufacturers the most. When regulators discover quality problems at facility inspections or a recall must be made, manufacturers must inform regulators of the possibility of a shortage that may result from these quality control actions. “Quality comes at a price,” said Vimala Raghavendran, vice president for Informatics Product Development at USP, in a press release (3). “The economics of generic drugs often leave manufacturers with razor-thin margins, making it challenging to prioritize investment in modern machinery or to elevate standards of quality. Without sufficient profitability, the cycle of innovation and improvement becomes difficult to sustain.”

“As we navigate the complex landscape of drug shortages, it is paramount to shift the market into a stable state,” said Anthony Lakavage, senior vice-president for Global External Affairs at USP. “Economic pressures, especially the very low prices that generics manufacturers recover for many medicines, along with contracts that are frequently broken, have left our generic medicine supply chain fragile. Unexpected shocks can break the system and disrupt the supply of quality medicines. This worrisome trajectory leads to more frequent drug shortages, prolonged scarcity, and more people at risk of not getting the medicines they need, when they need them.”

Report to Congress. Drug Shortages CY 2023

https://www.fda.gov/media/179156/download

 USP Annual Drug Shortages Report: Economic Factors Underpin 2023 Shortages. USP.org

. June 2024.
3. USP. U.S. Drug Shortages Reach Decade-high and Last Longer. Press Release, June 4, 2024. https://www.usp.org/news/us-drug-shortages-reach-decade-high-and-last-longer

USP and FDA publish reports detailing drug shortage numbers and challenges through 2023.

Drug Shortage Reports Emphasize Continuing Problems

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Raw materials are integral to developing and manufacturing safe and effective therapies. When the supply of these materials is in jeopardy, so are the final drug products those materials are used in. Any delay in the complex supply chain of a drug can lead to a shortage of much needed medications.

The COVID-19 pandemic highlighted some of the problems in supply chains of many different products, not just pharmaceuticals. The fast development and market delivery of COVID-19 vaccines and treatments, however, also created a belief that drugs can be developed, manufactured, and marketed quicker than the industry has been used to, according to Jordi Robinson, chief commercial officer, Navin Molecular. “As such, there has been a shift in the industry whereby delivery times of raw materials need to be faster, with the aim of getting molecules into the clinic more rapidly than ever,” says Robinson. In this post-pandemic world, pharmaceutical manufacturers are applying the lessons learned during COVID-19 in regard to the supply of the raw materials they procure.

Some pharma companies are choosing to make APIs and excipients in-house instead of relying on foreign suppliers, and others are diversifying the suppliers they choose to obtain materials from. “This helps ensure a steadier flow of materials, which is crucial to keep production lines humming. Of course, there’s a trade-off. Companies are also holding onto more safety stock—extra ingredients in case things get tight again. It might mean a bit more storage space needed, but it’s a small price to pay to avoid those production slowdowns,” says Ada Bedelek, director of Supply Chain and Demand Planning, C2 PHARMA.

“By lowering reliance on China and other vulnerable geographies and supplier de-risking through a diverse supply base, efforts have been made to diversify and build a robust supply chain,” says Sundar Narsimhan, chief procurement officer at Neuland Labs. “To lessen future interruptions, there is also a stronger focus on sourcing essential supplies from local production to secure critical materials and ensure supply continuity during crises, while aligning with broader economic and geopolitical strategies to decrease reliance on far-flung supply markets. Companies are also focusing on shortening the supply chain through better logistics and distribution practices, that help improve agility and responsiveness to market changes.”

Wherever they obtain their materials, manufacturers should find suppliers that provide quality materials in a reliable fashion because the final product is influenced by the consistency of the raw materials involved, asserts Bedelek. “Therefore, it’s crucial to thoroughly evaluate suppliers’ quality management systems, certifications, and track records to ensure they consistently meet specifications. When evaluating reliability, assessing the supplier’s capacity, production capabilities, and supply chain resilience helps avoid risks of disruptions,” she states.

