Challenges, Sustainability, and Big Trends in Outsourcing Today

Drug Solutions

Understanding is crucial to ensure the right balance in manufacturing technologies and proccesses is achieved.

Balancing Change and Certainty in Manufacturing

Obstacles remain before broader application of intensified processes can be implemented.

Formulating Drugs for Continuous Processing

Limitations in production platforms have impeded continuous manufacturing for advanced therapies.

Small Footprint Automated Closed Production Platforms

Considering the differences between small- and large-molecule drug products can help determine analytical testing methods for E&L.

Considerations for Analytical Testing for E&L

Fundamental Constriction Points in Emerging Therapies

Drug Digest

Chris Spivey is the editorial director of 

Chris Spivey, editorial director, speaks with Sean Hart, CEO and SCO of LumaCyte, on the topic of rapid accurate mRNA potency assay possibilities. 

Videos

Sean Hart, CEO and SCO of LumaCyte, discusses rapid accurate mRNA potency assay possibilities.

Discussing Rapid Accurate mRNA Potency Assay Possibilities with Sean Hart

Myrna Wilson, director, Global Marketing, Strategic Growth and Technical Sales, Pharmaceutical Ingredients, Univar Solutions, spoke with Grant Playter, associate editor, to discuss the state of the pharmaceutical ingredients industry shortly after this year's DCAT Week. Topics of discussion include the state of the biopharma supply chain, movements in the patent industry, and more.

Broadly speaking, can you give me your perspective on the state of the ingredients industry? Would you characterize it as in a state of flux? How can companies look to strategically maneuver in this space?

: As the world economy continues to recover and evolve post-pandemic and with geopolitical tensions, the ingredients industry is not immune from the impacts of those financial conditions.

As with most industries, the ingredients industry is constantly in a state of flux as it must continuously respond to global supply chain challenges, and – specifically as it pertains to pharmaceuticals – the need for drug manufacturers to continuously improve the medicinal efficacy of their offerings. Also, the increased focus on environmental, social, and governance factors means the ingredients industry will have to evolve to ensure it is either working on how to manufacture its product offerings with environmental footprint considerations or consider alternatives to its current lines that can address those requirements.

Strategic maneuvering all depends on the long-term strategy of each company. However, there are a few elements that should remain at the forefront of a strategy in this industry. For Univar Solutions’ pharmaceutical ingredients team, it means that as we position ourselves to respond to external dynamics, we always consider quality, security of supply, traceability, and documentation of adherence to quality and regulatory standards. If we keep those in the forefront of our planning, we are sticking to the core of what our customers need from us.

We recently passed the three-year mark of the COVID-19 emergency declaration (March 2020 in the U.S.) but many are still talking about its impact on the supply chain. What is your perspective on these alterations? Do you think the just-in-time model may return in full force at some point, or will efforts like onshoring stick around in the long-term?

: COVID-19 pushed the industry to respond faster and to become more efficient than ever before. It also highlighted supply chain pinch points and forced the entire pharmaceutical industry, and far beyond, to make swift moves to sustain the pressure. While I don’t think our industry has completely recovered from the many supply chain constraints we were presented with, businesses up and down the chain are making changes to their core infrastructure to better position themselves in the long-term.

Shortages that have gone unresolved over extended periods of time have caused the industry to either create or adapt to new supply sources or alter their existing supply chain paths. These sorts of adjustments are often both costly and time consuming, making it unlikely that entities would work to undo new paths created. Additionally, many may have found secondary benefits with these alternative paths, such as improved sustainability outcomes and supply chain optimization.

Also, there has been a push by government entities around the world to onshore their internal access to secure the health of their citizens, even offering incentives to build infrastructure within their borders. Again, the cost to make these moves is significant. Once those investments are made, it would be difficult and costly on a variety of fronts to undo them.

What are some recent technological innovations in your space? Can you illuminate them for our audience?

: Univar Solutions prides itself on the fact that we have a global network of pharmaceutical laboratories within our solution centers which serve as pharmaceutical application and formulation laboratories to help support the road to innovation and reformulation for our customers and suppliers. Because Univar Solutions sits at such a key intersection in the supply chain with science and technology, we strive to be a true solutions partner delivering benefits far beyond logistics for our customers and suppliers. Distributing the chemical or ingredient is only the bare minimum.

In terms of innovations based on trends in the pharmaceutical space, there has been a significant shift toward creating more palatable drugs and taste-making active pharmaceutical ingredients (APIs). Due to the influence of Generation Z on the drug market, today there is increased focus on not just the efficacy of a drug, but on its taste and ease of consumption.

