The market momentum of novel therapies targeting unmet needs is creating a new landscape for pharmaceutical drug manufacturers. As the focus on these smaller patient pools grows, so does the complexity of drug development. Companies must understand how the molecules filling today’s pipeline are changing our business, as they are causing a dramatic shift in how we plan for and execute drug development and manufacturing. As a CDMO, our customers’ needs give us a unique perspective on the evolution of the industry and how it is shaping today’s market. By passing this insight on to you, we at Patheon, part of Thermo Fisher Scientific, hope it gives you a better idea of industry trends in drug development.
Take a big picture approach to small molecules. Ensure that you always have the exact resources and expertise you need, especially for your most difficult to manufacture compounds. With Patheon you’ll have access to a vast array of small molecule API capabilities in Europe and the United States. Reactors ranging from 30 L up to 16 m3, comprehensive analytical services and expertise in all the chemistries you expect, as well as many unique solutions and innovative technologies you won’t find anywhere else. It’s a big-picture approach that delivers high-quality API via a seamlessly scalable process that will rapidly achieve your goals at each phase of development while laying a sound foundation for your future success.
The challenges, risks and costs of bringing complex large molecule products to market are growing exponentially. Gaining a competitive advantage is more difficult. Drawing on 20 years of biologic experience, Thermo Fisher Scientific offers you flexible, end-to-end solutions and expertise in development and manufacturing combined with advanced technical capabilities.
Crystallization is the most common unit operation for isolation and purification of solid intermediates and active pharmaceutical ingredients (APIs). As the end point of both the chemical development process and later manufacturing, the quality of the API delivered has a direct impact upon drug product formulation development and manufacturing.
The challenges for new drugs looking to enter the market are numerous and varied. But many are self-inflicted – especially in small molecule development. A dangerous perception persists that aside from highly potent APIs, small molecule medications have simple process requirements. The reality, however, is that most APIs will require numerous steps or significant work upfront to avoid development delays, rework or outright failure.
The biologics market is quickly evolving from a focus on developing blockbuster drugs to exploring niche markets with unmet needs. While the changes are exciting, they pose several risks to a molecule’s success as competition intensifies, timelines shorten and capacity challenges emerge. Yesterday’s solutions may not be a perfect fit for today’s molecules.
As the biopharmaceutical industry continues to evolve, the Quality by Design (QbD) holistic and proactive approach to drug development and manufacturing is transforming key processes. In response to increased interest from global regulatory agencies, QbD seeks to further reduce the risk associated with drug development and bring much-needed therapies to market quicker. Sponsors who implement QbD early can save money through increased product / process knowledge, less re-work, less product deviation, less product out-of-specification, fewer rejects and improved quality.
In small pharmaceutical start-ups, you have to move fast with a limited amount of budget and resources to get your molecule to first-in-human, and then to proof-of-concept (POC). You keep headcount low and outsource wherever you can, often to multiple vendors. Working with multiple vendors means investing significant time to negotiate terms and conditions as well as to oversee the project.
“Faster and better” has become the mantra for biopharmaceutical companies as they face intense pressure to get therapies to market quicker than ever before. The incentive of securing market share with first-to-market offerings is felt by all industry players. Whether biopharmaceutical companies have one candidate or 100, the directive is clear: moving quickly into FIH testing is essential. Learn key strategies for speeding time to clinic.
The pressure to file an IND makes accelerated Phase I safety testing a priority. With the Quick to Clinic program, Thermo Fisher Scientific can deliver your large molecule drug substance for First-in-Human studies in as little as 12 months. Now you can meet important milestones – such as filing the IND – or secure additional funding with all the confidence your project needs and, we can supply. Because helping you reduce the time it takes to get your discovery to the patients who need it matters, our Quick to Clinic for Biologics is made with speed and flexibility.
There are many parenteral dosage forms from which the pharmaceutical scientist can choose to develop their drug product. For primary pack choices, there are traditional vials, ampoules, cartridges, pre-filled syringes and complex containers such as the various types of dual chamber syringes. Additionally, there are newer dosage forms such as wearable injection devices or pump patches. Each have their own merits and advantages, but these advantages may not be realized until the product is marketed. Consideration must also be made on the form of the product within the container and the environment in which it will be used and needs to be (or is able to be) stored.