When choosing a raw materials supplier, Selwyn Lustman, senior vice president, Global Sourcing and Procurement, LGM Pharma, specifies that pharma companies should ensure that a supplier meet the basic criteria of quality, price, and delivery. Pharma companies should also consider how long the supplier has been in business and if the supplier’s goals and priorities align with those of the pharma company, he remarks. The supplier should be able to meet the pharma company’s short- and long-term needs and provide sufficient space capacity to meet requirements. Suppliers should also have all the needed approvals for the appropriate markets. Environmental requirements are also a consideration, according to Lustman.

Suppliers must follow current good manufacturing practices (CGMPs) and maintain a robust quality system, emphasizes Narsimhan. “Alongside this, factors such as reliability, financial stability, stringent quality controls, and ethical conduct are also crucial considerations,” he adds. “Additionally, when selecting a supplier, we keep a close eye on his/her past performance, innovative approaches to efficiency, and customer-centricity.”

Robinson points to sustainability as a “critical factor” in selecting a supplier. “The supplier’s approach to sustainability is also becoming a critical factor in materials sourcing, with a requirement that they achieve minimum standards in both industry metrics (such as their Ecovadis rating) and reporting,” he says.

“Additionally, sourcing groups are often under pressure to reduce the number of suppliers that they use, so ideally a chosen partner should offer a broad platform of technologies as well as the ability to support a wide range of manufacturing scales,” Robinson adds.

The type of raw material needed should also be a consideration for manufacturers when deciding on a supplier. The nature and complexity of raw materials, as well as the techniques needed to produce them, may require different supply chain securities, explains James Lawler, general manager, C2 PHARMA. “In addition, raw materials for APIs which are designated as lifesaving medicines or form part of niche or orphan drugs may require additional security measures,” he says. “These can vary widely and are critical factors when considering supply chain securities.”

“Alongside the increasing pressure to deliver new drugs to the market quickly and efficiently, is the complexity of new molecules, and, by extension, their raw materials,” says Robinson. “In order for the supply of such materials to meet clinical and commercial demand uninterrupted, it is critical that key materials can be sourced from multiple suppliers. These will often be strategically spread geographically, to mitigate against any potential manufacturing issues that might arise, or wider geopolitical issues that could affect the supply chain.”

Flexibility and adaptability can be ensured by having multiple suppliers of necessary raw materials. However, warns Bedelek, more suppliers mean performing more qualification actions. “If the demand is small, it may not be worth qualifying several suppliers,” she says. “While there are benefits to working with multiple suppliers, it’s essential for manufacturers to carefully manage these relationships to optimize performance effectively.”

Lustman agrees that additional suppliers may mean additional precautions and work. “When a manufacturer develops a new drug product, they will generally go with the source that meets the right quality, regulatory, pricing and delivery requirements,” he says. “Approving more than one API source requires significant time and manpower; specifications of both/all sources have to match to ensure approval of the drug product by the authorities. Some manufacturers may choose to work with one source for launch and then add a further source later. It is very rare to see more than two API sources being approved for any one drug product. The key is to work with reliable sources, have good relationships with them, give forecasts and confirm POs well in advance of need to ensure a continuous supply chain.”

Narsimhan counters that not having a good supply of materials outweighs the risk and cost of multiple suppliers. “Diversifying suppliers not only mitigates risks but also introduces new perspectives and strategies for achieving efficiency, fostering innovation throughout the supply organization, and promoting sustainable solutions across all business domains. However, it’s essential to allocate business shares appropriately and employ scientific criteria to ensure optimal outcomes from this practice,” he says.

Intermediates, used during API synthesis before the molecule becomes an API, are hygienically formulated using high-grade raw materials (1) and are often used in research and development. Advanced intermediates are advanced forms of drug intermediates used to perform drug interaction activity (1). According to Lawler, the supply of these important materials is tenuous. “Availability of key materials relies heavily on suppliers being able to produce intermediates utilizing a wide variety of, and often complex manufacturing techniques. However, the supply and availability of these may also be limited or restricted due to high manufacturing costs, high raw material costs, availability of materials, environmental concerns and/or restrictions, and on geo-political factors,” he says.