As an example, drug manufacturers now can create products specifically engineered to deliver two APIs that are unstable when combined with one another. These duo-capsules are game-changers for drug manufacturers and consumers alike, while also delivering significant benefits in sustainability.

Patents are in a bit of an interesting space at the moment, particularly in the United States. The Inflation Reduction Act was signed into law last year, which introduced new price controls and changed how certain drug exclusivities work. Meanwhile, broad genus clauses recently faced challenges at the Supreme Court level in the Amgen vs. Sanofi case, which could have upended how patents are handled in the biopharma space. Can you talk a bit about how the patent industry is preparing for these significant changes?

: The pharmaceutical industry is facing a big patent cliff. It’s creating urgency among manufacturers in the generics space in the race to get their Abbreviated New Drug Applications (ANDAs) in place so that they can enter the market with their generic. Simultaneously, large pharmaceutical companies who may have held back research and development projects so as not to cannibalize their current product offering in the market may be releasing the follow-up much faster than planned.

Between patent battles, competing offerings, the likelihood of success through the trial process, and the massive cost to take a drug from clinical trials to commercialization, the pipeline of projects should be constantly refilled. It would also seem prudent for drug manufacturers to weigh the commercial viability of their projects by ensuring that their recipes consider cost and security of supply of any materials built into the formulation in earlier trial phases.

As a distributor, it’s a partnership that we aim to offer our customers. It is critical that sourcing and cost implications be part of the planning as production needs to scale up. If a manufacturer partners early with us, we can source, provide secondary sources, and design efficient supply chains that consider quality and security of supply from small quantities to commercial consumption.

Do you have any bold predictions for where the biopharma industry will be ten years from now?

: The rate that technological developments accelerate in any space is increasingly exponential, and the life sciences industry is changing and evolving at an amazing pace. A 10-year prediction would be truly hypothetical based on where research and development are currently focused. Personalized medicine developed based on each person’s body could be leaps and bounds from where it is now. The biopharma industry already has a promising pipeline of therapies being evaluated for cancer treatment and rare diseases. Hopefully, the brilliant minds working on the next wave of projects will work to eradicate some of these rare diseases and begin finding cures for even the deadliest of cancers.

Idealistically in 10 years, targeted gene therapy can be used for everything, not just limited to rare diseases or those that scientists know the molecular pathways for. This could result in sought-after cures, with little to no side effects. The intensity around curative therapies for chronic conditions along with advances in early detection technology could reduce the need for medications considered to be lifelong medications.

An increasingly aging population with a longer average lifespan could also provide a new source of challenges for the biopharma industry, as scientists look for a way for to keep the population living with relatively good health and mobility into their 90’s and 100’s. Finally, 10 years from now, with that aging population and the continued push to make health care more affordable for everyone, we could see big movements to somehow make these sizable developments more accessible.

Articles

Myrna Wilson, director, Global Marketing, Strategic Growth and Technical Sales, Pharmaceutical Ingredients, Univar Solutions, discusses the state of the biopharma supply chain, movements in the patent industry, and more.

Investigating the Pharmaceutical Ingredients Industry with Myrna Wilson (DCAT Week 2023)

Jill Wechsler is Pharmaceutical Technology's Washington Editor, jillwechsler7@gmail.com.

Recent challenges to certain controversial approval decisions have prompted FDA officials to reexamine of the role and composition of the agency’s many advisory committees and to explore options for change. With more than 50 panels composed of academics, scientists, and various interested parties, the program has become overly complex and sometimes contentious, with some up-or-down votes on important approval decisions appearing at odds with ultimate decisions by agency reviewers.

Commissioner Robert Califf has been calling for changes to improve the operations and composition of its advisory panels for several months. In a 

 on May 17, 2023, at the annual meeting of the Food and Drug Law Institute (FDLI) in Washington, D.C., Califf emphasized the need for the agency to strengthen committee structure and methods to be “more efficient, flexible, and effective in the exercise of our regulatory responsibilities".He noted the value of interchange among FDA experts and those outside the agency, particularly on complex scientific issues, and that transparent discussion is important. But he also said that the advisory committee system “can be improved” to enable FDA scientists to “get the best advice possible.”

Similarly, Patrizia Cavazzoni, director of the Center for Drug Evaluation and Research (CDER), cited plans at the FDLI meeting for advisory committee “modernization” among numerous key initiatives for her office in the coming months. The process will include efforts to refine the selection of advisors so that their “expertise applies precisely to the matters under consideration.” That may involve adding to advisory panels more temporary members with special knowledge about the drug or disease under discussion and taking steps to ensure diversity in geographic areas represented.