Biologics have experienced steady double-digit growth over the last 15 years and now comprise slightly more than a quarter of all New Molecular Entity (NME) FDA approvals. Similarly, EvaluatePharma’s 2017 report on orphan drugs projects that by 2020, six of the 10 best-selling global drug therapies will be biologic sterile injectable drugs. Precision medicine is also on the rise, with the FDA approving a record number of precision drugs in 2017. The rise in these targeted therapies and precision medicine means big changes for drug development and manufacturing companies. Learn what pharma companies should look for when navigating this new era of small-volume manufacturing.
Whether your company is built on a single molecule or you’re a global pharmaceutical leader, you need fast, cost-effective and scientifically-based insights during early-phase development. Patheon can provide you with customized early development strategies and technical solutions to solve complex development challenges.
The numerous controls and processes in place to ensure a medication is safe, effective, and manufactured with the utmost efficiency make drug development extremely complicated. The challenges of drug development can increase if a manufacturer assumes an existing formulation for an adult can also be used for a child. Pediatric drug development requires a formulation designed to fit the specific needs of that patient population. Not considering these requirements early enough could add significant delays and costs to the development process.
Given the increasing pressure to speed up drug development and make the process more cost-effective, pharmaceutical companies want to ensure that their most promising drug candidates hit the market. However, while speed to the clinic – and then to market – is often thought to be the key to success, it is equally important that formulation, process development, scalability, and stability challenges are addressed by systematic, smart scientific solutions to de-risk the drug development process so that costly late-stage failures can be avoided.
With few potential blockbuster drugs in the pharma pipeline right now, drug companies are increasingly looking at other options to meet the needs of patients and increase revenue in the oral solid dosage (OSD) arena. Current areas of exploration include novel drug combinations, oral delivery of large molecules that were available only as injectables, and perhaps most interesting, drugs that carry digital, ingestible sensors that can send information directly to a physician.
The opioid abuse epidemic is a serious public health crisis that demands action on the part of many stakeholders. While abuse-deterrent opioids will not solve the opioid abuse epidemic alone, they play a critical role in the fight against it. While Collegium had come up with an innovative new approach to abuse deterrent formulations, it did not have the capacity or resources to manufacture its drug on a commercial scale.
Innovations in science and technology over the last few decades enable scientists to create far more advanced pharmaceuticals for today’s industry. As a result, patients rightfully expect medication with fewer side effects and physicians anticipate new and better cures for formerly untreatable diseases. Finding a balance between a complex API, its formulation, and its synthesis requires equipment, knowledge, and processes more extensive than those typically required for traditional drug development. It also calls for collaboration across several teams in order to break down the silos that can interrupt the flow of open and clear communication.
The pharmaceutical industry must constantly evolve as companies race to develop the next blockbuster drug. As they face pressure to bring new drugs to market more quickly and at minimal cost, pharmaceutical and biotechnology companies are increasingly outsourcing various parts of the drug development and manufacturing process. Outsourcing eliminates the need to maintain expensive in-house facilities while providing access to a broad range of different technologies and expertise.
Tufts Center for the Study of Drug Development (CSDD) recently completed research, titled “Assessing the Economics of Single-Source vs. Multi-Vendor Manufacturing” that compared cycle times and development economics between multi- and single-source CDMO models. While there are many studies that debate the total cost of drug development,1-3 the Tufts study sought a better understanding of which model offered the most accelerated time-to-market for its clients. By focusing on time as a primary value driver, a sponsor can lower the overall cost of bringing its drug to market, and more importantly, achieve the speed-to-market patients both want and need.
Traditionally, the development of a small-scale synthesis for an active pharmaceutical ingredient (API) and its scale-up to meet the materials demand for clinical trial phases is a sequential activity that passes through multiple sets of hands. Even if the synthesis used at a small scale is the same one used at a large scale, the developer must be prepared to encounter and react to any changes to the API’s quality attributes, such as by-product profile and physical form. Learn why a company must be aware of any potential conditions that could occur at a small-scale that could create major issues during commercial scale-up.
When aggressive timelines are a “must,” it’s critical that companies don’t gloss over early-phase scale-up throughout the development process. The time and effort spent on risk assessments and thinking about scalability early on will pay dividends in the long run as the path toward regulatory approval is smoother.
In drug development, designing a formulation for a drug product (a tablet, for example) calls for careful attention to both the physical and chemical properties of the active pharmaceutical ingredient (API or drug substance). It also requires awareness that certain physical attributes, such as particle size distribution of the drug substance, can change with processing conditions and changes in the synthesis route that is employed. Find out how a pharmaceutical company can recognize both unfavorable drug substance properties and incompatibility between an API and its formulation to avoid potential risks to the patient as well as costly interruptions during development.