According to Lee Karras, CEO, Noramco Group, “there is a gap in high-quality, domestically supplied advanced intermediates—most come from India and China. These advanced intermediates still require significant regulatory oversight, and in many cases, are regulated similarly to final raw materials/APIs.”

“The supply chain for advanced intermediates is fraught with challenges that tend to affect its resilience. The intricacies of synthesis, rigorous regulatory and quality control requirements, and the ever-changing dynamics of the global market and cost pressures brought about by competition are among the factors that pose hurdles in the supply chain for advanced intermediates used in API synthesis,” says Narsimhan. “To address these concerns and establish a robust supply chain, stakeholders often implement strategic sourcing strategy that focusses on continually generating options for diversifying/derisking the supplier base; [adopting] risk management practices to address supply risks; and relentlessly [monitoring] supply market signals. Additionally, collaboration among industry participants, regulatory bodies, and research institutions plays a crucial role in overcoming challenges and bolstering resilience in the supply of advanced intermediates.”

“There is a change in the market regarding advanced intermediates,” asserts Lustman. “Traditionally, starting intermediates and advanced intermediates were sourced from China. The Indian manufacturers understand that this may lead to supply chain issues with an overreliance on Chinese manufacturers of raw materials. Many Indian API manufacturers are now backward integrating their process so that they can start production of API from the early starting materials. This [integration] ensures a stable supply of needed advanced intermediates and better control over costs.”

Onshoring versus foreign supply is a debate that extends across many industries. The critical nature of patients in need of safe and effective medicines adds to the complicated conversation. Drug manufacturers have a variety of quality, regulatory, and cost considerations to evaluate. Ensuring a quality product means performing risk management and qualification of the materials used in drug products.

Narsimhan points out that countries have taken steps to stabilize the supply chain and there has been a move toward onshoring. “This [move] involves decreasing our dependency on certain international suppliers and establishing our own local supply lines. I’ve personally witnessed companies placing greater importance on strengthening partnerships with local suppliers. This strategic shift aims to reduce our reliance on unpredictable supply sources, resulting in a shorter supply chain, increased resilience, lower transportation costs, and ensuring a more secure and reliable provision of critical materials,” he says.

According to Lustman, there is a shift in industry away from suppliers located in China to those located in India and Europe, which has been driven by geopolitical and quality factors. “A US bill has recently branded certain Chinese biotechnology companies as security threats. The bill is a threat not just to a few specific companies in China, but also to the wider pharmaceutical industry based there,” he states. “With increased FDA inspections of foreign manufacturing facilities, we are seeing more scrutiny on the quality of APIs being shipped to the USA. To help ensure quality and reliability of API production, many drug product manufacturers are reassessing the sources of product they are purchasing from, with a move to Europe and India from China.”

“The increasing tensions around the China-Taiwan situation, as well as recent developments with respect to the [United States] and the use of Chinese CDMOs [contract development and manufacturing organizations] has led to changes in sourcing strategy for many big companies, with many now employing a ‘China +1’ approach, whereby at least one of the material suppliers has to be non-Chinese,” adds Robinson. “This has led to an increased preference for providers in other low-cost economies such as India, and in some cases the re-shoring of projects to Europe and the US. A requirement for manufacturing partners to similarly be ‘China independent’ in respect of their own supply chains is becoming an important factor in the selection of vendors, to ensure robust, secure provision of materials.”

So, should manufactures choose a supplier close to home? “For security of supply chain and risk mitigation, where possible, most companies look to have multiple sources of raw materials and advanced intermediates. It is always preferable to have reliable suppliers which are either based domestically, local, or both, and many companies now favor full or nearly full back integration for key intermediate supply especially for high value APIs and those under patent protection,” specifies Lawler.