Cavazzoni also noted the need for FDA to improve how it communicates about advisory committee operations and their relationship to the agency. This involves emphasizing to the public that these panels play an advisory role to the agency—and that FDA retains ultimate decision-making authority.

FDA’s interest in updating advisory committee composition and operations has become more visible in recent months, stemming from the uproar that resulted when FDA granted accelerated approval in 2021 to Biogen’s Alzheimer’s treatment, Aducanumab, despite a near-unanimous vote against approval at an advisory meeting in November 2020. Three panel members resigned in protest, and Medicare limited coverage to those patients participating in ongoing clinical trials.

That controversy, and subsequent heated debates over the approval of other treatments for critical diseases with questionable efficacy data, has prompted FDA officials to reconsider the advisory committee process, including the composition of the panels and the issues identified for discussion. A main change would be to shift away from “gladiator votes”—yes-or-no decisions on specific applications—and to provide more nuanced opinions on the main issues. But in some cases, the absence of up-or-down votes on key questions may generate confusion as to what the committee experts actually recommend. In the recent consideration of Sarepta’s new gene therapy to treat Duchenne’s muscular dystrophy, the advisory committee supported approval by a very slim margin. However, the patient advocate on the panel made a strong case for FDA to approve the drug as another treatment option for this devastating condition. FDA staff has gone back to the drawing boards, indicating it may limit treatment to a very young age group pending further clinical results.

Interchange among outside experts on scientific and technologic questions is important, Califf emphasized at the FDLI meeting. Such debate “makes our decisions better,” he noted, and “adds a level of transparency.” However, the commissioner also raised concerns about the steady stream of “misinformation and disinformation” in society that can undermine public confidence in science and “weaken faith in governmental and other institutions, including the FDA.”

Public debate among expert advisors can both support sometimes controversial decisions by FDA staffers, but also raise challenges to agency actions. The advisory committee process is one element in this ongoing debate that appears open to improvement, and Califf advised the regulatory community to “stay tuned for developments in this area.”

Jill Wechsler is Washington reporter for 

Challenges to approval decisions have prompted FDA officials to reexamine of the role and composition of the agency’s many advisory committees and to explore options for change.

FDA Eyes Advisory Committee Reform to Enhance Credibility

Astellas Pharma announced on May 25, 2023 that Astellas B.V., Astellas Pharma Europe B.V., and Astellas’ subsidiaries in the Netherlands have decided to sell and transfer the manufacturing plant located in Meppel to Delpharm Industries. This agreement is intended to be executed and see the impact of any financial transfers by the fiscal year ending March 31, 2024.

Astellas hopes to continue to strengthen its capabilities in the technology and manufacturing sector, and it hopes to partner with Delpharm for promoting a more stable supply of high-quality medicines, according to the company press release. Under the agreement, Delpharm will continue to manufacture the products that are currently manufactured at the Meppel plant, with these products being delivered to the Astellas group. Further, employees from Astellas will also transfer to Delpharm.

This agreement is intended to be executed and see the impact of any financial transfers by the fiscal year ending March 31, 2024.

Astellas Pharma to Transfer Manufacturing Plant, Business to Delpharm 

Feliza Mirasol is the science editor for 

FDA announced on May 19, 2023 that it granted approval to Krystal Biotech, a US-based biotechnology company focused on genetic medicines for rare diseases, for the company’s product, Vyjuvek (beremagene geperpavec-svdt), a herpes-simplex virus type 1 (HSV-1) vector-based gene therapy. The indication is for treating wounds in patients six months of age and older who have dystrophic epidermolysis bullosa (DEB) with mutation(s) in the collagen type VII alpha 1 chain (COL7A1) gene. According to an agency press release, Vyjuvek is the first topical gene therapy approved for this indication.

DEB is a genetic disorder affecting the connective tissue in the skin and nails. It is caused by mutation(s) in the COL7A1 gene, which encodes type VII collagen (COL7), an essential protein that helps strengthen and stabilize the outer and middle layers of the skin, according to the agency’s press release. A COL7A1 deficiency leads to separation of skin layers, which causes painful and debilitating blisters and wounds. The disorder usually shows at birth and is divided into two major types depending on the inheritance pattern: recessive dystrophic epidermolysis bullosa (RDEB) and dominant dystrophic epidermolysis bullosa (DDEB).

Symptoms can vary. Individuals with DDEB typically experience mild cases; blistering primarily affects the hands, feet, knees, and elbows. In comparison, RDEB cases can be painful and debilitating, and often involves widespread blistering that can lead to vision loss, disfigurement, and other serious medical complications that can be fatal, according to the FDA press release.