Changes in the Drug Substance (DS) process as it scales up can affect the Drug Product (DP). As processes change, many properties of the DS can also change. Therefore, as DS manufacturers evaluate and optimize the synthetic route, process conditions, crystallization solvents, etc., they must understand and track these changes, and discuss them with DP formulators to anticipate challenges in formulation.
In 2016, Patheon successfully completed 111 technology transfers to help our clients safeguard supply, improve distribution and reduce program costs and risks. This has allowed firms to take advantage of specialist expertise, solid processes and standardized operating procedures and equipment.
The traditional business model for in-house pharmaceutical manufacturing is nearly a thing of the past. More companies are turning to outsourcing to achieve flexibility and efficiency in a highly competitive market.
Regardless of whether your group has been diligently planning for scale-up since Phase I or you have delayed scale-up work until now, it would be a mistake to assume Phase III will be clear sailing. The reality is that several manufacturability problems could be brewing that will rain down during Phase III and cause costly delays, no matter how skilled the product and process development teams may be.
As part of the FDA’s efforts to address opioid addiction, the agency put an opioid action plan into effect in 2011 to “reduce opioid abuse, dependence, and overdose in the United States.” Part of this plan included a call to pharmaceutical manufacturers to develop and expand access to abuse-deterrent formulations (ADFs) in order to discourage abuse among patients and promote innovation in the industry.
The pharmaceutical industry’s past reliance on blockbuster drugs has evolved to include a focus on developing drugs that treat the unmet needs of smaller patient populations. These niche drugs most often come in the form of biologics, which are an increasingly larger share of new drug approvals in the past decade, from a low of 10 percent to a high of 27 percent. By 2022, 50% of the value of the top 100 products is expected to come from biologics.
When a biologics company prepares to launch a new product, it must forecast the manufacturing capacity it will need. To create this forecast, it must factor in its estimate of the size of future sales, the timing of the launch, the dosage of the product, its strategy for building its market and a host of other variables. Variations in any one of those factors can lead to drastically different demand scenarios. If a company overestimates demand, it may end up investing in too much capacity, and therefore find itself paying more per unit of the product than it needs to, thus impacting its margins. If it underestimates demand, it risks not being able to satisfy demand, therefore losing revenue. Forecasting demand is a complex endeavor. For instance, it’s not unusual for the forecasted and actual dosage of a product to vary by a factor of as much as three. Obviously, that makes a big difference to a demand forecast. If a manufacturer has built capacity in anticipation of a new product and its clinical trial is delayed (for any number of reasons), that manufacturer’s capital is tied up in a fallow facility. For a small company for which liquidity is critical, that can be catastrophic.
The road to take a drug compound from discovery to commercialization is long, expensive and often fraught with unforeseen challenges. While every project will undoubtedly face some bumps along its path, far too many programs hit insurmountable obstacles that require innovators to backtrack and correct their course before proceeding, further extending timelines and adding costs.
ORC International’s report “Implications of Inaccurate Forecasting on Biologics Drug Substance Manufacturing” explores the causes, consequences, and potential solutions to forecasting challenges specifically related to biopharmaceutical drug substance manufacturing. This analysis provides further insight and perspective on the key themes that emerge from the report and offers additional solutions to companies to better prepare for the inevitable forecast inaccuracies for biopharmaceuticals.
Consultants play a critical role in ensuring the long-term success of small biopharmaceutical companies, though much of their work happens behind the scenes. From lifecycle planning to marketing advice, consultants help fill gaps in knowledge while having their fingers on the pulse of new production strategies that might be a fit for clients. Counseling clients on such solutions—especially those that may help to de-risk the increasingly challenging biopharmaceutical development process—can be a win-win for the industry and consumers alike. What follows is a guide to some key strategies that consultants can keep in mind for their smaller biopharmaceutical clients.
Drug development is an expensive proposition. Discovery and preclinical work are estimated to cost $318 million per compound, with an additional $800 million to $1.1 billion required to advance a molecule from first-in-human testing to market approval. For small biopharmaceutical innovators, steep development costs are compounded by the fact that large molecules are becoming increasingly complex and serious clinical or manufacturing problems may not surface until late in the process. Building upon this risk, events such as mergers, acquisitions, restructurings, political uncertainty and even public criticism can all have a huge effect on a small company’s stock and monetary resources. With a limited amount of money at their disposal for generating clinical data, biopharma firms are often waiting for the perfect moment to pull the trigger and move products quickly through development. This creates a situation where highly compressed process development timelines lead companies to overlook critical factors that could delay— or even suspend—efforts down the road. In this whitepaper, we identify some important risks that consultants should put on the radars of their small biopharma clients. Doing so, along with choosing the right outsourcing partner, will ensure their risks—not their financial returns—are diminished.
