Susan Haigney

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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. 

Articles

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.

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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.

The PharmTech Group spoke with Stacey Treichler

Sustainability Goals Impacting Biopharma (BIO 2024)

Advanced therapies, such as monoclonal antibodies (mAbs) have transformed the pharma industry, according to Stacey Treichler, senior director of Marketing and Strategy for Purolite at Ecolab. Various other innovations are also making their impact.

“We're seeing the increasing approvals of cell and gene therapies. And that's really exciting, because they're treating rare disease, degenerative disease, other hereditary diseases that were previously untreatable. But even within the antibody space, there has been quite a bit of innovation and disruption. So, we even see newer antibody modalities [such as] antibody fusions, bispecifics, multispecific, and antibody drug conjugates. And what's really exciting about those is they're also addressing unmet needs for things [such as] relapsed refractory cancer and other complex disorders,” Treichler states in an interview with the PharmTech Group prior to the BIO 2024 convention.

When it comes to saving costs, process intensification is allowing manufacturers to make more product with less footprint, according to Treichler. “And that's improving cost of goods for each gram of drug product manufactured. This can be applied across the traditional modalities, but also the more advanced modalities.”

The industry is also being impacted by the push for sustainability in biopharmaceutical development and manufacturing, with companies factoring sustainability into their strategies. “One of the things that we would advise is, don't just think about your own internal operations, but think about the operations of your suppliers, because that's really an extension of your footprint,” says Treichler. “A key area that pharma companies can focus on is water usage. Moving cooling, heating, and treating water across any facility requires energy. And by reducing water usage, companies can lower their energy consumption and greenhouse gas.”

Watch the video for the full interview. Purolite/Ecolab will be showcasing its products and services at the 2024 BIO International Convention in San Diego, Calif., from June 3–6.

The PharmTech Group spoke with Stacey Treichler, senior director of Marketing and Strategy for Purolite at Ecolab, about the impact of advanced therapies, new innovations, and sustainability on the biopharmaceutical industry.

Pharmaceutical Technology spoke with Jeff Clement, PCI

Robotics in Sterile Processing

Using robotics in sterile fill/finish operations provides “hands-off” aseptic manufacturing, says Jeff Clement, executive director of Technical Sales for Development and Manufacturing Group at PCI Pharma Services, in an interview with 

® “Most of the robotic instruments don't even have a glove board. So, there's no human interaction with the equipment, which is great for contamination. You know, one source of contamination for a RABs [restricted access barriers] type of line would be the human operators, and with a robotic manufacturing system that takes that completely out of the equation.”

Companies already performing aseptic fill/finish are doing environmental monitoring and therefore have ISO 5 suites, according to Clement. “But with an isolator technology or a robotic system, which would incorporate isolator technology, basically, you can do that in an ISO 7 suite. So, actually, your classification is a little bit lower, so your environmental monitoring is lower. And basically, you can validate that the lower classification, which could be a quicker way to put in aseptic manufacturing.”

When adding robotic isolator technology to a new facility, modular systems are available that would require supporting services, such as HVAC systems, says Clement, “but with the lower classification required for your operating space for isolator and robotic technology,” he adds. “A lot of times, you can do that a little bit quicker and more economically than perhaps you could in the past [in comparison to] setting up a RAB system in an ISO 5 environment.”

PCI Pharma Services will be showcasing its products and services at the 2024 BIO International Convention in San Diego, Calif., from June 3–6.

Pharmaceutical Technology® spoke with Jeff Clement, executive director of Technical Sales for Development and Manufacturing Group at PCI Pharma Services, about the challenges and benefits of incorporating robotics into aseptic manufacturing.

On May 30, 2024, Enzene Biosciences, a contract development and manufacturing organization (CDMO), announced it is launching its Drug Discovery Division at the BIO 2024 International Convention, happening from June 3–6 in San Diego, Cali. The new division will expand the CDMO’s services to the biotech industry. It will also complement the company’s EnzeneX-equipped biologics manufacturing facility that is expected to open in summer 2024 in New Jersey.

The new division will be located at the company’s Pune, India, facility and have a state-of-the-art discovery laboratory. Services provided will feature end-to-end integrated discovery services, including antibody target validation, discovery, and engineering; reagent production ranging from custom peptides and proteins to advanced modalities such as plasmids; RNA and exosomes; and multi-platforms assays services.

The $50 million New Jersey facility, which was announced in June 2023, is expected to open in July 2024 and will be Enzene’s first site in the United States with a fully connected continuous manufacturing platform, according to the company. Capacity is available for the production of complex proteins with standard modalities via bothChinese hamster ovaryand mammalian cell lines.

“There is a global shortage of biology services, and our clients are increasingly looking to collaborate with us much earlier in the discovery phase to expedite their progress to IND [investigational new drug application] and beyond. We anticipate even greater demand for these services in the coming year as the resurgence in biotech funding leads to more targets entering discovery—with contract R&D empowering them to advance more targets simultaneously. For our big pharma partners, in addition to running the integrated programs, we provide the flexibility to easily outsource non-core activities. In particular, we have seen strong demand for high quality reagents and assay services that play a crucial role across drug discovery and development,” commented Himanshu Gadgil, CEO of Enzene Biosciences, in a company press release (1).

 in June of 2023 by Choose New Jersey, a nonprofit economic development organization for the state of New Jersey.

“The strong relationship between New Jersey and India has gained increasing momentum since we opened the New Jersey India Center to cultivate economic opportunities during our trip to the country in 2019,” said NJ Governor Phil Murphy, in a press release (2). “I am proud to welcome Enzene Biosciences and their expanding global presence to New Jersey’s flourishing life sciences industry. New Jersey’s favorable business environment, skilled workforce, strategic location, supportive ecosystem for growth, and deep cultural ties are why Indian companies thrive in our state.”

In a January 2024 press release (3), Himanshu Gadgil, CEO, Enzene Biosciences, stated, “While the [US] is home to most of the novel molecules that are the principle ingredients in creating many life-saving drugs, most of them have been developed by small biotech firms and start-ups that struggle to find clinical-phase capacity. Recognizing this gap and driven by our fundamental mission of creating access equity across the global healthcare ecosystem, Enzene Inc. has been launched in the US to establish a state-of-the-art manufacturing plant to cater to small and mid-sized biotech companies. We have successfully identified, leased, and set up our first manufacturing facility in the [US] in record time. We remain confident that our proprietary EnzeneX technology platform and proven track record in achieving cost-effective biologics manufacturing will see us emerge as a partner of choice for biotech companies as we support them in bringing promising molecules to market.”

Enzene Biosciences. Enzene Launches Discovery Services Division at BIO 2024. Press Release. May 30, 2024.

Choose New Jersey. Enzene Biosciences Expanding to New Jersey with $50M Investment in Bio Manufacturing Plant. Press Release. June 15, 2023. https://www.pharmtech.com/view/enzene-biosciences-invests-50-million-into-new-jersey-biomanufacturing-facility https://www.choosenj.com/news/enzene-expanding-to-new-jersey/

Enzene Biosciences. Enzene Biosciences Launches Its First Manufacturing Base in the US. Press Release. Jan. 8, 2024.

The company’s new division will provide end-to-end integrated discovery services.