Vyjuvek is a genetically modified herpes-simplex virus that is used to deliver normal copies of the COL7A1 gene to the wounds, which then helps to hold the layers of skin together, maintaining the integrity of the skin. The FDA release reports that Vyjuvek has also been modified such that it cannot replicate in normal cells. According to clinical study results, 65% of Vyjuvek-treated wounds completely closed compared to only 26% complete-wound-closure in placebo-treated subjects.

“Vyjuvek is the first FDA-approved gene therapy treatment for DEB, a rare and serious genetic skin disorder,” said Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, in the release. “Today’s action demonstrates [FDA]’s ongoing commitment to supporting the development and evaluation of new treatments that address unmet needs for rare diseases or conditions.”

FDA has approved the first topical gene therapy product for treating wounds in patients with dystrophic epidermolysis bullosa.

FDA Approves Topical Gene Therapy for Treating Wounds Associated with Rare Genetic Skin Disorder

AbbVie announced on May 19, 2023 that FDA has approved EPKINLY (epcoritamab-bysp), a T-cell engaging bispecific antibody for treating relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). The bispecific is particularly indicated for treating adult patients with R/R DLBCL, not otherwise specified, including DLBCL arising from indolent lymphoma and high-grade B–cell lymphoma (HGBL). Administration of the bispecific is intended for patients who have already had two or more lines of systemic therapies.

According to a company press release, DLBCL patients are typically treated with chemoimmunotherapy-based regimens, but several targeted therapies, including T-cell mediated treatments, have recently emerged for R/R patients. A single agent and ready-available or off-the-shelf treatment options, however, remain limited.

"DLBCL is an aggressive cancer type that can rapidly progress and resist treatment. The FDA approval of EPKINLY represents a new treatment mechanism of action for third-line DLBCL patients,” said Thomas Hudson, senior vice-president, research and development, chief scientific officer, AbbVie, in the press release. “As a non-chemotherapy, single-agent treatment for DLBCL patients, we hope that [epcoritamab-bysp] can effectively treat this aggressive cancer type and can be used for patient care quickly and in an off the shelf form for physicians."

"Patients with DLBCL who relapse or are refractory to currently available therapies have limited options. Generally, the prognosis for these patients is poor and management of this aggressive disease can be challenging," said Tycel Phillips, City of Hope associate professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, in the release. "Epcoritamab is a subcutaneous bispecific antibody that offers an additional treatment option for this patient population. With this approval, patients who are in need of additional therapy may have the opportunity to receive epcoritamab after failure to respond or relapse after two or more systemic therapies."

AbbVie co-developed epcoritamab-bysp with partner Genmab as part of an oncology collaboration between the companies.

FDA has approved AbbVie’s EPKINLY (epcoritamab-bysp), a bispecific antibody for treating relapsed or refractory diffuse large B-cell lymphoma.

FDA Approves AbbVie’s Bispecific Antibody for Treating Lymphoma

Andrea Lodetti, CEO of Bormioli Pharma, an Italian pharma primary packaging manufacturer, spoke with Grant Playter, associate editor, at this year's DCAT week. Topics of discussion include the company's approach to the US market, supply chain instabilities, sustainability, and more. A full transcript can be found below.

One of the big headlines Bormioli is coming into DCAT with is its 40% increase in North America sales year over year. Can you discuss some of the reasons behind the strong increase in terms of new strategy, certain investments, market forces, et cetera?

: Thank you for the question. I would say it's not the new strategy, we started the approach to the US market back in 2019 when we set up our commercial entity. The timing to get things done in pharma is quite long so you have to invest, especially in time, with money. And so what we did we started our commercial activities and our interaction with customer, showing them what were the benefits from our product, how good we were performing. Also, in some places of the same global pharma company in Europe, we're saying, "Hey, we serve this plant in Europe, why can’t we also serve your plant in the US." So, it all came with the longer work.

Of course, there were a couple of things in the last three years that made things a little bit not so easy as in the past. But we did work a lot in that; we set up our logistic platform here in the US, we have a very well-streamlined supply chain from Europe to US, especially for molded glass. And that is making us more and more credible, and customers that start working with us have immediately increased their volumes and ask, "Okay, you can do more?" And this is why we now are benefiting from this acceleration that is overall in the market, because after COVID, after the crisis we saw in the Russia and Ukraine war, all the pharma companies are nearshoring their supply chain a little bit more than in the past. I would say pharma has been always a risk adverse sector, but in terms of organizing its global supply chain, it was more looking for efficiency, cost efficiency, rather than risk protection.