“I fully expect that drug shortages will continue to be the norm and actually get worse, without a real commitment from the US government to ensure more high-quality domestic supply,” warns Karras.

BioSpace. Drug Intermediate Market: Fast Growing Biotechnology and Life Sciences Sectors Is Expected to Drive the Growth. 

When referring to this article, please cite it as Haigney, S. Diversifying the Supply of Raw Materials. 

The final drug product relies on the quality and reliability of the raw materials used in its production.

Diversifying the Supply of Raw Materials 

The PharmTech Group sat down with Himanshu Gadgil, CEO of Enzene 

Continuous Manufacturing and Cost of Goods (BIO 2024)

Continuous manufacture of biopharmaceuticals is a hot topic in the industry. According to Himanshu Gadgil, CEO of Enzene Biosciences, continuous manufacturing has an impact on a company’s cost of goods. “For example, in a 1500-square-foot cleanroom, we can manufacture in a month currently around 10 kilograms of mAbs [monoclonal antibodies], and we are enhancing that platform where we should be able to manufacture on 40 kilograms of mAbs,” Gadgil says. Therefore, he explains, if a company wanted the same productivity at the moment, they would need a huge plant.

This is where continuous manufacturing is truly beneficial, Gadgil continues. “So, one of the biggest advantages of continuous manufacturing is cost of goods, because the operational cost is much lower than the conventional manufacturing, [because] the footprint is more compact, and at the same time, the productivity is also very high,” he says. “Because when you do perfusion, you get significantly higher cell densities almost five to 10 times higher cell densities than the conventional fed batch.”

When building a new continuous manufacturing facility, unit operations should be connected so that the process flows continuously, remarks Gadgil. “So, that whole process connecting is very, very challenging when you're starting out, but once you have the platform set up … the advantage of continuous manufacturing is that the footprint is very small, so you can easily scale out so once you have the platform, it is very easy to put more of the these and also from a geographical perspective,” he summarizes.

Click the video to watch the full interview. Enzene Biosciences will be showcasing its services at the BIO 2024 convention in San Diego, Cali from June 3–6.

Videos

The PharmTech Group sat down with Himanshu Gadgil, CEO of Enzene Biosciences to discuss the benefits and challenges of continuous manufacturing of biopharmaceuticals.

Pharmaceutical Technology® spoke with Parviz Shamlou, senior vice-president of Science and Technology, Abzena

Impact of Biosecure Act on the Pharma Industry (BIO 2024)

As the bio/pharmaceutical industry gets ready for BIO 2024, the PharmTech Group sat down with Parviz Shamlou, senior vice-president of Science and Technology, Abzena, to discuss the impact of the Biosecure Act on the bio/pharmaceutical industry. Shalmou also provided his input on how companies can scale up manufacturing practices and how the use of continuous manufacturing in biopharma is progressing.

“We appreciate that [the Biosecure Act] is an important act designed to protect the health of citizens of this country. And we know we must do everything we can to avoid any unintended, potentially harmful use of our services as highlighted in the act,” says Shamlou. “[We] have put in place a robust contingency plan as well as a CMC [chemistry, manufacturing, and controls] strategy that are designed to mitigate any such risk to supply chain and the development of the assets that our clients bring to us.”

When it comes to continuous manufacturing in biopharmaceutical manufacturing, Shamlou believes the progress made in upstream processing can be made in downstream processing as well. “[In] the next few years, we'll see the introduction of continuous processing into downstream areas. And again, there are technologies out there, but those technologies will grow and will become, I believe, together with additional control strategy, more robust and will be ready for transition into manufacturing.”

View the video above for our full interview with Parviz Shamlou. Abzena is showcasing its services at the BIO 2024 convention in San Diego, Calif., which is being held June 3–6.

Pharmaceutical Technology® spoke with Parviz Shamlou, senior vice-president of Science and Technology, Abzena, about the impact of the Biosecure Act on the bio/pharmaceutical industry, as well as the progress of continuous manufacturing in biopharma.