Formulation can be challenging, particularly when working with excipients such as sugar alcohols. However, a new line extension from SPI Pharma offers a solution that leverages the patient-centric benefits of mannitol while avoiding common drug development problems and simplifying manufacturing
Having discussed the key elements of the line extension in Part I, the conversation turns to the somewhat turbulent situation that the world now finds itself in. As a US-headquartered company, I ask the panel about supply chain security and whether their location has provided any benefits during the COVID-19 crisis.
“To be honest,” says John, “we have a very robust security of supply programme that has been in place for years. We source our raw materials from across the globe but, without doubt, this has been a very unusual time; what we’re seeing is the virus affect certain areas for a while then, taking China for instance — where we source some of our raw materials and sell some of our products — it appears that they’ve been able to get their arms wrapped around the virus and manufacturing sites are reopening."
"Our expectation is that the virus will continue to move across the globe and follow the same pattern; after reaching a peak, it then starts coming down and factories start opening up.”
“At this point and, again, because of a lot of hard work that’s been done, our supply chain is so diversified that we don’t see it as an issue. But these are different times; it’s hard to know what’s going to happen next month, etc. But, right now, our diversity across the globe has provided us with a very stable supply chain.”
Also, perhaps, a contributing factor, I wondered whether the nitrosamine contamination incident had caused SPI any problems or whether the company had had to put any additional analytical tests in place.
“From a marketing perspective,” notes Bill, “it was really interesting to see because it started to catalyse things that we had experienced in the past in terms of supply chain security and supplies from different parts of the world. Contamination and quality are critical; yet, it was the security aspects and border closures that hit my radar.”
Commenting on the countermeasures that need to be in place during the development process, John states: “We have a duty of care, so we have to think beyond what makes business sense, we have to put people and patients first. When those nitrosamine contamination reports began to emerge, we looked at our top product line and asked the question: how are we [potentially] exposing our stakeholders?"
"What we found was that there was very limited exposure — if any — but we took every step to investigate and make sure our products were safe. It probably goes without saying that we would proactively inform anyone who might have been exposed by a product … as opposed to retroactively as the law requires.”
With the coronavirus pandemic showing no signs of abating, and the much-touted artificial intelligence and machine learning not predicting the outbreak, I posit that there should be more collaboration within the pharma industry to deal with such epidemics and ask what should be done to prevent it next time.
“That’s a loaded question!” laughs Bill: “Let me address it from a non-judgemental standpoint; to be prepared for pandemics (although it’s not 100% possible to know when a disease will transition from local to global), you need to have drugs that protect the most vulnerable populations.”
“We can always do more as an industry,” adds Don, “particularly those of us who help the drug industry to create simple dosage forms that don’t require novel processes or new technology … and that stay within the four key manufacturing tenets of the industry."
"For example, we produce dosage forms for children and geriatric patients that are inexpensive, that have IP protection, that are easy to manufacture and are known to the regulator. That’s what we do! We make excipients and drug formulation ingredients that fit those four key parameters and, we believe, will enable the pharma industry to more proactively address the challenges — wherever and however — that occur during a pandemic."
"There are always populations that are vulnerable, and being able to quickly address their needs with safe formulations that are convenient to take and result in efficacious treatment is paramount.”
“So, although clinical trials are significant in terms of time, cost and final approval, formulating the drug to be palatable is a perennial issue for geriatric and paediatric populations, for example, particularly as those two groups are going to move from being 30–40% of the global population to 50–60% in the next 50 years or so. The problem will only be exacerbated if we don’t have the right, easy-to-use tools in the hands of drug companies,” he adds.
“Another important point in situations such as this is that pharma companies are not only trying to make patient-centric doses, they’re also trying to bring the product to the market as quickly as possible. This is key … and with this type of direct compression formulation, we need to make these drugs and get them to patients in the shortest achievable timeframes.”
“From SPI’s standpoint,” says John, “one of our core tenets is that we take care of our people. Lots of companies say it but SPI — and our parent company, ABF (Associated British Foods) —really embodies it. It’s in our DNA. Both ABF and SPI recognise our responsibility during this crisis to continue to produce as much material as we can. Our role, because we don’t produce vaccines, is to support the production of the other life-saving drugs that people are taking on a regular basis.”
“While making sure that our people are safe, we’re doing everything that we can to manufacture products and make sure that this doesn’t become a domino effect whereby we not only have a pandemic outbreak, but we also run short of the other critical drugs that people need."
We see it as a primary responsibility to our people, to our regions and to the globe to continue to ensure a secure supply, ease the suffering of many and, hopefully, all get through these troubling times.”
“We need to be ready for more pandemics,” he continues, “and one way to do that is to have access to readily manufacturable, easy-to-use, highly compliant, simple delivery/dosage systems that drug companies have ‘on the shelf’ from a production standpoint, enabling them to take a molecule of interest, put it in a dosage form, get it into the clinic and go straight from trials to manufacturing. It will never be that simple, of course; but, if we can move towards that point now, when things like COVID-19 happen in the future, we’ll be better prepared.”
“We’ve spent years building our systems to make them robust. Security of supply is just one example, but that’s the kind of work that pharma companies should be doing to protect people in these unknown circumstances. Many manufacturers are going to run out of materials because they didn’t plan ahead; they never thought that anything like this could happen, so their supply chain is relatively fragile."
"That’s one of the values that SPI brings to its customers; we are constantly looking at external threats and how to mitigate them before they actually occur. That’s what we can do as a pharma company to protect ourselves and protect our people,” he concludes.
In closing, and thinking ahead to less turbulent times, I ask SPI why pharmaceutical companies should formulate with the new mannitol. “They should do so because it meets the needs of their patients and the needs of their organisation,” quips Don, adding: “We’re hopeful that the products we’ve brought to market address two sets of unmet needs for our customers and our customers’ customers.”
“We also provide a wide range of services; so, if a customer has a question, we can provide answers on drug development, processing, performance and beyond. It’s critically important to recognise that, among our serious competitors, we’re the only ones that have a development team on call in both the US and India to offer counsel, guidance and advice throughout the development process."
"We go deeper than the technical data sheet to provide an interactive and consultative answer that will help them to solve their problem. Plus, if the customer wants, we can give them the whole formula. We already have a number of examples already based on these products and can develop new ones for customers right across the regulatory spectrum.”
“From a manufacturing standpoint,” he summarises, “one of our goals is to provide new, unique tools that are relatively low risk. What we’re providing here are platforms that pharma companies have been using for many years … but with added benefits that are going to help them to improve their dosage forms, lower their costs and enhance the final product for the patient. It’s exactly what the industry has been asking for, and that’s what we’re providing!”