And what happened during COVID, and also in the in the last 12 months, everybody realized that you cannot afford any more to have your things supply there from the other part of the world. You can do it, but then when things become difficult, then you're immediately in trouble. So we're trying to follow up with this. So I think we will also invest a little bit more in US now and get possibly also an industrial footprint on site. But again, this is a long, long activity that is now paying back and we're quite happy about that. I think there's more to come later on.

You touched on this a little bit. But regarding the extended half-life of the COVID-19, disrupted the supply chain, do you think this basically spells the end for the just-in-time supply model? Or do you think we're going to look towards more onshoring production or whatnot?

: I mentioned the nearshoring or reshoring of some of the activity. I'm not saying that this is the end of the just-in-time, but definitely has to be redesigned along different concepts. I would say that, for instance, for glass production it was never a just-in-time because normally pharma companies they do buy at the very beginning of the year of what they need, and then they use it all over the year. So, it was never like a pure made to order.

But anyway, as I said before, what is now important is to make sure that you have a backup plan for any of the possible risk of disruption that you are facing. This is staying, because it's not like COVID-19 is now over — no, this is staying. It has hit us strong, and also following it up with the macro-economic crisis that we are living nowadays, it really has made everybody rethink that things are not that easy as we thought before. And we have to be sure that things are working perfectly, because in our segment in our industry we have a social responsibility. I mean, if people is left without health care, it is a big issue. And the risk was there during COVID-19 and I can tell you, we had a number of customers scared to death that suppliers were not able to provide the continuous API or whatever. And this lesson is being learned quite well.

So our audience is largely composed of biopharma industry members, but they might not know this between molded and tubular glass. Can you just talk a little bit about this in the biopharma context?

: It's a different process, because molded glass is a process that we dominate from the beginning to the end, where you really start from raw material like sand cullet and you come out with the finished container afterwards. With a little bit of different technology, but basically what you do is you melt all of these stuff in a 1600 degrees container and after that, you pull out a small portion of melted material that is then formed into different processes. And that is normally used for container that go from 30 ml up, so with the bottles.

When you go down, you move towards the vials, then you have the converting a glass, tubular converting technology that comes in. This is a technology you start from a pipe of glass that is made only by four companies in the world: Nipro, Schott, Corning. Three companies, actually, the good ones. And you buy these pipes, and then they run a cutting, heating, and forming process afterwards.

So, what is the benefit? The benefit is that you come out with a smaller container, because with the mold, you can go down to a limited capacity. And then, if you do things properly, the container is lighter, is less heavy, and has a better aesthetic look.

However, there are things that are good for the tubular technology, things that are much better with the molded technology, so it's always a trade off around capacity application and mechanical characteristics that you want. We demonstrated with a dedicated activity, as we mastered both technologies, that there is a huge, on some properties, you can really choose depending on the size and the aesthetic of the vial, but there are things for which molded is much better than tubular; for instance, stability over time, internal uniformity of the chemical aspect inside of the container, and also molded glass has not the issue of delamination, which is an issue that affects the tubular vials.

So, I would say different technologies, different processes, Bormioli can master both of them. We can also provide consulting to small companies, you mentioned the biotech; of course, these are company that totally focused on the drug, on the content. We are good at designing and developing their containers. So whenever we see that whenever we work together in the development phase, things are coming out much, much better.

Talk to me about the 50-in-5 program. Just, what are its goals, how you went about this, because everyone wants talk to me about sustainability. It's the new hot topic at DCAT this week.

: But we need to discriminate from greenwashing and real sustainability. Today, everybody's talking about that.

I watched this segment the other day talking about carbon offsetting. How a lot of companies who are carbon offsetting aren't really actually doing that.

: I want to be carbon-free. Okay, then there's a lot of work to do. And we came with this project that we call the 50-in-5, because when we launched, that was like two years ago, we said, "In five years, we want to get at least 50% of our raw material coming from recycling or sustainable sources by 2025." This means for molded glass to work a lot around the loop of collecting the cullet and using it back into the furnace.

And we are quite advanced with that on the plastic side, in the means to use any type of recycled material that comes from all sorts of industries and use it and convince customer that this can be used and has the same properties as the building material. We are on track for that; we have reached 39% in 2022. And we think we can get up to 50% in 2025. Also, because many of our customers are now in the rush of achieving a sustainable result. So, that will add quite a lot.

The last bit would be a little bit more help from regulatory bodies, that they have to allow a wider usage of recycled material. For instance, nowadays, there is a minor portion of whatever is used in hospital that you can put back into the recycling loop. So, we are also working on that, trying to make activities that basically demonstrate that you can collect material from the hospital with no harm for the people and put it back into the recycling loop.