ORC International’s 2016 study highlights issues inherent in forecasting biologic drug substances. From discussions with pharmaceutical and biotechnology industry leaders, it is clear that demand forecasting is a significant challenge when planning biologic drug substance production. The biologics development and approval process is typically long and complicated, increasing the risk of accurately forecasting demand. Overestimating demand can lead to higher per unit cost and disposal expenses, and underestimating it can result in missed market opportunities and negative reputational consequences for the company. Download and read Patheon’s perspective to the ORC study “Challenges, Risks and Strategies for Biologic Substance Manufacturing” and discover how biologics companies are increasingly demanding modular and disposable technologies and continuous manufacturing because of the need for flexible capacity.
We live in a time when breakthrough medicines are being discovered at an unprecedented rate. Yet whether from big pharmaceutical companies or small hubs of innovation, these treatments of tomorrow are often held up by a complex supply chain. Patheon offers a cure.
Formulation problems are arising with greater frequency, delaying development, and burdening developers with unanticipated and heavy costs. Find out how to best anticipate formulation challenges of complex molecules and APIs.
Pharmaceutical companies walk a tightrope in early drug development. They have to balance speed, quality, scientific risk, and API cost. Compromising on any one of these four crucial elements can prove fatal to a product candidate. Appropriate use of sound science applied at critical junctures will improve efficiency in the high-wire act of drug development.
Pharmaceutical companies around the world are under tremendous pressure – from regulators, legislators, payers, and patients – to reduce the cost of drugs. In response to the outcry for cost-cutting, pharmaceutical company leaders are examining every aspect of their business to determine where they can derive savings, particularly when planning for the launch of a new product.
Biopharmaceutical companies take on a lot of risk developing new large molecule drugs. With more complex molecules in development, changing capacity needs, uncertain forecasts and increased competition, the market demands flexibility and innovative approaches to address today’s new challenges.
We know the cost of developing a prescription drug is estimated at $2.6 billion, and takes 10 to 15 years from target selection to drug approval with an overall success rate around 10%. Furthermore, only about 35% of drug discovery projects succeed in delivering experimental drugs ready for clinical testing.
Poorly managed postoperative pain can have a significant impact on a patient’s recovery. Consequently, more patients relying in opioids furthers compounds the opioid epidemic. This case study discusses how Patheon and Pacira Pharma partnered to help curb this epidemic.
When pharmaceutical companies introduce a new drug to market, they invest enormous amounts of capital, and assume equally enormous amounts of risk. As it usually takes three-to-four years to prepare manufacturing capacity for the large scale production of a new product, the decision as to how much volume a company will need often must be made before Phase III trials are completed. At that point, it is difficult for developers to forecast demand. Therefore, deciding how much manufacturing capacity they will need is problematic, to say the least. Underestimating or overestimating demand can have a devastating impact on the bottom line.
Why revisit your supply chain? The cost of bringing new drugs to market continues to rise. Regulators are demanding more (and more detailed) clinical evidence. Today’s complex molecules – small and large – require an enormous range of technologies that usher in new challenges. Being first to market matters more than ever before. And when you factor in that a growing majority of new molecule development is coming from small and emerging companies, it’s clear that a new method of drug production has to emerge. Biopharma companies of all sizes look to vendors to help manage development, manufacturing, and capacity needs. The question is: are they keeping up?
The Biopharmaceutics Classification System (BCS), developed by the U.S. Food and Drug Administration to simplify and accelerate the drug development process, helps companies when they file for bioequivalence of dosage forms based on in vitro dissolution testing.The objective of the BCS system is to predict in vivo performance of drugs from in vitro measurements of solubility and permeability. The system has evolved to classify low-soluble drugs according to their permeability (BCS Class II or IV). A compound’s classification (I through IV) is indicative of its potential bioavailability.
The pharmaceutical industry lags in the sophistication and performance of its supply chains when they are compared with best-in-class companies in other industries. This is due to the complexity that has come with new drugs, more complex production technologies and evolving regulatory requirements. In this environment, integrating and aligning the supply chain makes it more flexible, bolstering operational performance and financial competitiveness.