Can you talk about that a little more in detail? Like say I have a vial and I put like, say COVID vaccine in it, and I use it and how would I go about recycling that while maintaining absolute sterility? Because that is what you need for things are going to be reused.

: So in order to ensure sterility, there's only one way, that is heating. And if you think that in the end of the cullet goes into a furnace at 1600 degrees, you are sure that whatever enters there, doesn't come out. Not alive, at least. So the real issue is the collection from the hospital up to the place where you fragmented it and then to the melting furnace. This is the area in which we have to work.

So our idea is that there is a first step of, I would say, sterilization or cleaning that can happen at the hospital level. So the hospital with a, not a huge facility, like imagine a container that is heated at a certain temperature can ensure that what gets in there is then free of virus, of contamination, and so on. And after that, the whole recycling loop is already defined for water, for food. And so just this step that has to be handled, because unfortunately, today, whatever goes into the hospital then goes to the burn on-site. And then that's not good for being sustainable.

We're in a weird state with the greater global economy. There's obviously a lot of geopolitical events going on in Europe at the moment and we also have the SVP collapse affecting the global market 

 Dow Jones is down, that sort of thing. So can you give me your perspective on how this is going to impact the biopharma space?

: For the pharma environment? This is an industry that requires a lot of investment, a lot of capital, a lot of money, but is pretty much backed up also by healthcare institution — it is a very much protected system. So it's difficult to make very, very, very wrong financial disasters like it is in some other industry. So, you don't have so many startups that are happening and needing a lot of money like in the high tech business, so, I do not expect any of the pharma player to be [affected] so much. There is only so much contagion that can get into our industry.

But on the other side, we have to be aware that not all the financial sources are any more as reliable as we thought in the past. And this is something that I think in our space is less affecting the business than in other space. We must be more aware of what is happening in the public healthcare system. That is really driving the performance of the pharma chain. If broad initiatives are taken by government in this space that you haven't, you are affected in the industry.

However, what is good, if we have to find something good about COVID-19, is that it has brought back into the agenda of the government and public institution. How important is it to ensure a solid and reliable healthcare system for these events that we understood, that can happen at any time, and they are quite fast in spreading around. And so I am confident that our industry will not be affected that much by this crisis.

And about the crisis in Europe, ongoing in Europe, unfortunately, this is very bad. But both Russia and Ukraine are not such a big player of the pharma industry. What I can see there is that, of course, there is a drawback in terms of reliance of government into each other, but not really a disruption that is relevant for our business.

Very fair take. It's an inelastic demand for this. The only concerns I really think people are highlighting are like with the startups, because investors might be a bit skittish for high-risk, high-reward startups, specifically in the biopharma space, but on the supplier end, which is where you're coming from, I don't think you're going to see much change.

: No, no. In this space, where we are coming from we don't see things much affected. The R&D investment will stay, we are keep on investing into that space. So at least for packaging industry, I don’t see that as a big issue.

I'm asking everyone this question, going to ask you it as well. You have any bold takes about the biopharma industry? Where are we going to be five years from now? Ten years from now?

: I like the space, is very much interesting, and is going to be supported a lot by the advance in other areas, like artificial intelligence, or high-speed computing — everything that is, you know, growing in the high tech environment, is bringing to biotech a lift. And this is where we have to go, right?

If, when we talk about personalized application, or very specific drugs for the so-called orphan disease, I mean, there is where we have to go. I mean, the standard was a classical pharma industry, works a lot on chemicals, on things that are good for everybody, don't care that much about the drawbacks effect, because what you are curing is the main thing. With biotech, you can go into really the DNA of people and try to assist it and to come fix it, if there is anything wrong. We saw it in the vaccine, which are the vaccines that work very well, they were the one that acting on the mRNA, rather than the one acting on the death virus and creating the antibody and so on. So that's the future.

And probably, we will see more and more big pharma companies acquiring small, high-performing biotech. So we'll have this increase in this kind of network of different developing hubs that when they get to a point where thing is found, then it is acquired by Big Pharma. So I see Big Pharma going into more being the hub that acquires whatever is developed by single companies, and going out more and more from the bottling and taking care of the distribution is not their topic. So that is where, what I think. Recently I have seen, I think Pfizer made-

: Wow. Credit Suisse was just acquired by three million from UBS, three million for a bank. And yeah, 53 billion is more. But if you think about it, if you get things done in that space, you're good forever.

One other question, before we get to final thoughts. I was just curious. If you would give one piece of advice when talking with biopharma companies who are making decisions about their packaging choices 

: This would be advice for everybody. Remember, people that use your drug will now be people with the disease, will be people maybe needing support from other people to get the medication. So the packaging cannot be like, I buy a vial that is there since many years and I just use it. No. Remember, people will have to use it in a time where it's not in good shape, where he would have limitation possibly in what he can do, or she can do, would have maybe cognitive limitation. So it will be difficult.

So remember, remember, remember, there is a patient at the end. There is a patient at the end. So of course you are saving his life, he's happy, he will take whatever, do whatever to get this drug. But if you can make his life or her life a little bit easier, then you've done a good thing. So I mean, I see treatments that go in drops for blind people. I mean, how a blind, but they're very good, so they can maybe hear it and, but why don't you make something that they can use it? Or a lot of drugs that are used for people that gets amputations that you need two hands to open? I mean, why do you do that? It's something that you have to take care of.

: Accessibility is a very important thing. Plus, nowadays, also self-medication is increasing. And COVID has made a huge step forward in that because people was not able to go to the hospital or to the doctor. So self-medication is important. But of course, the more that you allow people to self-medicate, and the more you have to have the packaging that helps them in the adherence to the administration of the drug. Because if they do wrong things, then they don't get good treatment.

I'm aware we're low on time, but do you have a concrete example of how you can make like glassware accessible?

: Glassware, more accessible? I mean, the total packaging you have to look into to make it more accessible. I may give you an example.

We are selling quite a lot of oral liquid application, especially for the antipyretics for children. Small children, when they are on fever, they cry. And you have to feed them with the oral liquid. So the standard application is a bottle with a syringe to have this, open the bottle, put the syringe, then make the right sizing, and then put it in the mouth of the baby, and then having him sucking it.

So we made this ethnographic with some moms. You see, you have to be, all of this operation. You have to check it and then put it in. And we did it, and we were explaining this to some mothers, you have to do this, very simple, easy, and they say it's very easy, but you have a baby, you're holding a baby that is crying. And you know, you cannot put them in, so how do you do it?

So we came up with this other solution, where we have put a kind of dosing system on top of the bottle and is like, I don't know if we have a sample here. But basically, what you have to do is just turn the bottle around with an end, push on the container, here you have the indication on where the content that you have applying goes, then you turn it up, you open it, and then there is this kind of biberon, like kind of bottle for babies, shape, and then you feed it like this, so you want it, you just put it there and do this, instead of doing this. But also from the look, you see this is very, you know, hospital things. The syringe, the thing-

If I'm a little kid and I see that, I'm running.

: You're scared already. You say, "What is happening?" Whereas if you see like a normal bottle, you just push it and you get it done. And then you feed your baby. I think that is one solution that can help.

Fantastic. Do you have any final thoughts you'd like to share with our audience?

: I will touch most of the things regarding today, is very much keen in the making health a positive practice available to everybody and kind to the planet. And in this sentence there is all what I spoke about.

Andrea Lodetti, CEO of Bormioli Pharma, an Italian pharma primary packaging manufacturer, speaks about his company's approach to the US market, supply chain instabilities, sustainability, and more.

Unpacking the Pharma Packaging Market with Andrea Lodetti (DCAT Week 2023)

Contract research organization (CRO) services are continuing to grow at an immense pace, driven in part by rapidly evolving technologies used in drug discovery and development. According to market research, the CRO services sector is forecast to be worth $127.3 billion by 2028, representing a double digit (10.7%) compound annual growth rate (1).

As the bio/pharma industry gravitates towards more complex clinical pipelines, outsourcing has been a necessity for many as it can control costs/minimize internal staff and resources, for example, in addition to getting products out in the most efficient way (1,2). An area that is not highlighted as much in industry commentary is the early phase development of outsourcing and what needs to be improved to remain in line with the fast pace of change happening within this industry.

 has been a partner at FinnBrit Consulting since 2007, providing consulting and advisory services in formulation and process design, development and scale up, and in aspects of excipients. Prior to FinnBrit Consulting, he spent approximately 35 years working mainly as a formulation scientist in large and small innovator companies, and in generic companies in the United Kingdom, Sweden, Canada and the United States. Dr. Moreton has worked on formulation development projects for tablets, hard gel capsules, soft gel capsules, oral liquids, parenteral solutions, creams, ointments, transdermal delivery, pessaries and suppositories. He has also worked in Technical Service, QA, QC and Regulatory Affairs for an excipient and drug delivery company. Dr. Moreton is a visiting tutor at the Manchester University (UK) on their Pharmaceutical Industry Advanced Training (PIAT) distance learning program covering Units on Oral Solid Dosage Forms, and Liquid and Semi-solid Dosage Forms. Dr Moreton holds a B.Pharm. (Nottingham University, UK), a M.Sc. in Pharmaceutical Analysis (University of Strathclyde, UK) and a Ph.D. in Pharmaceutics (University of Wales, College of Cardiff; now Cardiff University, UK).

 has been with Vetter since the early 1990s serving in various functions throughout the globally operating CDMO. Her roles have included customer service, supply chain and key account management. Fürst has supported multinational big-pharma companies at Vetter since 2001, bringing her background in economics to the forefront of her work. Beginning in 2011, Fürst began leading the Key Account Management Europe Team, incorporating additional global matrix functions like Demand Management and Pharmaceutical/Technical Alliance Management to her repertoire. Fürst began her career working in the electronics industry.

This episode of Drug Digest is sponsored by:

Drug Digest is a tech talk video series with the 

 editors, who interview industry experts to discuss the emerging opportunities, obstacles, and advances in the pharmaceutical and biopharmaceutical industry for the research, development, formulation, analysis, upstream and downstream processing, manufacturing, supply chain, and packaging of drug products.

In this episode of Drug Digest, Pharmaceutical Technology editors discuss what happens in early phase development, the role of CDMOs, and highlight the benefits and challenges of the outsourcing process. 

Drug Digest: Early Phase Development and CDMOs in the Outsourcing Landscape

TriLink BioTechnologies announced the expansion of its messenger RNA (mRNA) manufacturing capabilities on May 24, 2023. The new construction of the current good manufacturing practice (CGMP)-grade facility will help the company with its mission to advance the field as more mRNA-based therapeutics and vaccines enter later-stage clinical trials, according to the company press release.

Further, the new CGMP facility is expected to contribute to the development of mRNA therapeutics, with a building designed for the CGMP manufacture of mRNA-based 

 gene editing, gene-edited cell therapies, protein replacement therapies, cancer vaccines, and infectious disease vaccines.

“The expansion of our CGMP mRNA manufacturing capabilities marks a major milestone for TriLink and our partners,” said Becky Buzzeo, chief commercial officer at Maravai LifeSciences, in a press release. “Drug developers will soon be able to leverage our team’s 25-plus years of industry expertise, helping to take critical therapeutics from concept to plasmid DNA through to late-phase clinical mRNA drug substance manufacturing with ease.”

The facility will include ISO 7 cleanrooms and increased mRNA capacity, which will also feature comprehensive in-house analytical services, according to the press release.

“Our team took great care in building and designing our new facility– it’s truly been a labor of love,” added Rob Carpenter, vice president of Engineering at TriLink, in a press release. “In addition to having access to a state-of-the-art facility, developers will also have a direct line to our experienced team to help with process optimization, scale-up, validation, and qualification capabilities.”

The new CGMP facility is expected to contribute to the development of mRNA therapeutics, with a building designed for the CGMP manufacture of mRNA-based in-vivo gene editing, gene-edited cell therapies, protein replacement therapies, cancer vaccines, and infectious disease vaccines.

TriLink BioTechnologies to Expand Manufacturing Capabilities 

Blueprint Medicines announced FDA approval of Ayvakit (avapritinib) for treatment of adults with indolent systemic mastocytosis (ISM), a rare hematologic disorder, on May 22, 2023. Avapritinib, a tyrosine-kinase (KIT) inhibitor that selectively inhibits KIT D816V, was previously approved for the treatment of systemic mastocytosis (1). According to a company press release, it is the first and only FDA-approved medicine designed to treat ISM.

FDA’s approval is based in part on findings from a Phase II, double-blind, placebo-controlled clinical trial (PIONEER). Patients who received avapritinib demonstrated significant improvements versus placebo in both the primary and all key secondary endpoints, improving overall symptoms and measures of mast cell burden.

"After decades of caring for people with indolent systemic mastocytosis, I have seen firsthand its profound impact on patients' underlying mast cell burden, symptoms, physical and mental health, and ability to work and participate in daily activities," said Cem Akin, professor of Medicine at the University of Michigan, and an investigator on the Phase II clinical trial. "Despite the use of multiple supportive care treatments, a considerable number of patients with indolent systemic mastocytosis continue to experience a substantial disease burden. [Avapritinib] advances the treatment of indolent systemic mastocytosis by targeting KIT D816V, the primary underlying cause of the disease, and establishes a new standard of care for a broad population of patients with this disorder. [Avapritinib] delivered statistically significant and consistent clinical improvements in the PIONEER trial, and based on these practice-changing data, I feel a tremendous sense of hope for the future for all those affected by the disease."

1. FDA. FDA Approves Avapritinib for Advanced Systemic Mastocytosis. Press Release, June 16, 2021.

Blueprint Medicines’ avapritinib has been approved by FDA for the treatment of indolent systemic mastocytosis.